Dosimetric intercomparison of permanent Ho-166 seed's implants and HDR Ir-192 brachytherapy in breast cancer.

PubMed

de Campos, Tarcisio Passos Ribeiro; Nogueira, Luciana Batista; Trindade, Bruno; Cuperschmid, Ethel Mizrahy

2016-01-01

To provide a comparative dosimetric analysis of permanent implants of Ho(166)-seeds and temporary HDR Ir(192)-brachytherapy through computational simulation. Brachytherapy with Ir(192)-HDR or LDR based on temporary wires or permanent radioactive seed implants can be used as dose reinforcement for breast radiation therapy. Permanent breast implants have not been a practical clinical routine; although, I(125) and Pd(103)-seeds have already been reported. Biodegradable Ho(166)-ceramic-seeds have been addressed recently. Simulations of implants of nine Ho(166)-seeds and equivalent with HDR Ir(192)-brachytherapy were elaborated in MCNP5, shaped in a computational multivoxel simulator which reproduced a female thorax phantom. Spatial dose rate distributions and dose-volume histograms were generated. Protocol's analysis involving exposure time, seed's activities and dose were performed. Permanent Ho(166)-seed implants presented a maximum dose rate per unit of contained activity (MDR) of 1.1601 μGy h(-1) Bq(-1); and, a normalized MDR in standard points (8 mm, equidistant to 03-seeds - SP1, 10 mm - SP2) of 1.0% (SP1) and 0.5% (SP2), respectively. Ir(192)-brachytherapy presented MDR of 4.3945 × 10(-3) μGy h(-1) Bq(-1); and, 30% (SP1), and 20% (SP2). Therefore, seed's implant activities of 333 MBq (Ho(166)) and 259 GBq (Ir(192)) produced prescribed doses of 58 Gy (SP1; 5d) and 56 Gy (SP1, 5 fractions, 6 min), respectively. Breast Ho(166)-implants of 37-111 MBq are attractive due to the high dose rate near 6-10 mm from seeds, equivalent to Ir(192)-brachytherapy of 259 GBq (3 fractions, 6 min) providing similar dose in standard points at a week; however, with spatial dose distribution better confined. The seed positioning can be adjusted for controlling the breast tumor, in stages I and II, in flat and deep tumors, without any breast volumetric limitation.

Digital-Micromirror-Device Projection Printing System for Meniscus Tissue Engineering

PubMed Central

Grogan, Shawn P; Chung, Peter H; Soman, Pranav; Chen, Peter; Lotz, Martin K; Chen, Shaochen; D’Lima, Darryl D

2013-01-01

Meniscus degeneration due to age or injury can lead to osteoarthritis. Though promising, current cell-based approaches show limited success. Here we present three-dimensional methacrylated gelatin (GelMA) scaffolds patterned via projection stereolithography to emulate the circumferential alignment of cells in native meniscus tissue. Cultured human avascular zone meniscus cells from normal meniscus were seeded on the scaffolds. Cell viability was monitored, and neo-tissue formation was assessed by gene expression analysis and histology after two weeks in serum free culture with TGFβ1 (10ng/ml). Light, confocal and scanning electron microscopy was used to observe cell/GelMA interactions. Tensile mechanical testing was performed on unseeded, fresh scaffolds and two-week old cell-seeded and unseeded scaffolds. Two-week old cell/GelMA constructs were implanted into surgically created meniscus defects in an explant organ culture model. No cytotoxic effects were observed three weeks after implantation, and cells grew and aligned to the patterned GelMA strands. Gene expression profiles and histology indicated promotion of a fibrocartilage-like meniscus phenotype, and scaffold integration with repair tissue was observed in the explant model. We show that micropatterned GelMA scaffolds are non-toxic, produce organized cellular alignment, and promote meniscus-like tissue formation. Prefabrication of GelMA scaffolds with architectures mimicking meniscus collagen bundle organization shows promise for meniscal repair. Furthermore, the technique presented may be scaled to repair larger defects. PMID:23523536

Intraoperative 3D Navigation for Single or Multiple 125I-Seed Localization in Breast-Preserving Cancer Surgery.

PubMed

Pouw, Bas; de Wit-van der Veen, Linda J; van Duijnhoven, Frederieke; Rutgers, Emiel J Th; Stokkel, Marcel P M; Valdés Olmos, Renato A; Vrancken Peeters, Marie-Jeanne T F D

2016-05-01

Mammographic screening has led to the identification of more women with nonpalpable breast cancer, many of them to be treated with breast-preserving surgery. To accomplish radical tumor excision, adequate localization techniques such as radioactive seed localization (RSL) are required. For RSL, a radioactive I-seed is implanted central in the tumor to enable intraoperative localization using a γ-probe. In case of extensive tumor or multifocal carcinoma, multiple I-seeds can be used to delineate the involved area. Preoperative imaging is performed different from surgical positioning; therefore, exact I-seed depth remains unknown during surgery. Twenty patients (mean age, 56.8 years) with 25 implanted I-seeds scheduled for RSL were included. Sixteen patients had 1 I-seed implanted in the primary lesion, 3 patients had 2 I-seeds, and 1 patient had 3 I-seeds. Freehand SPECT localized I-seeds by measuring γ-counts from different directions, all registered by an optical tracking system. A reconstruction and visualization algorithm enabled 3-dimensional (3D) navigation toward the I-seeds. Freehand SPECT visualized all I-seeds in primary tumors and provided preincision depth information. The deviation, mean (SD), between the freehand SPECT depth and the surgical depth estimation was 1.9 (2.1) mm (range, 0-7 mm). Three-dimensional freehand SPECT was especially useful identifying multiple implanted I-seeds because the conventional γ-probe has more difficulty discriminating I-seeds transcutaneous. Freehand SPECT with 3D navigation is a valuable tool in RSL for both single and multiple implanted I-seeds in breast-preserving cancer surgery. Freehand SPECT provides continuous updating 3D imaging with information about depth and location of the I-seeds contributing to adequate excision of nonpalpable breast cancer.

Ectopic bone formation in nude rats using human osteoblasts seeded poly(3)hydroxybutyrate embroidery and hydroxyapatite-collagen tapes constructs.

PubMed

Mai, Ronald; Hagedorn, Manolo Gunnar; Gelinsky, Michael; Werner, Carsten; Turhani, Dritan; Späth, Heike; Gedrange, Tomas; Lauer, Günter

2006-09-01

The aim of this study was to evaluate the ectopic bone formation using tissue engineered cell-seeded constructs with two different scaffolds and primary human maxillary osteoblasts in nude rats over an implantation period of up to 96 days. Collagen I-coated Poly(3)hydroxybutyrate (PHB) embroidery and hydroxyapatite (HAP) collagen tapes were seeded with primary human maxillary osteoblasts (hOB) and implanted into athymic rnu/run rats. A total of 72 implants were placed into the back muscles of 18 rats. 24, 48 and 96 days after implantation, histological and histomorphometric analyses were made. The osteoblastic character of the cells was confirmed by immunocytochemistry and RT-PCR for osteocalcin. Histological analysis demonstrated that all cell-seeded constructs induced ectopic bone formation after 24, 48 and 96 days of implantation. There was more mineralized tissue in PHB constructs than in HAP-collagen tapes (at day 24; p < 0.05). Bone formation decreased with the increasing length of the implantation period. Osteocalcin expression verified the osteoblastic character of the cell-seeded constructs after implantation time. No bone formation and no osteocalcin expression were found in the control groups. Cell-seeded constructs either with PHB embroidery or HAP-collagen tapes can induce ectopic bone formation. However, the amount of bone formed decreased with increasing length of implantation.

Prostate Brachytherapy Seed Reconstruction with Gaussian Blurring and Optimal Coverage Cost

PubMed Central

Lee, Junghoon; Liu, Xiaofeng; Jain, Ameet K.; Song, Danny Y.; Burdette, E. Clif; Prince, Jerry L.; Fichtinger, Gabor

2009-01-01

Intraoperative dosimetry in prostate brachytherapy requires localization of the implanted radioactive seeds. A tomosynthesis-based seed reconstruction method is proposed. A three-dimensional volume is reconstructed from Gaussian-blurred projection images and candidate seed locations are computed from the reconstructed volume. A false positive seed removal process, formulated as an optimal coverage problem, iteratively removes “ghost” seeds that are created by tomosynthesis reconstruction. In an effort to minimize pose errors that are common in conventional C-arms, initial pose parameter estimates are iteratively corrected by using the detected candidate seeds as fiducials, which automatically “focuses” the collected images and improves successive reconstructed volumes. Simulation results imply that the implanted seed locations can be estimated with a detection rate of ≥ 97.9% and ≥ 99.3% from three and four images, respectively, when the C-arm is calibrated and the pose of the C-arm is known. The algorithm was also validated on phantom data sets successfully localizing the implanted seeds from four or five images. In a Phase-1 clinical trial, we were able to localize the implanted seeds from five intraoperative fluoroscopy images with 98.8% (STD=1.6) overall detection rate. PMID:19605321

BrachyView: multiple seed position reconstruction and comparison with CT post-implant dosimetry

NASA Astrophysics Data System (ADS)

Alnaghy, S.; Loo, K. J.; Cutajar, D. L.; Jalayer, M.; Tenconi, C.; Favoino, M.; Rietti, R.; Tartaglia, M.; Carriero, F.; Safavi-Naeini, M.; Bucci, J.; Jakubek, J.; Pospisil, S.; Zaider, M.; Lerch, M. L. F.; Rosenfeld, A. B.; Petasecca, M.

2016-05-01

BrachyView is a novel in-body imaging system utilising high-resolution pixelated silicon detectors (Timepix) and a pinhole collimator for brachytherapy source localisation. Recent studies have investigated various options for real-time intraoperative dynamic dose treatment planning to increase the quality of implants. In a previous proof-of-concept study, the justification of the pinhole concept was shown, allowing for the next step whereby multiple active seeds are implanted into a PMMA phantom to simulate a more realistic clinical scenario. In this study, 20 seeds were implanted and imaged using a lead pinhole of 400 μ m diameter. BrachyView was able to resolve the seed positions within 1-2 mm of expected positions, which was verified by co-registering with a full clinical post-implant CT scan.

Smooth muscle cells improve endothelial cell retention on polytetrafluoroethylene grafts in vivo.

PubMed

Yu, Hong; Dai, Wangde; Yang, Zhe; Kirkman, Paul; Weaver, Fred A; Eton, Darwin; Rowe, Vincent L

2003-09-01

We investigated the influence of smooth muscle cells (SMC) on endothelial cell (EC) retention on polytetrafluoroethylene (PTFE) grafts and the effect of SMC seeding on intimal hyperplasia in vivo in a rabbit model. Fibronectin-coated PTFE grafts (4 mm diameter) were seeded with either EC alone, SMC alone, or SMC followed 24 hours later by EC. The grafts were connected to an extracorporal aortic shunt for 1 hour or were individually implanted for 1, 30, and 100 days into the infrarenal aorta as an end-to-side bypass graft. The number of retained cells was compared at 1 hour and at 1 day after implantation. Neointimal thickness was measured 30 and 100 days after implantation. After 1-hour exposure to blood flow, EC retention rate was greater (P <.005) if seeded on top of SMC (98% +/- 2%; n = 8) versus being seeded alone (65 +/- 11%; n = 8). SMC retention rate was 95 +/- 5% (n = 8) when seeded alone. Similar cell retention was obtained 1 day after implantation. After 30-day implantation the neointima was thicker in grafts seeded with EC and SMC (282 +/- 136 microm; n = 3) than with EC only (52 +/- 45 microm; n = 3; P <.001). However, the neointimal thickness for dual-cell-seeded grafts (126 +/- 60 microm; n = 3) was not significantly different (P =.09) from EC-seeded grafts (79 +/- 48 microm; n = 3) after 100-day implantation. EC retention on PTFE grafts in vivo is improved if seeded over a layer of SMC. Further studies are needed to determine whether overlying EC modulate proliferation of underlying SMC.

Real-time intraoperative evaluation of implant quality and dose correction during prostate brachytherapy consistently improves target coverage using a novel image fusion and optimization program.

PubMed

Zelefsky, Michael J; Cohen, Gilad N; Taggar, Amandeep S; Kollmeier, Marisa; McBride, Sean; Mageras, Gig; Zaider, Marco

Our purpose was to describe the process and outcome of performing postimplantation dosimetric assessment and intraoperative dose correction during prostate brachytherapy using a novel image fusion-based treatment-planning program. Twenty-six consecutive patients underwent intraoperative real-time corrections of their dose distributions at the end of their permanent seed interstitial procedures. After intraoperatively planned seeds were implanted and while the patient remained in the lithotomy position, a cone beam computed tomography scan was obtained to assess adequacy of the prescription dose coverage. The implanted seed positions were automatically segmented from the cone-beam images, fused onto a new set of acquired ultrasound images, reimported into the planning system, and recontoured. Dose distributions were recalculated based upon actual implanted seed coordinates and recontoured ultrasound images and were reviewed. If any dose deficiencies within the prostate target were identified, additional needles and seeds were added. Once an implant was deemed acceptable, the procedure was completed, and anesthesia was reversed. When the intraoperative ultrasound-based quality assurance assessment was performed after seed placement, the median volume receiving 100% of the dose (V100) was 93% (range, 74% to 98%). Before seed correction, 23% (6/26) of cases were noted to have V100 <90%. Based on this intraoperative assessment and replanning, additional seeds were placed into dose-deficient regions within the target to improve target dose distributions. Postcorrection, the median V100 was 97% (range, 93% to 99%). Following intraoperative dose corrections, all implants achieved V100 >90%. In these patients, postimplantation evaluation during the actual prostate seed implant procedure was successfully applied to determine the need for additional seeds to correct dose deficiencies before anesthesia reversal. When applied, this approach should significantly reduce intraoperative errors and chances for suboptimal dose delivery during prostate brachytherapy. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Digital micromirror device projection printing system for meniscus tissue engineering.

PubMed

Grogan, Shawn P; Chung, Peter H; Soman, Pranav; Chen, Peter; Lotz, Martin K; Chen, Shaochen; D'Lima, Darryl D

2013-07-01

Meniscus degeneration due to age or injury can lead to osteoarthritis. Although promising, current cell-based approaches show limited success. Here we present three-dimensional methacrylated gelatin (GelMA) scaffolds patterned via projection stereolithography to emulate the circumferential alignment of cells in native meniscus tissue. Cultured human avascular zone meniscus cells from normal meniscus were seeded on the scaffolds. Cell viability was monitored, and new tissue formation was assessed by gene expression analysis and histology after 2weeks in serum-free culture with transforming growth factor β1 (10ngml(-1)). Light, confocal and scanning electron microscopy were used to observe cell-GelMA interactions. Tensile mechanical testing was performed on unseeded, fresh scaffolds and 2-week-old cell-seeded and unseeded scaffolds. 2-week-old cell-GelMA constructs were implanted into surgically created meniscus defects in an explant organ culture model. No cytotoxic effects were observed 3weeks after implantation, and cells grew and aligned to the patterned GelMA strands. Gene expression profiles and histology indicated promotion of a fibrocartilage-like meniscus phenotype, and scaffold integration with repair tissue was observed in the explant model. We show that micropatterned GelMA scaffolds are non-toxic, produce organized cellular alignment, and promote meniscus-like tissue formation. Prefabrication of GelMA scaffolds with architectures mimicking the meniscus collagen bundle organization shows promise for meniscal repair. Furthermore, the technique presented may be scaled up to repair larger defects. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A digital model individual template and CT-guided 125I seed implants for malignant tumors of the head and neck.

PubMed

Huang, Ming-Wei; Liu, Shu-Ming; Zheng, Lei; Shi, Yan; Zhang, Jie; Li, Yan-Sheng; Yu, Guang-Yan; Zhang, Jian-Guo

2012-11-01

To enhance the accuracy of radioactive seed implants in the head and neck, a digital model individual template, containing information simultaneously on needle pathway and facial features, was designed to guide implantation with CT imaging. Thirty-one patients with recurrent and local advanced malignant tumors of head and neck after prior surgery and radiotherapy were involved in this study. Before (125)I implants, patients received CT scans based on 0.75mm thickness. And the brachytherapy treatment planning system (BTPS) software was used to make the implantation plan based on the CT images. Mimics software and Geomagic software were used to read the data containing CT images and implantation plan, and to design the individual template. Then the individual template containing the information of needle pathway and face features simultaneously was made through rapid prototyping (RP) technique. All patients received (125)I seeds interstitial implantation under the guide of the individual template and CT. The individual templates were positioned easily and accurately, and were stable. After implants, treatment quality evaluation was made by CT and TPS. The seeds and dosages distribution (D(90),V(100),V(150)) were well meet the treatment requirement. Clinical practice confirms that this approach can facilitate easier and more accurate implantation.

Multilayer cell-seeded polymer nanofiber constructs for soft-tissue reconstruction.

PubMed

Barker, Daniel A; Bowers, Daniel T; Hughley, Brian; Chance, Elizabeth W; Klembczyk, Kevin J; Brayman, Kenneth L; Park, Stephen S; Botchwey, Edward A

2013-09-01

Cell seeding throughout the thickness of a nanofiber construct allows for patient-specific implant alternatives with long-lasting effects, earlier integration, and reduced inflammation when compared with traditional implants. Cell seeding may improve implant integration with host tissue; however, the effect of cell seeding on thick nanofiber constructs has not been studied. To use a novel cell-preseeded nanofiber tissue engineering technique to create a 3-dimensional biocompatible implant alternative to decellularized extracellular matrix. Animal study with mammalian cell culture to study tissue engineered scaffolds. Academic research laboratory. Thirty-six Sprague-Dawley rats. The rats each received 4 implant types. The grafts included rat primary (enhanced green fluorescent protein-positive [eGFP+]) fibroblast-seeded polycaprolactone (PCL)/collagen nanofiber scaffold, PCL/collagen cell-free nanofiber scaffold, acellular human cadaveric dermis (AlloDerm), and acellular porcine dermis (ENDURAGen). Rats were monitored postoperatively and received enrofloxacin in the drinking water for 4 days prophylactically and buprenorphine (0.2-0.5 mg/kg administered subcutaneously twice a day postoperatively for pain for 48 hours). The viability of NIH/3T3 fibroblasts cultured on PCL electrospun nanofibers was evaluated using fluorescence microscopy. Soft-tissue remodeling was examined histologically and with novel ex vivo volume determinations of implants using micro-computed tomography of cell-seeded implants relative to nanofibers without cells and commonly used dermal grafts of porcine and human origin (ENDURAGen and AlloDerm, respectively). The fate and distribution of eGFP+ seeded donor fibroblasts were assessed using immunohistochemistry. Fibroblasts migrated across nanofiber layers within 12 hours and remained viable on a single layer for up to 14 days. Scanning electron microscopy confirmed a nanoscale structure with a mean (SD) diameter of 158 (72) nm. Low extrusion rates demonstrated the excellent biocompatibility in vivo. Histological examination of the scaffolds demonstrated minimal inflammation. Cell seeding encouraged rapid vascularization of the nanofiber implants. Cells of donor origin (eGFP+) declined with the duration of implantation. Implant volume was not significantly affected for up to 8 weeks by the preseeding of cells (P > .05). Polymer nanofiber-based scaffolds mimic natural extracellular matrix. Preseeding the nanofiber construct with cells improved vascularization without notable effects on volume. An effect of cell preseeding on scaffold vascularization was evident beyond the presence of preseeded cells. This 3-dimensional, multilayer method of cell seeding throughout a 1-mm-thick construct is simple and feasible for clinical application. Further development of this technique may affect the clinical practice of facial plastic and reconstructive surgeons.

The side effects and complications of percutaneous iodine-125 seeds implantation under CT-guide for patients with advanced pancreatic cancer.

PubMed

Lv, Wei-Fu; Lu, Dong; Xiao, Jing-Kun; Mukhiya, Gauri; Tan, Zhong-Xiao; Cheng, De-Lei; Zhou, Chun-Ze; Zhang, Xing-Min; Zhang, Zheng-Feng; Hou, Chang-Long

2017-12-01

The present study investigates the side effects and complications of computed tomography (CT)-guided percutaneous iodine-125 (I-125) seeds implantation for advanced pancreatic cancer. The clinical data were retrospectively analyzed for patients treated with implantation of I-125 seeds under CT-guide in our hospital from May 2010 to April 2015. The side effects and complications were collected and their possible reasons were analyzed. A total of 78 patients were enrolled. The side effects were categorized as fever in 29 cases (37.18%), abdominal pain in 26 cases (33.33%), nausea and vomiting in 9 cases (11.54%), diarrhea in 5 cases (6.41%), and constipation in 4 cases (5.13%). Complications were composed of pancreatitis in 9 cases (11.54%), infection in 5 cases (6.41%), seed migration in 2 cases (2.56%), intestinal perforation in 1 case (1.28%), and intestinal obstruction in 1 case. The incidence of complication was 23.08% (18/78). The difference in incidence of complication was statistically significant between patients implanted with ≤27 seeds and those with >27 seeds (P = .032). The side effects and complications frequently occur in implantation of I-125 seeds for patients with advanced pancreatic cancer. More concern should be given to the patients treated by this technique. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Repair of Avascular Meniscus Tears with Electrospun Collagen Scaffolds Seeded with Human Cells

PubMed Central

Baek, Jihye; Sovani, Sujata; Glembotski, Nicholas E.; Du, Jiang; Jin, Sungho; Grogan, Shawn P.

2016-01-01

The self-healing capacity of an injured meniscus is limited to the vascularized regions and is especially challenging in the inner avascular regions. As such, we investigated the use of human meniscus cell-seeded electrospun (ES) collagen type I scaffolds to produce meniscal tissue and explored whether these cell-seeded scaffolds can be implanted to repair defects created in meniscal avascular tissue explants. Human meniscal cells (derived from vascular and avascular meniscal tissue) were seeded on ES scaffolds and cultured. Constructs were evaluated for cell viability, gene expression, and mechanical properties. To determine potential for repair of meniscal defects, human meniscus avascular cells were seeded and cultured on aligned ES collagen scaffolds for 4 weeks before implantation. Surgical defects resembling “longitudinal tears” were created in the avascular zone of bovine meniscus and implanted with cell-seeded collagen scaffolds and cultured for 3 weeks. Tissue regeneration and integration were evaluated by histology, immunohistochemistry, mechanical testing, and magentic resonance imaging. Ex vivo implantation with cell-seeded collagen scaffolds resulted in neotissue that was significantly better integrated with the native tissue than acellular collagen scaffolds or untreated defects. Human meniscal cell-seeded ES collagen scaffolds may therefore be useful in facilitating meniscal repair of avascular meniscus tears. PMID:26842062

Three-dimensional verification of ¹²⁵I seed stability after permanent implantation in the parotid gland and periparotid region.

PubMed

Fan, Yi; Huang, Ming-Wei; Zheng, Lei; Zhao, Yi-Jiao; Zhang, Jian-Guo

2015-11-24

To evaluate seed stability after permanent implantation in the parotid gland and periparotid region via a three-dimensional reconstruction of CT data. Fifteen patients treated from June 2008 to June 2012 at Peking University School and Hospital of Stomatology for parotid gland tumors with postoperative adjunctive (125)I interstitial brachytherapy were retrospectively reviewed in this study. Serial CT data were obtained during follow-up. Mimics and Geomagic Studio software were used for seed reconstruction and stability analysis, respectively. Seed loss and/or migration outside of the treated area were absent in all patients during follow-up (23-71 months). Total seed cluster volume was maximized on day 1 post-implantation due to edema and decreased significantly by an average of 13.5 % (SD = 9.80 %; 95 % CI, 6.82-17.68 %) during the first two months and an average of 4.5 % (SD = 3.60 %; 95 % CI, 2.29-6.29 %) during the next four months. Volume stabilized over the subsequent six months. (125)I seed number and location were stable with a general volumetric shrinkage tendency in the parotid gland and periparotid region. Three-dimensional seed reconstruction of CT images is feasible for visualization and verification of implanted seeds in parotid brachytherapy.

Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model: a pilot study.

PubMed

Li, Wan-Ju; Chiang, Hongsen; Kuo, Tzong-Fu; Lee, Hsuan-Shu; Jiang, Ching-Chuan; Tuan, Rocky S

2009-01-01

The aim of this study was to evaluate a cell-seeded nanofibrous scaffold for cartilage repair in vivo. We used a biodegradable poly(epsilon-caprolactone) (PCL) nanofibrous scaffold seeded with allogeneic chondrocytes or xenogeneic human mesenchymal stem cells (MSCs), or acellular PCL scaffolds, with no implant as a control to repair iatrogenic, 7 mm full-thickness cartilage defects in a swine model. Six months after implantation, MSC-seeded constructs showed the most complete repair in the defects compared to other groups. Macroscopically, the MSC-seeded constructs regenerated hyaline cartilage-like tissue and restored a smooth cartilage surface, while the chondrocyte-seeded constructs produced mostly fibrocartilage-like tissue with a discontinuous superficial cartilage contour. Incomplete repair containing fibrocartilage or fibrous tissue was found in the acellular constructs and the no-implant control group. Quantitative histological evaluation showed overall higher scores for the chondrocyte- and MSC-seeded constructs than the acellular construct and the no-implant groups. Mechanical testing showed the highest equilibrium compressive stress of 1.5 MPa in the regenerated cartilage produced by the MSC-seeded constructs, compared to 1.2 MPa in the chondrocyte-seeded constructs, 1.0 MPa in the acellular constructs and 0.2 MPa in the no-implant group. No evidence of immune reaction to the allogeneically- and xenogeneically-derived regenerated cartilage was observed, possibly related to the immunosuppressive activities of MSCs, suggesting the feasibility of allogeneic or xenogeneic transplantation of MSCs for cell-based therapy. Taken together, our results showed that biodegradable nanofibrous scaffolds seeded with MSCs effectively repair cartilage defects in vivo, and that the current approach is promising for cartilage repair. 2008 John Wiley & Sons, Ltd

Evaluation of articular cartilage repair using biodegradable nanofibrous scaffolds in a swine model: a pilot study

PubMed Central

Li, Wan-Ju; Chiang, Hongsen; Kuo, Tzong-Fu; Lee, Hsuan-Shu; Jiang, Ching-Chuan; Tuan, Rocky S.

2013-01-01

The aim of this study was to evaluate a cell-seeded nanofibrous scaffold for cartilage repair in vivo. We used a biodegradable poly(ε-caprolactone) (PCL) nanofibrous scaffold seeded with allogeneic chondrocytes or xenogeneic human mesenchymal stem cells (MSCs), or acellular PCL scaffolds, with no implant as a control to repair iatrogenic, 7 mm full-thickness cartilage defects in a swine model. Six months after implantation, MSC-seeded constructs showed the most complete repair in the defects compared to other groups. Macroscopically, the MSC-seeded constructs regenerated hyaline cartilage-like tissue and restored a smooth cartilage surface, while the chondrocyte-seeded constructs produced mostly fibrocartilage-like tissue with a discontinuous superficial cartilage contour. Incomplete repair containing fibrocartilage or fibrous tissue was found in the acellular constructs and the no-implant control group. Quantitative histological evaluation showed overall higher scores for the chondrocyte- and MSC-seeded constructs than the acellular construct and the no-implant groups. Mechanical testing showed the highest equilibrium compressive stress of 1.5 MPa in the regenerated cartilage produced by the MSC-seeded constructs, compared to 1.2 MPa in the chondrocyte-seeded constructs, 1.0 MPa in the acellular constructs and 0.2 MPa in the no-implant group. No evidence of immune reaction to the allogeneically- and xenogeneically-derived regenerated cartilage was observed, possibly related to the immunosuppressive activities of MSCs, suggesting the feasibility of allogeneic or xenogeneic transplantation of MSCs for cell-based therapy. Taken together, our results showed that biodegradable nanofibrous scaffolds seeded with MSCs effectively repair cartilage defects in vivo, and that the current approach is promising for cartilage repair. PMID:19004029

Radioactive implant migration in patients treated for localized prostate cancer with interstitial brachytherapy.

PubMed

Older, R A; Synder, B; Krupski, T L; Glembocki, D J; Gillenwater, J Y

2001-05-01

In several of the initial patients undergoing brachytherapy at our institution radioactive implants were visible in the thorax on chest radiography. The clinical ramifications of this unanticipated finding were unclear. Thus, we investigated the incidence of brachytherapy seed migration to the chest and whether these seeds were associated with any clinical significance. We retrospectively reviewed the records of all patients who underwent ultrasound or computerized tomography guided brachytherapy of 103palladium seeds from March 1997 to March 1999. This list of patients on brachytherapy was then matched against the radiology computer system to determine those who had undergone chest X-ray after brachytherapy. When the radiology report was unclear regarding brachytherapy seeds, chest x-rays were reviewed by one of us (R. O.) to determine the presence and position of the seeds. Post-brachytherapy chest x-rays were available in 110 of the 183 patients. In 78 cases no brachytherapy seeds were identified. Radioactive implants were identified on chest radiography in 32 patients (29%), including 1 to 5 seeds in 20, 8, 1, 2 and 1, respectively. No patients complained of any change in pulmonary symptoms after brachytherapy. Radioactive implants migrated after brachytherapy for localized prostate cancer in 29% of the patients who underwent post-procedure radiography. There did not appear to be a pattern to the seed distribution. However, while the incidence was not negligible, no patient appeared to have any acute pulmonary symptoms. Therefore, while the migration of radioactive implants to the chest is a real phenomenon, it appears to have no adverse clinical consequences in the early post-procedure period.

Preventive effects of 125I seeds on benign restenosis following esophageal stent implantation in a dog model

PubMed Central

GAN, ZHEN; JING, JIAN; ZHU, GUANGYU; QIN, YONGLIN; TENG, GAOJUN; GUO, JINHE

2015-01-01

The present study aimed to evaluate the effects of iodine-125 (125I) seeds on the proliferation of primary esophageal fibroblasts in dogs, and to assess the safety and preventive efficacy of 125I seed-pre-loaded esophageal stents in benign restenosis following implantation. Primary fibroblasts were cultured with various 125I seed activities, which were then evaluated using cell proliferation and apoptosis assays as well as cell cycle analysis using Annexin V/propidium iodide (PI) double staining and PI staining. Prior to sacrification, animals were submitted to esophageal radiography under digital subtraction angiography. Esophageal tissues were collected and examined for macroscopic, microscopic and pathological alterations. The results demonstrated a significant and dose-dependent inhibition of fibroblast proliferation and increased apoptosis following exposure to 125I seeds. G0/G1 fibroblast populations increased in a dose-dependent manner following treatment with 125I seeds, in contrast to cells in S phase. Four weeks following implantation, α-smooth muscle actin and proliferating cell nuclear antigen expression levels in the experimental group were significantly lower compared with those in the control group; in addition, eight weeks following implantation, esophageal inner diameters were increased in the experimental group. 125I seeds inhibited proliferation of dog esophageal fibroblasts via cell cycle arrest and apoptosis. In conclusion, 125I seed-pre-loaded esophageal stents inhibited benign hyperplasia in the upper edge of the stent to a certain extent, which relieved benign restenosis following implantation with a good safety profile. PMID:25543838

SU-F-T-39: Comparing Nomograms for Ordering of Palladium-103 Seeds for Dynamic Intraoperative Prostate Seed Implantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, P; Wang, L; Riegel, A

Purpose: Several nomograms exist for the purpose of ordering palladium- 103 seeds for permanent prostate seed implants. Excess seeds pose additional radiation safety risks and increase the cost of care. This study compared three seed ordering nomograms with seed counts from dynamic intra-operative PSI to determine (1) the cause of excess seeds and (2) the optimal nomogram for our institution. Methods: Pre-operative and intra-operative clinical data were collected for 100 Gy (n=151) and 125 Gy (n=224) prostate seed implants. The number of implanted seeds which would have given D90=100% was normalized to that criteria and seed strength of 2U. Thismore » was plotted against intra-operative prostate volume and compared to two previously published nomograms and an in-house nomogram. A linear fit was produced and confidence intervals were calculated. The causes of excess seeds were assessed by comparing pre- and intra-operative prostate volumes, variability of D90 around 100%, and variance of seed strength from 2U. Results: Of the 375 total cases, 97.6% had excess seeds. On average, 27.17±12.91% of ordered seeds were wasted. Of this percentage, 6.98±5.47% of excess seeds were due to overestimation of pre-operative prostate volume, 1.10±0.88% were due to D90<100%, 1.17±0.67% were due to seed strength over 2U, and 17.36±7.79% could not be directly attributed to a specific reason. The latter percentage may be due to overestimation of the in-house nomogram. Two of three nomograms substantially overestimated the number of seeds required. The third nomogram underestimated the required seed number for smaller prostate treatment volume. A linear fit to the clinical data was derived and 99.9% confidence intervals were calculated. Conclusion: Over 85% of clinical cases wasted over 15% of ordered seeds. Two of three nomograms overestimated the required number of seeds. The upper 99.9% C.I. of the clinical data may provide a more reasonable nomogram for Pd-103 seed ordering.« less

Prostate seed implant quality assessment using MR and CT image fusion.

PubMed

Amdur, R J; Gladstone, D; Leopold, K A; Harris, R D

1999-01-01

After a seed implant of the prostate, computerized tomography (CT) is ideal for determining seed distribution but soft tissue anatomy is frequently not well visualized. Magnetic resonance (MR) images soft tissue anatomy well but seed visualization is problematic. We describe a method of fusing CT and MR images to exploit the advantages of both of these modalities when assessing the quality of a prostate seed implant. Eleven consecutive prostate seed implant patients were imaged with axial MR and CT scans. MR and CT images were fused in three dimensions using the Pinnacle 3.0 version of the ADAC treatment planning system. The urethra and bladder base were used to "line up" MR and CT image sets during image fusion. Alignment was accomplished using translation and rotation in the three ortho-normal planes. Accuracy of image fusion was evaluated by calculating the maximum deviation in millimeters between the center of the urethra on axial MR versus CT images. Implant quality was determined by comparing dosimetric results to previously set parameters. Image fusion was performed with a high degree of accuracy. When lining up the urethra and base of bladder, the maximum difference in axial position of the urethra between MR and CT averaged 2.5 mm (range 1.3-4.0 mm, SD 0.9 mm). By projecting CT-derived dose distributions over MR images of soft tissue structures, qualitative and quantitative evaluation of implant quality is straightforward. The image-fusion process we describe provides a sophisticated way of assessing the quality of a prostate seed implant. Commercial software makes the process time-efficient and available to any clinical practice with a high-quality treatment planning system. While we use MR to image soft tissue structures, the process could be used with any imaging modality that is able to visualize the prostatic urethra (e.g., ultrasound).

TPS-guided interstitial Iodine-125 implantation in patients with oral cavity and maxillofacial carcinomas.

PubMed

Meng, J; Zhang, J; Zhuang, Q-W; Wang, X; Li, Z-P; Gu, Q-P

2014-10-01

To investigate the efficacy as well as the complications involved in the use of interstitial Iodine-125 implantation for the treatment of oral cavity and maxillofacial carcinomas. Fifteen patients with oral cavity and maxillofacial carcinomas received treatment planning system (TPS)-guided interstitial Iodine-125 implantation. The apparent activity per particle ranged from 0.6 mCi (2.22MBq) to 0.7 mCi (2.59MBq). The matched peripheral dose delivered by radioactive seeds ranged from 90 to 120 Gy. The efficacy of the treatment and the postoperative complications were evaluated during follow-up. The seeds were implanted successfully in all 15 patients and median number of seeds implanted was 36.53. CT scans were performed in all patients at 1-6 months postoperatively. During follow-up at 6-27 months, seed migration occurred and a good local tumor control was achieved with an overall response of 86.7%. No severe side effects were observed. TPS-guided interstitial Iodine-125 implantation is an effective and safe procedure with minimal invasiveness for the treatment of oral cavity and maxillofacial carcinomas, and it effectively prevents the recurrence of cancer and short-term lymphatic metastasis.

Dosimetric effects of seed anisotropy and interseed attenuation for {sup 103}Pd and {sup 125}I prostate implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chibani, Omar; Williamson, Jeffrey F.; Todor, Dorin

2005-08-15

A Monte Carlo study is carried out to quantify the effects of seed anisotropy and interseed attenuation for {sup 103}Pd and {sup 125}I prostate implants. Two idealized and two real prostate implants are considered. Full Monte Carlo simulation (FMCS) of implants (seeds are physically and simultaneously simulated) is compared with isotropic point-source dose-kernel superposition (PSKS) and line-source dose-kernel superposition (LSKS) methods. For clinical pre- and post-procedure implants, the dose to the different structures (prostate, rectum wall, and urethra) is calculated. The discretized volumes of these structures are reconstructed using transrectal ultrasound contours. Local dose differences (PSKS versus FMCS and LSKSmore » versus FMCS) are investigated. The dose contributions from primary versus scattered photons are calculated separately. For {sup 103}Pd, the average absolute total dose difference between FMCS and PSKS can be as high as 7.4% for the idealized model and 6.1% for the clinical preprocedure implant. Similarly, the total dose difference is lower for the case of {sup 125}I: 4.4% for the idealized model and 4.6% for a clinical post-procedure implant. Average absolute dose differences between LSKS and FMCS are less significant for both seed models: 3 to 3.6% for the idealized models and 2.9 to 3.2% for the clinical plans. Dose differences between PSKS and FMCS are due to the absence of both seed anisotropy and interseed attenuation modeling in the PSKS approach. LSKS accounts for seed anisotropy but not for the interseed effect, leading to systematically overestimated dose values in comparison with the more accurate FMCS method. For both idealized and clinical implants the dose from scattered photons represent less than 1/3 of the total dose. For all studied cases, LSKS prostate DVHs overestimate D{sub 90} by 2 to 5% because of the missing interseed attenuation effect. PSKS and LSKS predictions of V{sub 150} and V{sub 200} are overestimated by up to 9% in comparison with the FMCS results. Finally, effects of seed anisotropy and interseed attenuation must be viewed in the context of other significant sources of dose uncertainty, namely seed orientation, source misplacement, prostate morphological changes and tissue heterogeneity.« less

WE-AB-BRA-12: Post-Implant Dosimetry in Prostate Brachytherapy by X-Ray and MRI Fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, S; Song, D; Lee, J

Purpose: For post-implant dosimetric assessment after prostate brachytherapy, CT-MR fusion approach has been advocated due to the superior accuracy on both seeds localization and soft tissue delineation. However, CT deposits additional radiation to the patient, and seed identification in CT requires manual review and correction. In this study, we propose an accurate, low-dose, and cost-effective post-implant dosimetry approach based on X-ray and MRI. Methods: Implanted seeds are reconstructed using only three X-ray fluoroscopy images by solving a combinatorial optimization problem. The reconstructed seeds are then registered to MR images using an intensity-based points-to-volume registration. MR images are first pre-processed bymore » geometric and Gaussian filtering, yielding smooth candidate seed-only images. To accommodate potential soft tissue deformation, our registration is performed in two steps, an initial affine followed by local deformable registrations. An evolutionary optimizer in conjunction with a points-to-volume similarity metric is used for the affine registration. Local prostate deformation and seed migration are then adjusted by the deformable registration step with external and internal force constraints. Results: We tested our algorithm on twenty patient data sets. For quantitative evaluation, we obtained ground truth seed positions by fusing the post-implant CT-MR images. Seeds were semi-automatically extracted from CT and manually corrected and then registered to the MR images. Target registration error (TRE) was computed by measuring the Euclidean distances from the ground truth to the closest registered X-ray seeds. The overall TREs (mean±standard deviation in mm) are 1.6±1.1 (affine) and 1.3±0.8 (affine+deformable). The overall computation takes less than 1 minute. Conclusion: It has been reported that the CT-based seed localization error is ∼1.6mm and the seed localization uncertainty of 2mm results in less than 5% deviation of prostate D90. The average error of 1.3mm with our system outperforms the CT-based approach and is considered well within the clinically acceptable limit. Supported in part by NIH/NCI grant 5R01CA151395. The X-ray-based implant reconstruction method (US patent No. 8,233,686) was licensed to Acoustic MedSystems Inc.« less

Early fixation of cobalt-chromium based alloy surgical implants to bone using a tissue-engineering approach.

PubMed

Ogawa, Munehiro; Tohma, Yasuaki; Ohgushi, Hajime; Takakura, Yoshinori; Tanaka, Yasuhito

2012-01-01

To establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further cultured in the presence of ascorbic acid, β-glycerophosphate and dexamethasone, resulting in the appearance of osteoblasts and bone matrix on the implant surface. Thus, we succeeded in generating tissue-engineered bone on one side of the CoCr implant. The CoCr implants were then implanted in rabbit bone defects. Three weeks after the implantation, evaluations of mechanical test, undecalcified histological section and electron microscope analysis were performed. Histological and electron microscope images of the tissue engineered surface exhibited abundant new bone formation. However, newly formed bone tissue was difficult to detect on the side without cell seeding. In the mechanical test, the mean values of pull-out forces were 77.15 N and 44.94 N for the tissue-engineered and non-cell-seeded surfaces, respectively. These findings indicate early bone fixation of the tissue-engineered CoCr surface just three weeks after implantation.

Early Fixation of Cobalt-Chromium Based Alloy Surgical Implants to Bone Using a Tissue-engineering Approach

PubMed Central

Ogawa, Munehiro; Tohma, Yasuaki; Ohgushi, Hajime; Takakura, Yoshinori; Tanaka, Yasuhito

2012-01-01

To establish the methods of demonstrating early fixation of metal implants to bone, one side of a Cobalt-Chromium (CoCr) based alloy implant surface was seeded with rabbit marrow mesenchymal cells and the other side was left unseeded. The mesenchymal cells were further cultured in the presence of ascorbic acid, β-glycerophosphate and dexamethasone, resulting in the appearance of osteoblasts and bone matrix on the implant surface. Thus, we succeeded in generating tissue-engineered bone on one side of the CoCr implant. The CoCr implants were then implanted in rabbit bone defects. Three weeks after the implantation, evaluations of mechanical test, undecalcified histological section and electron microscope analysis were performed. Histological and electron microscope images of the tissue engineered surface exhibited abundant new bone formation. However, newly formed bone tissue was difficult to detect on the side without cell seeding. In the mechanical test, the mean values of pull-out forces were 77.15 N and 44.94 N for the tissue-engineered and non-cell-seeded surfaces, respectively. These findings indicate early bone fixation of the tissue-engineered CoCr surface just three weeks after implantation. PMID:22754313

[CT guidance 125I seed implantation for pelvic recurrent rectal cancer assisted by 3D printing individual non-coplanar template].

PubMed

Wang, H; Wang, J J; Jiang, Y L; Tian, S Q; Ji, Z; Guo, F X; Sun, H T; Fan, J H; Xu, Y P

2016-12-20

Objective: To analyze the difference of dosimetric parameters between pre-plan and post-plan of 125 I radioactive seed implantation assisted by 3D printing individual non-coplanar template (3D printing template) for locally recurrent rectal cancer (LRRC). Methods: From February 2016 to April 2016, a total of 10 patients with locally recurrent rectal cancer received 125 I seeds implantation under CT guidance assisted by 3D printing template in Department of Radiation Oncology, Peking University Third Hospital.Each patient underwent CT simulation, three-dimentional treatment planning pre-implantation, 3D printing template design, radioactive seed implantation assisted by 3D printing template and dosimetric verification post implantation. The median activity of seed was 0.63 mCi (0.58 to 0.7 mCi) (2.15- 2.59×10 7 Bq), and the median number of seeds was 80 (19 to 192). D 90 , D 100 , V 100 , V 150 , CI, EI, HI, D 5cc , D 2cc of bladder and bowel of pre-plan and post-plan were calculated, respectively.Paired t test was used to evaluate the difference of dosimetric parameters between pre-plan and post-plan. Results: The median D 90 of pre-plan and post-plan were 13 761.0 and 12 798.8 cGy, respectively.The median D 100 of pre-plan and post-plan were 5 293.6 and 5 397.9 cGy, respectively.The median V 100 of pre-plan and post-plan were 90.0% and 90.0%, respectively.The median V 150 of pre-plan and post-plan were 63.8% and 62.4%, respectively.The median CI of pre-plan and post-plan were 0.73 and 0.67.The median EI of pre-plan and post-plan were 0.22 and 0.30, respectively. The median HI of pre-plan and post-plan were 0.29 and 0.31.The median bladder D 2cc of pre-plan and post-plan were 3 088.8 and 4 240.4 cGy, respectively.The median bowel D 2cc of pre-plan and post-plan were 7 051.6 and 7 903.9 cGy, respectively. Conclusions: 3D printing template might be helpful for locally recurrent rectal cancer patients who received 125 I radioactive seed implantation assisted by 3D printing individual template.Seed implantation might have more chances to achieve prescription dose and dose limitation of organs at risk of pre-plan, which is important for precise implantation and quality control.

Sci-Thur PM – Brachytherapy 02: Positional accuracy in Pd-103 permanent breast seed implant (PBSI) brachytherapy at the Tom Baker Cancer Centre (TBCC)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frederick, Amy; Watt, Elizabeth; Peacock, Michael

Purpose: This retrospective study aims to quantify the positional accuracy of seed delivery in permanent breast seed implant (PBSI) brachytherapy at the Tom Baker Cancer Centre (TBCC). Methods: Treatment planning and post-implant CT scans for 5 patients were rigidly registered using the MIM Symphony™ software (MIM Software, Cleveland, OH) and used to evaluate differences between planned and implanted seed positions. Total and directional seed displacements were calculated for each patient in a clinically relevant ‘needle coordinate system’, defined relative to the angle of fiducial needle insertion. Results: The overall average total seed displacement was 10±8 mm. Systematic seed displacements weremore » observed in individual patients and the magnitude and direction of these offsets varied among patients. One patient showed a significant directional seed displacement in the shallow-deep direction compared with the other four patients. With the exception of this one patient outlier, no significant systematic directional displacements in the needle coordinate system were observed for this cohort; the average directional displacements were −1±5 mm, 2±3 mm, and −2±4 mm in the shallow-deep, up-down, and right-left directions respectively. Conclusion: With the exception of one patient outlier, the magnitude of seed displacements were relatively consistent among patients. The results indicate that the shallow-deep direction possesses the largest uncertainty for the seed delivery method used at the TBCC. The relatively large uncertainty in seed placement in this direction is expected, as this is the direction of needle insertion. Further work will involve evaluating deflections of delivered needle tracks from their planned positions.« less

Lessons Learned from Autopsying an Unidentified Body with Iodine-125 Seeds Implanted for Prostate Brachytherapy.

PubMed

Idota, Nozomi; Nakamura, Mami; Masui, Koji; Kakiuchi, Yasuhiro; Yamada, Kei; Ikegaya, Hiroshi

2017-03-01

We report here lessons learned from an autopsy case involving radioactive materials. We performed an autopsy of an unidentified mummified man with no available medical history whom from imaging findings we suspected had received radioactive seed implants for prostate brachytherapy. We returned the excised prostate and seeds to the body. A few days later, the body was identified by DNA matching and cremated. According to the man's medical record, he had undergone iodine-125 seeds implantation for prostate cancer 11 months earlier. We should have removed the radioactive seeds from the body to prevent radiation exposure to the bereaved family and/or environmental pollution due to cremation. Surprisingly, one seed was found in the stored prostate specimen. Forensic experts should be cognizant of the risk of both radiation exposure in the autopsy room and environmental pollution. We must remain abreast of the latest advances in medicine. © 2016 American Academy of Forensic Sciences.

A virtual fluoroscopy system to verify seed positioning accuracy during prostate permanent seed implants.

PubMed

Sarkar, V; Gutierrez, A N; Stathakis, S; Swanson, G P; Papanikolaou, N

2009-01-01

The purpose of this project was to develop a software platform to produce a virtual fluoroscopic image as an aid for permanent prostate seed implants. Seed location information from a pre-plan was extracted and used as input to in-house developed software to produce a virtual fluoroscopic image. In order to account for differences in patient positioning on the day of treatment, the user was given the ability to make changes to the virtual image. The system has been shown to work as expected for all test cases. The system allows for quick (on average less than 10 sec) generation of a virtual fluoroscopic image of the planned seed pattern. The image can be used as a verification tool to aid the physician in evaluating how close the implant is to the planned distribution throughout the procedure and enable remedial action should a large deviation be observed.

Influence of Prostatic Edema on {sup 131}CS Permanent Prostate Seed Implants: A Dosimetric and Radiobiological Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kehwar, Than S., E-mail: kehwarts@upmc.ed; Jones, Heather A.; Huq, M. Saiful

2011-06-01

Purpose: To study the influence of prostatic edema on postimplant physical and radiobiological parameters using {sup 131}Cs permanent prostate seed implants. Methods and Materials: Thirty-one patients with early prostate cancer who underwent {sup 131}Cs permanent seed implantation were evaluated. Dose-volume histograms were generated for each set of prostate volumes obtained at preimplantation and postimplantion days 0, 14, and 28 to compute quality indices (QIs) and fractional doses at level x (FD{sub x}). A set of equations for QI, FD{sub x}, and biologically effective doses at dose level D{sub x} (BED{sub x}) were defined to account for edema changes with timemore » after implant. Results: There were statistically significant differences found between QIs of pre- and postimplant plans at day 0, except for the overdose index (ODI). QIs correlated with postimplant time, and FD{sub x} was found to increase with increasing postimplant time. With the effect of edema, BED at different dose levels showed less improvement due to the short half-life of {sup 131}Cs, which delivers about 85% of the prescribed dose before the prostate reaches its original volume due to dissipation of edema. Conclusions: Results of the study show that QIs, FD{sub x}, and BEDs at the level of D{sub x} changed from preneedle plans to postimplant plans and have statistically significant differences (p < 0.05), except for the ODI (p = 0.106), which suggests that at the time of {sup 131}C seed implantation, the effect of edema must be accounted for when defining the seed positions, to avoid the possibility of poor dosimetric and radiobiologic results for {sup 131}Cs seed implants.« less

Intra-operative Localization of Brachytherapy Implants Using Intensity-based Registration

PubMed Central

KarimAghaloo, Z.; Abolmaesumi, P.; Ahmidi, N.; Chen, T.K.; Gobbi, D. G.; Fichtinger, G.

2010-01-01

In prostate brachytherapy, a transrectal ultrasound (TRUS) will show the prostate boundary but not all the implanted seeds, while fluoroscopy will show all the seeds clearly but not the boundary. We propose an intensity-based registration between TRUS images and the implant reconstructed from uoroscopy as a means of achieving accurate intra-operative dosimetry. The TRUS images are first filtered and compounded, and then registered to the uoroscopy model via mutual information. A training phantom was implanted with 48 seeds and imaged. Various ultrasound filtering techniques were analyzed, and the best results were achieved with the Bayesian combination of adaptive thresholding, phase congruency, and compensation for the non-uniform ultrasound beam profile in the elevation and lateral directions. The average registration error between corresponding seeds relative to the ground truth was 0.78 mm. The effect of false positives and false negatives in ultrasound were investigated by masking true seeds in the uoroscopy volume or adding false seeds. The registration error remained below 1.01 mm when the false positive rate was 31%, and 0.96 mm when the false negative rate was 31%. This fully automated method delivers excellent registration accuracy and robustness in phantom studies, and promises to demonstrate clinically adequate performance on human data as well. Keywords: Prostate brachytherapy, Ultrasound, Fluoroscopy, Registration. PMID:21152376

SU-E-T-12: A Comparative Dosimetric Study of Pre and Post Prostate Iodine-125 Permanent Seed Implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, X; Rahimian, J; Goy, B

Purpose: Post-implant dosimetry has become the gold standard for prostate implant evaluation. The goal of this research is to compare the dosimetry between pre-plan and post-plan in permanent prostate seed implant brachytherapy. Methods: A retrospective study of 91 patients treated with Iodine-125 prostate seed implant between year 2012∼2014 were performed. All plans were created using a VariSeed 8.0 planning system. Pre-plan ultrasound images were acquired using 0.5 cm slice thickness. Post-plan CT images acquired about 1–4 weeks after implant, fused with the preplan ultrasound images. The prostate and urethra contours were generated using the fusion of ultrasound and CT images.more » Iodine-125 seed source activities varied between 0.382 to 0.414 mCi per seed. The loading patterns varied slightly between patients depending on the prostate size. Statistical analysis of pre and post plans for prostate and urethra volumes, V100%, V150% and D90, and urethra D10 were performed and reported. Results: The pre and post implant average prostate size was 36.90cc vs. 38.58cc; V100% was 98.33% vs. 96.89%; V150% was 47.09% vs. 56.95%; D90 was 116.35Gy vs. 116.12Gy, urethra volume was 1.72cc vs. 1.85cc, urethra D10% was 122.0% vs. 135.35%, respectively. There was no statistically significant difference between the pre and post-plan values for D90(p-value=0.43). However, there are significant differences between other parameters most likely due to post surgical edema; prostate size (p-value= 0.00015); V100% (p-value=3.7803E-07); V150% (p-value=1.49E-09); urethra volume (p-value= 2.77E-06); Urethra D10 (p-value=7.37E-11). Conclusion: The post-plan dosimetry using CT image set showed similar D90 dose coverage to the pre-plan using the ultrasound image dataset. The study showed that our prostate seed implants have consistently delivered adequate therapeutic dose to the prostate while sparing urethra. Future studies to correlate dose versus biochemical response using patients’ PSA values as well as patients’ survival are warranted.« less

A technical evaluation of the Nucletron FIRST system: conformance of a remote afterloading brachytherapy seed implantation system to manufacturer specifications and AAPM Task Group report recommendations.

PubMed

Rivard, Mark J; Evans, Dee-Ann Radford; Kay, Ian

2005-01-01

The Fully Integrated Real-time Seed Treatment (FIRST) system by Nucletron has been available in Europe since November 2001 and is being used more and more in Canada and the United States. Like the conventional transrectal ultrasound implant procedure, the FIRST system utilizes an ultrasound probe, needles, and brachytherapy seeds. However, this system is unique in that it (1) utilizes a low-dose-rate brachytherapy seed remote afterloader (the seedSelectron), (2) utilizes 3D image reconstruction acquired from electromechanically controlled, nonstepping rotation of the ultrasound probe, (3) integrates the control of a remote afterloader with electromechanical control of the ultrasound probe for integrating the clinical procedure into a single system, and (4) automates the transfer of planning information and seed delivery to improve quality assurance and radiation safety. This automated delivery system is specifically intended to address reproducibility and accuracy of seed positioning during implantation. The FIRST computer system includes two software environments: SPOT PRO and seedSelectron; both are used to facilitate treatment planning and brachytherapy seed implantation from beginning to completion of the entire procedure. In addition to these features, the system is reported to meet certain product specifications for seed delivery positioning accuracy and reproducibility, seed calibration accuracy and reliability, and brachytherapy dosimetry calculations. Consequently, a technical evaluation of the FIRST system was performed to determine adherence to manufacturer specifications and to the American Association of Physicists in Medicine (AAPM) Task Group Reports 43, 53, 56, 59, and 64 and recommendations of the American Brachytherapy Society (ABS). The United States Nuclear Regulatory Commission (NRC) has recently added Licensing Guidance for the seedSelectron system under 10 CFR 35.1000. Adherence to licensing guidance is made by referencing applicable AAPM Task Group recommendations. In general, results of this evaluation indicated that the system met its claimed specifications as well as the applicable recommendations outlined in the AAPM and ABS reports.

The effects of metallic implants on electroporation therapies: feasibility of irreversible electroporation for brachytherapy salvage.

PubMed

Neal, Robert E; Smith, Ryan L; Kavnoudias, Helen; Rosenfeldt, Franklin; Ou, Ruchong; Mclean, Catriona A; Davalos, Rafael V; Thomson, Kenneth R

2013-12-01

Electroporation-based therapies deliver brief electric pulses into a targeted volume to destabilize cellular membranes. Nonthermal irreversible electroporation (IRE) provides focal ablation with effects dependent on the electric field distribution, which changes in heterogeneous environments. It should be determined if highly conductive metallic implants in targeted regions, such as radiotherapy brachytherapy seeds in prostate tissue, will alter treatment outcomes. Theoretical and experimental models determine the impact of prostate brachytherapy seeds on IRE treatments. This study delivered IRE pulses in nonanimal, as well as in ex vivo and in vivo tissue, with and in the absence of expired radiotherapy seeds. Electrical current was measured and lesion dimensions were examined macroscopically and with magnetic resonance imaging. Finite-element treatment simulations predicted the effects of brachytherapy seeds in the targeted region on electrical current, electric field, and temperature distributions. There was no significant difference in electrical behavior in tissue containing a grid of expired radiotherapy seeds relative to those without seeds for nonanimal, ex vivo, and in vivo experiments (all p > 0.1). Numerical simulations predict no significant alteration of electric field or thermal effects (all p > 0.1). Histology showed cellular necrosis in the region near the electrodes and seeds within the ablation region; however, there were no seeds beyond the ablation margins. This study suggests that electroporation therapies can be implemented in regions containing small metallic implants without significant changes to electrical and thermal effects relative to use in tissue without the implants. This supports the ability to use IRE as a salvage therapy option for brachytherapy.

Feasibility of vibro-acoustography with a quasi-2D ultrasound array transducer for detection and localizing of permanent prostate brachytherapy seeds: A pilot ex vivo study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mehrmohammadi, Mohammad; Kinnick, Randall R.; Fatemi, Mostafa, E-mail: fatemi.mostafa@mayo.edu

2014-09-15

Purpose: Effective permanent prostate brachytherapy (PPB) requires precise placement of radioactive seeds in and around the prostate. The impetus for this research is to examine a new ultrasound-based imaging modality, vibro-acoustography (VA), which may serve to provide a high rate of PPB seed detection while also effecting enhanced prostate imaging. The authors investigate the ability of VA, implemented on a clinical ultrasound (US) scanner and equipped with a quasi-2D (Q2D) array US transducer, to detect and localize PPB seeds in excised prostate specimens. Methods: Nonradioactive brachytherapy seeds were implanted into four excised cadaver prostates. A clinical US scanner equipped withmore » a Q2D array US transducer was customized to acquire both US and C-scan VA images at various depths. The VA images were then used to detect and localize the implanted seeds in prostate tissue. To validate the VA results, computed tomography (CT) images of the same tissue samples were obtained to serve as the reference by which to evaluate the performance of VA in PPB seed detection. Results: The results indicate that VA is capable of accurately identifying the presence and distribution of PPB seeds with a high imaging contrast. Moreover, a large ratio of the PPB seeds implanted into prostate tissue samples could be detected through acquired VA images. Using CT-based seed identification as the standard, VA was capable of detecting 74%–92% of the implanted seeds. Additionally, the angular independency of VA in detecting PPB seeds was demonstrated through a well-controlled phantom experiment. Conclusions: Q2DVA detected a substantial portion of the seeds by using a 2D array US transducer in excised prostate tissue specimens. While VA has inherent advantages associated with conventional US imaging, it has the additional advantage of permitting detection of PPB seeds independent of their orientation. These results suggest the potential of VA as a method for PPB imaging that ultimately may allow US-based real-time intraoperative dosimetry.« less

Feasibility of vibro-acoustography with a quasi-2D ultrasound array transducer for detection and localizing of permanent prostate brachytherapy seeds: A pilot ex vivo study

PubMed Central

Mehrmohammadi, Mohammad; Alizad, Azra; Kinnick, Randall R.; Davis, Brian J.; Fatemi, Mostafa

2014-01-01

Purpose: Effective permanent prostate brachytherapy (PPB) requires precise placement of radioactive seeds in and around the prostate. The impetus for this research is to examine a new ultrasound-based imaging modality, vibro-acoustography (VA), which may serve to provide a high rate of PPB seed detection while also effecting enhanced prostate imaging. The authors investigate the ability of VA, implemented on a clinical ultrasound (US) scanner and equipped with a quasi-2D (Q2D) array US transducer, to detect and localize PPB seeds in excised prostate specimens. Methods: Nonradioactive brachytherapy seeds were implanted into four excised cadaver prostates. A clinical US scanner equipped with a Q2D array US transducer was customized to acquire both US and C-scan VA images at various depths. The VA images were then used to detect and localize the implanted seeds in prostate tissue. To validate the VA results, computed tomography (CT) images of the same tissue samples were obtained to serve as the reference by which to evaluate the performance of VA in PPB seed detection. Results: The results indicate that VA is capable of accurately identifying the presence and distribution of PPB seeds with a high imaging contrast. Moreover, a large ratio of the PPB seeds implanted into prostate tissue samples could be detected through acquired VA images. Using CT-based seed identification as the standard, VA was capable of detecting 74%–92% of the implanted seeds. Additionally, the angular independency of VA in detecting PPB seeds was demonstrated through a well-controlled phantom experiment. Conclusions: Q2DVA detected a substantial portion of the seeds by using a 2D array US transducer in excised prostate tissue specimens. While VA has inherent advantages associated with conventional US imaging, it has the additional advantage of permitting detection of PPB seeds independent of their orientation. These results suggest the potential of VA as a method for PPB imaging that ultimately may allow US-based real-time intraoperative dosimetry. PMID:25186418

Automatic seed picking for brachytherapy postimplant validation with 3D CT images.

PubMed

Zhang, Guobin; Sun, Qiyuan; Jiang, Shan; Yang, Zhiyong; Ma, Xiaodong; Jiang, Haisong

2017-11-01

Postimplant validation is an indispensable part in the brachytherapy technique. It provides the necessary feedback to ensure the quality of operation. The ability to pick implanted seed relates directly to the accuracy of validation. To address it, an automatic approach is proposed for picking implanted brachytherapy seeds in 3D CT images. In order to pick seed configuration (location and orientation) efficiently, the approach starts with the segmentation of seed from CT images using a thresholding filter which based on gray-level histogram. Through the process of filtering and denoising, the touching seed and single seed are classified. The true novelty of this approach is found in the application of the canny edge detection and improved concave points matching algorithm to separate touching seeds. Through the computation of image moments, the seed configuration can be determined efficiently. Finally, two different experiments are designed to verify the performance of the proposed approach: (1) physical phantom with 60 model seeds, and (2) patient data with 16 cases. Through assessment of validated results by a medical physicist, the proposed method exhibited promising results. Experiment on phantom demonstrates that the error of seed location and orientation is within ([Formula: see text]) mm and ([Formula: see text])[Formula: see text], respectively. In addition, the most seed location and orientation error is controlled within 0.8 mm and 3.5[Formula: see text] in all cases, respectively. The average process time of seed picking is 8.7 s per 100 seeds. In this paper, an automatic, efficient and robust approach, performed on CT images, is proposed to determine the implanted seed location as well as orientation in a 3D workspace. Through the experiments with phantom and patient data, this approach also successfully exhibits good performance.

Prostate brachytherapy

MedlinePlus

Implant therapy - prostate cancer; Radioactive seed placement; Internal radiation therapy - prostate; High dose radiation (HDR) ... CT scan to plan and then place the seeds that deliver radiation into your prostate. The seeds ...

The N-terminal strand modulates immunoglobulin light chain fibrillogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pozo-Yauner, Luis del, E-mail: ldelpozo@inmegen.gob.mx; Wall, Jonathan S.; González Andrade, Martín

2014-01-10

Highlights: •We evaluated the impact of mutations in the N-terminal strand of 6aJL2 protein. •Mutations destabilized the protein in a position-dependent manner. •Destabilizing mutations accelerated the fibrillogenesis by shortening the lag time. •The effect on the kinetic of fibril elongation by seeding was of different nature. •The N-terminal strand is buried in the fibrillar state of 6aJL2 protein. -- Abstract: It has been suggested that the N-terminal strand of the light chain variable domain (V{sub L}) protects the molecule from aggregation by hindering spurious intermolecular contacts. We evaluated the impact of mutations in the N-terminal strand on the thermodynamic stabilitymore » and kinetic of fibrillogenesis of the V{sub L} protein 6aJL2. Mutations in this strand destabilized the protein in a position-dependent manner, accelerating the fibrillogenesis by shortening the lag time; an effect that correlated with the extent of destabilization. In contrast, the effect on the kinetics of fibril elongation, as assessed in seeding experiments was of different nature, as it was not directly dependant on the degree of destabilization. This finding suggests different factors drive the nucleation-dependent and elongation phases of light chain fibrillogenesis. Finally, taking advantage of the dependence of the Trp fluorescence upon environment, four single Trp substitutions were made in the N-terminal strand, and changes in solvent exposure during aggregation were evaluated by acrylamide-quenching. The results suggest that the N-terminal strand is buried in the fibrillar state of 6aJL2 protein. This finding suggest a possible explanation for the modulating effect exerted by the mutations in this strand on the aggregation behavior of 6aJL2 protein.« less

Impact of target area selection in 125 Iodine seed brachytherapy on locoregional recurrence in patients with non-small cell lung cancer.

PubMed

Yan, Wei-Liang; Lv, Jin-Shuang; Guan, Zhi-Yu; Wang, Li-Yang; Yang, Jing-Kui; Liang, Ji-Xiang

2017-05-01

Computed tomography (CT)-guided percutaneous implantation of 125 Iodine radioactive seeds requires the precise arrangement of seeds by tumor shape. We tested whether selecting target areas, including subclinical areas around tumors, can influence locoregional recurrence in patients with non-small cell lung cancer (NSCLC). We divided 82 patients with NSCLC into two groups. Target areas in group 1 (n = 40) were defined along tumor margins based on lung-window CT. Target areas in group 2 (n = 42) were extended by 0.5 cm in all dimensions outside tumor margins. Preoperative plans for both groups were based on a treatment plan system, which guided 125 I seed implantation. Six months later, patients underwent chest CT to evaluate treatment efficacy (per Response Evaluation Criteria in Solid Tumors version 1). We compared locoregional recurrences between the groups after a year of follow-up. We then used the treatment plan system to extend target areas for group 1 patients by 0.5 cm (defined as group 3 data) and compared these hypothetical group 3 planned seeds with the actual seed numbers used in group 1 patients. All patients successfully underwent implantation; none died during the follow-up period. Recurrence was significantly lower in group 2 than in group 1 ( P  < 0.05). Group 1 patients and group 3 data significantly differed in seed numbers ( P  < 0.01). Our results imply that extending the implantation area for 125 I seeds can decrease recurrence risk by eradicating cancerous lymph-duct blockades within the extended areas. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Sci-Sat AM(2): Brachy-05: Dosimetry effects of the TG-43 approximations for two iodine seeds in LDR brachytherapy.

PubMed

Furstoss, C; Bertrand, M J; Poon, E; Reniers, B; Pignol, J P; Carrier, J F; Beaulieu, L; Verhaegen, F

2008-07-01

This work consists of studying the interseed and tissue composition effects for two model iodine seeds: the IBt Interseed-125 and the 6711 model seed. Three seeds were modeled with the MCNP MC code in a water sphere to evaluate the interseed effect. The dose calculated at different distances from the centre was compared to the dose summed when the seeds were simulated separately. The tissue composition effect was studied calculating the radial dose function for different tissues. Before carrying out post-implant studies, the absolute dose calculated by MC was compared to experiment results: with LiF TLDs in an acrylic breast phantom and with an EBT Gafchromic film placed in a water tank. Afterwards, the TG-43 approximation effects were studied for a prostate and breast post-implant. The interseed effect study shows that this effect is more important for model 6711 (15%) than for IBt (10%) due to the silver rod in 6711. For both seed models the variations of the radial dose function as a function of the tissue composition are quasi similar. The absolute dose comparisons between MC calculations and experiments give good agreement (inferior to 3% in general). For the prostate and breast post-implant studies, a 10% difference between MC calculations and the TG-43 is found for both models of seeds. This study shows that the differences in dose distributions between TG43 and MC are quite similar for the two models of seeds and are about 10% for the studied post-implant treatments. © 2008 American Association of Physicists in Medicine.

The Effects of Metallic Implants on Electroporation Therapies: Feasibility of Irreversible Electroporation for Brachytherapy Salvage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neal, Robert E., E-mail: robert.neal@alfred.org.au; Smith, Ryan L., E-mail: ryan.smith@wbrc.org.au; Kavnoudias, Helen, E-mail: H.Kavnoudias@alfred.org.au

2013-12-15

Purpose: Electroporation-based therapies deliver brief electric pulses into a targeted volume to destabilize cellular membranes. Nonthermal irreversible electroporation (IRE) provides focal ablation with effects dependent on the electric field distribution, which changes in heterogeneous environments. It should be determined if highly conductive metallic implants in targeted regions, such as radiotherapy brachytherapy seeds in prostate tissue, will alter treatment outcomes. Theoretical and experimental models determine the impact of prostate brachytherapy seeds on IRE treatments. Materials and Methods: This study delivered IRE pulses in nonanimal, as well as in ex vivo and in vivo tissue, with and in the absence of expiredmore » radiotherapy seeds. Electrical current was measured and lesion dimensions were examined macroscopically and with magnetic resonance imaging. Finite-element treatment simulations predicted the effects of brachytherapy seeds in the targeted region on electrical current, electric field, and temperature distributions. Results: There was no significant difference in electrical behavior in tissue containing a grid of expired radiotherapy seeds relative to those without seeds for nonanimal, ex vivo, and in vivo experiments (all p > 0.1). Numerical simulations predict no significant alteration of electric field or thermal effects (all p > 0.1). Histology showed cellular necrosis in the region near the electrodes and seeds within the ablation region; however, there were no seeds beyond the ablation margins. Conclusion: This study suggests that electroporation therapies can be implemented in regions containing small metallic implants without significant changes to electrical and thermal effects relative to use in tissue without the implants. This supports the ability to use IRE as a salvage therapy option for brachytherapy.« less

Trans-bronchoscopy with implantation of 125I radioactive seeds in patients with pulmonary atelectasis induced by lung cancer

PubMed Central

LU, MINGJIAN; PU, DELI; ZHANG, WEIDONG; LIAO, JIANGRONG; ZHANG, TAO; YANG, GUANG; LIU, ZHENYIN; SINGH, SRISTI; GAO, FEI; ZHANG, FUJUN

2015-01-01

To evaluate the role of low-dose-rate interstitial brachytherapy using trans-bronchoscope 125I radioactive seeds implantation in patients with pulmonary atelectasis induced by lung cancer, in terms of feasibility, safety, quality of life (QOL), and survival time. Between April 2008 and June 2011, 15 patients from two medical institutions that had obstructive pulmonary atelectasis caused by inoperable lung cancer were assigned to receive 125I implantation endoluminal brachytherapy by bronchoscopy. Subsequent to the implantation of 125I seeds, the outcomes were measured in terms of procedure success rate, reopening of atelectasis, complications associated with the procedure, Karnofsky performance status (KPS) scores and survival time. The surgical procedure was successfully performed in all 15 patients. No procedure-associated mortality occurred and the complications were mild and considered acceptable. Irritable cough and temporary increase of hemoptysis occurred in 11 (73.3%) and 10 (66.7%) patients respectively, and were the most common complications. The pulmonary atelectasis reopening rate subsequent to the procedure was 86.7, 76.9, 80.0, 75.0 and 50.0% at 2, 6, 12, 18 and 24 months, respectively. The KPS score significantly improved following the implantation of 125I seeds and the duration of improvement ranged between 3 and 27 months. The median and mean survival times were 15.6 and 16 months, respectively. Actuarial survival rates at 6, 12 and 24 months after the procedure were 86.7, 66.7 and 13.3%, respectively. In patients with advanced lung cancer and those presenting with obstructive pulmonary atelectasis, treatment with intraluminal implantation of 125I seeds is a safe and effective therapy option with easy accessibility. PMID:26171002

Trans-bronchoscopy with implantation of 125I radioactive seeds in patients with pulmonary atelectasis induced by lung cancer.

PubMed

Lu, Mingjian; Pu, Deli; Zhang, Weidong; Liao, Jiangrong; Zhang, Tao; Yang, Guang; Liu, Zhenyin; Singh, Sristi; Gao, Fei; Zhang, Fujun

2015-07-01

To evaluate the role of low-dose-rate interstitial brachytherapy using trans-bronchoscope 125 I radioactive seeds implantation in patients with pulmonary atelectasis induced by lung cancer, in terms of feasibility, safety, quality of life (QOL), and survival time. Between April 2008 and June 2011, 15 patients from two medical institutions that had obstructive pulmonary atelectasis caused by inoperable lung cancer were assigned to receive 125 I implantation endoluminal brachytherapy by bronchoscopy. Subsequent to the implantation of 125 I seeds, the outcomes were measured in terms of procedure success rate, reopening of atelectasis, complications associated with the procedure, Karnofsky performance status (KPS) scores and survival time. The surgical procedure was successfully performed in all 15 patients. No procedure-associated mortality occurred and the complications were mild and considered acceptable. Irritable cough and temporary increase of hemoptysis occurred in 11 (73.3%) and 10 (66.7%) patients respectively, and were the most common complications. The pulmonary atelectasis reopening rate subsequent to the procedure was 86.7, 76.9, 80.0, 75.0 and 50.0% at 2, 6, 12, 18 and 24 months, respectively. The KPS score significantly improved following the implantation of 125 I seeds and the duration of improvement ranged between 3 and 27 months. The median and mean survival times were 15.6 and 16 months, respectively. Actuarial survival rates at 6, 12 and 24 months after the procedure were 86.7, 66.7 and 13.3%, respectively. In patients with advanced lung cancer and those presenting with obstructive pulmonary atelectasis, treatment with intraluminal implantation of 125 I seeds is a safe and effective therapy option with easy accessibility.

SU-E-J-214: MR Protocol Development to Visualize Sirius MRI Markers in Prostate Brachytherapy Patients for MR-Based Post-Implant Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, T; Wang, J; Frank, S

Purpose: The current CT-based post-implant dosimetry allows precise seed localization but limited anatomical delineation. Switching to MR-based post-implant dosimetry is confounded by imprecise seed localization. One approach is to place positive-contrast markers (Sirius) adjacent to the negative-contrast seeds. This patient study aims to assess the utility of a 3D fast spoiled gradient-recalled echo (FSPGR) sequence to visualize Sirius markers for post-implant dosimetry. Methods: MRI images were acquired in prostate implant patients (n=10) on Day 0 (day-of-implant) and Day 30. The post-implant MR protocol consisted of 3D T2-weighted fast-spin-echo (FSE), T2-weighted 2D-FSE (axial) and T1-weighted 2D-FSE (axial/sagittal/coronal). We incorporated a 3D-FSPGRmore » sequence into the post-implant MR protocol to visualize the Sirius markers. Patients were scanned with different number-of-excitations (6, 8, 10), field-of-view (10cm, 14cm, 18cm), slice thickness (1mm, 0.8mm), flip angle (14 degrees, 20 degrees), bandwidth (122.070 Hz/pixel, 325.508 Hz/pixel, 390.625 Hz/pixel), phase encoding steps (160, 192, 224, 256), frequency-encoding direction (right/left, anterior/posterior), echo-time type (minimum-full, out-of-phase), field strength (1.5T, 3T), contrast (with, without), scanner vendor (Siemens, GE), coil (endorectal-coil only, endorectal-and-torso-coil, torsocoil only), endorectal-coil filling (30cc, 50cc) and endorectal-coil filling type (air, perfluorocarbon [PFC]). For post-implant dosimetric evaluation with greater anatomical detail, 3D-FSE images were fused with 3D-FSPGR images. For comparison with CT-based post-implant dosimetry, CT images were fused with 3D-FSPGR images. Results: The 3D-FSPGR sequence facilitated visualization of markers in patients. Marker visualization helped distinguish signal voids as seeds versus needle tracks for more definitive MR-based post-implant dosimetry. On the CT-MR fused images, the distance between the seed on CT to MR images was 3.2±1.6mm in patients with no endorectal coil, 2.3±0.8mm in patients with 30cc-PFC-filled endorectal-coil and 5.0±1.8mm in patients with 50cc-PFC-filled endorectal-coil. Conclusion: An MR protocol to visualize positive-contrast Sirius markers to assist in the identification of negative-contrast seeds was demonstrated. S Frank is a co-founder of C4 Imaging LLC, the manufacturer of the MRI markers.« less

TACE Combined with Implantation of Irradiation Stent Versus TACE Combine with Bare Stent for HCC Complicated by IVCTT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Qing-hui; Zhang, Wen; Liu, Qing-xin

PurposeThis study was designed to evaluate the safety and efficacy of transarterial chemoembolization (TACE) combined with intra-IVC implantation of an irradiation stent for the treatment of hepatocellular carcinoma (HCC) complicated by inferior vena cava tumor thrombosis (IVCTT).MethodsSixty-one consecutive patients with HCC complicated by IVCTT treated by TACE combined with IVC stenting were retrospectively analysed. IVC stenting was performed using a stent loaded with {sup 125}I seeds strands (the irradiation stent) in 33 patients (Group A) and 28 patients with a bare stent (Group B). Propensity score matching eliminated the baseline differences. Overall survival, oedema related to IVC obstruction remission ratemore » and procedure-related adverse events were compared between the two groups.ResultsThe adverse effect rate was similar for both Group A and Group B patients, and complications were adequately handled by medical treatment. TACE combined with implantation of an irradiation stent showed a significant median survival benefit over TACE combined with a bare stent, with a median survival time of 203.0 ± 28.135 days versus 93.0 ± 24.341 days (p = 0.006). The propensity score-matched (24 pairs) cohort analyses (200 ± 31.231 days vs. 66 ± 23.270 days, p = 0.019). The oedema remission rate was 97.0 % in group A patients and 96.4 % in group B, respectively. TACE-irradiation stent and object tumor response were the independent prognostic factors of favorable survival.ConclusionsTACE combined with irradiation stent implantation is a safe and effective treatment modality for patients with HCC complicated by IVCTT and may extend their survival time.« less

Sowing seeds: transperineal implantation.

PubMed

Amerine, E; Nagle, G M; Bollinger, J R

2000-02-01

Prostate cancer, the second leading cause of male deaths in the United States, has increased by 126% since 1987 (Stephenson, 1998). Early diagnosis is attributed to public awareness and technologic advances. Multiple options for definitive treatment with equally positive outcomes dramatically influence the patient's decision-making process. One popular option for these patients is transperineal implantation of radioactive seeds into the prostate.

SU-F-J-167: Use of MR for Permanent Prostate Implant Preplanning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Narayana, V; McLaughlin, P; University of Michigan, Ann Arbor, MI

Purpose: To study the feasibility using MR imaging to improve target definition on ultrasound during permanent prostate implants and aid in source strength determination for treatment planning in the OR. Methods: Patients who receive permanent prostate implants undergo MR and CT imaging prior to the implant procedure to determine the volume of the prostate, bony restriction to the procedure, bladder extension, external sphincter length and neurovascular bundle. The volume of the prostate is generally used to order seeds for the procedure. In 10 patients, the MR was used as the preplanning study with the PTV defined as a 2 mmmore » expansion of the MR prostate in all directions except the posterior. Various dose volume parameters for the MR prostate and the PTV were compared to the actual preplan developed and executed in the OR. In addition, there parameters were compared to the post implant dosimetry performed 3 weeks after the implant procedure. Results: The results show that the number of seeds used using MR and US (ultrasound) planning was generally with 2 seeds and the maximum difference was 7 seeds. There is no significant difference between any of the dose index parameters of V100, V150, V200, D99 and D90 parameters between MR planning, US planning and postimplant evaluation There was a significant difference between planned D99 (avg of 105%) and achieved D99 (avg 91%). Conclusion: MR imaging is an invaluable tool to improve target definition for permanent prostate implants. Use of MR images for preplanning improves the confidence with which source can be ordered for the procedure that is OR planned. Ordering a maximum of 10 seeds more than planned would be sufficient to deliver a plan in the OR using US. Moving ahead to non-rigid registration between MR ad US images could further increase the confidence level of MR planning.« less

Clinical application and validation of an iterative forward projection matching algorithm for permanent brachytherapy seed localization from conebeam-CT x-ray projections.

PubMed

Pokhrel, Damodar; Murphy, Martin J; Todor, Dorin A; Weiss, Elisabeth; Williamson, Jeffrey F

2010-09-01

To experimentally validate a new algorithm for reconstructing the 3D positions of implanted brachytherapy seeds from postoperatively acquired 2D conebeam-CT (CBCT) projection images. The iterative forward projection matching (IFPM) algorithm finds the 3D seed geometry that minimizes the sum of the squared intensity differences between computed projections of an initial estimate of the seed configuration and radiographic projections of the implant. In-house machined phantoms, containing arrays of 12 and 72 seeds, respectively, are used to validate this method. Also, four 103Pd postimplant patients are scanned using an ACUITY digital simulator. Three to ten x-ray images are selected from the CBCT projection set and processed to create binary seed-only images. To quantify IFPM accuracy, the reconstructed seed positions are forward projected and overlaid on the measured seed images to find the nearest-neighbor distance between measured and computed seed positions for each image pair. Also, the estimated 3D seed coordinates are compared to known seed positions in the phantom and clinically obtained VariSeed planning coordinates for the patient data. For the phantom study, seed localization error is (0.58 +/- 0.33) mm. For all four patient cases, the mean registration error is better than 1 mm while compared against the measured seed projections. IFPM converges in 20-28 iterations, with a computation time of about 1.9-2.8 min/ iteration on a 1 GHz processor. The IFPM algorithm avoids the need to match corresponding seeds in each projection as required by standard back-projection methods. The authors' results demonstrate approximately 1 mm accuracy in reconstructing the 3D positions of brachytherapy seeds from the measured 2D projections. This algorithm also successfully localizes overlapping clustered and highly migrated seeds in the implant.

Clinical application and validation of an iterative forward projection matching algorithm for permanent brachytherapy seed localization from conebeam-CT x-ray projections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, Damodar; Murphy, Martin J.; Todor, Dorin A.

2010-09-15

Purpose: To experimentally validate a new algorithm for reconstructing the 3D positions of implanted brachytherapy seeds from postoperatively acquired 2D conebeam-CT (CBCT) projection images. Methods: The iterative forward projection matching (IFPM) algorithm finds the 3D seed geometry that minimizes the sum of the squared intensity differences between computed projections of an initial estimate of the seed configuration and radiographic projections of the implant. In-house machined phantoms, containing arrays of 12 and 72 seeds, respectively, are used to validate this method. Also, four {sup 103}Pd postimplant patients are scanned using an ACUITY digital simulator. Three to ten x-ray images are selectedmore » from the CBCT projection set and processed to create binary seed-only images. To quantify IFPM accuracy, the reconstructed seed positions are forward projected and overlaid on the measured seed images to find the nearest-neighbor distance between measured and computed seed positions for each image pair. Also, the estimated 3D seed coordinates are compared to known seed positions in the phantom and clinically obtained VariSeed planning coordinates for the patient data. Results: For the phantom study, seed localization error is (0.58{+-}0.33) mm. For all four patient cases, the mean registration error is better than 1 mm while compared against the measured seed projections. IFPM converges in 20-28 iterations, with a computation time of about 1.9-2.8 min/iteration on a 1 GHz processor. Conclusions: The IFPM algorithm avoids the need to match corresponding seeds in each projection as required by standard back-projection methods. The authors' results demonstrate {approx}1 mm accuracy in reconstructing the 3D positions of brachytherapy seeds from the measured 2D projections. This algorithm also successfully localizes overlapping clustered and highly migrated seeds in the implant.« less

SU-E-T-378: Evaluation of An Analytical Model for the Inter-Seed Attenuation Effect in 103-Pd Multi-Seed Implant Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Safigholi, H; Soliman, A; Song, W

Purpose: Brachytherapy treatment planning systems based on TG-43 protocol calculate the dose in water and neglects the heterogeneity effect of seeds in multi-seed implant brachytherapy. In this research, the accuracy of a novel analytical model that we propose for the inter-seed attenuation effect (ISA) for 103-Pd seed model is evaluated. Methods: In the analytical model, dose perturbation due to the ISA effect for each seed in an LDR multi-seed implant for 103-Pd is calculated by assuming that the seed of interest is active and the other surrounding seeds are inactive. The cumulative dosimetric effect of all seeds is then summedmore » using the superposition principle. The model is based on pre Monte Carlo (MC) simulated 3D kernels of the dose perturbations caused by the ISA effect. The cumulative ISA effect due to multiple surrounding seeds is obtained by a simple multiplication of the individual ISA effect by each seed, the effect of which is determined by the distance from the seed of interest. This novel algorithm is then compared with full MC water-based simulations (FMCW). Results: The results show that the dose perturbation model we propose is in excellent agreement with the FMCW values for a case with three seeds separated by 1 cm. The average difference of the model and the FMCW simulations was less than 8%±2%. Conclusion: Using the proposed novel analytical ISA effect model, one could expedite the corrections due to the ISA dose perturbation effects during permanent seed 103-Pd brachytherapy planning with minimal increase in time since the model is based on multiplications and superposition. This model can be applied, in principle, to any other brachytherapy seeds. Further work is necessary to validate this model on a more complicated geometry as well.« less

In vivo biofunctional evaluation of hydrogels for disc regeneration.

PubMed

Reitmaier, Sandra; Kreja, Ludwika; Gruchenberg, Katharina; Kanter, Britta; Silva-Correia, Joana; Oliveira, Joaquim Miguel; Reis, Rui Luís; Perugini, Valeria; Santin, Matteo; Ignatius, Anita; Wilke, Hans-Joachim

2014-01-01

Regenerative strategies aim to restore the original biofunctionality of the intervertebral disc. Different biomaterials are available, which might support disc regeneration. In the present study, the prospects of success of two hydrogels functionalized with anti-angiogenic peptides and seeded with bone marrow derived mononuclear cells (BMC), respectively, were investigated in an ovine nucleotomy model. In a one-step procedure iliac crest aspirates were harvested and, subsequently, separated BMC were seeded on hydrogels and implanted into the ovine disc. For the cell-seeded approach a hyaluronic acid-based hydrogel was used. The anti-angiogenic potential of newly developed VEGF-blockers was investigated on ionically crosslinked metacrylated gellan gum hydrogels. Untreated discs served as nucleotomy controls. 24 adult merino sheep were used. After 6 weeks histological, after 12 weeks histological and biomechanical analyses were conducted. Biomechanical tests revealed no differences between any of the implanted and nucleotomized discs. All implanted discs significantly degenerated compared to intact discs. In contrast, there was no marked difference between implanted and nucleotomized discs. In tendency, albeit not significant, degeneration score and disc height index deteriorated for all but not for the cell-seeded hydrogels from 6 to 12 weeks. Cell-seeded hydrogels slightly decelerated degeneration. None of the hydrogel configurations was able to regenerate biofunctionality of the intervertebral disc. This might presumably be caused by hydrogel extrusion. Great importance should be given to the development of annulus sealants, which effectively exploit the potential of (cell-seeded) hydrogels for biological disc regeneration and restoration of intervertebral disc functioning.

Control of Insects in Slash Pine Cones with Trunk Implantations of Bidrin® Systemic Insecticide - First-Year Results

Treesearch

Edward P. Merkel

1969-01-01

Initial experiments with the implantation of the systemic insecticide Bidrin® into the trunks of slash pines in a seed production area resulted in various degrees of control of coneworms, Dioryctria spp., and the pine seed-worm, Laspeyresia anaronjada Miller, depending on dosage rates and time of application. When applied in early...

Neointimal hyperplasia on a cell-seeded polytetrafluoroethylene graft is promoted by transfer of tissue plasminogen activator gene and inhibited by transfer of nitric oxide synthase gene.

PubMed

Yu, Hong; Dai, Wangde; Yang, Zhe; Romaguera, Rita L; Kirkman, Paul; Rowe, Vincent L

2005-01-01

The objective of this study was to examine the effect of tissue plasminogen activator (tPA) and endothelial nitric oxide synthase (eNOS) on thrombosis and neointimal hyperplasia on a polytetrafluoroethylene (PTFE) graft seeded with smooth muscle cells (SMCs). SMCs retrovirally transduced with tPA and eNOS genes were seeded on PTFE grafts and then implanted into the infrarenal rabbit aorta. Thrombosis and neointimal hyperplasia on the grafts were examined after 30 and 100 days of implantation. At 30 days of implantation, thrombus was observed on the luminal surface of both unseeded and SMC seeded control grafts, whereas grafts seeded with SMCs secreting tPA were nearly free of thrombus. At 100 days, the neointima on grafts seeded with tPA transduced SMCs was significantly thicker (925 +/- 150 microm, n = 5) than neointima on the other grafts (range, 132 to 374 microm; P < .001). Neointima thickness on grafts seeded with eNOS transduced SMCs (154 +/- 27 microm) was similar to that of unseeded grafts (132 +/- 16 microm, P > .05); both were thinner than those on grafts seeded with SMCs transduced with only lacZ gene (287 +/- 35 microm). The ratio of seeded cells in the neointima was significantly higher on SMC/tPA grafts (46% +/- 8%) than SMC/NOS grafts (21% +/- 6%, P < .05), indicating tPA transduced cells proliferated more than eNOS transduced cells. Engineered tPA expression in seeded SMCs causes significantly more neointimal hyperplasia, despite the favorable inhibition of luminal thrombus. eNOS expression in the seeded cells inhibits neointimal hyperplasia.

Optimal matching for prostate brachytherapy seed localization with dimension reduction.

PubMed

Lee, Junghoon; Labat, Christian; Jain, Ameet K; Song, Danny Y; Burdette, Everette C; Fichtinger, Gabor; Prince, Jerry L

2009-01-01

In prostate brachytherapy, x-ray fluoroscopy has been used for intra-operative dosimetry to provide qualitative assessment of implant quality. More recent developments have made possible 3D localization of the implanted radioactive seeds. This is usually modeled as an assignment problem and solved by resolving the correspondence of seeds. It is, however, NP-hard, and the problem is even harder in practice due to the significant number of hidden seeds. In this paper, we propose an algorithm that can find an optimal solution from multiple projection images with hidden seeds. It solves an equivalent problem with reduced dimensional complexity, thus allowing us to find an optimal solution in polynomial time. Simulation results show the robustness of the algorithm. It was validated on 5 phantom and 18 patient datasets, successfully localizing the seeds with detection rate of > or = 97.6% and reconstruction error of < or = 1.2 mm. This is considered to be clinically excellent performance.

WE-A-17A-11: Implanted Brachytherapy Seed Movement Due to Transrectal Ultrasound Probe-Induced Prostate Deformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, D; Usmani, N; Sloboda, R

Purpose: To characterize the movement of implanted brachytherapy seeds due to transrectal ultrasound probe-induced prostate deformation and to estimate the effects on prostate dosimetry. Methods: Implanted probe-in and probe-removed seed distributions were reconstructed for 10 patients using C-arm fluoroscopy imaging. The prostate was delineated on ultrasound and registered to the fluoroscopy seeds using a visible subset of seeds and residual needle tracks. A linear tensor and shearing model correlated the seed movement with position. The seed movement model was used to infer the underlying prostate deformation and to simulate the prostate contour without probe compression. Changes in prostate and surrogatemore » urethra dosimetry were calculated. Results: Seed movement patterns reflecting elastic decompression, lateral shearing, and rectal bending were observed. Elastic decompression was characterized by anterior-posterior expansion and superior-inferior and lateral contractions. For lateral shearing, anterior movement up to 6 mm was observed for extraprostatic seeds in the lateral peripheral region. The average intra-prostatic seed movement was 1.3 mm, and the residual after linear modeling was 0.6 mm. Prostate D90 increased by 4 Gy on average (8 Gy max) and was correlated with elastic decompression. For selected patients, lateral shearing resulted in differential change in D90 of 7 Gy between anterior and posterior quadrants, and increase in whole prostate D90 of 4 Gy. Urethra D10 increased by 4 Gy. Conclusion: Seed movement upon probe removal was characterized. The proposed model captured the linear correlation between seed movement and position. Whole prostate dose coverage increased slightly, due to the small but systematic seed movement associated with elastic decompression. Lateral shearing movement increased dose coverage in the anterior-lateral region, at the expense of the posterior-lateral region. The effect on whole prostate D90 was smaller due to the subset of peripheral seeds involved, but lateral shearing movement can have greater consequences for local dose coverage.« less

Biological effects of low energy nitrogen ion implantation on Jatropha curcas L. seed germination

NASA Astrophysics Data System (ADS)

Xu, Gang; Wang, Xiao-teng; Gan, Cai-ling; Fang, Yan-qiong; Zhang, Meng

2012-09-01

To explore the biological effects of nitrogen ion beam implantation on dry Jatropha curcas seed, a beam of N+ with energy of 25 keV was applied to treat the dry seed at six different doses. N+ beam implantation greatly decreased germination rate and seedling survival rate. The doses within the range of 12 × 1016 to 15 × 1016 ions cm-2 severely damaged the seeds: total antioxidant capacity (TAC), germination rate, seedling survival rate, reduced ascorbate acid (HAsA) and reduced glutathione (GSH) contents, and most of the tested antioxidases activity (i.e. catalase (CAT), ascorbate peroxidase (APX) and superoxide dismutase (SOD)) reached their lowest levels. At a dose of 18 × 1016 ion cm-2, biological repair took place: moderate increases were found in TAC, germination rate, seedling survival rate, HAsA and GSH contents, and some antioxidant enzyme activities (i.e. CAT, APX, SOD and GPX). The dose of 18 × 1016 ions cm-2 may be the optimum dose for use in dry J. curcas seed mutation breeding. CAT, HAsA and GSH contributed to the increase of TAC, but CAT was the most important. POD performed its important role as seed was severely damaged. The main role of the HAsA-GSH cycle appeared to be for regeneration of HAsA.

[Application of (125)I seeds combined with biliary stent implantation in the treatment of malignant obstructive jaundice].

PubMed

Wang, T; Liu, S; Zheng, Y B; Song, X P; Jiang, W J; Sun, B L; Wang, L G

2016-03-23

To study the feasibility and therapeutic effect of the application of (125)I seeds combined with biliary stent implantation on the treatment of malignant obstructive jaundice. Fifty patients with malignant obstructive jaundice treated from September 2010 to February 2013 in Yantai Yuhuangding Hospital were included in this study. Among them, 24 patients received biliary stent implantation combined with (125)I seeds intraluminal brachytherapy as experimental group, and 26 were treated by biliary stent implantation as control group.The total bilirubin, direct bilirubin and tumor markers (CA-199, CA-242, CEA) before and after surgery, the biliary stent patency status was assessed, and the survival time was evaluated. The 24 patients in experimental group were implanted with 30 (125)I seeds successfully in a total of 450 seeds. Jaundice was improved greatly in both groups. The CA-199 and CA-242 after treatment in the experimental group were significantly decreased than that before treatment (P=0.003 and P=0.004). CEA was also decreased, but showed no statistical significance (P>0.05). There were no significant improvement comparing the CA-199, CA-242 and CEA before and 2 months after surgery in the control group (P>0.05). The rate of biliary stent patency was 83.3% (20/24) in the experimental group and 57.7% (15/26) in the control group (P=0.048). The mean biliary stent patency time in the experimental group was 9.84 months (range 1-15.5 months). The mean biliary stent patency time in the control group was 5.57 months (range 0.8-9 months). There was a significant difference between the two groups (P=0.018). The median survival time was 10.2 months in the experimental group and 5.4 months in the control group (P<0.05). (125)I seeds combined with biliary stent implantation can inhibit the proliferation of vascular endothelial cells and the growth of tumor effectively, and can prolong the biliary stent patency time and the survival time obviously for patients with malignant obstructive jaundice, therefore, is a safe and effective treatment in this malignancy.

Computational and Experimental Evaluations of a Novel Thermo-Brachytherapy Seed for Treatment of Solid Tumors

NASA Astrophysics Data System (ADS)

Warrell, Gregory R.

Hyperthermia has long been known as a radiation therapy sensitizer of high potential; however successful delivery of this modality and integrating it with radiation have often proved technically difficult. We present the dual-modality thermobrachytherapy (TB) seed, based on the ubiquitous low dose-rate (LDR) brachytherapy permanent implant, as a simple and effective combination of hyperthermia and radiation therapy. Heat is generated from a ferromagnetic or ferrimagnetic core within the seed, which produces Joule heating by eddy currents. A strategically-selected Curie temperature provides thermal self-regulation. In order to obtain a uniform and sufficiently high temperature distribution, additional hyperthermia-only (HT-only) seeds are proposed to be used in vacant spots within the needles used to implant the TB seeds; this permits a high seed density without the use of additional needles. Experimental and computational studies were done both to optimize the design of the TB and HT-only seeds and to quantitatively assess their ability to heat and irradiate defined, patient-specific targets. Experiments were performed with seed-sized ferromagnetic samples in tissue-mimicking phantoms heated by an industrial induction heater. The magnetic and thermal properties of the seeds were studied computationally in the finite element analysis (FEA) solver COMSOL Multiphysics, modelling realistic patient-specific seed distributions. These distributions were derived from LDR permanent prostate implants previously conducted at our institution; various modifications of the seeds' design were studied. The calculated temperature distributions were analyzed by generating temperature-volume histograms, which were used to quantify coverage and temperature homogeneity for a range of blood perfusion rates, as well as for a range of seed Curie temperatures and thermal power production rates. The impact of the interseed attenuation and scatter (ISA) effect on radiation dose distributions of this seed was also quantified by Monte Carlo studies in the software package MCNP5. Experimental and computational analyses agree that the proposed seeds may heat a defined target with safe and attainable seed spacing and magnetic field parameters. These studies also point to the use of a ferrite-based ferrimagnetic core within the seeds, a design that would deliver hyperthermia of acceptable quality even for the high rate of blood perfusion in prostate tissue. The loss of radiation coverage due to the ISA effect of distributions of TB and HT-only seeds may be rectified by slightly increasing the prescribed dose in standard dose superposition-based treatment planning software. A systematic approach of combining LDR prostate brachytherapy with hyperthermia is thus described, and its ability to provide sufficient and uniform temperature distributions in realistic patient-specific implants evaluated. Potential improvements to the previously reported TB seed design are discussed based on quantitative evaluation of its operation and performance.

CT, MR, and ultrasound image artifacts from prostate brachytherapy seed implants: The impact of seed size

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, Andrew K. H.; Basran, Parminder S.; Thomas, Steven D.

Purpose: To investigate the effects of brachytherapy seed size on the quality of x-ray computed tomography (CT), ultrasound (US), and magnetic resonance (MR) images and seed localization through comparison of the 6711 and 9011 {sup 125}I sources. Methods: For CT images, an acrylic phantom mimicking a clinical implantation plan and embedded with low contrast regions of interest (ROIs) was designed for both the 0.774 mm diameter 6711 (standard) and the 0.508 mm diameter 9011 (thin) seed models (Oncura, Inc., and GE Healthcare, Arlington Heights, IL). Image quality metrics were assessed using the standard deviation of ROIs between the seeds andmore » the contrast to noise ratio (CNR) within the low contrast ROIs. For US images, water phantoms with both single and multiseed arrangements were constructed for both seed sizes. For MR images, both seeds were implanted into a porcine gel and imaged with pelvic imaging protocols. The standard deviation of ROIs and CNR values were used as metrics of artifact quantification. Seed localization within the CT images was assessed using the automated seed finder in a commercial brachytherapy treatment planning system. The number of erroneous seed placements and the average and maximum error in seed placements were recorded as metrics of the localization accuracy. Results: With the thin seeds, CT image noise was reduced from 48.5 {+-} 0.2 to 32.0 {+-} 0.2 HU and CNR improved by a median value of 74% when compared with the standard seeds. Ultrasound image noise was measured at 50.3 {+-} 17.1 dB for the thin seed images and 50.0 {+-} 19.8 dB for the standard seed images, and artifacts directly behind the seeds were smaller and less prominent with the thin seed model. For MR images, CNR of the standard seeds reduced on average 17% when using the thin seeds for all different imaging sequences and seed orientations, but these differences are not appreciable. Automated seed localization required an average ({+-}SD) of 7.0 {+-} 3.5 manual corrections in seed positions for the thin seed scans and 3.0 {+-} 1.2 manual corrections in seed positions for the standard seed scans. The average error in seed placement was 1.2 mm for both seed types and the maximum error in seed placement was 2.1 mm for the thin seed scans and 1.8 mm for the standard seed scans. Conclusions: The 9011 thin seeds yielded significantly improved image quality for CT and US images but no significant differences in MR image quality.« less

Clinical application of computed tomography-guided (125)I seed interstitial implantation for head and neck cancer patients with unmanageable cervical lymph node metastases.

PubMed

Huang, Hai; Xu, Shaonian; Li, Fusheng; Du, Zhenguang; Wang, Liang

2016-04-27

To assess clinical application of computed tomography (CT)-guided (125)I seed implantation for patients who cannot endure or unwillingly receive repeated surgery, chemotherapy, or radiotherapy for unmanageable cervical lymph node metastases in head and neck cancer (HNC). Thirty-one consecutive patients received CT-guided (125)I seed implantation between February 2010 and December 2013. To evaluate the clinical efficiency, karnofsky performance score (KPS), numeric rating scale (NRS), and tumor volume at 3-, and 6-month post-implantation were compared with pre-implantation, along with local control rate (LCR), overall survival rate (OSR), and complications at 3, 6 months, 1, and 2 years. The tumor volume was obviously decreased at 3-, and 6-month post-implantation (21.23 ± 8.83 versus 9.19 ± 7.52 cm(2); 21.23 ± 8.83 versus 6.42 ± 9.79 cm(2); P < 0.05) compared with pre-implantation. The NRS was statistically reduced (3.06 ± 1.06 versus 7.77 ± 0.92; 2.39 ± 1.15 versus 7.77 ± 0.92; P < 0.05), while KPS was significantly improved (83.18 ± 5.97 versus 73.60 ± 7.90; 82.86 ± 5.43 versus 73.60 ± 7.90; P < 0.05) postoperatively at 3 and 6 months, respectively. The LCR at 3, 6 months, 1, and 2 years was 96.30, 83.87, 64.51, and 45.16%, respectively. The OSR was 100, 100, 67.74, and 45.16%, respectively. Three cases experienced grade I and two had grade II acute radiation toxicity. CT-guided seed implantation may be feasible and safe for HNC patients whose neck nodes are not manageable by routine strategies with fewer complications, higher LCR, and significant pain relief.

Dose reduction in LDR brachytherapy by implanted prostate gold fiducial markers.

PubMed

Landry, Guillaume; Reniers, Brigitte; Lutgens, Ludy; Murrer, Lars; Afsharpour, Hossein; de Haas-Kock, Danielle; Visser, Peter; van Gils, Francis; Verhaegen, Frank

2012-03-01

The dosimetric impact of gold fiducial markers (FM) implanted prior to external beam radiotherapy of prostate cancer on low dose rate (LDR) brachytherapy seed implants performed in the context of combined therapy was investigated. A virtual water phantom was designed containing a single FM. Single and multi source scenarios were investigated by performing Monte Carlo dose calculations, along with the influence of varying orientation and distance of the FM with respect to the sources. Three prostate cancer patients treated with LDR brachytherapy for a recurrence following external beam radiotherapy with implanted FM were studied as surrogate cases to combined therapy. FM and brachytherapy seeds were identified on post implant CT scans and Monte Carlo dose calculations were performed with and without FM. The dosimetric impact of the FM was evaluated by quantifying the amplitude of dose shadows and the volume of cold spots. D(90) was reported based on the post implant CT prostate contour. Large shadows are observed in the single source-FM scenarios. As expected from geometric considerations, the shadows are dependent on source-FM distance and orientation. Large dose reductions are observed at the distal side of FM, while at the proximal side a dose enhancement is observed. In multisource scenarios, the importance of shadows appears mitigated, although FM at the periphery of the seed distribution caused underdosage (

Comparison of intraoperative dosimetric implant representation with postimplant dosimetry in patients receiving prostate brachytherapy.

PubMed

Stone, Nelson N; Hong, Suzanne; Lo, Yeh-Chi; Howard, Victor; Stock, Richard G

2003-01-01

To compare the results of intraoperative dosimetry with those of CT-based postimplant dosimetry in patients undergoing prostate seed implantation. Seventy-seven patients with T1-T3 prostate cancer received an ultrasound-guided permanent seed implant (36 received (125)I, 7 (103)Pd, and 34 a partial (103)Pd implant plus external beam radiation therapy). The implantation was augmented with an intraoperative dosimetric planning system. After the peripheral needles were placed, 5-mm axial images were acquired into the treatment planning system. Soft tissue structures (prostate, urethra, and rectum) were contoured, and exact needle positions were registered. Seeds were placed with an applicator, and their positions were entered into the planning system. The dose distributions for the implant were calculated after interior needle and seed placement. Postimplant dosimetry was performed 1 month later on the basis of CT imaging. Prostate and urethral doses were compared, by using paired t tests, for the real-time dosimetry in the operating room (OR) and the postimplant dosimetry. The mean preimplant prostate volume was 39.8 cm(3), the postneedle planning volume was 41.5 cm(3) (p<0.001), and the 1-month CT volume was 43.6 cm(3) (p<0.001). The mean difference between the OR dose received by 90% of the prostate (D(90)) and the CT D(90) was 3.4% (95% confidence interval, 2.5-6.6%; p=0.034). The mean dose to 30% of the urethra was 120% of prescription in the OR and 138% on CT. The mean difference was 18% (95% confidence interval, 13-24%; p<0.001). Although small differences exist between the OR and CT dosimetry results, these data suggest that this intraoperative implant dosimetric representation system provides a close match to the actual delivered doses. These data support the use of this system to modify the implant during surgery to achieve more consistent dosimetry results.

Examining the relationship between pre- and postimplant geometry in prostate low-dose-rate brachytherapy and its correlation with dosimetric quality using the similarity concept.

PubMed

Todor, Dorin A; Anscher, Mitchell S; Karlin, Jeremy D; Hagan, Michael P

2014-01-01

This is a retrospective study in which we define multiple metrics for similarity and then inquire on the relationship between similarity and currently used dosimetric quantities describing preimplant and postimplant plans. We analyzed a unique cohort of 94 consecutively performed prostate seed implant patients, associated with excellent dosimetric and clinical outcomes. For each patient, an ultrasound (US) preimplant and two CT postimplant (Day 0 and Day 30) studies were available. Measures for similarity were created and computed using feature vectors based on two classes of moments: first, invariant to rotation and translation, and the second polar-radius moments invariant to rotation, translation, and scaling. Both similarity measures were calibrated using controlled perturbations (random and systematic) of seed positions and contours in different size implants, thus producing meaningful numerical threshold values used in the clinical analysis. An important finding is that similarity, for both seed distributions and contours, improves significantly when scaling invariance is added to translation and rotation. No correlation between seed and contours similarity was found. In the setting of preplanned prostate seed implants using preloaded needles, based on our data, similarity between preimplant and postimplant plans does not correlate with either minimum dose to 90% of the volume of the prostate or analogous similarity metrics for prostate contours. We have developed novel tools and metrics, which will allow practitioners to better understand the relationship between preimplant and postimplant plans. Geometrical similarity between a preplan and an actual implant, although useful, does not seem to be necessary to achieve minimum dose to 90% of the volume of the prostate-good dosimetric implants. Copyright © 2014 American Brachytherapy Society. All rights reserved.

Deformable registration of x-ray to MRI for post-implant dosimetry in prostate brachytherapy

NASA Astrophysics Data System (ADS)

Park, Seyoun; Song, Danny Y.; Lee, Junghoon

2016-03-01

Post-implant dosimetric assessment in prostate brachytherapy is typically performed using CT as the standard imaging modality. However, poor soft tissue contrast in CT causes significant variability in target contouring, resulting in incorrect dose calculations for organs of interest. CT-MR fusion-based approach has been advocated taking advantage of the complementary capabilities of CT (seed identification) and MRI (soft tissue visibility), and has proved to provide more accurate dosimetry calculations. However, seed segmentation in CT requires manual review, and the accuracy is limited by the reconstructed voxel resolution. In addition, CT deposits considerable amount of radiation to the patient. In this paper, we propose an X-ray and MRI based post-implant dosimetry approach. Implanted seeds are localized using three X-ray images by solving a combinatorial optimization problem, and the identified seeds are registered to MR images by an intensity-based points-to-volume registration. We pre-process the MR images using geometric and Gaussian filtering. To accommodate potential soft tissue deformation, our registration is performed in two steps, an initial affine transformation and local deformable registration. An evolutionary optimizer in conjunction with a points-to-volume similarity metric is used for the affine registration. Local prostate deformation and seed migration are then adjusted by the deformable registration step with external and internal force constraints. We tested our algorithm on six patient data sets, achieving registration error of (1.2+/-0.8) mm in < 30 sec. Our proposed approach has the potential to be a fast and cost-effective solution for post-implant dosimetry with equivalent accuracy as the CT-MR fusion-based approach.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yanli; Juranek, Stefan; Li, Haitao

Here we report on a 3.0 {angstrom} crystal structure of a ternary complex of wild-type Thermus thermophilus argonaute bound to a 5'-phosphorylated 21-nucleotide guide DNA and a 20-nucleotide target RNA containing cleavage-preventing mismatches at the 10-11 step. The seed segment (positions 2 to 8) adopts an A-helical-like Watson-Crick paired duplex, with both ends of the guide strand anchored in the complex. An arginine, inserted between guide-strand bases 10 and 11 in the binary complex, locking it in an inactive conformation, is released on ternary complex formation. The nucleic-acid-binding channel between the PAZ- and PIWI-containing lobes of argonaute widens on formationmore » of a more open ternary complex. The relationship of structure to function was established by determining cleavage activity of ternary complexes containing position-dependent base mismatch, bulge and 2'-O-methyl modifications. Consistent with the geometry of the ternary complex, bulges residing in the seed segments of the target, but not the guide strand, were better accommodated and their complexes were catalytically active.« less

The siRNA Non-seed Region and Its Target Sequences Are Auxiliary Determinants of Off-Target Effects.

PubMed

Kamola, Piotr J; Nakano, Yuko; Takahashi, Tomoko; Wilson, Paul A; Ui-Tei, Kumiko

2015-12-01

RNA interference (RNAi) is a powerful tool for post-transcriptional gene silencing. However, the siRNA guide strand may bind unintended off-target transcripts via partial sequence complementarity by a mechanism closely mirroring micro RNA (miRNA) silencing. To better understand these off-target effects, we investigated the correlation between sequence features within various subsections of siRNA guide strands, and its corresponding target sequences, with off-target activities. Our results confirm previous reports that strength of base-pairing in the siRNA seed region is the primary factor determining the efficiency of off-target silencing. However, the degree of downregulation of off-target transcripts with shared seed sequence is not necessarily similar, suggesting that there are additional auxiliary factors that influence the silencing potential. Here, we demonstrate that both the melting temperature (Tm) in a subsection of siRNA non-seed region, and the GC contents of its corresponding target sequences, are negatively correlated with the efficiency of off-target effect. Analysis of experimentally validated miRNA targets demonstrated a similar trend, indicating a putative conserved mechanistic feature of seed region-dependent targeting mechanism. These observations may prove useful as parameters for off-target prediction algorithms and improve siRNA 'specificity' design rules.

Poster — Thur Eve — 77: Implanted Brachythearpy Seed Movement due to Transrectal Ultrasound Probe-Induced Prostate Deformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, D; Usmani, N; Sloboda, R

The study investigated the movement of implanted brachytherapy seeds upon transrectal US probe removal, providing insight into the underlying prostate deformation and an estimate of the impact on prostate dosimetry. Implanted seed distributions, one obtained with the prostate under probe compression and another with the probe removed, were reconstructed using C-arm fluoroscopy imaging. The prostate, delineated on ultrasound images, was registered to the fluoroscopy images using seeds and needle tracks identified on ultrasound. A deformation tensor and shearing model was developed to correlate probe-induced seed movement with position. Changes in prostate TG-43 dosimetry were calculated. The model was used tomore » infer the underlying prostate deformation and to estimate the location of the prostate surface in the absence of probe compression. Seed movement patterns upon probe removal reflected elastic decompression, lateral shearing, and rectal bending. Elastic decompression was characterized by expansion in the anterior-posterior direction and contraction in the superior-inferior and lateral directions. Lateral shearing resulted in large anterior movement for extra-prostatic seeds in the lateral peripheral region. Whole prostate D90 increased up to 8 Gy, mainly due to the small but systematic seed movement associated with elastic decompression. For selected patients, lateral shearing movement increased prostate D90 by 4 Gy, due to increased dose coverage in the anterior-lateral region at the expense of the posterior-lateral region. The effect of shearing movement on whole prostate D90 was small compared to elastic decompression due to the subset of peripheral seeds involved, but is expected to have greater consequences for local dose coverage.« less

Effect of Ar Ion Beam Implantation on Morphological and Physiological Characteristics of Liquorice (Glycyrrhiza uralensis Fisch) Under Short-Term Artificial Drought Conditions

NASA Astrophysics Data System (ADS)

Zhang, Xiangsheng; Wu, Lijun; Yu, Lixiang; Wei, Shenglin; Liu, Jingnan; Yu, Zengliang

2007-04-01

Ar+ ion beam with low energy of 30 keV was implanted into liquorice (Glycyrrhiza uralensis Fisch) seeds at the doses of 0, 600, 900 and 1200 × (2.6 × 1013) ions/cm2, respectively. The seeds were sowed in pots and after one month the plants were subjected to different drought conditions for two months. Then the plants' morphological and physiological characteristics, anti-oxidation enzymes and levels of endogenous hormones were investigated. The results showed that ion implantation at a proper dose can greatly enhance the liquorice seedlings' resistance against drought stress.

Reconstruction of brachytherapy seed positions and orientations from cone-beam CT x-ray projections via a novel iterative forward projection matching method.

PubMed

Pokhrel, Damodar; Murphy, Martin J; Todor, Dorin A; Weiss, Elisabeth; Williamson, Jeffrey F

2011-01-01

To generalize and experimentally validate a novel algorithm for reconstructing the 3D pose (position and orientation) of implanted brachytherapy seeds from a set of a few measured 2D cone-beam CT (CBCT) x-ray projections. The iterative forward projection matching (IFPM) algorithm was generalized to reconstruct the 3D pose, as well as the centroid, of brachytherapy seeds from three to ten measured 2D projections. The gIFPM algorithm finds the set of seed poses that minimizes the sum-of-squared-difference of the pixel-by-pixel intensities between computed and measured autosegmented radiographic projections of the implant. Numerical simulations of clinically realistic brachytherapy seed configurations were performed to demonstrate the proof of principle. An in-house machined brachytherapy phantom, which supports precise specification of seed position and orientation at known values for simulated implant geometries, was used to experimentally validate this algorithm. The phantom was scanned on an ACUITY CBCT digital simulator over a full 660 sinogram projections. Three to ten x-ray images were selected from the full set of CBCT sinogram projections and postprocessed to create binary seed-only images. In the numerical simulations, seed reconstruction position and orientation errors were approximately 0.6 mm and 5 degrees, respectively. The physical phantom measurements demonstrated an absolute positional accuracy of (0.78 +/- 0.57) mm or less. The theta and phi angle errors were found to be (5.7 +/- 4.9) degrees and (6.0 +/- 4.1) degrees, respectively, or less when using three projections; with six projections, results were slightly better. The mean registration error was better than 1 mm/6 degrees compared to the measured seed projections. Each test trial converged in 10-20 iterations with computation time of 12-18 min/iteration on a 1 GHz processor. This work describes a novel, accurate, and completely automatic method for reconstructing seed orientations, as well as centroids, from a small number of radiographic projections, in support of intraoperative planning and adaptive replanning. Unlike standard back-projection methods, gIFPM avoids the need to match corresponding seed images on the projections. This algorithm also successfully reconstructs overlapping clustered and highly migrated seeds in the implant. The accuracy of better than 1 mm and 6 degrees demonstrates that gIFPM has the potential to support 2D Task Group 43 calculations in clinical practice.

Reconstruction of brachytherapy seed positions and orientations from cone-beam CT x-ray projections via a novel iterative forward projection matching method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, Damodar; Murphy, Martin J.; Todor, Dorin A.

2011-01-15

Purpose: To generalize and experimentally validate a novel algorithm for reconstructing the 3D pose (position and orientation) of implanted brachytherapy seeds from a set of a few measured 2D cone-beam CT (CBCT) x-ray projections. Methods: The iterative forward projection matching (IFPM) algorithm was generalized to reconstruct the 3D pose, as well as the centroid, of brachytherapy seeds from three to ten measured 2D projections. The gIFPM algorithm finds the set of seed poses that minimizes the sum-of-squared-difference of the pixel-by-pixel intensities between computed and measured autosegmented radiographic projections of the implant. Numerical simulations of clinically realistic brachytherapy seed configurations weremore » performed to demonstrate the proof of principle. An in-house machined brachytherapy phantom, which supports precise specification of seed position and orientation at known values for simulated implant geometries, was used to experimentally validate this algorithm. The phantom was scanned on an ACUITY CBCT digital simulator over a full 660 sinogram projections. Three to ten x-ray images were selected from the full set of CBCT sinogram projections and postprocessed to create binary seed-only images. Results: In the numerical simulations, seed reconstruction position and orientation errors were approximately 0.6 mm and 5 deg., respectively. The physical phantom measurements demonstrated an absolute positional accuracy of (0.78{+-}0.57) mm or less. The {theta} and {phi} angle errors were found to be (5.7{+-}4.9) deg. and (6.0{+-}4.1) deg., respectively, or less when using three projections; with six projections, results were slightly better. The mean registration error was better than 1 mm/6 deg. compared to the measured seed projections. Each test trial converged in 10-20 iterations with computation time of 12-18 min/iteration on a 1 GHz processor. Conclusions: This work describes a novel, accurate, and completely automatic method for reconstructing seed orientations, as well as centroids, from a small number of radiographic projections, in support of intraoperative planning and adaptive replanning. Unlike standard back-projection methods, gIFPM avoids the need to match corresponding seed images on the projections. This algorithm also successfully reconstructs overlapping clustered and highly migrated seeds in the implant. The accuracy of better than 1 mm and 6 deg. demonstrates that gIFPM has the potential to support 2D Task Group 43 calculations in clinical practice.« less

[Effect of image fusion technology of radioactive particles implantation before and after the planning target and dosimetry].

PubMed

Jiang, Y L; Yu, J P; Sun, H T; Guo, F X; Ji, Z; Fan, J H; Zhang, L J; Li, X; Wang, J J

2017-08-01

Objective: To compare the post-implant target volumes and dosimetric evaluation with pre-plan, the gross tumor volume(GTV) by CT image fusion-based and the manual delineation of target volume in CT guided radioactive seeds implantation. Methods: A total of 10 patients treated under CT-guidance (125)I seed implantation during March 2016 to April 2016 were analyzed in Peking University Third Hospital.All patients underwent pre-operative CT simulation, pre-operative planning, implantation seeds, CT scanning after seed implantation and dosimetric evaluation of GTV.In every patient, post-implant target volumes were delineated by both two methods, and were divided into two groups. Group 1: image fusion pre-implantation simulation and post-operative CT image, then the contours of GTV were automatically performed by brachytherapy treatment planning system; Group 2: the contouring of the GTV on post-operative CT image were performed manually by three senior radiation oncologists independently. The average of three data was sets. Statistical analyses were performed using SPSS software, version 3.2.0. The paired t -test was used to compare the target volumes and D(90) parameters in two modality. Results: In Group 1, average volume of GTV in post-operation group was 12-167(73±56) cm(3). D(90) was 101-153 (142±19)Gy. In Group 2, they were 14-186(80±58)cm(3) and 96-146(122±16) Gy respectively. In both target volumes and D(90), there was no statistical difference between pre-operation and post-operation in Group 1.The D(90) was slightly lower than that of pre-plan group, but there was no statistical difference ( P =0.142); in Group 2, between pre-operation and post-operation group, there was a significant statistical difference in the GTV ( P =0.002). The difference of D(90) was similarly ( P <0.01). Conclusion: The method of delineation of post-implant GTV through fusion pre-implantation simulation and post-operative CT scan images, the contours of GTV are automatically performed by brachytherapy treatment planning system appears to have improved more accuracy, reproducibility and convenience than manual delineation of target volume by maximum reduce the interference from artificial factor and metal artifacts. Further work and more cases are required in the future.

Repair of traumatic skeletal muscle injury with bone-marrow-derived mesenchymal stem cells seeded on extracellular matrix.

PubMed

Merritt, Edward K; Cannon, Megan V; Hammers, David W; Le, Long N; Gokhale, Rohit; Sarathy, Apurva; Song, Tae J; Tierney, Matthew T; Suggs, Laura J; Walters, Thomas J; Farrar, Roger P

2010-09-01

Skeletal muscle injury resulting in tissue loss poses unique challenges for surgical repair. Despite the regenerative potential of skeletal muscle, if a significant amount of tissue is lost, skeletal myofibers will not grow to fill the injured area completely. Prior work in our lab has shown the potential to fill the void with an extracellular matrix (ECM) scaffold, resulting in restoration of morphology, but not functional recovery. To improve the functional outcome of the injured muscle, a muscle-derived ECM was implanted into a 1 x 1 cm(2), full-thickness defect in the lateral gastrocnemius (LGAS) of Lewis rats. Seven days later, bone-marrow-derived mesenchymal stem cells (MSCs) were injected directly into the implanted ECM. Partial functional recovery occurred over the course of 42 days when the LGAS was repaired with an MSC-seeded ECM producing 85.4 +/- 3.6% of the contralateral LGAS. This was significantly higher than earlier recovery time points (p < 0.05). The specific tension returned to 94 +/- 9% of the contralateral limb. The implanted MSC-seeded ECM had more blood vessels and regenerating skeletal myofibers than the ECM without cells (p < 0.05). The data suggest that the repair of a skeletal muscle defect injury by the implantation of a muscle-derived ECM seeded with MSCs can improve functional recovery after 42 days.

SU-E-T-123: Anomalous Altitude Effect in Permanent Implant Brachytherapy Seeds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watt, E; Spencer, DP; Meyer, T

Purpose: Permanent seed implant brachytherapy procedures require the measurement of the air kerma strength of seeds prior to implant. This is typically accomplished using a well-type ionization chamber. Previous measurements (Griffin et al., 2005; Bohm et al., 2005) of several low-energy seeds using the air-communicating HDR 1000 Plus chamber have demonstrated that the standard temperature-pressure correction factor, P{sub TP}, may overcompensate for air density changes induced by altitude variations by up to 18%. The purpose of this work is to present empirical correction factors for two clinically-used seeds (IsoAid ADVANTAGE™ {sup 103}Pd and Nucletron selectSeed {sup 125}I) for which empiricalmore » altitude correction factors do not yet exist in the literature when measured with the HDR 1000 Plus chamber. Methods: An in-house constructed pressure vessel containing the HDR 1000 Plus well chamber and a digital barometer/thermometer was pumped or evacuated, as appropriate, to a variety of pressures from 725 to 1075 mbar. Current measurements, corrected with P{sub TP}, were acquired for each seed at these pressures and normalized to the reading at ‘standard’ pressure (1013.25 mbar). Results: Measurements in this study have shown that utilization of P{sub TP} can overcompensate in the corrected current reading by up to 20% and 17% for the IsoAid Pd-103 and the Nucletron I-125 seed respectively. Compared to literature correction factors for other seed models, the correction factors in this study diverge by up to 2.6% and 3.0% for iodine (with silver) and palladium respectively, indicating the need for seed-specific factors. Conclusion: The use of seed specific altitude correction factors can reduce uncertainty in the determination of air kerma strength. The empirical correction factors determined in this work can be applied in clinical quality assurance measurements of air kerma strength for two previously unpublished seed designs (IsoAid ADVANTAGE™ {sup 103}Pd and Nucletron selectSeed {sup 125}I) with the HDR 1000 Plus well chamber.« less

Transperineal implantation of gold fiducial markers (gold seeds) for prostate image-guided radiation therapy: a feasible technique associated with a low risk of complications.

PubMed

Saad, Akram; Goldstein, Jeffrey; Lawrence, Yaacov Richard; Weiss, Ilana; Saad, Rasha; Spieler, Benjamin; Symon, Zvi

2015-12-01

The purpose is to describe the method, safety and efficacy of transperineal gold seed placement for image-guided radiation therapy. An ethics committee approved database was used to review records of consecutive patients from October 2008 through December 2013, who underwent transperineal implantation of three gold markers into the prostate using staged local anaesthesia and transrectal ultrasound. Seeds were counted on radiographs from CT simulation, first treatment and last treatment. Retention and use of at least three markers for kV/kV matching was considered a successful implant. A visual analogue scale (VAS) pain assessment was performed. SAS was used for data analysis. Fiducial marker placement was successful for kV/kV matching in 556/581 patients (95.7%). The procedure was aborted due to pain in two patients. Additional sedation during the procedure was required in two patients. Complications include urinary infections (2 patients, <0.5%) and transient haematuria (2 patients, <0.5%). There were no recorded calls requesting additional pain medication or delays in radiation due to complications. The number of seeds identified at simulation: 4 (2 patients), 3 (554 patients), 2 (21 patients), 1 (1 patient), 0 (1 patient). One patient with three seeds and two patients with <2 seeds had cone beam CT instead of kV/kV imaging for image guidance. No seeds were lost after simulation. The mean visual analogue pain score associated with transperineal gold seed insertion met patients' expectations (respectively 4.1 vs. 4.4 P = 0.19). Outpatient transperineal insertion of fiducials avoids the rectum, is effective, convenient, well tolerated and has few side effects.

Bone Marrow–Derived Mesenchymal Stem Cells Enhance Bacterial Clearance and Preserve Bioprosthetic Integrity in a Model of Mesh Infection

PubMed Central

Criman, Erik T.; Kurata, Wendy E.; Matsumoto, Karen W.; Aubin, Harry T.; Campbell, Carmen E.

2016-01-01

Background: The reported incidence of mesh infection in contaminated operative fields is as high as 30% regardless of the material used. Recently, mesenchymal stem cells (MSCs) have been shown to possess favorable immunomodulatory properties and improve tissue incorporation when seeded onto bioprosthetics. The aim of this study was to evaluate whether seeding noncrosslinked bovine pericardium (Veritas Collagen Matrix) with allogeneic bone marrow–derived MSCs improves infection resistance in vivo after inoculation with Escherichia coli (E. coli). Methods: Rat bone marrow–derived MSCs at passage 3 were seeded onto bovine pericardium and cultured for 7 days before implantation. Additional rats (n = 24) were implanted subcutaneously with MSC-seeded or unseeded mesh and inoculated with 7 × 105 colony-forming units of E. coli or saline before wound closure (group 1, unseeded mesh/saline; group 2, unseeded mesh/E. coli; group 3, MSC-seeded mesh/E. coli; 8 rats per group). Meshes were explanted at 4 weeks and underwent microbiologic and histologic analyses. Results: MSC-seeded meshes inoculated with E. coli demonstrated superior bacterial clearance and preservation of mesh integrity compared with E. coli–inoculated unseeded meshes (87.5% versus 0% clearance; p = 0.001). Complete mesh degradation concurrent with abscess formation was observed in 100% of rats in the unseeded/E. coli group, which is in contrast to 12.5% of rats in the MSC-seeded/E. coli group. Histologic evaluation determined that remodeling characteristics of E. coli–inoculated MSC-seeded meshes were similar to those of uninfected meshes 4 weeks after implantation. Conclusions: Augmenting a bioprosthetic material with stem cells seems to markedly enhance resistance to bacterial infection in vivo and preserve mesh integrity. PMID:27482490

Vibro-acoustography with 1.75D ultrasound array transducer for detection and localization of permanent prostate brachytherapy seeds: ex vivo study

NASA Astrophysics Data System (ADS)

Mehrmohammadi, Mohammad; Alizad, Azra; Kinnick, Randall R.; Davis, Brian J.; Fatemi, Mostafa

2013-03-01

Effective brachytherapy procedures require precise placement of radioactive seeds in the prostate. Currently, transrectal ultrasound (TRUS) imaging is one of the main intraoperative imaging modalities to assist physicians in placement of brachytherapy seeds. However, the seed detection rate with TRUS is poor mainly because ultrasound imaging is highly sensitive to variations in seed orientation. The purpose of this study is to investigate the abilities of a new acoustic radiation force imaging modality, vibro-acoustography (VA), equipped with a 1.75D array transducer and implemented on a customized clinical ultrasound scanner, to image and localize brachytherapy seeds in prostatic tissue. To perform experiments, excised cadaver prostate specimens were implanted with dummy brachytherapy seeds, and embedded in tissue mimicking gel to simulate the properties of the surrounding soft tissues. The samples were scanned using the VA system and the resulting VA signals were used to reconstruct VA images at several depths inside the tissue. To further evaluate the performance of VA in detecting seeds, X-ray computed tomography (CT) images of the same tissue sample, were obtained and used as a gold-standard to compare the number of seeds detected by the two methods. Our results indicate that VA is capable of imaging of brachytherapy seeds with accuracy and high contrast, and can detect a large percentage of the seeds implanted within the tissue samples.

Conventional Versus Automated Implantation of Loose Seeds in Prostate Brachytherapy: Analysis of Dosimetric and Clinical Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Genebes, Caroline, E-mail: genebes.caroline@claudiusregaud.fr; Filleron, Thomas; Graff, Pierre

2013-11-15

Purpose: To review the clinical outcome of I-125 permanent prostate brachytherapy (PPB) for low-risk and intermediate-risk prostate cancer and to compare 2 techniques of loose-seed implantation. Methods and Materials: 574 consecutive patients underwent I-125 PPB for low-risk and intermediate-risk prostate cancer between 2000 and 2008. Two successive techniques were used: conventional implantation from 2000 to 2004 and automated implantation (Nucletron, FIRST system) from 2004 to 2008. Dosimetric and biochemical recurrence-free (bNED) survival results were reported and compared for the 2 techniques. Univariate and multivariate analysis researched independent predictors for bNED survival. Results: 419 (73%) and 155 (27%) patients with low-riskmore » and intermediate-risk disease, respectively, were treated (median follow-up time, 69.3 months). The 60-month bNED survival rates were 95.2% and 85.7%, respectively, for patients with low-risk and intermediate-risk disease (P=.04). In univariate analysis, patients treated with automated implantation had worse bNED survival rates than did those treated with conventional implantation (P<.0001). By day 30, patients treated with automated implantation showed lower values of dose delivered to 90% of prostate volume (D90) and volume of prostate receiving 100% of prescribed dose (V100). In multivariate analysis, implantation technique, Gleason score, and V100 on day 30 were independent predictors of recurrence-free status. Grade 3 urethritis and urinary incontinence were observed in 2.6% and 1.6% of the cohort, respectively, with no significant differences between the 2 techniques. No grade 3 proctitis was observed. Conclusion: Satisfactory 60-month bNED survival rates (93.1%) and acceptable toxicity (grade 3 urethritis <3%) were achieved by loose-seed implantation. Automated implantation was associated with worse dosimetric and bNED survival outcomes.« less

Comparison of Intraoperatively Built Custom Linked Seeds Versus Loose Seed Gun Applicator Technique Using Real-Time Intraoperative Planning for Permanent Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zauls, A. Jason; Ashenafi, Michael S.; Onicescu, Georgiana

2011-11-15

Purpose: To report our dosimetric results using a novel push-button seed delivery system that constructs custom links of seeds intraoperatively. Methods and Materials: From 2005 to 2007, 43 patients underwent implantation using a gun applicator (GA), and from 2007 to 2008, 48 patientsunderwent implantation with a novel technique allowing creation of intraoperatively built custom links of seeds (IBCL). Specific endpoint analyses were prostate D90% (pD90%), rV100% > 1.3 cc, and overall time under anesthesia. Results: Final analyses included 91 patients, 43 GA and 48 IBCL. Absolute change in pD90% ({Delta}pD90%) between intraoperative and postoperative plans was evaluated. Using GA method,more » the {Delta}pD90% was -8.1Gy and -12.8Gy for I-125 and Pd-103 implants, respectively. Similarly, the IBCL technique resulted in a {Delta}pD90% of -8.7Gy and -9.8Gy for I-125 and Pd-103 implants, respectively. No statistically significant difference in {Delta}pD90% was found comparing methods. The GA method had two intraoperative and 10 postoperative rV100% >1.3 cc. For IBCL, five intraoperative and eight postoperative plans had rV100% >1.3 cc. For GA, the mean time under anesthesia was 75 min and 87 min for Pd-103 and I-125 implants, respectively. For IBCL, the mean time was 86 and 98 min for Pd-103 and I-125. There was a statistical difference between the methods when comparing mean time under anesthesia. Conclusions: Dosimetrically relevant endpoints were equivalent between the two methods. Currently, time under anesthesia is longer using the IBCL technique but has decreased over time. IBCL is a straightforward brachytherapy technique that can be implemented into clinical practice as an alternative to gun applicators.« less

Iodine 125 source in interstitial tumor therapy. Clinical and biological considerations.

PubMed

Kim, J H; Hilaris, B

1975-01-01

Our clinical experience with interstitial tumor therapy is presented in 2 groups of patients: 98 patients with metastatic carcinoma in neck lymph nodes implanted with iodine 125, iridium 192 or radon 222 encapsulated sources, and 105 patients with primary unresectable lung tumors, which were implanted either with radon 222 or iodine 125 seeds. The local tumor control rates with iodine 125, radon 222 and iridium 192 were 78 per cent (38/49), 65 per cent (15/23) and 58 per cent (7/12), while the local complication rates were 17 per cent, 35 per cent and 43 per cent, respectively. An analysis of the tumor control rate as a function of the implanted tumor dose shows that the iodine 125 implants with a delivery of the minimal effective tumor dose of 16,000 rads have a higher therapeutic effect than either radon 222 or iridium 192. The results of the patients with unresectable lung tumors similarly show that the implants with iodine 125 sources are superior to those with radon 222. The advantages could stem from the better spatial dose distribution, and from radiobiologic considerations associated with low dose rates, continous irradiation, and possibly gains in RBE. There present clinical data clearly demonstrate that iodine 125 seeds have a higher therapeutic ratio than radon 222 seeds. There are, in addition, distinct physical advantages making iodine 125 an attractive substitute for radon 222 for the interstitial implantation of malignant tumors.

Monte Carlo study of LDR seed dosimetry with an application in a clinical brachytherapy breast implant.

PubMed

Furstoss, C; Reniers, B; Bertrand, M J; Poon, E; Carrier, J-F; Keller, B M; Pignol, J P; Beaulieu, L; Verhaegen, F

2009-05-01

A Monte Carlo (MC) study was carried out to evaluate the effects of the interseed attenuation and the tissue composition for two models of 125I low dose rate (LDR) brachytherapy seeds (Medi-Physics 6711, IBt InterSource) in a permanent breast implant. The effect of the tissue composition was investigated because the breast localization presents heterogeneities such as glandular and adipose tissue surrounded by air, lungs, and ribs. The absolute MC dose calculations were benchmarked by comparison to the absolute dose obtained from experimental results. Before modeling a clinical case of an implant in heterogeneous breast, the effects of the tissue composition and the interseed attenuation were studied in homogeneous phantoms. To investigate the tissue composition effect, the dose along the transverse axis of the two seed models were calculated and compared in different materials. For each seed model, three seeds sharing the same transverse axis were simulated to evaluate the interseed effect in water as a function of the distance from the seed. A clinical study of a permanent breast 125I implant for a single patient was carried out using four dose calculation techniques: (1) A TG-43 based calculation, (2) a full MC simulation with realistic tissues and seed models, (3) a MC simulation in water and modeled seeds, and (4) a MC simulation without modeling the seed geometry but with realistic tissues. In the latter, a phase space file corresponding to the particles emitted from the external surface of the seed is used at each seed location. The results were compared by calculating the relevant clinical metrics V85, V100, and V200 for this kind of treatment in the target. D90 and D50 were also determined to evaluate the differences in dose and compare the results to the studies published for permanent prostate seed implants in literature. The experimental results are in agreement with the MC absolute doses (within 5% for EBT Gafchromic film and within 7% for TLD-100). Important differences between the dose along the transverse axis of the seed in water and in adipose tissue are obtained (10% at 3.5 cm). The comparisons between the full MC and the TG-43 calculations show that there are no significant differences for V85 and V100. For V200, 8.4% difference is found coming mainly from the tissue composition effect. Larger differences (about 10.5% for the model 6711 seed and about 13% for the InterSource125) are determined for D90 and D50. These differences depend on the composition of the breast tissue modeled in the simulation. A variation in percentage by mass of the mammary gland and adipose tissue can cause important differences in the clinical dose metrics V200, D90, and D50. Even if the authors can conclude that clinically, the differences in V85, V100, and V200 are acceptable in comparison to the large variation in dose in the treated volume, this work demonstrates that the development of a MC treatment planning system for LDR brachytherapy will improve the dose determination in the treated region and consequently the dose-outcome relationship, especially for the skin toxicity.

Radioactive seed migration following parotid gland interstitial brachytherapy.

PubMed

Fan, Yi; Huang, Ming-Wei; Zhao, Yi-Jiao; Gao, Hong; Zhang, Jian-Guo

To evaluate the incidence and associated factors of pulmonary seed migration after parotid brachytherapy using a novel migrated seed detection technique. Patients diagnosed with parotid cancer who underwent permanent parotid brachytherapy from January 2006 to December 2011 were reviewed retrospectively. Head and neck CT scans and chest X-rays were evaluated during routine follow-up. Mimics software and Geomagic Studio software were used for seed reconstruction and migrated seed detection from the original implanted region, respectively. Postimplant dosimetry analysis was performed after seeds migration if the seeds were still in their emitting count. Adverse clinical sequelae from seed embolization to the lung were documented. The radioactive seed implants were identified on chest X-rays in 6 patients. The incidence rate of seed migration in 321 parotid brachytherapy patients was 1.87% (6/321) and that of individual seed migration was 0.04% (6/15218 seeds). All migrated seeds were originally from the retromandibular region. No adverse dosimetric consequences were found in the target region. Pulmonary symptoms were not reported by any patient in this study. In our patient set, migration of radioactive seeds with an initial radioactivity of 0.6-0.7 mCi to the chest following parotid brachytherapy was rare. Late migration of a single seed from the central target region did not affect the dosimetry significantly, and patients did not have severe short-term complications. This study proposed a novel technique to localize the anatomical origin of the migrated seeds during brachytherapy. Our evidence suggested that placement of seeds adjacent to blood vessels was associated with an increased likelihood of seed migration to the lungs. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Evaluation of inductively heated ferromagnetic alloy implants for therapeutic interstitial hyperthermia.

PubMed

Paulus, J A; Richardson, J S; Tucker, R D; Park, J B

1996-04-01

Ferromagnetic alloys heated by magnetic induction have been investigated as interstitial hyperthermia delivery implants for over a decade, utilizing low Curie temperatures to provide thermal self-regulation. The minimally invasive method is attractive for fractionated thermal treatment of tumors which are not easily heated by focused microwave or ultrasound techniques. Past analyses of ferromagnetic seeds by other authors depict poor experimental correlation with theoretical heating predictions. Improvements in computer hardware and commercially available finite element analysis software have simplified the analysis of inductively heated thermal seeds considerably. This manuscript examines end effects of finite length implants and nonlinear magnetic material properties to account for previous inconsistencies. Two alloys, Ni-28 wt% Cu (NiCu) and Pd-6.15 wt% Co (PdCo), were used for comparison of theoretical and experimental calorimetric results. Length to diameter (L/d) ratios of over 20 for cylindrical seeds are necessary for minimization of end effects. Magnetic properties tested for alloys of NiCu and PdCo illustrate considerable nonlinearity of these materials in field strength ranges used for induction heating. Field strength dependent magnetic permeabilities and calorimetric data illustrate that more detailed material information must be included to accurately estimate induction power loss for these implants.

CT-Guided Radioactive {sup 125}I Seed Implantation Therapy of Symptomatic Retroperitoneal Lymph Node Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Zhongmin, E-mail: wzm0722@hotmail.com; Lu, Jian; Gong, Ju

2013-04-12

PurposeThis study explored the clinical efficacy of CT-guided radioactive {sup 125}I seed implantation in treating patients with symptomatic retroperitoneal lymph node metastases.MethodsTwenty-five patients with pathologically confirmed malignant tumors received CT-guided radioactive {sup 125}I seed implantation to treat metastatic lymph nodes. The diameter of the metastatic lymph nodes ranged from 1.5 to 4.5 cm. Treatment planning system (TPS) was used to reconstruct the three-dimensional image of the tumor and then calculate the corresponding quantity and distribution of {sup 125}I seeds.ResultsFollow-up period for this group of patients was 2–30 months, and median time was 16 months. Symptoms of refractory pain were significantly resolved postimplantationmore » (P < 0.05), and Karnofsky score rose dramatically (P < 0.05). Most patients reported pain relief 2–5 days after treatment. Follow-up imaging studies were performed 2 months later, which revealed CR in 7 patients, PR in 13 patients, SD in 3 patients, and PD in 2 patients. The overall effective rate (CR + PR) was 80 %. Median survival time was 25.5 months. Seven patients died of recurrent tumor; 16 patients died of multiorgan failure or other metastases. Two patients survived after 30 months follow-up. Two patients reported localized skin erythema 1 week postimplantation, which disappeared after topical treatment.ConclusionsCT-guided radioactive {sup 125}I seed implantation, which showed good palliative pain relief with acceptable short-term effects, has proved in our study to be a new, safe, effective, and relatively uncomplicated treatment option for symptomatic retroperitoneal metastatic lymph nodes.« less

Clinical Study on Using 125I Seeds Articles Combined with Biliary Stent Implantation in the Treatment of Malignant Obstructive Jaundice.

PubMed

Wang, Tao; Liu, Sheng; Zheng, Yan-Bo; Song, Xue-Peng; Sun, Bo-Lin; Jiang, Wen-Jin; Wang, Li-Gang

2017-08-01

Aim: To study the feasibility and curative effect of 125 I seeds articles combined with biliary stent implantation in the treatment of malignant obstructive jaundice. Patients and Methods: Fifty patients with malignant obstructive jaundice were included. Twenty-four were treated by biliary stent implantation combined with intraluminal brachytherapy by 125 I seeds articles as the experimental group, while the remaining 26 were treated by biliary stent implantation only as the control group. The goal of this study was to evaluate total bilirubin, direct bilirubin and tumor markers (cancer antigen (CA)-199, CA-242 and carcinoembryonic antigen (CEA)), as well as biliary stent patency status and survival time before and after surgery. Results: Jaundice improved greatly in both groups. The decreases of CA-199 and CA-242 had statistical significance (p=0.003 and p=0.004) in the experimental group. The ratio of biliary stent patency was 83.3% (20/24) in the experimental group and 57.7% (15/26) in the control group (p=0.048). The biliary stent patency time in the experimental group was 1~15.5 (mean=9.84) months. The biliary stent patency time in the control group was 0.8~9 (mean=5.57) months, which was statistically significant (p=0.018). The median survival time was 10.2 months in the experimental group, while 5.4 months in control group (p<0.05). Conclusion: 125 I seeds articles combined with biliary stent implantation significantly prolongs biliary stent patency time and survival time for patients with malignant obstructive jaundice possibly by inhibiting the proliferation of vascular endothelial cells and the growth of tumor. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Urethral toxicity after LDR brachytherapy: experience in Japan.

PubMed

Tanaka, Nobumichi; Asakawa, Isao; Hasegawa, Masatoshi; Fujimoto, Kiyohide

2015-01-01

Urinary toxicity is common after low-dose-rate (LDR) brachytherapy, and the resolution of urinary toxicity is a concern. In particular, urinary frequency is the most common adverse event among the urinary toxicities. We have previously reported that approximately 70% of patients experience urinary frequency during the first 6 months after seed implantation. Most urinary adverse events were classified as Grade 1, and Grade 2 or higher adverse events were rare. The incidence of urinary retention was approximately 2-4%. A high International Prostate Symptom Score before seed implantation was an independent predictor of acute urinary toxicity of Grade 2 or higher. Several previous reports from the United States also supported this trend. In Japan, LDR brachytherapy was legally approved in 2003. A nationwide prospective cohort study entitled Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation was initiated in July 2005. It is an important issue to limit urinary toxicities in patients who undergo LDR brachytherapy. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Multilayer checkpoints for microRNA authenticity during RISC assembly.

PubMed

Kawamata, Tomoko; Yoda, Mayuko; Tomari, Yukihide

2011-09-01

MicroRNAs (miRNAs) function through the RNA-induced silencing complex (RISC), which contains an Argonaute (Ago) protein at the core. RISC assembly follows a two-step pathway: miRNA/miRNA* duplex loading into Ago, and separation of the two strands within Ago. Here we show that the 5' phosphate of the miRNA strand is essential for duplex loading into Ago, whereas the preferred 5' nucleotide of the miRNA strand and the base-pairing status in the seed region and the middle of the 3' region function as additive anchors to Ago. Consequently, the miRNA authenticity is inspected at multiple steps during RISC assembly.

Repeated iodine-125 seed implantations combined with external beam radiotherapy for the treatment of locally recurrent or metastatic stage III/IV non-small cell lung cancer: a retrospective study.

PubMed

Li, Wei; Dan, Gang; Jiang, Jianqing; Zheng, Yifeng; Zheng, Xiushan; Deng, Dan

2016-09-13

Recurrent or metastatic lung cancer is difficult to manage. This retrospective study aimed to assess the efficacy of repeated iodine-125 seed implantations combined with external beam radiotherapy (EBRT) for locally recurrent or metastatic stage-III/IV non-small cell lung cancer (NSCLC). Eighteen previously treated stage-III/IV NSCLC patients with local or metastatic recurrences underwent 1-to-3 iodine-125 implantations. Six of these patients received palliative EBRT and six patients received combined chemotherapy using gemcitabine and cisplatin. Near-term treatment efficacy was evaluated 3 months after seed implantation by comparing changes in tumor size on computed tomography images; the evaluated outcomes were complete response, partial response, stable disease, and local tumor control rate. Long-term efficacy was assessed based on 1- and 2-year survival rates. Patients were followed up for 6 to 50 months. The overall (i.e., complete + partial) response rate was 87.4 %. The local control rates after the first, second, and third years were 94.1, 58.8 and 41.2 %, respectively. The results of this study demonstrated that repeated implantation of radioactive particles combined with EBRT is a safe treatment that effectively controlled local recurrence and metastasis of stage III/IV NSCLC.

Hanging by a coastal strand: breeding system of a federally endangered morning-glory of the south-eastern Florida coast, Jacquemontia reclinata

PubMed Central

Pinto-Torres, Elena; Koptur, Suzanne

2009-01-01

Background and Aims Coastal development has led to extensive habitat destruction and the near extinction of the beach clustervine, Jacquemontia reclinata (Convolvulaceae), an endangered, perennial vine endemic to dune and coastal strand communities in south-eastern Florida. We examined the breeding system of this rare species, and observed visitors to its flowers, as part of a larger effort to document its status and facilitate its recovery. Methods Reproductively mature experimental plants were grown from seed collected from wild plants in two of the largest remaining populations. Controlled hand pollinations on potted plants were conducted to determine the level of compatibility of the species and to investigate compatibility within and between populations. Seeds from the hand pollinations were planted in soil, and they were monitored individually, recording time to seed germination (cotyledon emergence). Wild plants were observed in several of the remaining populations to determine which species visited the flowers. Key Results Hand pollination and seed planting experiments indicate that J. reclinata has a mixed mating system: flowers are able to set fruit with viable seeds with self-pollen, but outcross pollen produces significantly greater fruit and seed set than self-pollen (≥50 % for crosses vs. <25 % for self-pollinations). Visitors included a wide array of insect species, primarily of the orders Diptera, Hymenoptera and Lepidoptera. All visitors captured and examined carried J. reclinata pollen, and usually several other types of pollen. Conclusions Remnant populations of beach clustervine will have greater reproductive success not only if floral visitor populations are maintained, but also if movement of either pollen or seed takes place between populations. Restoration efforts should include provisions for the establishment and maintenance of pollinator populations. PMID:19797424

Automated seed localization from CT datasets of the prostate.

PubMed

Brinkmann, D H; Kline, R W

1998-09-01

With the increasing utilization of permanent brachytherapy implants for treating carcinoma of the prostate, the importance of accurate post-treatment dose calculation also increases for assessing patient outcome and planning future treatments. An automatic method for seed localization of permanent brachytherapy implants, using CT datasets of the prostate, has been developed and tested on a phantom using an actual patient planned seed distribution. This method was also compared to results with the three-film technique for three patient datasets. The automatic method is as accurate or more accurate than the three film technique for 1 mm, 3 mm, and 5 mm contiguous CT slices, and eliminates the inter- and intra-observer variability of the manual methods. The automated method improves the localization of brachytherapy seeds while reducing the time required for the user to input information, and is demonstrated to be less operator dependent, less time consuming, and potentially more accurate than the three-film technique.

A novel curvilinear approach for prostate seed implantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Podder, Tarun K.; Dicker, Adam P.; Hutapea, Parsaoran

Purpose: A new technique called ''curvilinear approach'' for prostate seed implantation has been proposed. The purpose of this study is to evaluate the dosimetric benefit of curvilinear distribution of seeds for low-dose-rate (LDR) prostate brachytherapy. Methods: Twenty LDR prostate brachytherapy cases planned intraoperatively with VariSeed planning system and I-125 seeds were randomly selected as reference rectilinear cases. All the cases were replanned by using curved-needle approach keeping the same individual source strength and the volume receiving 100% of prescribed dose 145 Gy (V{sub 100}). Parameters such as number of needles, seeds, and the dose coverage of the prostate (D{sub 90},more » V{sub 150}, V{sub 200}), urethra (D{sub 30}, D{sub 10}) and rectum (D{sub 5}, V{sub 100}) were compared for the rectilinear and the curvilinear methods. Statistical significance was assessed using two-tailed student's t-test. Results: Reduction of the required number of needles and seeds in curvilinear method were 30.5% (p < 0.001) and 11.8% (p < 0.49), respectively. Dose to the urethra was reduced significantly; D{sub 30} reduced by 10.1% (p < 0.01) and D{sub 10} reduced by 9.9% (p < 0.02). Reduction in rectum dose D{sub 5} was 18.5% (p < 0.03) and V{sub 100} was also reduced from 0.93 cc in rectilinear to 0.21 cc in curvilinear (p < 0.001). Also the V{sub 150} and V{sub 200} coverage of prostate reduced by 18.8% (p < 0.01) and 33.9% (p < 0.001), respectively. Conclusions: Significant improvement in the relevant dosimetric parameters was observed in curvilinear needle approach. Prostate dose homogeneity (V{sub 150}, V{sub 200}) improved while urethral dose was reduced, which might potentially result in better treatment outcome. Reduction in rectal dose could potentially reduce rectal toxicity and complications. Reduction in number of needles would minimize edema and thereby could improve postimplant urinary incontinence. This study indicates that the curvilinear implantation approach is dosimetrically superior to conventional rectilinear implantation technique.« less

PLDLA/PCL-T Scaffold for Meniscus Tissue Engineering

PubMed Central

Moda, Marlon; Cattani, Silvia Mara de Melo; de Santana, Gracy Mara; Barbieri, Juliana Abreu; Munhoz, Monique Moron; Cardoso, Túlio Pereira; Barbo, Maria Lourdes Peris; Russo, Teresa; D'Amora, Ugo; Gloria, Antonio; Ambrosio, Luigi; Duek, Eliana Aparecida de Rezende

2013-01-01

Abstract The inability of the avascular region of the meniscus to regenerate has led to the use of tissue engineering to treat meniscal injuries. The aim of this study was to evaluate the ability of fibrochondrocytes preseeded on PLDLA/PCL-T [poly(L-co-D,L-lactic acid)/poly(caprolactone-triol)] scaffolds to stimulate regeneration of the whole meniscus. Porous PLDLA/PCL-T (90/10) scaffolds were obtained by solvent casting and particulate leaching. Compressive modulus of 9.5±1.0 MPa and maximum stress of 4.7±0.9 MPa were evaluated. Fibrochondrocytes from rabbit menisci were isolated, seeded directly on the scaffolds, and cultured for 21 days. New Zealand rabbits underwent total meniscectomy, after which implants consisting of cell-free scaffolds or cell-seeded scaffolds were introduced into the medial knee meniscus; the negative control group consisted of rabbits that received no implant. Macroscopic and histological evaluations of the neomeniscus were performed 12 and 24 weeks after implantation. The polymer scaffold implants adapted well to surrounding tissues, without apparent rejection, infection, or chronic inflammatory response. Fibrocartilaginous tissue with mature collagen fibers was observed predominantly in implants with seeded scaffolds compared to cell-free implants after 24 weeks. Similar results were not observed in the control group. Articular cartilage was preserved in the polymeric implants and showed higher chondrocyte cell number than the control group. These findings show that the PLDLA/PCL-T 90/10 scaffold has potential for orthopedic applications since this material allowed the formation of fibrocartilaginous tissue, a structure of crucial importance for repairing injuries to joints, including replacement of the meniscus and the protection of articular cartilage from degeneration. PMID:23593566

Establishing High-Quality Prostate Brachytherapy Using a Phantom Simulator Training Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thaker, Nikhil G.; Kudchadker, Rajat J.; Swanson, David A.

2014-11-01

Purpose: To design and implement a unique training program that uses a phantom-based simulator to teach the process of prostate brachytherapy (PB) quality assurance and improve the quality of education. Methods and Materials: Trainees in our simulator program were practicing radiation oncologists, radiation oncology residents, and fellows of the American Brachytherapy Society. The program emphasized 6 core areas of quality assurance: patient selection, simulation, treatment planning, implant technique, treatment evaluation, and outcome assessment. Using the Iodine 125 ({sup 125}I) preoperative treatment planning technique, trainees implanted their ultrasound phantoms with dummy seeds (ie, seeds with no activity). Pre- and postimplant dosimetric parametersmore » were compared and correlated using regression analysis. Results: Thirty-one trainees successfully completed the simulator program during the period under study. The mean phantom prostate size, number of seeds used, and total activity were generally consistent between trainees. All trainees met the V100 >95% objective both before and after implantation. Regardless of the initial volume of the prostate phantom, trainees' ability to cover the target volume with at least 100% of the dose (V100) was not compromised (R=0.99 pre- and postimplant). However, the V150 had lower concordance (R=0.37) and may better reflect heterogeneity control of the implant process. Conclusions: Analysis of implants from this phantom-based simulator shows a high degree of consistency between trainees and uniformly high-quality implants with respect to parameters used in clinical practice. This training program provides a valuable educational opportunity that improves the quality of PB training and likely accelerates the learning curve inherent in PB. Prostate phantom implantation can be a valuable first step in the acquisition of the required skills to safely perform PB.« less

SU-F-J-157: Effect of Contouring Uncertainty in Post Implant Dosimetry of Low-Dose-Rate Prostate Permanent Seed Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mashouf, S; Merino, T; Ravi, A

Purpose: There is strong evidence relating post-implant dosimetry for low-dose-rate (LDR) prostate seed brachytherapy to local control rates. The delineation of the prostate on CT images, however, represents a challenge due to the lack of soft tissue contrast in order to identify the prostate borders. This study aims at quantifying the sensitivity of clinically relevant dosimetric parameters to uncertainty in the contouring of prostate. Methods: CT images, post-op plans and contours of a cohort of patients (n=43) (low risk=55.8%, intermediate risk=39.5%, high risk=4.7%), who had received prostate seed brachytherapy, were imported into MIM Symphony treatment planning system. The prostate contoursmore » in post-implant CT images were expanded/contracted uniformly for margins of ±1.00 mm, ±2.00 mm, ±3.00 mm, ±4.00 mm and ±5.00 mm. The values for V100 and D90 were extracted from Dose Volume Histograms for each contour and compared. Results: Significant changes were observed in the values of D90 and V100 as well as the number of suboptimal plans for expansion or contraction margins of only few millimeters. Evaluation of coverage based on D90 was found to be less sensitive to expansion errors compared to V100. D90 led to a lower number of implants incorrectly identified with insufficient coverage for expanded contours which increases the accuracy of post-implant QA using CT images compared to V100. Conclusion: In order to establish a successful post implant QA for LDR prostate seed brachytherapy, it is necessary to identify the low and high thresholds of important dose metrics of the target volume such as D90 and V100. Since these parameters are sensitive to target volume definition, accurate identification of prostate borders would help to improve accuracy and predictive value of the post-implant QA process. In this respect, use of imaging modalities such as MRI where prostate is well delineated should prove useful.« less

Demonstration of a forward iterative method to reconstruct brachytherapy seed configurations from x-ray projections

NASA Astrophysics Data System (ADS)

Murphy, Martin J.; Todor, Dorin A.

2005-06-01

By monitoring brachytherapy seed placement and determining the actual configuration of the seeds in vivo, one can optimize the treatment plan during the process of implantation. Two or more radiographic images from different viewpoints can in principle allow one to reconstruct the configuration of implanted seeds uniquely. However, the reconstruction problem is complicated by several factors: (1) the seeds can overlap and cluster in the images; (2) the images can have distortion that varies with viewpoint when a C-arm fluoroscope is used; (3) there can be uncertainty in the imaging viewpoints; (4) the angular separation of the imaging viewpoints can be small owing to physical space constraints; (5) there can be inconsistency in the number of seeds detected in the images; and (6) the patient can move while being imaged. We propose and conceptually demonstrate a novel reconstruction method that handles all of these complications and uncertainties in a unified process. The method represents the three-dimensional seed and camera configurations as parametrized models that are adjusted iteratively to conform to the observed radiographic images. The morphed model seed configuration that best reproduces the appearance of the seeds in the radiographs is the best estimate of the actual seed configuration. All of the information needed to establish both the seed configuration and the camera model is derived from the seed images without resort to external calibration fixtures. Furthermore, by comparing overall image content rather than individual seed coordinates, the process avoids the need to establish correspondence between seed identities in the several images. The method has been shown to work robustly in simulation tests that simultaneously allow for unknown individual seed positions, uncertainties in the imaging viewpoints and variable image distortion.

Monte Carlo investigation of I-125 interseed attenuation for standard and thinner seeds in prostate brachytherapy with phantom validation using a MOSFET.

PubMed

Mason, J; Al-Qaisieh, B; Bownes, P; Henry, A; Thwaites, D

2013-03-01

In permanent seed implant prostate brachytherapy the actual dose delivered to the patient may be less than that calculated by TG-43U1 due to interseed attenuation (ISA) and differences between prostate tissue composition and water. In this study the magnitude of the ISA effect is assessed in a phantom and in clinical prostate postimplant cases. Results are compared for seed models 6711 and 9011 with 0.8 and 0.5 mm diameters, respectively. A polymethyl methacrylate (PMMA) phantom was designed to perform ISA measurements in a simple eight-seed arrangement and at the center of an implant of 36 seeds. Monte Carlo (MC) simulation and experimental measurements using a MOSFET dosimeter were used to measure dose rate and the ISA effect. MC simulations of 15 CT-based postimplant prostate treatment plans were performed to compare the clinical impact of ISA on dose to prostate, urethra, rectum, and the volume enclosed by the 100% isodose, for 6711 and 9011 seed models. In the phantom, ISA reduced the dose rate at the MOSFET position by 8.6%-18.3% (6711) and 7.8%-16.7% (9011) depending on the measurement configuration. MOSFET measured dose rates agreed with MC simulation predictions within the MOSFET measurement uncertainty, which ranged from 5.5% to 7.2% depending on the measurement configuration (k = 1, for the mean of four measurements). For 15 clinical implants, the mean ISA effect for 6711 was to reduce prostate D90 by 4.2 Gy (3%), prostate V100 by 0.5 cc (1.4%), urethra D10 by 11.3 Gy (4.4%), rectal D2cc by 5.5 Gy (4.6%), and the 100% isodose volume by 2.3 cc. For the 9011 seed the mean ISA effect reduced prostate D90 by 2.2 Gy (1.6%), prostate V100 by 0.3 cc (0.7%), urethra D10 by 8.0 Gy (3.2%), rectal D2cc by 3.1 Gy (2.7%), and the 100% isodose volume by 1.2 cc. Differences between the MC simulation and TG-43U1 consensus data for the 6711 seed model had a similar impact, reducing mean prostate D90 by 6 Gy (4.2%) and V100 by 0.6 cc (1.8%). ISA causes the delivered dose in prostate seed implant brachytherapy to be lower than the dose calculated by TG-43U1. MC simulation of phantom seed arrangements show that dose at a point can be reduced by up to 18% and this has been validated using a MOSFET dosimeter. Clinical simulations show that ISA reduces DVH parameter values, but the reduction is less for thinner seeds.

SU-E-J-215: Towards MR-Only Image Guided Identification of Calcifications and Brachytherapy Seeds: Application to Prostate and Breast LDR Implant Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elzibak, A; Fatemi-Ardekani, A; Soliman, A

Purpose: To identify and analyze the appearance of calcifications and brachytherapy seeds on magnitude and phase MRI images and to investigate whether they can be distinguished from each other on corrected phase images for application to prostate and breast low dose rate (LDR) implant dosimetry. Methods: An agar-based gel phantom containing two LDR brachytherapy seeds (Advantage Pd-103, IsoAid, 0.8mm diameter, 4.5mm length) and two spherical calcifications (large: 7mm diameter and small: 4mm diameter) was constructed and imaged on a 3T Philips MR scanner using a 16-channel head coil and a susceptibility weighted imaging (SWI) sequence (2mm slices, 320mm FOV, TR/more » TE= 26.5/5.3ms, 15 degree flip angle). The phase images were unwrapped and corrected using a 32×32, 2D Hanning high pass filter to remove background phase noise. Appearance of the seeds and calcifications was assessed visually and quantitatively using Osirix (http://www.osirix-viewer.com/). Results: As expected, calcifications and brachytherapy seeds appeared dark (hypointense) relative to the surrounding gel on the magnitude MRI images. The diameter of each seed without the surrounding artifact was measured to be 0.1 cm on the magnitude image, while diameters of 0.79 and 0.37 cm were measured for the larger and smaller calcifications, respectively. On the corrected phase images, the brachytherapy seeds and the calcifications appeared bright (hyperintense). The diameter of the seeds was larger on the phase images (0.17 cm) likely due to the dipole effect. Conclusion: MRI has the best soft tissue contrast for accurate organ delineation leading to most accurate implant dosimetry. This work demonstrated that phase images can potentially be useful in identifying brachytherapy seeds and calcifications in the prostate and breast due to their bright appearance, which helps in their visualization and quantification for accurate dosimetry using MR-only. Future work includes optimizing phase filters to best identify and delineate seeds and calcifications.« less

The value of spectral imaging to reduce artefacts in the body after 125 I seed implantation.

PubMed

Liu, Jingang; Wang, Wenjuan; Zhao, Xingsheng; Shen, Zhen; Shao, Weiguang; Wang, Xizhen; Li, Lixin; Wang, Bin

2016-10-01

To explore the value of gemstone spectral imaging (GSI) and metal artefact reduction sequence (MARs) to reduce the artefacts of metal seeds. Thirty-five patients with 125 I seed implantation in their abdomens underwent GSI CT. Six types of monochromatic images and the corresponding MARs images at 60-110 keV (interval of 10 keV) were reconstructed. The differences in the quality of the images of three imaging methods were subjectively assessed by three radiologists. Length of artefacts, the CT value and noise value of tissue adjacent to 125 I seeds, contrast-to-noise ratio (CNR), and artefact index (AI) were recorded. The differences in subjective scoring were statistically significant (t = 10.87, P < 0.001). Images at 70 keV showed the best CNR (0.84 ± 0.17) of tissues adjacent to 125 I seeds, and received the highest subjective score (2.82 ± 0.18). Images at 80 keV had the lowest AI (70.67 ± 19.17). Images at 110 keV had the shortest artefact lengths. High-density metal artefacts in the MARs spectral images were reduced. The length of metal artefacts in images at 110 keV was shorter than that of the polychromatic images and MARs spectral images (t = 3.35, 3.89, P < 0.05). The difference in CNR between MARs spectral images and polychromatic images, and images at 70 keV was statistically significant (t = 3.57, 4.16, P < 0.01). Gemstone spectral imaging technique can reduce metal artefacts of 125 I seeds effectively in CT images, and improve the quality of images, and improve the display of tissues adjacent to 125 I seeds after implantation. MARs technique cannot reduce the artefacts caused by radioactive seeds effectively. © 2016 The Royal Australian and New Zealand College of Radiologists.

Salvage low-dose-rate 125I partial prostate brachytherapy after dose-escalated external beam radiotherapy

PubMed Central

Chang, Lynn

2014-01-01

Purpose To report outcomes on 5 patients treated with salvage partial low-dose-rate (LDR) 125-iodine (125I) permanent prostate seed brachytherapy (BT) for biopsy-proven locally persistent prostate cancer, following failure of dose-escalated external beam radiotherapy (EBRT). Material and methods A retrospective review of the Fox Chase Cancer Center prostate cancer database identified five patients treated with salvage partial LDR 125I seed implant for locally persistent disease following dose-escalated EBRT to 76-84 Gy in 2 Gy per fraction equivalent. All patients had post-EBRT biopsies confirming unilateral locally persistent prostate cancer. Pre-treatment, EBRT and BT details, as well as post-treatment characteristics were documented and assessed. Results The median follow-up post-implant was 41 months. All five patients exhibited low acute genitourinary and gastrointestinal toxicities. Increased erectile dysfunction was noted in three patients. There were no biochemical failures following salvage LDR 125I seed BT to date, with a median post-salvage PSA of 0.4 ng/mL. Conclusions In carefully selected patients with local persistence of disease, partial LDR 125I permanent prostate seed implant appears to be a feasible option for salvage local therapy with an acceptable toxicity profile. Further study is needed to determine long-term results of this approach. PMID:25337135

Gene expression profiles in promoted-growth rice seedlings that germinated from the seeds implanted by low-energy N+ beam

PubMed Central

Ya, Huiyuan; Chen, Qiufang; Wang, Weidong; Chen, Wanguang; Qin, Guangyong; Jiao, Zhen

2012-01-01

The stimulation effect that some beneficial agronomic qualities have exhibited in present-generation plants have also been observed due to ion implantation on plants. However, there is relatively little knowledge regarding the molecular mechanism of the stimulation effects of ion-beam implantation. In order to extend our current knowledge about the functional genes related to this stimulation effect, we have reported a comprehensive microarray analysis of the transcriptome features of the promoted-growth rice seedlings germinating from seeds implanted by a low-energy N+ beam. The results showed that 351 up-regulated transcripts and 470 down-regulated transcripts, including signaling proteins, kinases, plant hormones, transposable elements, transcription factors, non-coding protein RNA (including miRNA), secondary metabolites, resistance proteins, peroxidase and chromatin modification, are all involved in the stimulating effects of ion-beam implantation. The divergences of the functional catalog between the vacuum and ion implantation suggest that ion implantation is the principle cause of the ion-beam implantation biological effects, and revealed the complex molecular networks required to adapt to ion-beam implantation stress in plants, including enhanced transposition of transposable elements, promoted ABA biosynthesis and changes in chromatin modification. Our data will extend the current understanding of the molecular mechanisms and gene regulation of stimulation effects. Further research on the candidates reported in this study should provide new insights into the molecular mechanisms of biological effects induced by ion-beam implantation. PMID:22843621

On the use of Kodak CR film for quality assurance of needle loading in I-125 seed prostate brachytherapy.

PubMed

Fog, L S; Nicholls, R; van Doom, T

2007-09-01

Low dose rate brachytherapy using implanted I-125 seeds as a monotherapy for prostate cancer is now in use in many hospitals. In contrast to fractionated brachytherapy treatments, where the effect of incorrect positioning of the source in one treatment fraction can be diminished by correcting the position in subsequent fractions, the I-125 seed implant is permanent, making correct positioning of the seeds in the prostate essential. The seeds are inserted into the prostate using needles. Correct configuration of seeds in the needles is essential in order to deliver the planned treatment. A comparison of an autoradiograph obtained by exposing film to the seed-loaded needles with the patient treatment plan is a valuable quality assurance tool. However, the time required to sufficiently expose Kodak XOMAT V film, currently used in this department is significant. This technical note presents the use of Kodak CR film for acquisition of the radiograph. The digital radiograph can be acquired significantly faster, has superior signal-to-noise ratio and contrast and has the usual benefits of digital film, e.g. a processing time which is shorter than that required for non-digital film, the possibility of image manipulation, possibility of paper printing and electronic storage.

Multilayer checkpoints for microRNA authenticity during RISC assembly

PubMed Central

Kawamata, Tomoko; Yoda, Mayuko; Tomari, Yukihide

2011-01-01

MicroRNAs (miRNAs) function through the RNA-induced silencing complex (RISC), which contains an Argonaute (Ago) protein at the core. RISC assembly follows a two-step pathway: miRNA/miRNA* duplex loading into Ago, and separation of the two strands within Ago. Here we show that the 5′ phosphate of the miRNA strand is essential for duplex loading into Ago, whereas the preferred 5′ nucleotide of the miRNA strand and the base-pairing status in the seed region and the middle of the 3′ region function as additive anchors to Ago. Consequently, the miRNA authenticity is inspected at multiple steps during RISC assembly. PMID:21738221

Cell Seeding Densities in Autologous Chondrocyte Implantation Techniques for Cartilage Repair.

PubMed

Foldager, Casper Bindzus; Gomoll, Andreas H; Lind, Martin; Spector, Myron

2012-04-01

Cartilage repair techniques have been among the most intensively investigated treatments in orthopedics for the past decade, and several different treatment modalities are currently available. Despite the extensive research effort within this field, the generation of hyaline cartilage remains a considerable challenge. There are many parameters attendant to each of the cartilage repair techniques that can affect the amount and types of reparative tissue generated in the cartilage defect, and some of the most fundamental of these parameters have yet to be fully investigated. For procedures in which in vitro-cultured autologous chondrocytes are implanted under a periosteal or synthetic membrane cover, or seeded onto a porous membrane or scaffold, little is known about how the number of cells affects the clinical outcome. Few published clinical studies address the cell seeding density that was employed. The principal objective of this review is to provide an overview of the cell seeding densities used in cell-based treatments currently available in the clinic for cartilage repair. Select preclinical studies that have informed the use of specific cell seeding densities in the clinic are also discussed.

SLM produced porous titanium implant improvements for enhanced vascularization and osteoblast seeding.

PubMed

Matena, Julia; Petersen, Svea; Gieseke, Matthias; Kampmann, Andreas; Teske, Michael; Beyerbach, Martin; Murua Escobar, Hugo; Haferkamp, Heinz; Gellrich, Nils-Claudius; Nolte, Ingo

2015-04-02

To improve well-known titanium implants, pores can be used for increasing bone formation and close bone-implant interface. Selective Laser Melting (SLM) enables the production of any geometry and was used for implant production with 250-µm pore size. The used pore size supports vessel ingrowth, as bone formation is strongly dependent on fast vascularization. Additionally, proangiogenic factors promote implant vascularization. To functionalize the titanium with proangiogenic factors, polycaprolactone (PCL) coating can be used. The following proangiogenic factors were examined: vascular endothelial growth factor (VEGF), high mobility group box 1 (HMGB1) and chemokine (C-X-C motif) ligand 12 (CXCL12). As different surfaces lead to different cell reactions, titanium and PCL coating were compared. The growing into the porous titanium structure of primary osteoblasts was examined by cross sections. Primary osteoblasts seeded on the different surfaces were compared using Live Cell Imaging (LCI). Cross sections showed cells had proliferated, but not migrated after seven days. Although the cell count was lower on titanium PCL implants in LCI, the cell count and cell spreading area development showed promising results for titanium PCL implants. HMGB1 showed the highest migration capacity for stimulating the endothelial cell line. Future perspective would be the incorporation of HMGB1 into PCL polymer for the realization of a slow factor release.

Adipose-derived stem-cell-implanted poly(ϵ-caprolactone)/chitosan scaffold improves bladder regeneration in a rat model.

PubMed

Zhou, Zhe; Yan, Hao; Liu, Yidong; Xiao, Dongdong; Li, Wei; Wang, Qiong; Zhao, Yang; Sun, Kang; Zhang, Ming; Lu, Mujun

2018-04-01

The study investigated the feasibility of seeding adipose-derived stem cells (ASCs) onto a poly(ϵ-caprolactone)/chitosan (PCL/CS) scaffold for bladder reconstruction using a rat model of bladder augmentation. In the experimental group, the autologous ASCs were seeded onto the PCL/CS scaffold for bladder augmentation. An unseeded scaffold was used for bladder augmentation as control group. The sham group was also set. 8 weeks after implantation, more densely smooth muscles were detected in the experimental group with a larger bladder capacity and more intensive blood vessels. Immunofluorescence staining demonstrated that some of the smooth muscle cells were transdifferentiated from the ASCs. Our findings indicated that ASC-seeded PCL/CS may be a potential scaffold for bladder tissue engineering.

[Dosimetry verification of radioactive seed implantation with 3D printing template and CT guidance for paravertebral/retroperitoneal malignant tumor].

PubMed

Ji, Z; Jiang, Y L; Guo, F X; Peng, R; Sun, H T; Fan, J H; Wang, J J

2017-04-04

Objective: To compare the dose distributions of postoperative plans with preoperative plans for seeds implantations of paravertebral/retroperitoneal tumors assisted by 3D printing guide template and CT guidance, explore the effects of the technology for seeds implantations in dosimetry level and provide data support for the optimization and standardization in seeds implantation. Methods: Between December 2015 and July 2016, a total of 10 patients with paravertebral/retroperitoneal tumors (12 lesions) received 3D printing template assist radioactive seeds implantations in department of radiation oncology of Peking University Third Hospital, and included in the study. The diseases included cervical cancer, kidney cancer, abdominal stromal tumor, leiomyosarcoma of kidney, esophageal cancer and carcinoma of ureter. The prescribed doses was 110-150 Gy. All patients received preoperative planning design, individual template design and production, and the dose distribution of postoperative plan was compared with preoperative plan. Dose parameters including D(90), MPD, V(100), V(150,)conformal index(CI), EI of target volume and D(2cc) of organs at risk (spinal cord, aorta, kidney). Statistical software was SPSS 19.0 and statistical method was non-parameters Wilcoxon symbols test. Results: A total of 10 3D printing templates were designed and produced which were including 12 treatment areas.The mean D(90) of postoperative target area (GTV) was 131.1 (97.8-167.4 Gy) Gy. The actual seeds number of post operation increased by 3 to 12 in 5 cases (42.0%). The needle was well distributed. For postoperative plans, the mean D(90,)MPD, V(100,)V(150) was 131.1 Gy, 69.3 Gy, 90.2% and 65.2%, respectively, and which was 140.2 Gy, 65.6 Gy, 91.7% and 26.8%, respectively, in preoperative plans. This meant that the actual dose of target volume was slightly lower than preplanned dose, and the high dose area of target volume was larger than preplanned range, but there was no statistical difference in P value between the two groups except V(150)( P =0.004). The actual dose conformity of target volume was worse than preplanned (CI was 0.58 and 0.62, respectively) and the difference was statistically significant( P =0.019). The actual dose of external target volume was higher than preplanned (EI was 55% and 45.9%, respectively) and the difference had no significance. For organs at risk, the actual mean D(2cc) of spinal cord, aorta and kidney was 24.7, 54.4 and 29.7 Gy, respectively, which was higher than preplanned(20.6, 51.6 and 28.6 Gy, respectively), and there was no significant difference in two groups. Conclusions: Most parameters of postoperative validations for 3D printing template assisted seeds implantation in paravertebral/retroperitoneal are closed to the expectations of preoperative plans which means the improvement of accuracy in treatment.

Beginnings of Song in Young Deaf Children Using Cochlear Implants: The Song They Move, the Song They Feel, the Song They Share

ERIC Educational Resources Information Center

Yennari, Maria

2010-01-01

This paper focuses on the singing activity of prelingually deaf children under four years of age who are using cochlear implants (CIs) and presents a strand of a larger study that aimed to observe, record and analyse the musical activity of seven profoundly deaf children using CIs in the UK, for a period of one calendar year. The singing activity…

SU-G-JeP1-10: Feasibility of CyberKnife Tracking Using the Previously-Implanted Permanent Brachytherapy Seed Cloud

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheung, J; Cunha, J; Sudhyadhom, A

Purpose: Robotic radiosurgery is a salvage treatment option for patients with recurrent prostate cancer. We explored the feasibility of tracking the bolus of permanent prostate implants (PPI) using image recognition software optimized to track spinal anatomy. Methods: Forty-five inert iodine seeds were implanted into a gelatin-based prostate phantom. Four superficial gold seeds were inserted to provide ground-truth alignment. A CT scan of the phantom (120 kVp, 1 mm slice thickness) was acquired and a single-energy iterative metal artifact reduction (MAR) algorithm was used to enhance the quality of the DRR used for tracking. CyberKnife treatment plans were generated from themore » MAR CT and regular CT (no-MAR) using spine tracking. The spine-tracking grid was centered on the bolus of seeds and resized to encompass the full seed cloud. A third plan was created from the regular CT scan, using fiducial tracking based on the 4 superficial gold seeds with identical align-center coordinates. The phantom was initially aligned using the fiducial-tracking plan. Then the MAR and no-MAR spine-tracking plans were loaded without moving the phantom. Differences in couch correction parameters were recorded in the case of perfect alignment and after the application of known rotations and translations (roll/pitch of 2 degrees; translations XYZ of 2 cm). Results: The spine tracking software was able to lock on to the bolus of seeds and provide couch corrections both in the MAR and no-MAR plans. In all cases, differences in the couch correction parameters from fiducial alignment were <0.5 mm in translations and <1 degree in rotations. Conclusion: We were able to successfully track the bolus of seeds with the spine-tracking grid in phantom experiments. For clinical applications, further investigation and developments to adapt the spine-tracking algorithm to optimize for PPI seed cloud tracking is needed to provide reliable tracking in patients. One of the authors (MD) has received research support and speaker honoraria from Accuray.« less

Brachytherapy in early prostate cancer--early experience.

PubMed

Jose, B O; Bailen, J L; Albrink, F H; Steinbock, G S; Cornett, M S; Benson, D C; Schmied, W K; Medley, R N; Spanos, W J; Paris, K J; Koerner, P D; Gatenby, R A; Wilson, D L; Meyer, R

1999-01-01

Use of brachytherapy with radioactive seeds in the management of early prostate cancer is commonly used in the United States. The early experience has been reported from the prostate treatment centers in Seattle for the last 10 years. In this manuscript we are reporting our early experience of 150 radioactive seed implantations in early stage prostate cancer using either Iodine 125 or Palladium 103 seeds. The average age of the patient is 66 years and the median Gleason score is 5.4 with a median PSA of 6. A brief description of the evolution of the treatment of prostate cancer as well as the preparation for the seed implantation using the volume study with ultrasound of the prostate, pubic arch study using CT scan of the pelvis and the complete planning using the treatment planning computers are discussed. We also have described the current technique which is used in our experience based on the Seattle guidelines. We plan a follow-up report with the results of the studies with longer follow-up.

Prospective study of direct radiation exposure measurements for family members living with patients with prostate (125)I seed implantation: Evidence of radiation safety.

PubMed

Hanada, Takashi; Yorozu, Atsunori; Shinya, Yukiko; Kuroiwa, Nobuko; Ohashi, Toshio; Saito, Shiro; Shigematsu, Naoyuki

2016-01-01

To broaden the current understanding of radiation exposure and risk and to provide concrete evidence of radiation safety related to (125)I seed implantation. Direct radiation exposure measurements were obtained from dosimeters provided to 25 patients who underwent (125)I seed implantation, along with their family members. The estimated lifetime exposure dose and the precaution time for holding children near the patient's chest were calculated in two study periods. During the first and second study period, the mean estimated lifetime exposure doses were, respectively, 7.61 (range: 0.45, 20.21) mSv and 6.84 (range: 0.41, 19.20) mSv for patients, and 0.19 (range: 0.02, 0.54) mSv and 0.25 (range: 0.04, 1.00) mSv for family members. The mean ratios of first and second period measurements were 1.05 (range: 0.44, 3.18) for patients and 1.82 (range: 0.21, 7.04) for family members. The corresponding absolute differences between first and second period measurements were -0.77 (range: -11.40, 7.63) mSv and 0.06 (range: -0.26, 0.79) mSv, respectively. Assuming a dose limit of 1 mSv, the precaution times for holding a child every day of the first and second periods were 250.9 (range: 71.3, 849.4) min and 275.2 (range: 75.0, 883.4) min, respectively. Assuming a dose limit of 0.5 mSv, the corresponding precaution times were 179.0 (range: 35.6, 811.5) min and 178.9 (range: 37.5, 1131.8) min, respectively. Our study demonstrated low radiation exposures to family members of patients undergoing (125)I prostate implantation. It was clear that (125)I seed implantation did not pose a threat to the safety of family members. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

SU-F-BRA-03: Integrating Novel Electromagnetic Tracking Hollow Needle Assistance in Permanent Implant Brachytherapy Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Racine, E; Hautvast, G; Binnekamp, D

Purpose: To report on the results of a complete permanent implant brachytherapy procedure assisted by an electromagnetic (EM) hollow needle possessing both 3D tracking and seed drop detection abilities. Methods: End-to-end in-phantom EM-assisted LDR procedures were conducted. The novel system consisted of an EM tracking apparatus (NDI Aurora V2, Planar Field Generator), a 3D US scanner (Philips CX50), a hollow needle prototype allowing 3D tracking and seed drop detection and a specially designed treatment planning software (Philips Healthcare). A tungsten-doped 30 cc spherical agarose prostate immersed in gelatin was used for the treatment. A cylindrical shape of 0.8 cc wasmore » carved along its diameter to mimic the urethra. An initial plan of 26 needles and 47 seeds was established with the system. The plan was delivered with the EM-tracked hollow needle, and individual seed drop locations were recorded on the fly. The phantom was subsequently imaged with a CT scanner from which seed positions and contour definitions were obtained. The DVHs were then independently recomputed and compared with those produced by the planning system, both before and after the treatment. Results: Of the 47 seeds, 45 (96%) were detected by the EM technology embedded in the hollow needle design. The executed plan (from CT analysis) differed from the initial plan by 2%, 14% and 8% respectively in terms of V100, D90 and V150 for the prostate, and by 8%, 7% and 10% respectively in terms of D5, V100 and V120 for the urethra. Conclusion: The average DVH deviations between initial and executed plans were within a 5% tolerance imposed for this proof-of-concept assessment. This relatively good concordance demonstrates the feasibility and potential benefits of combining EM tracking and seed drop detection for real-time dosimetry validation and assistance in permanent implant brachytherapy procedures. This project has been entirely funded by Philips Healthcare.« less

Optimized cell survival and seeding efficiency for craniofacial tissue engineering using clinical stem cell therapy.

PubMed

Rajan, Archana; Eubanks, Emily; Edwards, Sean; Aronovich, Sharon; Travan, Suncica; Rudek, Ivan; Wang, Feng; Lanis, Alejandro; Kaigler, Darnell

2014-12-01

Traumatic injuries involving the face are very common, yet the clinical management of the resulting craniofacial deficiencies is challenging. These injuries are commonly associated with missing teeth, for which replacement is compromised due to inadequate jawbone support. Using cell therapy, we report the upper jaw reconstruction of a patient who lost teeth and 75% of the supporting jawbone following injury. A mixed population of bone marrow-derived autologous stem and progenitor cells was seeded onto β-tricalcium phosphate (β-TCP), which served as a scaffold to deliver cells directly to the defect. Conditions (temperature, incubation time) to achieve the highest cell survival and seeding efficiency were optimized. Four months after cell therapy, cone beam computed tomography and a bone biopsy were performed, and oral implants were placed to support an engineered dental prosthesis. Cell seeding efficiency (>81%) of the β-TCP and survival during the seeding process (94%) were highest when cells were incubated with β-TCP for 30 minutes, regardless of incubation temperature; however, at 1 hour, cell survival was highest when incubated at 4°C. Clinical, radiographic, and histological analyses confirmed that by 4 months, the cell therapy regenerated 80% of the original jawbone deficiency with vascularized, mineralized bone sufficient to stably place oral implants. Functional and aesthetic rehabilitation of the patient was successfully completed with installation of a dental prosthesis 6 months following implant placement. This proof-of-concept clinical report used an evidence-based approach for the cell transplantation protocol used and is the first to describe a cell therapy for craniofacial trauma reconstruction. ©AlphaMed Press.

A novel MSC-seeded triphasic construct for the repair of osteochondral defects.

PubMed

Marquass, B; Somerson, J S; Hepp, P; Aigner, T; Schwan, S; Bader, A; Josten, C; Zscharnack, M; Schulz, R M

2010-12-01

Mesenchymal stem cells (MSC) are increasingly replacing chondrocytes in tissue engineering based research for treatment of osteochondral defects. The aim of this work was to determine whether repair of critical-size chronic osteochondral defects in an ovine model using MSC-seeded triphasic constructs would show results comparable to osteochondral autografting (OATS). Triphasic implants were engineered using a beta-tricalcium phosphate osseous phase, an intermediate activated plasma phase, and a collagen I hydrogel chondral phase. Autologous MSCs were used to seed the implants, with chondrogenic predifferentiation of the cells used in the cartilage phase. Osteochondral defects of 4.0 mm diameter were created bilaterally in ovine knees (n = 10). Six weeks later, half of the lesions were treated with OATS and half with triphasic constructs. The knees were dissected at 6 or 12 months. With the chosen study design we were not able to demonstrate significant differences between the histological scores of both groups. Subcategory analysis of O'Driscoll scores showed superior cartilage bonding in the 6-month triphasic group compared to the autograft group. The 12-month autograft group showed superior cartilage matrix morphology compared to the 12-month triphasic group. Macroscopic and biomechanical analysis showed no significant differences at 12 months. Autologous MSC-seeded triphasic implants showed comparable repair quality to osteochondral autografts in terms of histology and biomechanical testing. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

MR and CT image fusion for postimplant analysis in permanent prostate seed implants.

PubMed

Polo, Alfredo; Cattani, Federica; Vavassori, Andrea; Origgi, Daniela; Villa, Gaetano; Marsiglia, Hugo; Bellomi, Massimo; Tosi, Giampiero; De Cobelli, Ottavio; Orecchia, Roberto

2004-12-01

To compare the outcome of two different image-based postimplant dosimetry methods in permanent seed implantation. Between October 1999 and October 2002, 150 patients with low-risk prostate carcinoma were treated with (125)I and (103)Pd in our institution. A CT-MRI image fusion protocol was used in 21 consecutive patients treated with exclusive brachytherapy. The accuracy and reproducibility of the method was calculated, and then the CT-based dosimetry was compared with the CT-MRI-based dosimetry using the dose-volume histogram (DVH) related parameters recommended by the American Brachytherapy Society and the American Association of Physicists in Medicine. Our method for CT-MRI image fusion was accurate and reproducible (median shift <1 mm). Differences in prostate volume were found, depending on the image modality used. Quality assurance DVH-related parameters strongly depended on the image modality (CT vs. CT-MRI): V(100) = 82% vs. 88%, p < 0.05. D(90) = 96% vs. 115%, p < 0.05. Those results depend on the institutional implant technique and reflect the importance of lowering inter- and intraobserver discrepancies when outlining prostate and organs at risk for postimplant dosimetry. Computed tomography-MRI fused images allow accurate determination of prostate size, significantly improving the dosimetric evaluation based on DVH analysis. This provides a consistent method to judge a prostate seed implant's quality.

A Stem Cell-Seeded Nanofibrous Scaffold for Auditory Nerve Replacement

DTIC Science & Technology

2015-10-01

guinea pigs . Initial results show improved electrically-evoked auditory brainstem responses in cell-seeded implants compared to control, cell-free...scaffold’s conduit, but the IAM of the guinea pig and limits imposed by the surgical approach make this difficult. Alternatives are being pursued...transplantation of the seeded nanofibrous scaffold Task 13. Group 1: Pilot deafening. Confirm efficacy of ß-bungarotoxin in guinea pig and time point of

Photoacoustic imaging of prostate brachytherapy seeds with transurethral light delivery

NASA Astrophysics Data System (ADS)

Lediju Bell, Muyinatu A.; Guo, Xiaoyu; Song, Danny Y.; Boctor, Emad M.

2014-03-01

We present a novel approach to photoacoustic imaging of prostate brachytherapy seeds utilizing an existing urinary catheter for transurethral light delivery. Two canine prostates were surgically implanted with brachyther- apy seeds under transrectal ultrasound guidance. One prostate was excised shortly after euthanasia and fixed in gelatin. The second prostate was imaged in the native tissue environment shortly after euthanasia. A urinary catheter was inserted in the urethra of each prostate. A 1-mm core diameter optical fiber coupled to a 1064 nm Nd:YAG laser was inserted into the urinary catheter. Light from the fiber was either directed mostly parallel to the fiber axis (i.e. end-fire fire) or mostly 90° to the fiber axis (i.e. side-fire fiber). An Ultrasonix SonixTouch scanner, transrectal ultrasound probe with curvilinear (BPC8-4) and linear (BPL9-5) arrays, and DAQ unit were utilized for synchronized laser light emission and photoacoustic signal acquisition. The implanted brachytherapy seeds were visualized at radial distances of 6-16 mm from the catheter. Multiple brachytherapy seeds were si- multaneously visualized with each array of the transrectal probe using both delay-and-sum (DAS) and short-lag spatial coherence (SLSC) beamforming. This work is the first to demonstrate the feasibility of photoacoustic imaging of prostate brachytherapy seeds using a transurethral light delivery method.

Prostate implant reconstruction from C-arm images with motion-compensated tomosynthesis

PubMed Central

Dehghan, Ehsan; Moradi, Mehdi; Wen, Xu; French, Danny; Lobo, Julio; Morris, W. James; Salcudean, Septimiu E.; Fichtinger, Gabor

2011-01-01

Purpose: Accurate localization of prostate implants from several C-arm images is necessary for ultrasound-fluoroscopy fusion and intraoperative dosimetry. The authors propose a computational motion compensation method for tomosynthesis-based reconstruction that enables 3D localization of prostate implants from C-arm images despite C-arm oscillation and sagging. Methods: Five C-arm images are captured by rotating the C-arm around its primary axis, while measuring its rotation angle using a protractor or the C-arm joint encoder. The C-arm images are processed to obtain binary seed-only images from which a volume of interest is reconstructed. The motion compensation algorithm, iteratively, compensates for 2D translational motion of the C-arm by maximizing the number of voxels that project on a seed projection in all of the images. This obviates the need for C-arm full pose tracking traditionally implemented using radio-opaque fiducials or external trackers. The proposed reconstruction method is tested in simulations, in a phantom study and on ten patient data sets. Results: In a phantom implanted with 136 dummy seeds, the seed detection rate was 100% with a localization error of 0.86 ± 0.44 mm (Mean ± STD) compared to CT. For patient data sets, a detection rate of 99.5% was achieved in approximately 1 min per patient. The reconstruction results for patient data sets were compared against an available matching-based reconstruction method and showed relative localization difference of 0.5 ± 0.4 mm. Conclusions: The motion compensation method can successfully compensate for large C-arm motion without using radio-opaque fiducial or external trackers. Considering the efficacy of the algorithm, its successful reconstruction rate and low computational burden, the algorithm is feasible for clinical use. PMID:21992346

Cardiovascular tissue engineering: where we come from and where are we now?

PubMed

Smit, Francis E; Dohmen, Pascal M

2015-01-27

Abstract Tissue engineering was introduced by Vacanti and Langer in the 80's, exploring the potential of this new technology starting with the well-known "human ear on the mouse back". The goal is to create a substitute which supplies an individual therapy for patients with regeneration, remodeling and growth potential. The growth potential of these subjects is of special interest in congenital cardiac surgery, avoiding repeated interventions and surgery. Initial applications of tissue engineered created substitutes were relatively simple cardiovascular grafts seeded initially by end-differentiated autologous endothelial cells. Important data were collected from these initial clinical autologous endothelial cell seeded grafts in peripheral and coronary vessel disease. After these initial successfully implantation bone marrow cell were used to seed patches and pulmonary conduits were implanted in patients. Driven by the positive results of tissue engineered material implanted under low pressure circumstances, first tissue engineered patches were implanted in the systemic circulation followed by the implantation of tissue engineered aortic heart valves. Tissue engineering is an extreme dynamic technology with continuously modifications and improvements to optimize clinical products. New technologies are unified and so this has also be done with tissue engineering and new application features, so called transcatheter valve intervention. First studies are initiated to apply tissue engineered heart valves with this new transcatheter delivery system less invasive. Simultaneously studies have been started on tissue engineering of so-called whole organs since organ transplantation is restricted due to donor shortage and tissue engineering could overcome this problem. Initial studies of whole heart engineering in the rat model are promising and larger size models are initiated.

SLM Produced Porous Titanium Implant Improvements for Enhanced Vascularization and Osteoblast Seeding

PubMed Central

Matena, Julia; Petersen, Svea; Gieseke, Matthias; Kampmann, Andreas; Teske, Michael; Beyerbach, Martin; Murua Escobar, Hugo; Haferkamp, Heinz; Gellrich, Nils-Claudius; Nolte, Ingo

2015-01-01

To improve well-known titanium implants, pores can be used for increasing bone formation and close bone-implant interface. Selective Laser Melting (SLM) enables the production of any geometry and was used for implant production with 250-µm pore size. The used pore size supports vessel ingrowth, as bone formation is strongly dependent on fast vascularization. Additionally, proangiogenic factors promote implant vascularization. To functionalize the titanium with proangiogenic factors, polycaprolactone (PCL) coating can be used. The following proangiogenic factors were examined: vascular endothelial growth factor (VEGF), high mobility group box 1 (HMGB1) and chemokine (C-X-C motif) ligand 12 (CXCL12). As different surfaces lead to different cell reactions, titanium and PCL coating were compared. The growing into the porous titanium structure of primary osteoblasts was examined by cross sections. Primary osteoblasts seeded on the different surfaces were compared using Live Cell Imaging (LCI). Cross sections showed cells had proliferated, but not migrated after seven days. Although the cell count was lower on titanium PCL implants in LCI, the cell count and cell spreading area development showed promising results for titanium PCL implants. HMGB1 showed the highest migration capacity for stimulating the endothelial cell line. Future perspective would be the incorporation of HMGB1 into PCL polymer for the realization of a slow factor release. PMID:25849656

The N-terminal strand modulates immunoglobulin light chain fibrillogenesis.

PubMed

del Pozo-Yauner, Luis; Wall, Jonathan S; González Andrade, Martín; Sánchez-López, Rosana; Rodríguez-Ambriz, Sandra L; Pérez Carreón, Julio I; Ochoa-Leyva, Adrián; Fernández-Velasco, D Alejandro

2014-01-10

It has been suggested that the N-terminal strand of the light chain variable domain (V(L)) protects the molecule from aggregation by hindering spurious intermolecular contacts. We evaluated the impact of mutations in the N-terminal strand on the thermodynamic stability and kinetic of fibrillogenesis of the V(L) protein 6aJL2. Mutations in this strand destabilized the protein in a position-dependent manner, accelerating the fibrillogenesis by shortening the lag time; an effect that correlated with the extent of destabilization. In contrast, the effect on the kinetics of fibril elongation, as assessed in seeding experiments was of different nature, as it was not directly dependant on the degree of destabilization. This finding suggests different factors drive the nucleation-dependent and elongation phases of light chain fibrillogenesis. Finally, taking advantage of the dependence of the Trp fluorescence upon environment, four single Trp substitutions were made in the N-terminal strand, and changes in solvent exposure during aggregation were evaluated by acrylamide-quenching. The results suggest that the N-terminal strand is buried in the fibrillar state of 6aJL2 protein. This finding suggest a possible explanation for the modulating effect exerted by the mutations in this strand on the aggregation behavior of 6aJL2 protein. Copyright © 2013 Elsevier Inc. All rights reserved.

Is Graphene a Promising Nano-Material for Promoting Surface Modification of Implants or Scaffold Materials in Bone Tissue Engineering?

PubMed Central

Gu, Ming; Liu, Yunsong; Chen, Tong; Du, Feng; Zhao, Xianghui; Xiong, Chunyang

2014-01-01

Bone tissue engineering promises to restore bone defects that are caused by severe trauma, congenital malformations, tumors, and nonunion fractures. How to effectively promote the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) or seed cells has become a hot topic in this field. Many researchers are studying the ways of conferring a pro-osteodifferentiation or osteoinductive capability on implants or scaffold materials, where osteogenesis of seed cells is promoted. Graphene (G) provides a new kind of coating material that may confer the pro-osteodifferentiation capability on implants and scaffold materials by surface modification. Here, we review recent studies on the effects of graphene on surface modifications of implants or scaffold materials. The ability of graphene to improve the mechanical and biological properties of implants or scaffold materials, such as nitinol and carbon nanotubes, and its ability to promote the adhesion, proliferation, and osteogenic differentiation of MSCs or osteoblasts have been demonstrated in several studies. Most previous studies were performed in vitro, but further studies will explore the mechanisms of graphene's effects on bone regeneration, its in vivo biocompatibility, its ability to promote osteodifferentiation, and its potential applications in bone tissue engineering. PMID:24447041

Is graphene a promising nano-material for promoting surface modification of implants or scaffold materials in bone tissue engineering?

PubMed

Gu, Ming; Liu, Yunsong; Chen, Tong; Du, Feng; Zhao, Xianghui; Xiong, Chunyang; Zhou, Yongsheng

2014-10-01

Bone tissue engineering promises to restore bone defects that are caused by severe trauma, congenital malformations, tumors, and nonunion fractures. How to effectively promote the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) or seed cells has become a hot topic in this field. Many researchers are studying the ways of conferring a pro-osteodifferentiation or osteoinductive capability on implants or scaffold materials, where osteogenesis of seed cells is promoted. Graphene (G) provides a new kind of coating material that may confer the pro-osteodifferentiation capability on implants and scaffold materials by surface modification. Here, we review recent studies on the effects of graphene on surface modifications of implants or scaffold materials. The ability of graphene to improve the mechanical and biological properties of implants or scaffold materials, such as nitinol and carbon nanotubes, and its ability to promote the adhesion, proliferation, and osteogenic differentiation of MSCs or osteoblasts have been demonstrated in several studies. Most previous studies were performed in vitro, but further studies will explore the mechanisms of graphene's effects on bone regeneration, its in vivo biocompatibility, its ability to promote osteodifferentiation, and its potential applications in bone tissue engineering.

Sci-Sat AM(2): Brachy-07: Tomosynthesis-based seed reconstruction in LDR prostate brachytherapy: A clinical study.

PubMed

Brunet-Benkhoucha, M; Verhaegen, F; Lassalle, S; Béliveau-Nadeau, D; Reniers, B; Donath, D; Taussky, D; Carrier, J-F

2008-07-01

To develop a tomosynthesis-based dose assessment procedure that can be performed after an I-125 prostate seed implantation, while the patient is still under anaesthesia on the treatment table. Our seed detection procedure involves the reconstruction of a volume of interest based on the backprojection of 7 seed-only binary images acquired over an angle of 60° with an isocentric imaging system. A binary seed-only volume is generated by a simple thresholding of the volume of interest. Seeds positions are extracted from this volume with a 3D connected component analysis and a statistical classifier that determines the number of seeds in each cluster of connected voxels. A graphical user interface (GUI) allows to visualize the result and to introduce corrections, if needed. A phantom and a clinical study (24 patients) were carried out to validate the technique. A phantom study demonstrated a very good localization accuracy of (0.4+/-0.4) mm when compared to CT-based reconstruction. This leads to dosimetric error on D90 and V100 of respectively 0.5% and 0.1%. In a patient study with an average of 56 seeds per implant, the automatic tomosynthesis-based reconstruction yields a detection rate of 96% of the seeds and less than 1.5% of false-positives. With the help of the GUI, the user can achieve a 100% detection rate in an average of 3 minutes. This technique would allow to identify possible underdosage and to correct it by potentially reimplanting additional seeds. A more uniform dose coverage could then be achieved in LDR prostate brachytherapy. © 2008 American Association of Physicists in Medicine.

Experimental and theoretical studies of implant assisted magnetic drug targeting

NASA Astrophysics Data System (ADS)

Aviles, Misael O.

One way to achieve drug targeting in the body is to incorporate magnetic nanoparticles into drug carriers and then retain them at the site using an externally applied magnetic field. This process is referred to as magnetic drug targeting (MDT). However, the main limitation of MDT is that an externally applied magnetic field alone may not be able to retain a sufficient number of magnetic drug carrier particles (MDCPs) to justify its use. Such a limitation might not exist when high gradient magnetic separation (HGMS) principles are applied to assist MDT by means of ferromagnetic implants. It was hypothesized that an Implant Assisted -- MDT (IA-MDT) system would increase the retention of the MDCPs at a target site where an implant had been previously located, since the magnetic forces are produced internally. With this in mind, the overall objective of this work was to demonstrate the feasibility of an IA-MDT system through mathematical modeling and in vitro experimentation. The mathematical models were developed and used to demonstrate the behavior and limitations of IA-MDT, and the in vitro experiments were designed and used to validate the models and to further elucidate the important parameters that affect the performance of the system. IA-MDT was studied with three plausible implants, ferromagnetic stents, seed particles, and wires. All implants were studied theoretically and experimentally using flow through systems with polymer particles containing magnetite nanoparticles as MDCPs. In the stent studies, a wire coil or mesh was simply placed in a flow field and the capture of the MDCPs was studied. In the other cases, a porous polymer matrix was used as a surrogate capillary tissue scaffold to study the capture of the MDCPs using wires or particle seeds as the implant, with the seeds either fixed within the polymer matrix or captured prior to capturing the MDCPs. An in vitro heart tissue perfusion model was also used to study the use of stents. In general, all the results demonstrated that IA-MDT is indeed feasible and that careful modification of the MDCP properties and implant properties are fundamental to the success of this technology.

New transurethral system for interstitial radiation of prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baumgartner, G.; Callahan, D.; McKiel, C.F. Jr.

Direct endoscopic implantation of radioactive materials for carcinoma of the prostate without an open operation was accomplished by the use of modified existing transurethral instrumentation and techniques. The closed approach seems applicable particularly to the geriatric population, which is afflicted more commonly but is frequently not treated because of concurrent diseases or because the patient had transurethral resection of the prostate as a diagnostic procedure. Eleven patients were implanted using the transurethral route. Implantations were accomplished successfully with extremely low morbidity. Along with more conventional dosimetry studies, computer tomography was used to assess the placement of seeds. The direct visualizationmore » of the method suggests a potential for greater precision of seed placement as illustrated by computer tomography. In addition, this new instrumentation and method offers a low-risk procedure for carcinoma of the prostate that can be performed on an outpatient basis for selected patients.« less

Effect of cell-seeded hydroxyapatite scaffolds on rabbit radius bone regeneration.

PubMed

Rathbone, C R; Guda, T; Singleton, B M; Oh, D S; Appleford, M R; Ong, J L; Wenke, J C

2014-05-01

Highly porous hydroxyapatite (HA) scaffolds were developed as bone graft substitutes using a template coating process, characterized, and seeded with bone marrow-derived mesenchymal stem cells (BMSCs). To test the hypothesis that cell-seeded HA scaffolds improve bone regeneration, HA scaffolds without cell seeding (HA-empty), HA scaffolds with 1.5 × 10(4) BMSCs (HA-low), and HA scaffolds with 1.5 × 10(6) BMSCs (HA-high) were implanted in a 10-mm rabbit radius segmental defect model for 4 and 8 weeks. Three different fluorochromes were administered at 2, 4, and 6 weeks after implantation to identify differences in temporal bone growth patterns. It was observed from fluorescence histomorphometry analyses that an increased rate of bone infiltration occurred from 0 to 2 weeks (p < 0.05) of implantation for the HA-high group (2.9 ± 0.5 mm) as compared with HA-empty (1.8 ± 0.8 mm) and HA-low (1.3 ± 0.2 mm) groups. No significant differences in bone formation within the scaffold or callus formation was observed between all groups after 4 weeks, with a significant increase in bone regenerated for all groups from 4 to 8 weeks (28.4% across groups). Although there was no difference in bone formation within scaffolds, callus formation was significantly higher in HA-empty scaffolds (100.9 ± 14.1 mm(3) ) when compared with HA-low (57.8 ± 7.3 mm(3) ; p ≤ 0.003) and HA-high (69.2 ± 10.4 mm(3) ; p ≤ 0.02) after 8 weeks. These data highlight the need for a better understanding of the parameters critical to the success of cell-seeded HA scaffolds for bone regeneration. Copyright © 2013 Wiley Periodicals, Inc.

Continuous Low-dose-rate Irradiation of Iodine-125 Seeds Inhibiting Perineural Invasion in Pancreatic Cancer.

PubMed

Lu, Zheng; Dong, Teng-Hui; Si, Pei-Ren; Shen, Wei; Bi, Yi-Liang; Min, Min; Chen, Xin; Liu, Yan

2016-10-20

Perineural invasion (PNI) is a histopathological characteristic of pancreatic cancer (PanCa). The aim of this study was to observe the treatment effect of continuous low-dose-rate (CLDR) irradiation to PNI and assess the PNI-related pain relief caused by iodine-125 ( 125 I) seed implantation. The in vitro PNI model established by co-culture with dorsal root ganglion (DRG) and cancer cells was interfered under 2 and 4 Gy of 125 I seeds CLDR irradiation. The orthotopic models of PNI were established, and 125 I seeds were implanted in tumor. The PNI-related molecules were analyzed. In 30 patients with panCa, the pain relief was assessed using a visual analog scale (VAS). Pain intensity was measured before and 1 week, 2 weeks, and 1, 3, and 6 months after 125 I seed implantation. The co-culture of DRG and PanCa cells could promote the growth of PanCa cells and DRG neurites. In co-culture groups, the increased number of DRG neurites and pancreatic cells in radiation group was significantly less. In orthotopic models, the PNI-positive rate in radiation and control group was 3/11 and 7/11; meanwhile, the degrees of PNI between radiation and control groups was significant difference (P < 0.05). At week 2, the mean VAS pain score in patients decreased by 50% and significantly improved than the score at baseline (P < 0.05). The pain scores were lower in all patients, and the pain-relieving effect was retained about 3 months. The CLDR irradiation could inhibit PNI of PanCa with the value of further study. The CLDR irradiation could do great favor in preventing local recurrence and alleviating pain.

SU-E-T-301: Dosimetric Comparison Between Adaptive and Rectilinear Template-Based Prostate Seed Implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sugar, E Neubauer; Buzurovic, I; O’Farrell, D

2015-06-15

Purpose: To compare the dosimetry of a standard rectilinear and an adaptive technique used in I125 prostate seed implants. Methods: To achieve favorable dosimetry in prostate implants we used adaptive needle updates to match actual positions in real-time. The seed locations were optimized based on actual needle locations. The seeds were delivered automatically with a robotic device seedSelectron™ (Elekta Brachytherapy). In this study, we evaluated the former approach against the standard rectilinear technique in which the needles have a parallel distribution. The treatment plans for 10 patients were analyzed. For comparison, the actual treatment plans were revised so each needlemore » was repositioned to its original parallel location through the template. The analysis was performed by comparing the target coverage and dose to the organs at risk. The comparison was done using the following planning goals: the target D90> 90%, V100% > 90%, V50% <70% and V200% <30%; the urethra V125% < 1cm3 and V150%= 0cm3; and the Rectum V100%<1cm3 and V69% < 8cm3. The prescription dose to the target was 145Gy. Results: The average target volume and number of seeds were 44.39cm3(SD=11.14) and 74(SD=12), respectively. The D90 for adaptive and rectilinear plans was 159.9Gy(SD=2.99) and 155.53Gy(SD=4.04) resulting in a 2.74% difference for the average target coverage. A similar difference (1.75%) was noticed in the target V100[%]. No significant difference was noticed in the dose to the urethra and rectum. All planning goals were met with both the adaptive and rectilinear approach for each plan. Conclusion: The study reveals enhanced coverage of the target when using the adaptive needle adjustments as compared to the rectilinear approach for the analyzed cases. However, the differences in dosimetry did not translate to meaningful clinical outcomes.« less

BrachyView: Combining LDR seed positions with transrectal ultrasound imaging in a prostate gel phantom.

PubMed

Alnaghy, S; Cutajar, D L; Bucci, J A; Enari, K; Safavi-Naeini, M; Favoino, M; Tartaglia, M; Carriero, F; Jakubek, J; Pospisil, S; Lerch, M; Rosenfeld, A B; Petasecca, M

2017-02-01

BrachyView is a novel in-body imaging system which aims to provide LDR brachytherapy seeds position reconstruction within the prostate in real-time. The first prototype is presented in this study: the probe consists of a gamma camera featuring three single cone pinhole collimators embedded in a tungsten tube, above three, high resolution pixelated detectors (Timepix). The prostate was imaged with a TRUS system using a sagittal crystal with a 2.5mm slice thickness. Eleven needles containing a total of thirty 0.508U 125 I seeds were implanted under ultrasound guidance. A CT scan was used to localise the seed positions, as well as provide a reference when performing the image co-registration between the BrachyView coordinate system and the TRUS coordinate system. An in-house visualisation software interface was developed to provide a quantitative 3D reconstructed prostate based on the TRUS images and co-registered with the LDR seeds in situ. A rigid body image registration was performed between the BrachyView and TRUS systems, with the BrachyView and CT-derived source locations compared. The reconstructed seed positions determined by the BrachyView probe showed a maximum discrepancy of 1.78mm, with 75% of the seeds reconstructed within 1mm of their nominal location. An accurate co-registration between the BrachyView and TRUS coordinate system was established. The BrachyView system has shown its ability to reconstruct all implanted LDR seeds within a tissue equivalent prostate gel phantom, providing both anatomical and seed position information in a single interface. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Co-precipitation of tobramycin into biomimetically coated orthopedic fixation pins employing submicron-thin seed layers of hydroxyapatite.

PubMed

Sörensen, Jan H; Lilja, Mirjam; Åstrand, Maria; Sörensen, Torben C; Procter, Philip; Strømme, Maria; Steckel, Hartwig

2014-01-01

The migration, loosening and cut-out of implants and nosocomial infections are current problems associated with implant surgery. New innovative strategies to overcome these issues are emphasized in today's research. The current work presents a novel strategy involving co-precipitation of tobramycin with biomimetic hydroxyapatite (HA) formation to produce implant coatings that control local drug delivery to prevent early bacterial colonization of the implant. A submicron- thin HA layer served as seed layer for the co-precipitation process and allowed for incorporation of tobramycin in the coating from a stock solution of antibiotic concentrations as high as 20 mg/ml. Concentrations from 0.5 to 20 mg/ml tobramycin and process temperatures of 37 °C and 60 °C were tested to assess the optimal parameters for a thin tobramycin- delivering HA coating on discs and orthopedic fixation pins. The morphology and thickness of the coating and the drug-release profile were evaluated via scanning electron microscopy and high performance liquid chromatography. The coatings delivered pharmaceutically relevant amounts of tobramycin over a period of 12 days. To the best of our knowledge, this is the longest release period ever observed for a fast-loaded biomimetic implant coating. The presented approach could form the foundation for development of combination device/antibiotic delivery vehicles tailored to meet well-defined clinical needs while combating infections and ensuring fast implant in-growth.

TU-AB-201-11: A Novel Theoretical Framework for MRI-Only Image Guided LDR Prostate and Breast Brachytherapy Implant Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soliman, A; Elzibak, A; Fatemi, A

Purpose: To propose a novel framework for accurate model-based dose calculations using only MR images for LDR prostate and breast seed implant brachytherapy. Methods: Model-based dose calculation methodologies recommended by TG-186 require further knowledge about specific tissue composition, which is challenging with MRI. However, relying on MRI-only for implant dosimetry would reduce the soft tissue delineation uncertainty, costs, and uncertainties associated with multi-modality registration and fusion processes. We propose a novel framework to address this problem using quantitative MRI acquisitions and reconstruction techniques. The framework includes three steps: (1) Identify the locations of seeds(2) Identify the presence (or absence) ofmore » calcification(s)(3) Quantify the water and fat content in the underlying tissueSteps (1) and (2) consider the sources that limit patient dosimetry, particularly the inter-seed attenuation and the calcified regions; while step (3) targets the quantification of the tissue composition to consider the heterogeneities in the medium. Our preliminary work has shown that the seeds and the calcifications can be identified with MRI using both the magnitude and the phase images. By employing susceptibility-weighted imaging with specific post-processing techniques, the phase images can be further explored to distinguish the seeds from the calcifications. Absolute quantification of tissue, water, and fat content is feasible and was previously demonstrated in phantoms and in-vivo applications, particularly for brain diseases. The approach relies on the proportionality of the MR signal to the number of protons in an image volume. By employing appropriate correction algorithms for T1 - and T2*-related biases, B1 transmit and receive field inhomogeneities, absolute water/fat content can be determined. Results: By considering calcification and interseed attenuation, and through the knowledge of water and fat mass density, accurate patient-specific implant dosimetry can be achieved with MRI-only. Conclusion: The proposed framework showed that model-based dose calculation is feasible using MRI-only state-of-the-art techniques.« less

A simple ion implanter for material modifications in agriculture and gemmology

NASA Astrophysics Data System (ADS)

Singkarat, S.; Wijaikhum, A.; Suwannakachorn, D.; Tippawan, U.; Intarasiri, S.; Bootkul, D.; Phanchaisri, B.; Techarung, J.; Rhodes, M. W.; Suwankosum, R.; Rattanarin, S.; Yu, L. D.

2015-12-01

In our efforts in developing ion beam technology for novel applications in biology and gemmology, an economic simple compact ion implanter especially for the purpose was constructed. The designing of the machine was aimed at providing our users with a simple, economic, user friendly, convenient and easily operateable ion implanter for ion implantation of biological living materials and gemstones for biotechnological applications and modification of gemstones, which would eventually contribute to the national agriculture, biomedicine and gem-industry developments. The machine was in a vertical setup so that the samples could be placed horizontally and even without fixing; in a non-mass-analyzing ion implanter style using mixed molecular and atomic nitrogen (N) ions so that material modifications could be more effective; equipped with a focusing/defocusing lens and an X-Y beam scanner so that a broad beam could be possible; and also equipped with a relatively small target chamber so that living biological samples could survive from the vacuum period during ion implantation. To save equipment materials and costs, most of the components of the machine were taken from decommissioned ion beam facilities. The maximum accelerating voltage of the accelerator was 100 kV, ideally necessary for crop mutation induction and gem modification by ion beams from our experience. N-ion implantation of local rice seeds and cut gemstones was carried out. Various phenotype changes of grown rice from the ion-implanted seeds and improvements in gemmological quality of the ion-bombarded gemstones were observed. The success in development of such a low-cost and simple-structured ion implanter provides developing countries with a model of utilizing our limited resources to develop novel accelerator-based technologies and applications.

ERRATUM: In vivo evaluation of a neural stem cell-seeded prosthesis In vivo evaluation of a neural stem cell-seeded prosthesis

NASA Astrophysics Data System (ADS)

Purcell, E. K.; Seymour, J. P.; Yandamuri, S.; Kipke, D. R.

2009-08-01

In the published article, an error was made in figure 5. Specifically, the three-month, NSC-seeded image is a duplicate of the six-week image, and the one-day, probe alone image is a duplicate of the three-month image. The corrected figure is reproduced below. Figure 5 Figure 5. Glial encapsulation of each probe condition over the 3 month time course. Ox-42 labeled microglia and GFAP labeled astrocytes are shown. Images are taken from probes implanted in the same animal at each time point. NSC seeding was associated with reduced non-neuronal density at 1 day post-implantation in comparison to alginate coated probes and at the 1 week time point in comparison to untreated probes (P < 0.001). Glial activation is at its overall peak 1 week after insertion. A thin encapsulation layer surrounds probes at the 6 week and 3 month time points, with NSC-seeded probes having the greatest surrounding non-neuronal density P < 0.001). Interestingly, microglia appeared to have a ramified, or `surveilling', morphology surrounding a neural stem cell-alginate probe initially, whereas activated cells with an amoeboid structure were found near an alginate probe in the same hemisphere of one animal (left panels).

Accomplishments of the Oak Ridge National Laboratory Seed Money program

DOE R&D Accomplishments Database

1986-09-01

In 1974, a modest program for funding new, innovative research was initiated at ORNL. It was called the "Seed Money" program and has become part of a larger program, called Exploratory R and D, which is being carried out at all DOE national laboratories. This report highlights 12 accomplishments of the Seed Money Program: nickel aluminide, ion implantation, laser annealing, burn meter, Legionnaires' disease, whole-body radiation counter, the ANFLOW system, genetics and molecular biology, high-voltage equipment, microcalorimeter, positron probe, and atom science. (DLC)

Determinants of host species range in plant viruses.

PubMed

Moury, Benoît; Fabre, Frédéric; Hébrard, Eugénie; Froissart, Rémy

2017-04-01

Prediction of pathogen emergence is an important field of research, both in human health and in agronomy. Most studies of pathogen emergence have focused on the ecological or anthropic factors involved rather than on the role of intrinsic pathogen properties. The capacity of pathogens to infect a large set of host species, i.e. to possess a large host range breadth (HRB), is tightly linked to their emergence propensity. Using an extensive plant virus database, we found that four traits related to virus genome or transmission properties were strongly and robustly linked to virus HRB. Broader host ranges were observed for viruses with single-stranded genomes, those with three genome segments and nematode-transmitted viruses. Also, two contrasted groups of seed-transmitted viruses were evidenced. Those with a single-stranded genome had larger HRB than non-seed-transmitted viruses, whereas those with a double-stranded genome (almost exclusively RNA) had an extremely small HRB. From the plant side, the family taxonomic rank appeared as a critical threshold for virus host range, with a highly significant increase in barriers to infection between plant families. Accordingly, the plant-virus infectivity matrix shows a dual structure pattern: a modular pattern mainly due to viruses specialized to infect plants of a given family and a nested pattern due to generalist viruses. These results contribute to a better prediction of virus host jumps and emergence risks.

Genotoxicity of corrosion eluates obtained from endosseous implants.

PubMed

Ribeiro, Daniel Araki; Matsumoto, Mariza Akemi; Padovan, Luís Eduardo Marques; Marques, Mariângela Esther Alencar; Salvadori, Daisy Maria Fávero

2007-03-01

Commercially pure titanium alloys are currently used as metallic biomaterials in implantology. Corrosion phenomena appear to play a decisive role in metallic implant long-term behavior. Thus, the goal of this study was to examine the genotoxic potential of corrosion eluates obtained from dental implants using Chinese ovary hamster cells in vitro by the single-cell gel (comet) assay. This technique detects deoxyribonucleic acid strand breaks in individual cells in alkaline conditions. The materials tested included 3 dental implants commercially available. Each of the tested materials was corroded in a solution consisting of equal amounts of acetic acid and sodium chloride (0.1 M) for 1, 3, 7, 14, and 21 days. The Chinese ovary hamster cultures were then exposed to all corrosion eluates obtained from endosseous dental implants for 30 minutes at 37 degrees C. None of the eluates was found to exhibit genotoxicity, regardless of the type of dental implant used. The results suggest that all dental implants tested in this study did not induce deoxyribonucleic acid breakage as depicted by the single-cell gel (comet) assay.

Survey of diagnostic tools for detection of viroids and impacts of test results on the seed industry

USDA-ARS?s Scientific Manuscript database

Viroids are unencapsidated, single-stranded, covalently closed circular, highly structured noncoding RNAs of 239 – 401 nucleotides that are replicated by host enzymes and cause disease in several economically important crop plants. Although viroids are primarily and easily transmitted mechanically t...

A case-cohort study of recurrent salivary adenoid cystic carcinoma after iodine 125 brachytherapy and resection treatment.

PubMed

Li, Bin-bin; Xie, Xiao-Yan; Jia, Sheng-Nan

2015-02-01

Recurrent adenoid cystic carcinoma (rAdCC) can be challenging to be treated with brachytherapy, although brachytherapy is safe and effective in treating head and neck cancers. Patients of adenoid cystic carcinoma (AdCC), who underwent resection and iodine 125 ((125)I) radioactive seed implantation, were recruited for this study. Clinical data, surgical details of resection and seed implantation, histologic characteristics, and prognosis were studied. There were 16 rAdCC cases among 140 cases of AdCC treated with brachytherapy and resection. The mean follow-up duration for the recurrent cases was 61 months. The 3-year local control rate of rAdCC was 51.6%, and the overall disease-specific survival rate was 49.4%. Eight patients showed distant metastasis (50%, 8/16). The histologic grades of 10 rAdCCs were upgraded (62.5%, 10/16).Two cases displayed sarcomatous transformation after brachytherapy (1.4%, 2/140). Although the overall local control rate and survival rate were relatively favorable, some rAdCCs with an aggressive phenotype appeared to respond poorly to (125)I seed implantation. Preventive adjuvant chemotherapy should be prescribed for these rAdCCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Sequential self-assembly of DNA functionalized droplets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Yin; McMullen, Angus; Pontani, Lea-Laetitia

Complex structures and devices, both natural and manmade, are often constructed sequentially. From crystallization to embryogenesis, a nucleus or seed is formed and built upon. Sequential assembly allows for initiation, signaling, and logical programming, which are necessary for making enclosed, hierarchical structures. Though biology relies on such schemes, they have not been available in materials science. We demonstrate programmed sequential self-assembly of DNA functionalized emulsions. The droplets are initially inert because the grafted DNA strands are pre-hybridized in pairs. Active strands on initiator droplets then displace one of the paired strands and thus release its complement, which in turn activatesmore » the next droplet in the sequence, akin to living polymerization. This strategy provides time and logic control during the self-assembly process, and offers a new perspective on the synthesis of materials.« less

Sequential self-assembly of DNA functionalized droplets

DOE PAGES

Zhang, Yin; McMullen, Angus; Pontani, Lea-Laetitia; ...

2017-06-16

Complex structures and devices, both natural and manmade, are often constructed sequentially. From crystallization to embryogenesis, a nucleus or seed is formed and built upon. Sequential assembly allows for initiation, signaling, and logical programming, which are necessary for making enclosed, hierarchical structures. Though biology relies on such schemes, they have not been available in materials science. We demonstrate programmed sequential self-assembly of DNA functionalized emulsions. The droplets are initially inert because the grafted DNA strands are pre-hybridized in pairs. Active strands on initiator droplets then displace one of the paired strands and thus release its complement, which in turn activatesmore » the next droplet in the sequence, akin to living polymerization. This strategy provides time and logic control during the self-assembly process, and offers a new perspective on the synthesis of materials.« less

Clinical investigations on the spinal osteoblastic metastasis treated by combination of percutaneous vertebroplasty and (125)I seeds implantation versus radiotherapy.

PubMed

Yang, Zuozhang; Tan, Jing; Zhao, Ruilian; Wang, Jiaping; Sun, Hongpu; Wang, Xiaoxue; Xu, Lei; Jiang, Hua; Zhang, Jinlei

2013-02-01

To investigate the clinical efficacy of combining digital subtraction angiography-guided percutaneous vertebroplasty (PVP) and (125)I seeds implantation for the treatment of spinal osteoplastic metastasis. A combination of PVP and (125)I implantation was conducted for 50 patients with spinal osteoplastic metastasis, while the other 50 patients who received regular radiation therapy were used as a comparison. Visual analogue pain scale (VAS) and score of life quality (EORTCQLQ-30) were determined for all the patients. Surgery was successful in 89 spinal segments of vertebral body in 50 patients. Each segment of vertebral body was injected with 1-5 mL (2.8 mL for thoracic and 3.1 mL for lumbar vertebral body on average) of bone cement. Postoperative X-ray and CT examination showed that all the patients in the PVP group achieved spinal stability. During the follow-up examination from 6 months to 5 years, 49 patients (98.0%) had significantly relieved back pain, and only 1 case (2.0%) had no obvious improvement. Postoperative VAS score and Karnofsky performance score (KPS) were significantly different from the preoperative scores (p<0.05); and compared to the regular treatment group, PVP combined (125)I seeds showed much better clinical efficacy (p<0.05). PVP is a minimally invasive treatment with easy operation and less complications. PVP can effectively relieve the pain, stabilize the spine, improve the life quality, and reduce the occurrence of paraplegia in patients with spinal osteoplastic metastasis. Utilization of (125)I seeds with PVP can enhance the clinical efficacy.

Biomechanical properties of 3D-printed bone scaffolds are improved by treatment with CRFP.

PubMed

Helguero, Carlos G; Mustahsan, Vamiq M; Parmar, Sunjit; Pentyala, Sahana; Pfail, John L; Kao, Imin; Komatsu, David E; Pentyala, Srinivas

2017-12-22

One of the major challenges in orthopedics is to develop implants that overcome current postoperative problems such as osteointegration, proper load bearing, and stress shielding. Current implant techniques such as allografts or endoprostheses never reach full bone integration, and the risk of fracture due to stress shielding is a major concern. To overcome this, a novel technique of reverse engineering to create artificial scaffolds was designed and tested. The purpose of the study is to create a new generation of implants that are both biocompatible and biomimetic. 3D-printed scaffolds based on physiological trabecular bone patterning were printed. MC3T3 cells were cultured on these scaffolds in osteogenic media, with and without the addition of Calcitonin Receptor Fragment Peptide (CRFP) in order to assess bone formation on the surfaces of the scaffolds. Integrity of these cell-seeded bone-coated scaffolds was tested for their mechanical strength. The results show that cellular proliferation and bone matrix formation are both supported by our 3D-printed scaffolds. The mechanical strength of the scaffolds was enhanced by trabecular patterning in the order of 20% for compression strength and 60% for compressive modulus. Furthermore, cell-seeded trabecular scaffolds modulus increased fourfold when treated with CRFP. Upon mineralization, the cell-seeded trabecular implants treated with osteo-inductive agents and pretreated with CRFP showed a significant increase in the compressive modulus. This work will lead to creating 3D structures that can be used in the replacement of not only bone segments, but entire bones.

Bone regeneration by nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) scaffolds seeded with human umbilical cord mesenchymal stem cells in the calvarial defects of the nude mice.

PubMed

Wang, Fei; Su, Xiao-Xia; Guo, Yu-Cheng; Li, Ang; Zhang, Yin-Cheng; Zhou, Hong; Qiao, Hu; Guan, Li-Min; Zou, Min; Si, Xin-Qin

2015-01-01

In the preliminary study, we have found an excellent osteogenic property of nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) (nHA/CS/PLGA) scaffolds seeded with human umbilical cord mesenchymal stem cells (hUCMSCs) in vitro and subcutaneously in the nude mice. The aim of this study was to further evaluate the osteogenic capacity of nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice. Totally 108 nude mice were included and divided into 6 groups: PLGA scaffolds + hUCMSCs; nHA/PLGA scaffolds + hUCMSCs; CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds without seeding; the control group (no scaffolds) (n = 18). The scaffolds were implanted into the calvarial defects of nude mice. The amount of new bones was evaluated by fluorescence labeling, H&E staining, and Van Gieson staining at 4 and 8 weeks, respectively. The results demonstrated that the amount of new bones was significantly increased in the group of nHA/CS/PLGA scaffolds seeded with hUCMSCs (p < 0.01). On the basis of previous studies in vitro and in subcutaneous implantation of the nude mice, the results revealed that the nHA and CS also enhanced the bone regeneration by nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice at early stage.

AAPM and GEC-ESTRO guidelines for image-guided robotic brachytherapy: report of Task Group 192.

PubMed

Podder, Tarun K; Beaulieu, Luc; Caldwell, Barrett; Cormack, Robert A; Crass, Jostin B; Dicker, Adam P; Fenster, Aaron; Fichtinger, Gabor; Meltsner, Michael A; Moerland, Marinus A; Nath, Ravinder; Rivard, Mark J; Salcudean, Tim; Song, Danny Y; Thomadsen, Bruce R; Yu, Yan

2014-10-01

In the last decade, there have been significant developments into integration of robots and automation tools with brachytherapy delivery systems. These systems aim to improve the current paradigm by executing higher precision and accuracy in seed placement, improving calculation of optimal seed locations, minimizing surgical trauma, and reducing radiation exposure to medical staff. Most of the applications of this technology have been in the implantation of seeds in patients with early-stage prostate cancer. Nevertheless, the techniques apply to any clinical site where interstitial brachytherapy is appropriate. In consideration of the rapid developments in this area, the American Association of Physicists in Medicine (AAPM) commissioned Task Group 192 to review the state-of-the-art in the field of robotic interstitial brachytherapy. This is a joint Task Group with the Groupe Européen de Curiethérapie-European Society for Radiotherapy & Oncology (GEC-ESTRO). All developed and reported robotic brachytherapy systems were reviewed. Commissioning and quality assurance procedures for the safe and consistent use of these systems are also provided. Manual seed placement techniques with a rigid template have an estimated in vivo accuracy of 3-6 mm. In addition to the placement accuracy, factors such as tissue deformation, needle deviation, and edema may result in a delivered dose distribution that differs from the preimplant or intraoperative plan. However, real-time needle tracking and seed identification for dynamic updating of dosimetry may improve the quality of seed implantation. The AAPM and GEC-ESTRO recommend that robotic systems should demonstrate a spatial accuracy of seed placement ≤1.0 mm in a phantom. This recommendation is based on the current performance of existing robotic brachytherapy systems and propagation of uncertainties. During clinical commissioning, tests should be conducted to ensure that this level of accuracy is achieved. These tests should mimic the real operating procedure as closely as possible. Additional recommendations on robotic brachytherapy systems include display of the operational state; capability of manual override; documented policies for independent check and data verification; intuitive interface displaying the implantation plan and visualization of needle positions and seed locations relative to the target anatomy; needle insertion in a sequential order; robot-clinician and robot-patient interactions robustness, reliability, and safety while delivering the correct dose at the correct site for the correct patient; avoidance of excessive force on radioactive sources; delivery confirmation of the required number or position of seeds; incorporation of a collision avoidance system; system cleaning, decontamination, and sterilization procedures. These recommendations are applicable to end users and manufacturers of robotic brachytherapy systems.

Structural Basis for Guide RNA Processing and Seed-Dependent DNA Targeting by CRISPR-Cas12a.

PubMed

Swarts, Daan C; van der Oost, John; Jinek, Martin

2017-04-20

The CRISPR-associated protein Cas12a (Cpf1), which has been repurposed for genome editing, possesses two distinct nuclease activities: endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage. To elucidate the molecular basis of both activities, we determined crystal structures of Francisella novicida Cas12a bound to guide RNA and in complex with an R-loop formed by a non-cleavable guide RNA precursor and a full-length target DNA. Corroborated by biochemical experiments, these structures reveal the mechanisms of guide RNA processing and pre-ordering of the seed sequence in the guide RNA that primes Cas12a for target DNA binding. Furthermore, the R-loop complex structure reveals the strand displacement mechanism that facilitates guide-target hybridization and suggests a mechanism for double-stranded DNA cleavage involving a single active site. Together, these insights advance our mechanistic understanding of Cas12a enzymes and may contribute to further development of genome editing technologies. Copyright © 2017 Elsevier Inc. All rights reserved.

The Seed Repair Response during Germination: Disclosing Correlations between DNA Repair, Antioxidant Response, and Chromatin Remodeling in Medicago truncatula

PubMed Central

Pagano, Andrea; Araújo, Susana de Sousa; Macovei, Anca; Leonetti, Paola; Balestrazzi, Alma

2017-01-01

This work provides novel insights into the effects caused by the histone deacetylase inhibitor trichostatin A (TSA) during Medicago truncatula seed germination, with emphasis on the seed repair response. Seeds treated with H2O and TSA (10 and 20 μM) were collected during imbibition (8 h) and at the radicle protrusion phase. Biometric data showed delayed germination and impaired seedling growth in TSA-treated samples. Comet assay, performed on radicles at the protrusion phase and 4-days old M. truncatula seedlings, revealed accumulation of DNA strand breaks upon exposure to TSA. Activation of DNA repair toward TSA-mediated genotoxic damage was evidenced by the up-regulation of MtOGG1(8-OXOGUANINE GLYCOSYLASE/LYASE) gene involved in the removal of oxidative DNA lesions, MtLIGIV(LIGASE IV) gene, a key determinant of seed quality, required for the rejoining of DNA double strand breaks and TDP(TYROSYL-DNA PHOSPHODIESTERASE) genes encoding the multipurpose DNA repair enzymes tyrosyl-DNA phosphodiesterases. Since radical scavenging can prevent DNA damage, the specific antioxidant activity (SAA) was measured by DPPH (1,1-diphenyl-2-picrylhydrazyl) and Folin-Ciocalteu reagent assays. Fluctuations of SAA were observed in TSA-treated seeds/seedlings concomitant with the up-regulation of antioxidant genes MtSOD(SUPEROXIDE DISMUTASE, MtAPX(ASCORBATE PEROXIDASE) and MtMT2(TYPE 2 METALLOTHIONEIN). Chromatin remodeling, required to facilitate the access of DNA repair enzymes at the damaged sites, is also part of the multifaceted seed repair response. To address this aspect, still poorly explored in plants, the MtTRRAP(TRANSFORMATION/TRANSACTIVATION DOMAIN-ASSOCIATED PROTEIN) gene was analyzed. TRRAP is a transcriptional adaptor, so far characterized only in human cells where it is needed for the recruitment of histone acetyltransferase complexes to chromatin during DNA repair. The MtTRRAP gene and the predicted interacting partners MtHAM2 (HISTONE ACETYLTRANSFERASE OF THE MYST FAMILY) and MtADA2A (TRANSCRIPTIONAL ADAPTOR) showed tissue- and dose-dependent fluctuations in transcript levels. PCA (Principal Component Analysis) and correlation analyses suggest for a new putative link between DNA repair and chromatin remodeling that involves MtOGG1 and MtTRRAP genes, in the context of seed germination. Interesting correlations also connect DNA repair and chromatin remodeling with antioxidant players and proliferation markers. PMID:29184569

Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

PubMed

Boecker, Arne Hendrik; van Neerven, Sabien Geraldine Antonia; Scheffel, Juliane; Tank, Julian; Altinova, Haktan; Seidensticker, Katrin; Deumens, Ronald; Tolba, Rene; Weis, Joachim; Brook, Gary Anthony; Pallua, Norbert; Bozkurt, Ahmet

2016-02-01

Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Automated matching of corresponding seed images of three simulator radiographs to allow 3D triangulation of implanted seeds.

PubMed

Altschuler, M D; Kassaee, A

1997-02-01

To match corresponding seed images in different radiographs so that the 3D seed locations can be triangulated automatically and without ambiguity requires (at least) three radiographs taken from different perspectives, and an algorithm that finds the proper permutations of the seed-image indices. Matching corresponding images in only two radiographs introduces inherent ambiguities which can be resolved only with the use of non-positional information obtained with intensive human effort. Matching images in three or more radiographs is an 'NP (Non-determinant in Polynomial time)-complete' problem. Although the matching problem is fundamental, current methods for three-radiograph seed-image matching use 'local' (seed-by-seed) methods that may lead to incorrect matchings. We describe a permutation-sampling method which not only gives good 'global' (full permutation) matches for the NP-complete three-radiograph seed-matching problem, but also determines the reliability of the radiographic data themselves, namely, whether the patient moved in the interval between radiographic perspectives.

Automated matching of corresponding seed images of three simulator radiographs to allow 3D triangulation of implanted seeds

NASA Astrophysics Data System (ADS)

Altschuler, Martin D.; Kassaee, Alireza

1997-02-01

To match corresponding seed images in different radiographs so that the 3D seed locations can be triangulated automatically and without ambiguity requires (at least) three radiographs taken from different perspectives, and an algorithm that finds the proper permutations of the seed-image indices. Matching corresponding images in only two radiographs introduces inherent ambiguities which can be resolved only with the use of non-positional information obtained with intensive human effort. Matching images in three or more radiographs is an `NP (Non-determinant in Polynomial time)-complete' problem. Although the matching problem is fundamental, current methods for three-radiograph seed-image matching use `local' (seed-by-seed) methods that may lead to incorrect matchings. We describe a permutation-sampling method which not only gives good `global' (full permutation) matches for the NP-complete three-radiograph seed-matching problem, but also determines the reliability of the radiographic data themselves, namely, whether the patient moved in the interval between radiographic perspectives.

Calculation of heating power generated from ferromagnetic thermal seed (PdCo-PdNi-CuNi) alloys used as interstitial hyperthermia implants.

PubMed

El-Sayed, Adly H; Aly, A A; EI-Sayed, N I; Mekawy, M M; EI-Gendy, A A

2007-03-01

High quality heating device made of ferromagnetic alloy (thermal seed) was developed for hyperthermia treatment of cancer. The device generates sufficient heat at room temperature and stops heating at the Curie temperature T (c). The power dissipated from each seed was calculated from the area enclosed by the hysteresis loop. A new mathematical formula for the calculation of heating power was derived and showed good agreement with those calculated from hysteresis loop and calorimetric method.

Structure/cleavage-based insights into helical perturbations at bulge sites within T. thermophilus Argonaute silencing complexes

PubMed Central

Sheng, Gang; Gogakos, Tasos; Wang, Jiuyu; Zhao, Hongtu; Serganov, Artem; Juranek, Stefan

2017-01-01

Abstract We have undertaken a systematic structural study of Thermus thermophilus Argonaute (TtAgo) ternary complexes containing single-base bulges positioned either within the seed segment of the guide or target strands and at the cleavage site. Our studies establish that single-base bulges 7T8, 5A6 and 4A5 on the guide strand are stacked-into the duplex, with conformational changes localized to the bulge site, thereby having minimal impact on the cleavage site. By contrast, single-base bulges 6’U7’ and 6’A7’ on the target strand are looped-out of the duplex, with the resulting conformational transitions shifting the cleavable phosphate by one step. We observe a stable alignment for the looped-out 6’N7’ bulge base, which stacks on the unpaired first base of the guide strand, with the looped-out alignment facilitated by weakened Watson–Crick and reversed non-canonical flanking pairs. These structural studies are complemented by cleavage assays that independently monitor the impact of bulges on TtAgo-mediated cleavage reaction. PMID:28911094

Synthesis of 4'-C-aminoalkyl-2'-O-methyl modified RNA and their biological properties.

PubMed

Koizumi, Kana; Maeda, Yusuke; Kano, Toshifumi; Yoshida, Hisae; Sakamoto, Taiichi; Yamagishi, Kenji; Ueno, Yoshihito

2018-05-17

In this paper, we describe the synthesis of 4'-C-aminoalkyl-2'-O-methylnucleosides and the properties of RNAs containing these analogs. Phosphoramidites of 4'-C-aminoethyl and 4'-C-aminopropyl-2'-O-methyluridines were prepared using glucose as starting material, and RNAs containing the analogs were synthesized using the phosphoramidites. Thermal denaturation studies revealed that these nucleoside analogs decreased the thermal stabilities of double-stranded RNAs (dsRNAs). Results of NMR, molecular modeling, and CD spectra measurements suggested that 4'-C-aminoalkyl-2'-O-methyluridine adopts an C2'-endo sugar puckering in dsRNA. The 4'-C-aminoalkyl modifications in the passenger strand and the guide strand outside the seed region were well tolerated for RNAi activity of siRNAs. Single-stranded RNAs (ssRNAs) and siRNAs containing the 4'-C-aminoethyl and 4'-C-aminopropyl analogs showed high stability in buffer containing bovine serum. Thus, siRNAs containing the 4'-C-aminoethyl and 4'-C-aminopropyl analogs are good candidates for the development of therapeutic siRNA molecules. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of the antiproliferative, proapoptotic, and antiangiogenic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of leiomyoma.

PubMed

García-Pascual, Carmen Maria; Ferrero, Hortensia; Juarez, Irene; Martínez, Jessica; Villanueva, Ana; Pozuelo-Rubio, Mercedes; Soengas, Marisol; Tormo, Damiá; Simón, Carlos; Gómez, Raúl; Pellicer, Antonio

2016-02-01

To assess the antiproliferative, proapoptotic, and antiangiogenic effects of the double-stranded RNA mimic polyinosine-polycytidylic acid (pIC) complexed with polyethylenimine [pIC(PEI)] in xenografted human leiomyomas. Heterologous leiomyoma mouse model. University-affiliated infertility center. Ovariectomized and hormone-replaced nude mice (n = 16) who received human leiomyoma fragment transplantation. Leiomyoma fragments placed in the peritoneum of 5-week-old nude female mice and treated with the vehicle (n = 8) or 0.6 mg/kg [pIC(PEI)] (n = 8) for 4 weeks. The size of the leiomyoma implants, and cellular proliferation (Ki67), vascularization (PECAM), and apoptosis (OH-ends) assessed by quantitative immunohistochemical/immunofluorescent analysis of the recovered implants. No significant differences were observed in the size of the leiomyoma implants between groups. Vascularization and proliferation were significantly decreased, and apoptosis was increased in the [pIC(PEI)]-treated group versus control. We hypothesize that the antiangiogenic and apoptotic effects exerted by [pIC(PEI)] might lead to a decrease in lesion size in this animal model if the compound is administered for longer periods of time. This study provides promising data on [pIC(PEI)] as a potential novel therapeutic agent against human leiomyoma. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Method of electroplating a conversion electron emitting source on implant

DOEpatents

Srivastava, Suresh C [Setauket, NY; Gonzales, Gilbert R [New York, NY; Adzic, Radoslav [East Setauket, NY; Meinken, George E [Middle Island, NY

2012-02-14

Methods for preparing an implant coated with a conversion electron emitting source (CEES) are disclosed. The typical method includes cleaning the surface of the implant; placing the implant in an activating solution comprising hydrochloric acid to activate the surface; reducing the surface by H.sub.2 evolution in H.sub.2SO.sub.4 solution; and placing the implant in an electroplating solution that includes ions of the CEES, HCl, H.sub.2SO.sub.4, and resorcinol, gelatin, or a combination thereof. Alternatively, before tin plating, a seed layer is formed on the surface. The electroplated CEES coating can be further protected and stabilized by annealing in a heated oven, by passivation, or by being covered with a protective film. The invention also relates to a holding device for holding an implant, wherein the device selectively prevents electrodeposition on the portions of the implant contacting the device.

MRI/TRUS data fusion for prostate brachytherapy. Preliminary results.

PubMed

Reynier, Christophe; Troccaz, Jocelyne; Fourneret, Philippe; Dusserre, André; Gay-Jeune, Cécile; Descotes, Jean-Luc; Bolla, Michel; Giraud, Jean-Yves

2004-06-01

Prostate brachytherapy involves implanting radioactive seeds (I125 for instance) permanently in the gland for the treatment of localized prostate cancers, e.g., cT1c-T2a N0 M0 with good prognostic factors. Treatment planning and seed implanting are most often based on the intensive use of transrectal ultrasound (TRUS) imaging. This is not easy because prostate visualization is difficult in this imaging modality particularly as regards the apex of the gland and from an intra- and interobserver variability standpoint. Radioactive seeds are implanted inside open interventional MR machines in some centers. Since MRI was shown to be sensitive and specific for prostate imaging whilst open MR is prohibitive for most centers and makes surgical procedures very complex, this work suggests bringing the MR virtually in the operating room with MRI/TRUS data fusion. This involves providing the physician with bi-modality images (TRUS plus MRI) intended to improve treatment planning from the data registration stage. The paper describes the method developed and implemented in the PROCUR system. Results are reported for a phantom and first series of patients. Phantom experiments helped characterize the accuracy of the process. Patient experiments have shown that using MRI data linked with TRUS data improves TRUS image segmentation especially regarding the apex and base of the prostate. This may significantly modify prostate volume definition and have an impact on treatment planning.

Moving toward focal therapy in prostate cancer: dual-isotope permanent seed implants as a possible solution.

PubMed

Todor, Dorin A; Barani, Igor J; Lin, Peck-Sun; Anscher, Mitchell S

2011-09-01

To compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate. Nine plans, using 125I, 103Pd, and 131Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTVi) were delineated along with PTV (prostate+5 mm), rectum, and urethra. Single-isotope implants, prescribed to conventional doses, were generated to achieve good PTV coverage. The PTVi were prospectively used to generate implants using mixtures of isotopes. For mixed-radioisotope implants, we also explored the impact on EUBED of lowering prescription doses by 15%. The EUBED of PTVi in the setting of primary 125I implant increased 20-66% when 103Pd and 131Cs were used compared with 125I boost. Decreasing prescription dose by 15% in mixed-isotope implants results in a potential 10% reduction in urethral EUBED with preservation of PTV coverage while still boosting PTVi (up to 80%). When radiobiologic parameters corresponding to more-aggressive disease are assigned to foci, faster-decaying isotopes used in mixed implants have the potential to preserve the equivalent biological effect of mono-isotope implants considering less-aggressive disease distributed in the entire prostate. This is a hypothesis-generating study proposing a treatment paradigm that could be the middle ground between whole-gland irradiation and focal-only treatment. The use of two isotopes concurrent with decreasing the minimal peripheral dose is shown to increase EUBED of selected subvolumes while preserving the therapeutic effect at the level of the gland. Copyright © 2011 Elsevier Inc. All rights reserved.

Moving Toward Focal Therapy in Prostate Cancer: Dual-Isotope Permanent Seed Implants as a Possible Solution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Todor, Dorin A., E-mail: dtodor@mcvh-vcu.edu; Barani, Igor J.; Lin, Peck-Sun

2011-09-01

Purpose: To compare the ability of single- and dual-isotope prostate seed implants to escalate biologically effective dose (BED) to foci of disease while reducing prescription dose to the prostate. Methods and Materials: Nine plans, using {sup 125}I, {sup 103}Pd, and {sup 131}Cs alone and in combination were created retrospectively for 2 patients. Ultrasound and MRI/MRS datasets were used for treatment planning. Voxel-by-voxel BED was calculated for single- and dual-isotope plans. Equivalent uniform BED (EUBED) was used to compare plans. The MRS-positive planning target volumes (PTV{sub i}) were delineated along with PTV (prostate + 5 mm), rectum, and urethra. Single-isotope implants,more » prescribed to conventional doses, were generated to achieve good PTV coverage. The PTV{sub i} were prospectively used to generate implants using mixtures of isotopes. For mixed-radioisotope implants, we also explored the impact on EUBED of lowering prescription doses by 15%. Results: The EUBED of PTV{sub i} in the setting of primary {sup 125}I implant increased 20-66% when {sup 103}Pd and {sup 131}Cs were used compared with {sup 125}I boost. Decreasing prescription dose by 15% in mixed-isotope implants results in a potential 10% reduction in urethral EUBED with preservation of PTV coverage while still boosting PTV{sub i} (up to 80%). When radiobiologic parameters corresponding to more-aggressive disease are assigned to foci, faster-decaying isotopes used in mixed implants have the potential to preserve the equivalent biological effect of mono-isotope implants considering less-aggressive disease distributed in the entire prostate. Conclusions: This is a hypothesis-generating study proposing a treatment paradigm that could be the middle ground between whole-gland irradiation and focal-only treatment. The use of two isotopes concurrent with decreasing the minimal peripheral dose is shown to increase EUBED of selected subvolumes while preserving the therapeutic effect at the level of the gland.« less

A new Late Devonian genus with seed plant affinities.

PubMed

Wang, Deming; Liu, Le

2015-02-26

Many ovules of Late Devonian (Famennian) seed plants have been well studied. However, because few taxa occur with anatomically preserved stems and/or petioles, the vascular system of these earliest spermatophytes is little understood and available data come mostly from Euramerica. There remains great controversy over the anatomical differentiation of Late Devonian and Carboniferous seed plant groups of Buteoxylonales, Calamopityales and Lyginopteridales. Protostele evolution of these early spermatophytes needs more research. A new taxon Yiduxylon trilobum gen. et sp. nov. with seed plant affinities has been discovered in the Upper Devonian (Famennian) Tizikou Formation of Hubei Province, China. It is represented by stems, helically arranged and bifurcate fronds with two orders of pinnae and planate pinnules. Both secondary pinnae and pinnules are borne alternately. Stems contain a small protostele with three primary xylem ribs possessing a single peripheral protoxylem strand. Thick secondary xylem displays multiseriate bordered pitting on the tangential and radial walls of the tracheids, and has biseriate to multiseriate and high rays. A narrow cortex consists of inner cortex without sclerotic nests and sparganum-type outer cortex with peripheral bands of vertically aligned sclerenchyma cells. Two leaf traces successively arise tangentially from each primary xylem rib and they divide once to produce four circular-oval traces in the stem cortex. Four vascular bundles occur in two C-shaped groups at each petiole base with ground tissue and peripheral bands of sclerenchyma cells. Yiduxylon justifies the assignment to a new genus mainly because of the protostele with protoxylem strands only near the periphery of primary xylem ribs, leaf trace origination and petiolar vascular supply structure. It shares many definitive characters with Calamopityales and Lyginopteridales, further underscoring the anatomical similarities among early seed plants. The primary vascular system, pycnoxylic-manoxylic secondary xylem with bordered pits on both tangential and radial walls of a tracheid and leaf trace divergence of Yiduxylon suggest transitional features between the early spermatophytes and ancestral aneurophyte progymnosperms.

Methods for prostate stabilization during transperineal LDR brachytherapy.

PubMed

Podder, Tarun; Sherman, Jason; Rubens, Deborah; Messing, Edward; Strang, John; Ng, Wan-Sing; Yu, Yan

2008-03-21

In traditional prostate brachytherapy procedures for a low-dose-rate (LDR) radiation seed implant, stabilizing needles are first inserted to provide some rigidity and support to the prostate. Ideally this will provide better seed placement and an overall improved treatment. However, there is much speculation regarding the effectiveness of using regular brachytherapy needles as stabilizers. In this study, we explored the efficacy of two types of needle geometries (regular brachytherapy needle and hooked needle) and several clinically feasible configurations of the stabilization needles. To understand and assess the prostate movement during seed implantation, we collected in vivo data from patients during actual brachytherapy procedures. In vitro experimentation with tissue-equivalent phantoms allowed us to further understand the mechanics behind prostate stabilization. We observed superior stabilization with the hooked needles compared to the regular brachytherapy needles (more than 40% in bilateral parallel needle configuration). Prostate movement was also reduced significantly when regular brachytherapy needles were in an angulated configuration as compared to the parallel configuration (more than 60%). When the hooked needles were angulated for stabilization, further reduction in prostate displacement was observed. In general, for convenience of dosimetric planning and to avoid needle collision, all needles are desired to be in a parallel configuration. In this configuration, hooked needles provide improved stabilization of the prostate. On the other hand, both regular and hooked needles appear to be equally effective in reducing prostate movement when they are in angulated configurations, which will be useful in seed implantation using a robotic system. We have developed nonlinear spring-damper model for the prostate movement which can be used for adapting dosimetric planning during brachytherapy as well as for developing more realistic haptic devices and training simulators.

Erythropoietin promotes network formation of transplanted adipose tissue-derived microvascular fragments.

PubMed

Karschnia, P; Scheuer, C; Heß, A; Später, T; Menger, M D; Laschke, M W

2018-05-09

The seeding of tissue constructs with adipose tissue-derived microvascular fragments (ad-MVF) is an emerging pre-vascularisation strategy. Ad-MVF rapidly reassemble into new microvascular networks after in vivo implantation. Herein it was analysed whether this process was improved by erythropoietin (EPO). Ad-MVF were isolated from green fluorescent protein (GFP)+ as well as wild-type C57BL/6 mice and cultivated for 24 h in medium supplemented with EPO (20 IU/mL) or vehicle. Freshly isolated, non-cultivated ad-MVF served as controls. Protein expression, cell viability and proliferation of ad-MVF were assessed by proteome profiler array and fluorescence microscopy. GFP+ ad-MVF were seeded on collagen-glycosaminoglycan matrices, which were implanted into dorsal skinfold chambers of C57BL/6 mice, to analyse their vascularisation over 14 d by intravital fluorescence microscopy, histology and immunohistochemistry. Cultivation up-regulated the expression of pro- and anti-angiogenic factors within both vehicle- and EPO-treated ad-MVF when compared with non-cultivated controls. Moreover, EPO treatment suppressed cultivation-associated apoptosis and significantly increased the number of proliferating endothelial cells in ad-MVF when compared with vehicle-treated and non-cultivated ad-MVF. Accordingly, implanted matrices seeded with EPO-treated ad-MVF exhibited an improved vascularisation, as indicated by a significantly higher functional microvessel density. The matrices of the three groups contained a comparably large fraction of GFP+ microvessels originating from the ad-MVF, whereas the tissue surrounding the matrices seeded with EPO-treated ad-MVF exhibited a significantly increased microvessel density when compared with the other two groups. These findings indicated that EPO represents a promising cytokine to further boost the excellent vascularisation properties of ad-MVF in tissue-engineering applications.

Porous biphasic calcium phosphate ceramics coated with nano-hydroxyapatite and seeded with mesenchymal stem cells for reconstruction of radius segmental defects in rabbits.

PubMed

Hu, Jianzhong; Yang, Zhiming; Zhou, Yongchun; Liu, Yong; Li, Kaiyang; Lu, Hongbin

2015-11-01

The osteoconduction of porous biphasic calcium phosphate (BCP) ceramics has been widely reported. In a previous study, we demonstrated that applying a nano-hydroxyapatite (nHA) coating enhances the osteoinductive potential of BCP ceramics, making these scaffolds more suitable for bone tissue engineering applications. The aim of the present study was to determine the effects of reconstructing radius defects in rabbits using nHA-coated BCP ceramics seeded with mesenchymal stem cells (MSCs) and to compare the bone regeneration induced by different scaffolds. Radius defects were created in 20 New Zealand rabbits, which were divided into four groups by treatment: porous BCP ceramics (Group A), nHA-coated porous BCP ceramics (Group B), porous BCP ceramics seeded with rabbit MSCs (Group C), and nHA-coated porous BCP ceramics seeded with rabbit MSCs (Group D). After in vitro incubation, the cell/scaffold complexes were implanted into the defects. Twelve weeks after implantation, the specimens were examined macroscopically and histologically. Both the nHA coating and seeding with MSCs enhanced the formation of new bone tissue in the BCP ceramics, though the osteoinductive potential of the scaffolds with MSCs was greater than that of the nHA-coated scaffolds. Notably, the combination of nHA coating and MSCs significantly improved the bone regeneration capability of the BCP ceramics. Thus, MSCs seeded into porous BCP ceramics coated with nHA may be an effective bone substitute to reconstruct bone defects in the clinic.

Prostate-specific antigen density is predictive of outcome in suboptimal prostate seed brachytherapy.

PubMed

Benzaquen, David; Delouya, Guila; Ménard, Cynthia; Barkati, Maroie; Taussky, Daniel

In prostate seed brachytherapy, a D 90 of <130 Gy is an accepted predictive factor for biochemical failure (BF). We studied whether there is a subpopulation that does not need additional treatment after a suboptimal permanent seed brachytherapy implantation. A total of 486 patients who had either BF or a minimum followup of 48 months without BF were identified. BF was defined according to the Phoenix definition (nadir prostate-specific antigen + 2). Univariate and multivariate analyses were performed, adjusting for known prognostic factors such as D 90 and prostate-specific antigen density (PSAD) of ≥0.15 ng/mL/cm 3 , to evaluate their ability to predict BF. Median followup for patients without BF was 72 months (interquartile range 56-96). BF-free recurrence rate at 5 years was 95% and at 8 years 88%. In univariate analysis, PSAD and cancer of the prostate risk assessment score were predictive of BF. On multivariate analysis, none of the factors remained significant. The best prognosis had patients with a low PSAD (<0.15 ng/mL/cm 3 ) and an optimal implant at 30 days after implantation (as defined by D 90  ≥ 130 Gy) compared to patients with both factors unfavorable (p = 0.006). A favorable PSAD was associate with a good prognosis, independently of the D 90 (<130 Gy vs. ≥130 Gy, p = 0.7). Patients with a PSAD of <0.15 ng/mL/cm 3 have little risk of BF, even in the case of a suboptimal implant. These results need to be validated in other patients' cohorts. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Periodontitis and periimplantitis: one and the same?

PubMed

Meffert, R M

1993-12-01

Research shows that the same anaerobic, gram-negative pathogens are present in the periodontal and implant pocket or crevice. The implants in a partially edentulous case are probably more at risk due to the bacteria being more pathogenic and a seeding mechanism from the tooth pocket to the implant crevice. In the face of a normal microbial flora, retrograde periimplantitis or radiographic bone loss without gingival changes may be due to trauma because of overloading, loading too soon, and/or loading in a lateral direction. Finally, the combination of an infective process (periimplantitis) and noninfective or traumatic process (retrograde periimplantitis) will result in rapid osseous destruction and, possibly, loss of the implant fixture(s).

Functional Reconstruction of Tracheal Defects by Protein-Loaded, Cell-Seeded, Fibrous Constructs in Rabbits

PubMed Central

Ott, Lindsey M.; Vu, Cindy H.; Farris, Ashley L.; Fox, Katrina D.; Galbraith, Richard A.; Weiss, Mark L.; Weatherly, Robert A.

2015-01-01

Tracheal stenosis is a life-threatening disease and current treatments include surgical reconstruction with autologous rib cartilage and the highly complex slide tracheoplasty surgical technique. We propose using a sustainable implant, composed of a tunable, fibrous scaffold with encapsulated chondrogenic growth factor (transforming growth factor-beta3 [TGF-β3]) or seeded allogeneic rabbit bone marrow mesenchymal stromal cells (BMSCs). In vivo functionality of these constructs was determined by implanting them in induced tracheal defects in rabbits for 6 or 12 weeks. The scaffolds maintained functional airways in a majority of the cases, with the BMSC-seeded group having an improved survival rate and the Scaffold-only group having a higher occurrence of more patent airways as determined by microcomputed tomography. The BMSC group had a greater accumulation of inflammatory cells over the graft, while also exhibiting normal epithelium, subepithelium, and cartilage formation. Overall, it was concluded that a simple, acellular scaffold is a viable option for tracheal tissue engineering, with the intraoperative addition of cells being an optional variation to the scaffolds. PMID:26094554

AAPM and GEC-ESTRO guidelines for image-guided robotic brachytherapy: Report of Task Group 192

DOE Office of Scientific and Technical Information (OSTI.GOV)

Podder, Tarun K., E-mail: tarun.podder@uhhospitals.org; Beaulieu, Luc; Caldwell, Barrett

In the last decade, there have been significant developments into integration of robots and automation tools with brachytherapy delivery systems. These systems aim to improve the current paradigm by executing higher precision and accuracy in seed placement, improving calculation of optimal seed locations, minimizing surgical trauma, and reducing radiation exposure to medical staff. Most of the applications of this technology have been in the implantation of seeds in patients with early-stage prostate cancer. Nevertheless, the techniques apply to any clinical site where interstitial brachytherapy is appropriate. In consideration of the rapid developments in this area, the American Association of Physicistsmore » in Medicine (AAPM) commissioned Task Group 192 to review the state-of-the-art in the field of robotic interstitial brachytherapy. This is a joint Task Group with the Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology (GEC-ESTRO). All developed and reported robotic brachytherapy systems were reviewed. Commissioning and quality assurance procedures for the safe and consistent use of these systems are also provided. Manual seed placement techniques with a rigid template have an estimated in vivo accuracy of 3–6 mm. In addition to the placement accuracy, factors such as tissue deformation, needle deviation, and edema may result in a delivered dose distribution that differs from the preimplant or intraoperative plan. However, real-time needle tracking and seed identification for dynamic updating of dosimetry may improve the quality of seed implantation. The AAPM and GEC-ESTRO recommend that robotic systems should demonstrate a spatial accuracy of seed placement ≤1.0 mm in a phantom. This recommendation is based on the current performance of existing robotic brachytherapy systems and propagation of uncertainties. During clinical commissioning, tests should be conducted to ensure that this level of accuracy is achieved. These tests should mimic the real operating procedure as closely as possible. Additional recommendations on robotic brachytherapy systems include display of the operational state; capability of manual override; documented policies for independent check and data verification; intuitive interface displaying the implantation plan and visualization of needle positions and seed locations relative to the target anatomy; needle insertion in a sequential order; robot–clinician and robot–patient interactions robustness, reliability, and safety while delivering the correct dose at the correct site for the correct patient; avoidance of excessive force on radioactive sources; delivery confirmation of the required number or position of seeds; incorporation of a collision avoidance system; system cleaning, decontamination, and sterilization procedures. These recommendations are applicable to end users and manufacturers of robotic brachytherapy systems.« less

DTI and pathological changes in a rabbit model of radiation injury to the spinal cord after 125I radioactive seed implantation

PubMed Central

Cao, Xia; Fang, Le; Cui, Chuan-yu; Gao, Shi; Wang, Tian-wei

2018-01-01

Excessive radiation exposure may lead to edema of the spinal cord and deterioration of the nervous system. Magnetic resonance imaging can be used to judge and assess the extent of edema and to evaluate pathological changes and thus may be used for the evaluation of spinal cord injuries caused by radiation therapy. Radioactive 125I seeds to irradiate 90% of the spinal cord tissue at doses of 40–100 Gy (D90) were implanted in rabbits at T10 to induce radiation injury, and we evaluated their safety for use in the spinal cord. Diffusion tensor imaging showed that with increased D90, the apparent diffusion coefficient and fractional anisotropy values were increased. Moreover, pathological damage of neurons and microvessels in the gray matter and white matter was aggravated. At 2 months after implantation, obvious pathological injury was visible in the spinal cords of each group. Magnetic resonance diffusion tensor imaging revealed the radiation injury to the spinal cord, and we quantified the degree of spinal cord injury through apparent diffusion coefficient and fractional anisotropy. PMID:29623940

Implantation of Vascular Grafts Lined with Genetically Modified Endothelial Cells

NASA Astrophysics Data System (ADS)

Wilson, James M.; Birinyi, Louis K.; Salomon, Robert N.; Libby, Peter; Callow, Allan D.; Mulligan, Richard C.

1989-06-01

The possibility of using the vascular endothelial cell as a target for gene replacement therapy was explored. Recombinant retroviruses were used to transduce the lacZ gene into endothelial cells harvested from mongrel dogs. Prosthetic vascular grafts seeded with the genetically modified cells were implanted as carotid interposition grafts into the dogs from which the original cells were harvested. Analysis of the graft 5 weeks after implantation revealed genetically modified endothelial cells lining the luminal surface of the graft. This technology could be used in the treatment of atherosclerosis disease and the design of new drug delivery systems.

Understanding the cone scale in Cupressaceae: insights from seed-cone teratology in Glyptostrobus pensilis.

PubMed

Dörken, Veit Martin; Rudall, Paula J

2018-01-01

Both wild-type and teratological seed cones are described in the monoecious conifer Glyptostrobus pensilis and compared with those of other Cupressaceae sensu lato and other conifers. Some Cupressaceae apparently possess a proliferation of axillary structures in their cone scales. In our interpretation, in Glyptostrobus each bract of both typical and atypical seed cones bears two descending accessory shoots, interpreted here as seed scales (ovuliferous scales). The primary seed scale is fertile and forms the ovules, the second is sterile and forms characteristic tooth-like structures. The bract and the two axillary seed scales are each supplied with a single distinct vascular bundle that enters the cone axis as a separate strand; this vasculature also characterises the descending accessory short shoots in the vegetative parts of the crown. In wild-type seed cones, the fertile seed scale is reduced to its ovules, and the ovules are always axillary. In contrast, the ovules of some of the teratological seed cones examined were located at the centre of the cone scale. An additional tissue found on the upper surface of the sterile lower seed scale is here interpreted as the axis of the fertile seed scale. Thus, the central position of the ovules can be explained by recaulescent fusion of the upper fertile and lower sterile seed scales. In several teratological cone scales, the ovules were enveloped by an additional sterile tissue that is uniseriate and represents an epidermal outgrowth of the fertile seed scale. Close to the ovules, the epidermis was detached from lower tissue and surrounded the ovule completely, except at the micropyle. These teratological features are potentially significant in understanding seed-cone homologies among extant conifers.

Real-time photoacoustic imaging of prostate brachytherapy seeds using a clinical ultrasound system.

PubMed

Kuo, Nathanael; Kang, Hyun Jae; Song, Danny Y; Kang, Jin U; Boctor, Emad M

2012-06-01

Prostate brachytherapy is a popular prostate cancer treatment option that involves the permanent implantation of radioactive seeds into the prostate. However, contemporary brachytherapy procedure is limited by the lack of an imaging system that can provide real-time seed-position feedback. While many other imaging systems have been proposed, photoacoustic imaging has emerged as a potential ideal modality to address this need, since it could easily be incorporated into the current ultrasound system used in the operating room. We present such a photoacoustic imaging system built around a clinical ultrasound system to achieve the task of visualizing and localizing seeds. We performed several experiments to analyze the effects of various parameters on the appearance of brachytherapy seeds in photoacoustic images. We also imaged multiple seeds in an ex vivo dog prostate phantom to demonstrate the possibility of using this system in a clinical setting. Although still in its infancy, these initial results of a photoacoustic imaging system for the application of prostate brachytherapy seed localization are highly promising.

High Intensity Focused Ultrasound (HIFU) as a Salvage Treatment for Recurrent Prostate Cancer after Brachytherapy — a Feasibility Study

NASA Astrophysics Data System (ADS)

Chapman, Alexander T.; Rivens, Ian H.; Thompson, Alan C.; ter Haar, Gail R.

2007-05-01

HIFU may be an effective salvage treatment for patients who develop local recurrence after permanent low-dose brachytherapy. It has been suggested that the presence of seeds in the prostate may obstruct the HIFU beam or alter the heating characteristics of the prostate tissue. Acoustic field measurements were made using a membrane hydrophone and lesioning experiments were carried out in ex vivo bovine liver. These revealed a significant effect of the seeds on the HIFU focal region as well as a reduction in lesion length when seeds were placed in a pre-focal position. Further work is needed to evaluate the full effects of implanted brachytherapy seeds on the clinical delivery of HIFU.

Tissue-engineered tracheal reconstruction using three-dimensionally printed artificial tracheal graft: preliminary report.

PubMed

Chang, Jae Won; Park, Su A; Park, Ju-Kyeong; Choi, Jae Won; Kim, Yoo-Suk; Shin, Yoo Seob; Kim, Chul-Ho

2014-06-01

Three-dimensional printing has come into the spotlight in the realm of tissue engineering. We intended to evaluate the plausibility of 3D-printed (3DP) scaffold coated with mesenchymal stem cells (MSCs) seeded in fibrin for the repair of partial tracheal defects. MSCs from rabbit bone marrow were expanded and cultured. A half-pipe-shaped 3DP polycaprolactone scaffold was coated with the MSCs seeded in fibrin. The half-pipe tracheal graft was implanted on a 10 × 10-mm artificial tracheal defect in four rabbits. Four and eight weeks after the operation, the reconstructed sites were evaluated bronchoscopically, radiologically, histologically, and functionally. None of the four rabbits showed any sign of respiratory distress. Endoscopic examination and computed tomography showed successful reconstruction of trachea without any collapse or blockage. The replaced tracheas were completely covered with regenerated respiratory mucosa. Histologic analysis showed that the implanted 3DP tracheal grafts were successfully integrated with the adjacent trachea without disruption or granulation tissue formation. Neo-cartilage formation inside the implanted graft was sufficient to maintain the patency of the reconstructed trachea. Scanning electron microscope examination confirmed the regeneration of the cilia, and beating frequency of regenerated cilia was not different from those of the normal adjacent mucosa. The shape and function of reconstructed trachea using 3DP scaffold coated with MSCs seeded in fibrin were restored successfully without any graft rejection. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Characterization of the PTW SourceCheck ionization chamber with the Valencia lodgment for (125)I seed verification.

PubMed

Tornero-López, Ana M; Torres Del Río, Julia; Ruiz, Carmen; Perez-Calatayud, Jose; Guirado, Damián; Lallena, Antonio M

2015-12-01

In brachytherapy using (125)I seed implants, a verification of the air kerma strength of the sources used is required. Typically, between 40 and 100 seeds are implanted. Checking all of them is unaffordable, especially when seeds are disposed in sterile cartridges. Recently, a new procedure allowing the accomplishment of the international recommendations has been proposed for the seedSelectron system of Elekta Brachytherapy. In this procedure, the SourceCheck ionization chamber is used with a special lodgment (Valencia lodgment) that allows to measure up to 10 seeds simultaneously. In this work we analyze this procedure, showing the feasibility of the approximations required for its application, as well as the effect of the additional dependence with the air density that shows the chamber model used. Uncertainty calculations and the verification of the approximation needed to obtain a calibration factor for the Valencia lodgment are carried out. The results of the present work show that the chamber dependence with the air density is the same whether the Valencia lodgment is used or not. On the contrary, the chamber response profile is influenced by the presence of the lodgment. The determination of this profile requires various measurements due to the nonnegligible variability found between different experiments. If it is considered, the uncertainty in the determination of the air-kerma strength increases from 0.5% to 1%. Otherwise, a systematic additional uncertainty of 1% would occur. This could be relevant for the comparison between user and manufacturer measurements that is mandatory in the case studied here. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

A duplex real-time RT-PCR system with an internal control offers sensitive and reliable broad spectrum detection of Squash mosaic virus variants

USDA-ARS?s Scientific Manuscript database

Squash mosaic virus (SqMV) is a seed-borne virus, belonging to the genus Commovirus in the subfamily Comoviridae of family Secoviridae. SqMV has a bipartite single-stranded ribonucleic acid (RNA) genome (RNA1 and RNA2) encapsidated separately with two capsid proteins. Two serotypes (genotypes) of ...

DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds

PubMed Central

Waterworth, Wanda M.; Footitt, Steven; Bray, Clifford M.; Finch-Savage, William E.; West, Christopher E.

2016-01-01

Genome integrity is crucial for cellular survival and the faithful transmission of genetic information. The eukaryotic cellular response to DNA damage is orchestrated by the DNA damage checkpoint kinases ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological roles for these sensor kinases in control of seed germination. We demonstrate that double-strand breaks (DSBs) are rate-limiting for germination. We identify that desiccation tolerant seeds exhibit a striking transcriptional DSB damage response during germination, indicative of high levels of genotoxic stress, which is induced following maturation drying and quiescence. Mutant atr and atm seeds are highly resistant to aging, establishing ATM and ATR as determinants of seed viability. In response to aging, ATM delays germination, whereas atm mutant seeds germinate with extensive chromosomal abnormalities. This identifies ATM as a major factor that controls germination in aged seeds, integrating progression through germination with surveillance of genome integrity. Mechanistically, ATM functions through control of DNA replication in imbibing seeds. ATM signaling is mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED 5, an essential factor required for the aging-induced delay to germination. In the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR, with changes in dormancy and germination potential modulated by environmental signals, including temperature and soil moisture. Collectively, our findings reveal physiological functions for these sensor kinases in linking genome integrity to germination, thereby influencing seed quality, crucial for plant survival in the natural environment and sustainable crop production. PMID:27503884

DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds.

PubMed

Waterworth, Wanda M; Footitt, Steven; Bray, Clifford M; Finch-Savage, William E; West, Christopher E

2016-08-23

Genome integrity is crucial for cellular survival and the faithful transmission of genetic information. The eukaryotic cellular response to DNA damage is orchestrated by the DNA damage checkpoint kinases ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological roles for these sensor kinases in control of seed germination. We demonstrate that double-strand breaks (DSBs) are rate-limiting for germination. We identify that desiccation tolerant seeds exhibit a striking transcriptional DSB damage response during germination, indicative of high levels of genotoxic stress, which is induced following maturation drying and quiescence. Mutant atr and atm seeds are highly resistant to aging, establishing ATM and ATR as determinants of seed viability. In response to aging, ATM delays germination, whereas atm mutant seeds germinate with extensive chromosomal abnormalities. This identifies ATM as a major factor that controls germination in aged seeds, integrating progression through germination with surveillance of genome integrity. Mechanistically, ATM functions through control of DNA replication in imbibing seeds. ATM signaling is mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED 5, an essential factor required for the aging-induced delay to germination. In the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR, with changes in dormancy and germination potential modulated by environmental signals, including temperature and soil moisture. Collectively, our findings reveal physiological functions for these sensor kinases in linking genome integrity to germination, thereby influencing seed quality, crucial for plant survival in the natural environment and sustainable crop production.

Management of corneal decompensation 4 decades after Sputnik intraocular lens implantation.

PubMed

Hirji, Nashila; Nanavaty, Mayank A

2015-01-01

We report an unusual case of corneal decompensation occurring four decades after complicated cataract extraction with implantation of a Sputnik intraocular lens (IOL) and highlight the clinical and practical issues faced in managing corneal decompensation with a Sputnik IOL. A 72-year-old woman presented with deterioration of the vision in her left eye, four decades after intracapsular cataract extraction with Sputnik IOL implantation. Ocular examination revealed diffuse corneal edema and thickened vitreous strands in the anterior chamber. Her best-corrected visual acuity (BCVA) worsened to 6/60 within 3 months. Anterior vitrectomy and inferior iridectomy combined with Desçemet-stripping automated endothelial keratoplasty was performed. The procedure was successful, with the patient achieving best-corrected visual acuity of 6/6 at 8 months postoperatively. Corneal decompensation after Sputnik IOL implantation can occur four decades later. When the historical preoperative visual acuity is good in such cases, careful anterior vitrectomy with Desçemet-stripping automated endothelial keratoplasty provides good visual rehabilitation.

SU-E-T-546: Use of Implant Volume for Quality Assurance of Low Dose Rate Brachytherapy Treatment Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilkinson, D; Kolar, M

Purpose: To analyze the application of volume implant (V100) data as a method for a global check of low dose rate (LDR) brachytherapy plans. Methods: Treatment plans for 335 consecutive patients undergoing permanent seed implants for prostate cancer and for 113 patients treated with plaque therapy for ocular melanoma were analyzed. Plaques used were 54 COMS (10 to 20 mm, notched and regular) and 59 Eye Physics EP917s with variable loading. Plots of treatment time x implanted activity per unit dose versus v100 ^.667 were made. V100 values were obtained using dose volume histograms calculated by the treatment planning systemsmore » (Variseed 8.02 and Plaque Simulator 5.4). Four different physicists were involved in planning the prostate seed cases; two physicists for the eye plaques. Results: Since the time and dose for the prostate cases did not vary, a plot of implanted activity vs V100 ^.667 was made. A linear fit with no intercept had an r{sup 2} = 0.978; more than 94% of the actual activities fell within 5% of the activities calculated from the linear fit. The greatest deviations were in cases where the implant volumes were large (> 100 cc). Both COMS and EP917 plaque linear fits were good (r{sup 2} = .967 and .957); the largest deviations were seen for large volumes. Conclusions: The method outlined here is effective for checking planning consistency and quality assurance of two types of LDR brachytherapy treatment plans (temporary and permanent). A spreadsheet for the calculations enables a quick check of the plan in situations were time is short (e.g. OR-based prostate planning)« less

Novel Silicone-Coated 125I Seeds for the Treatment of Extrahepatic Cholangiocarcinoma

PubMed Central

Zhang, Weixing; Cai, Xiaobo; Chen, Dafan; Wan, Xinjian

2016-01-01

125I seeds coated with titanium are considered a safe and effective interstitial brachytherapy for tumors, while the cost of 125I seeds is a major problem for the patients implanting lots of seeds. The aim of this paper was to develop a novel silicone coating for 125I seeds with a lower cost. In order to show the radionuclide utilization ratio, the silicone was coated onto the seeds using the electro-spinning method and the radioactivity was evaluated, then the anti-tumor efficacy of silicone 125I seeds was compared with titanium 125I seeds. The seeds were divided into four groups: A (control), B (pure silicone), C (silicone 125I), D (titanium 125I) at 2 Gy or 4 Gy. Their anti-tumour activity and mechanism were assessed in vitro and in vivo using a human extrahepatic cholangiocarcinoma cell line FRH-0201 and tumor-bearing BALB/c nude mice. The silicone 125I seeds showed higher radioactivity; the rate of cell apoptosis in vitro and the histopathology in vivo demonstrated that the silicone 125I seeds shared similar anti-tumor efficacy with the titanium 125I seeds for the treatment of extrahepatic cholangiocarcinoma, while they have a much lower cost. PMID:26840346

SU-F-T-653: Radiation Exposure from Cs-131 Permanent Seed Implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giaddui, T; Hardin, M; To, D

Purpose: Permanent seed implants have traditionally been used to treat prostate, lung and head or neck cancers using I-125 and Pd-103. Cs-131, which has higher dose rate is being used to treat brain, head and/or neck cancers in our clinic, therefore, we chose to monitor the dose received by surgeons during the extensive procedure. The aims of this work are to assess the level of radiation exposure to surgeons and the instantaneous exposure at bedside and 1 m from patients. Methods: Ten patients received Cs-131 implants for recurrent brain,head and/or neck cancer; the median implanted activity, number of implanted seedsmore » and prescription dose at 0.5 cm from the perpendicular plane of the implant were: 54.3 mCi (14.52 – 77); 19 (4 – 24) and 60 Gy (range 42 – 60) respectively. Radiation exposure was recorded at bedside and 1 m from the patient using Victoreen ion chamber (Fluke Biomedical, Cleveland, OH). Exposure to surgeons was measured using TLD (Mirion Technologies (GDS), Inc., USA). Results: The median equivalent dose rate at 1 m and bedside immediately following implantation were 1.49×10-2 mSv/h (8.77×10-3–2.63×10-2) and 7.76×10-2 mSv/h (3.1×10-2– 1.53×10-1) respectively. Median equivalent dose to surgeons’ hands was 0.60 mSv (0.33 – 1.48) and no doses were detected for whole-body. Surgical reconstruction for one patient was performed 71 days post-implant and resulted in zero exposure to surgeons. Conclusion: The recorded exposure rates were low when compared with the literature. Post procedure surveys at bed site and 1 m indicated that all patients were within safe limits for discharge (< 0.05 mSv/h at 1 m). However, as a precautionary measure, patients were advised to avoid direct contact with children and pregnant women within four weeks of the implant and stay at least at 3 ft from other people. Surgeons doses were well within occupational dose limits.« less

Stability of miRNA 5′terminal and seed regions is correlated with experimentally observed miRNA-mediated silencing efficacy

PubMed Central

Hibio, Naoki; Hino, Kimihiro; Shimizu, Eigo; Nagata, Yoshiro; Ui-Tei, Kumiko

2012-01-01

MicroRNAs (miRNAs) are key regulators of sequence-specific gene silencing. However, crucial factors that determine the efficacy of miRNA-mediated target gene silencing are poorly understood. Here we mathematized base-pairing stability and showed that miRNAs with an unstable 5′ terminal duplex and stable seed-target duplex exhibit strong silencing activity. The results are consistent with the previous findings that an RNA strand with unstable 5′ terminal in miRNA duplex easily loads onto the RNA-induced silencing complex (RISC), and miRNA recognizes target mRNAs with seed-complementary sequences to direct posttranscriptional repression. Our results suggested that both the unwinding and target recognition processes of miRNAs could be proficiently controlled by the thermodynamics of base-pairing in protein-free condition. Interestingly, such thermodynamic parameters might be evolutionarily well adapted to the body temperatures of various species. PMID:23251782

Sci-Thur PM – Brachytherapy 03: Identifying the impact of seroma visualization on permanent breast seed implant brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morton, Daniel; Batchelar, Deidre; Hilts, Michelle

Purpose: Uncertainties in target identification can reduce treatment accuracy in permanent breast seed implant (PBSI) brachytherapy. This study evaluates the relationship between seroma visualization and seed placement accuracy. Methods: Spatially co-registered CT and 3D ultrasound (US) images were acquired for 10 patients receiving PBSI. Seromas were retrospectively contoured independently by 3 radiation oncologists on both CT and US and respective consensus volumes were defined, CTV{sub CT} and CTV{sub US}. The seroma clarity and inter-user conformity index (CI), as well as inter-modality CI, volume, and positional differences were evaluated. Correlations with seed placement accuracy were then assessed. CTVs were expanded bymore » 1.25cm to create PTV{sub CT} and PTV{sub US} and evaluate the conformity with PTV{sub Clinical} (CTV{sub Clinical}+1.25cm) used in treatment planning. The change in PTV coincidence by expanding PTV{sub Clinical} by 0.25cm was determined. Results: CTV{sub US} were a mean 68 ± 12% smaller than CTV{sub CT} and generally had improved clarity and inter-user conformity. No correlations between seed displacement and CTV{sub US}-CTV{sub CT} positional difference or CI were observed. Greater seed displacements were associated with larger CTV{sub US}-CTV{sub CT} volume differences (r=−0.65) and inter-user CT CI (r=−0.74). A median (range) 88% (71–99%) of PTV{sub CT} and 83% (69–100%) of PTV{sub US} were contained within PTV{sub Clinical}. Expanding treatment margins to 1.5cm increased coincidence to 98% (86–100%) and 94% (82–100%), respectively. Conclusions: Differences in seroma visualization impacts seed displacement in PBSI. Reducing dependence on CT by incorporating 3DUS into target identification, or expanding CT-based treatment margins to 1.5cm may reduce or mitigate uncertainties related to seroma visualization.« less

Biostable scaffolds of polyacrylate polymers implanted in the articular cartilage induce hyaline-like cartilage regeneration in rabbits.

PubMed

Sancho-Tello, María; Forriol, Francisco; Martín de Llano, José J; Antolinos-Turpin, Carmen; Gómez-Tejedor, José A; Gómez Ribelles, José L; Carda, Carmen

2017-07-05

To study the influence of scaffold properties on the organization of in vivo cartilage regeneration. Our hypothesis was that stress transmission to the cells seeded inside the pores of the scaffold or surrounding it, which is highly dependent on the scaffold properties, determines the differentiation of both mesenchymal cells and dedifferentiated autologous chondrocytes. 4 series of porous scaffolds made of different polyacrylate polymers, previously seeded with cultured rabbit chondrocytes or without cells, were implanted in cartilage defects in rabbits. Subchondral bone was injured during the surgery to allow blood to reach the implantation site and fill the scaffold pores. At 3 months after implantation, excellent tissue regeneration was obtained, with a well-organized layer of hyaline-like cartilage at the condylar surface in most cases of the hydrophobic or slightly hydrophilic series. The most hydrophilic material induced the poorest regeneration. However, no statistically significant difference was observed between preseeded and non-preseeded scaffolds. All of the materials used were biocompatible, biostable polymers, so, in contrast to some other studies, our results were not perturbed by possible effects attributable to material degradation products or to the loss of scaffold mechanical properties over time due to degradation. Cartilage regeneration depends mainly on the properties of the scaffold, such as stiffness and hydrophilicity, whereas little difference was observed between preseeded and non-preseeded scaffolds.

The use of nomograms in LDR-HDR prostate brachytherapy.

PubMed

Pujades, Ma Carmen; Camacho, Cristina; Perez-Calatayud, Jose; Richart, José; Gimeno, Jose; Lliso, Françoise; Carmona, Vicente; Ballester, Facundo; Crispín, Vicente; Rodríguez, Silvia; Tormo, Alejandro

2011-09-01

The common use of nomograms in Low Dose Rate (LDR) permanent prostate brachytherapy (BT) allows to estimate the number of seeds required for an implant. Independent dosimetry verification is recommended for each clinical dosimetry in BT. Also, nomograms can be useful for dose calculation quality assurance and they could be adapted to High Dose Rate (HDR). This work sets nomograms for LDR and HDR prostate-BT implants, which are applied to three different institutions that use different implant techniques. Patients treated throughout 2010 till April 2011 were considered for this study. This example was chosen to be the representative of the latest implant techniques and to ensure consistency in the planning. A sufficient number of cases for both BT modalities, prescription dose and different work methodology (depending on the institution) were taken into account. The specific nomograms were built using the correlation between the prostate volume and some characteristic parameters of each BT modality, such as the source Air Kerma Strength, number of implanted seeds in LDR or total radiation time in HDR. For each institution and BT modality, nomograms normalized to the prescribed dose were obtained and fitted to a linear function. The parameters of the adjustment show a good agreement between data and the fitting. It should be noted that for each institution these linear function parameters are different, indicating that each centre should construct its own nomograms. Nomograms for LDR and HDR prostate brachytherapy are simple quality assurance tools, specific for each institution. Nevertheless, their use should be complementary to the necessary independent verification.

The use of nomograms in LDR-HDR prostate brachytherapy

PubMed Central

Camacho, Cristina; Perez-Calatayud, Jose; Richart, José; Gimeno, Jose; Lliso, Françoise; Carmona, Vicente; Ballester, Facundo; Crispín, Vicente; Rodríguez, Silvia; Tormo, Alejandro

2011-01-01

Purpose The common use of nomograms in Low Dose Rate (LDR) permanent prostate brachytherapy (BT) allows to estimate the number of seeds required for an implant. Independent dosimetry verification is recommended for each clinical dosimetry in BT. Also, nomograms can be useful for dose calculation quality assurance and they could be adapted to High Dose Rate (HDR). This work sets nomograms for LDR and HDR prostate-BT implants, which are applied to three different institutions that use different implant techniques. Material and methods Patients treated throughout 2010 till April 2011 were considered for this study. This example was chosen to be the representative of the latest implant techniques and to ensure consistency in the planning. A sufficient number of cases for both BT modalities, prescription dose and different work methodology (depending on the institution) were taken into account. The specific nomograms were built using the correlation between the prostate volume and some characteristic parameters of each BT modality, such as the source Air Kerma Strength, number of implanted seeds in LDR or total radiation time in HDR. Results For each institution and BT modality, nomograms normalized to the prescribed dose were obtained and fitted to a linear function. The parameters of the adjustment show a good agreement between data and the fitting. It should be noted that for each institution these linear function parameters are different, indicating that each centre should construct its own nomograms. Conclusions Nomograms for LDR and HDR prostate brachytherapy are simple quality assurance tools, specific for each institution. Nevertheless, their use should be complementary to the necessary independent verification. PMID:23346120

Extractions of High Quality RNA from the Seeds of Jerusalem Artichoke and Other Plant Species with High Levels of Starch and Lipid.

PubMed

Mornkham, Tanupat; Wangsomnuk, Preeya Puangsomlee; Fu, Yong-Bi; Wangsomnuk, Pinich; Jogloy, Sanun; Patanothai, Aran

2013-04-29

Jerusalem artichoke (Helianthus tuberosus L.) is an important tuber crop. However, Jerusalem artichoke seeds contain high levels of starch and lipid, making the extraction of high-quality RNA extremely difficult and the gene expression analysis challenging. This study was aimed to improve existing methods for extracting total RNA from Jerusalem artichoke dry seeds and to assess the applicability of the improved method in other plant species. Five RNA extraction methods were evaluated on Jerusalem artichoke seeds and two were modified. One modified method with the significant improvement was applied to assay seeds of diverse Jerusalem artichoke accessions, sunflower, rice, maize, peanut and marigold. The effectiveness of the improved method to extract total RNA from seeds was assessed using qPCR analysis of four selected genes. The improved method of Ma and Yang (2011) yielded a maximum RNA solubility and removed most interfering substances. The improved protocol generated 29 to 41 µg RNA/30 mg fresh weight. An A260/A280 ratio of 1.79 to 2.22 showed their RNA purity. Extracted RNA was effective for downstream applications such as first-stranded cDNA synthesis, cDNA cloning and qPCR. The improved method was also effective to extract total RNA from seeds of sunflower, rice, maize and peanut that are rich in polyphenols, lipids and polysaccharides.

Favorable toxicity and biochemical control using real-time inverse optimization technique for prostate brachytherapy.

PubMed

Raben, Adam; Rusthoven, Kyle E; Sarkar, Abrihup; Glick, Andrew; Benge, Bruce; Jacobs, Dayee; Raben, David

2009-01-01

Favorable dosimetric results have been reported using intraoperative inverse optimization (IO) for permanent prostate brachytherapy. The clinical implications of these improvements in dosimetry are unclear. We review toxicity and early biochemical outcomes for patients implanted using IO technique. Between 2001 and 2007, 165 patients received permanent prostate implants using real-time IO and had >/=3 months of followup. Dose constraints for inverse planning were: the prostate volume receiving 100% of the prescription dose [prostate V(100)] was >95%; the dose received by 90% of the gland [prostate D(90)] was within the 140-180 by dose range; the volume of urethra receiving 150% of the prescription dose [urethra V(150)] was <30%; and the volume of rectal wall receiving 110% of the prescription dose [rectal V(110)] was <1.0 cc. Toxicity was prospectively scored using the Radiation Therapy Oncology Group toxicity scale and the International Prostate Symptom Score questionnaire. Biochemical control was determined using the nadir + 2 ng/mL definition. Mean followup was 30 months (range, 6-63 months). Risk classification was low risk in 89% and intermediate risk in 11%. Iodine-125 sources were used for 161 implants and palladium-103 sources for four implants. The median number of seeds and total activity implanted were 61 and 999 MBq, respectively, for a median prostate volume of 33.6 cc. Late GU and GI morbidity was uncommon. Among patients with at least 24 months followup, 16% had persistent Grade 2-3 urinary morbidity. Grade 2 rectal bleeding occurred in 1 patient (0.6%). Biochemical failure has occurred in only 4 patients at last followup. IO technique for prostate brachytherapy is associated with low rates of late morbidity and excellent early biochemical control. Additionally, the number of seeds and total implanted activity required to achieve a high-quality implant are lower compared with historical controls.

Rational design of an improved tissue-engineered vascular graft: determining the optimal cell dose and incubation time.

PubMed

Lee, Yong-Ung; Mahler, Nathan; Best, Cameron A; Tara, Shuhei; Sugiura, Tadahisa; Lee, Avione Y; Yi, Tai; Hibino, Narutoshi; Shinoka, Toshiharu; Breuer, Christopher

2016-03-01

We investigated the effect of cell seeding dose and incubation time on tissue-engineered vascular graft (TEVG) patency. Various doses of bone marrow-derived mononuclear cells (BM-MNCs) were seeded onto TEVGs, incubated for 0 or 12 h, and implanted in C57BL/6 mice. Different doses of human BM-MNCs were seeded onto TEVGs and measured for cell attachment. The incubation time showed no significant effect on TEVG patency. However, TEVG patency was significantly increased in a dose-dependent manner. In the human graft, more bone marrow used for seeding resulted in increased cell attachment in a dose-dependent manner. Increasing the BM-MNC dose and reducing incubation time is a viable strategy for improving the performance and utility of the graft.

Brachytherapy optimization using radiobiological-based planning for high dose rate and permanent implants for prostate cancer treatment

NASA Astrophysics Data System (ADS)

Seeley, Kaelyn; Cunha, J. Adam; Hong, Tae Min

2017-01-01

We discuss an improvement in brachytherapy--a prostate cancer treatment method that directly places radioactive seeds inside target cancerous regions--by optimizing the current standard for delivering dose. Currently, the seeds' spatiotemporal placement is determined by optimizing the dose based on a set of physical, user-defined constraints. One particular approach is the ``inverse planning'' algorithms that allow for tightly fit isodose lines around the target volumes in order to reduce dose to the patient's organs at risk. However, these dose distributions are typically computed assuming the same biological response to radiation for different types of tissues. In our work, we consider radiobiological parameters to account for the differences in the individual sensitivities and responses to radiation for tissues surrounding the target. Among the benefits are a more accurate toxicity rate and more coverage to target regions for planning high-dose-rate treatments as well as permanent implants.

Development of chondrocyte-seeded electrosprayed nanoparticles for repair of articular cartilage defects in rabbits.

PubMed

Yang, Shan-Wei; Ku, Kai-Chi; Chen, Shu-Ying; Kuo, Shyh-Ming; Chen, I-Fen; Wang, Ting-Yi; Chang, Shwu-Jen

2018-01-01

Due to limited self-healing capacity in cartilages, there is a rising demand for an innovative therapy that promotes chondrocyte proliferation while maintaining its biofunctionality for transplantation. Chondrocyte transplantation has received notable attention; however, the tendencies of cell de-differentiation and de-activation of biofunctionality have been major hurdles in its development, delaying this therapy from reaching the clinic. We believe it is due to the non-stimulative environment in the injured cartilage, which is unable to provide sustainable physical and biological supports to the newly grafted chondrocytes. Therefore, we evaluated whether providing an appropriate matrix to the transplanted chondrocytes could manipulate cell fate and recovery outcomes. Here, we proposed the development of electrosprayed nanoparticles composed of cartilage specific proteins, namely collagen type II and hyaluronic acid, for implantation with pre-seeded chondrocytes into articular cartilage defects. The fabricated nanoparticles were pre-cultured with chondrocytes before implantation into injured articular cartilage. The study revealed a significant potential for nanoparticles to support pre-seeded chondrocytes in cartilage repair, serving as a protein delivery system while improving the survival and biofunctionality of transplanted chondrocytes for prolonged period of time.

Characterization and optimization of cell seeding in scaffolds by factorial design: quality by design approach for skeletal tissue engineering.

PubMed

Chen, Yantian; Bloemen, Veerle; Impens, Saartje; Moesen, Maarten; Luyten, Frank P; Schrooten, Jan

2011-12-01

Cell seeding into scaffolds plays a crucial role in the development of efficient bone tissue engineering constructs. Hence, it becomes imperative to identify the key factors that quantitatively predict reproducible and efficient seeding protocols. In this study, the optimization of a cell seeding process was investigated using design of experiments (DOE) statistical methods. Five seeding factors (cell type, scaffold type, seeding volume, seeding density, and seeding time) were selected and investigated by means of two response parameters, critically related to the cell seeding process: cell seeding efficiency (CSE) and cell-specific viability (CSV). In addition, cell spatial distribution (CSD) was analyzed by Live/Dead staining assays. Analysis identified a number of statistically significant main factor effects and interactions. Among the five seeding factors, only seeding volume and seeding time significantly affected CSE and CSV. Also, cell and scaffold type were involved in the interactions with other seeding factors. Within the investigated ranges, optimal conditions in terms of CSV and CSD were obtained when seeding cells in a regular scaffold with an excess of medium. The results of this case study contribute to a better understanding and definition of optimal process parameters for cell seeding. A DOE strategy can identify and optimize critical process variables to reduce the variability and assists in determining which variables should be carefully controlled during good manufacturing practice production to enable a clinically relevant implant.

Phase transformations in ion-irradiated silicides

NASA Technical Reports Server (NTRS)

Hewett, C. A.; Lau, S. S.; Suni, I.; Hung, L. S.

1985-01-01

The present investigation has three objectives. The first is concerned with the phase transformation of CoSi2 under ion implantation and the subsequent crystallization characteristics during annealing, taking into account epitaxial and nonepitaxial recrystallization behavior. The second objective is related to a study of the general trend of implantation-induced damage and crystallization behavior for a number of commonly used silicides. The last objective involves a comparison of the recrystallization behavior of cosputtered refractory silicides with that of the ion-implanted silicides. It was found that epitaxial regrowth of ion-irradiated CoSi2 occurred for samples with an epitaxial seed left at the Si/CoSi2 interface. A structural investigation of CoSi2 involving transmission electron microscopy (TEM) showed that after high-dose implantation CoSi2 is amorphous.

Report on the Clinical Outcomes of Permanent Breast Seed Implant for Early-Stage Breast Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pignol, Jean-Philippe, E-mail: j.p.pignol@erasmusmc.nl; Radiation Oncology Department, Erasmus Medical Center Cancer Institute, Rotterdam; Caudrelier, Jean-Michel

Purpose: Permanent breast seed implant is an accelerated partial breast irradiation technique realizing the insertion of {sup 103}Pd seeds in the seroma after lumpectomy. We report the 5-year efficacy and tolerance for a cohort, pooling patients from 3 clinical trials. Methods and Materials: The trials accrued postmenopausal patients with infiltrating ductal carcinoma or ductal carcinoma in situ ≤3 cm and clear surgical margins, who were node negative, and had a planning target volume <120 cm{sup 3}. The outcomes included overall and disease-free survival and local and contralateral recurrence at 5 years. The true local recurrence rate was compared using 2-tailed paired t testsmore » for estimates calculated using the Tufts University ipsilateral breast tumor recurrence and Memorial Sloan Kettering ductal carcinoma in situ nomograms. Results: The cohort included 134 patients, and the observed local recurrence rate at a median follow-up period of 63 months was 1.2% ± 1.2%, similar to the estimate for whole breast irradiation (P=.23), significantly better than for surgery alone (relative risk 0.27; P<.001), and significantly lower than contralateral recurrence (relative risk 0.33; P<.001). The 5-year overall survival rate was 97.4% ± 1.9%, and the disease-free survival rate was 96.4% ± 2.1%. At 2 months, 42% of the patients had erythema, 20% induration, and 16% moist desquamation. The rate of mainly grade 1 telangiectasia was 22.4% at 2 years and 24% at 5 years. The rate of asymptomatic induration was 23% at 2 years and 40% at 5 years. Conclusions: The 5-year data suggest that permanent breast seed implantation is a safe accelerated partial breast irradiation option after lumpectomy for early-stage breast cancer with a tolerance profile similar to that of whole breast irradiation.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Zhongmin, E-mail: wzm0722@hotmail.com; Huang Xunbo, E-mail: huangxunbo0722@hotmail.com; Cao Jun, E-mail: caojun88888@hotmail.com

Objective: This study was designed to compare the clinical effectiveness of intraluminal radioactive stent loaded with iodine-125 seeds implantation versus covered stent alone insertion in patients with malignant esophageal stricture. Methods: We studied two groups of patients with malignant esophageal stricture. Group A comprised 28 patients (19 men and 9 women) who underwent intraluminal radioactive stent loaded with iodine-125 seeds implantation and were followed prospectively. Group B comprised 30 patients (18 men and 12 women) who had previously received covered stent alone insertion; these patients were evaluated retrospectively. There was no crossover between the two groups during follow-up. Informed consentmore » was obtained from each patient, and our institutional review board approved the study. The dysphagia score, overall survival rates, complication rates, and reintervention rates were compared in the two groups. Results: There were no significant differences between the two groups in terms of baseline characteristics. Stent placement was technically successful and well tolerated in all patients. The dysphagia score was improved in both groups after stent placement. The median survival was significantly longer in group A than in group B: 11 versus 4.9 months, respectively (P < 0.001). The complications of chest pain, esophageal reflux, and stent migration was more frequent in group B, but this difference did not reach statistical significance. There was no statistical difference in reintervention between two groups. Conclusions: Intraluminal radioactive stent loaded with iodine-125 seeds implantation was a feasible and practical management in treating malignant esophageal stricture and was superior to covered stent alone insertion, as measured by survival.« less

Microbial diversity of supra- and subgingival biofilms on freshly colonized titanium implant abutments in the human mouth.

PubMed

Heuer, W; Stiesch, M; Abraham, W R

2011-02-01

Supra- and subgingival biofilm formation is considered to be mainly responsible for early implant failure caused by inflammations of periimplant tissues. Nevertheless, little is known about the complex microbial diversity and interindividual similarities around dental implants. An atraumatic assessment was made of the diversity of microbial communities around titanium implants by single strand conformation polymorphism (SSCP) analysis of the 16S rRNA gene amplicons as well as subsequent sequence analysis. Samples of adherent supra- and subgingival periimplant biofilms were collected from ten patients. Additionally, samples of sulcusfluid were taken at titanium implant abutments and remaining teeth. The bacteria in the samples were characterized by SSCP and sequence analysis. A high diversity of bacteria varying between patients and within one patient at different locations was found. Bacteria characteristic for sulcusfluid and supra- and subgingival biofilm communities were identified. Sulcusfluid of the abutments showed higher abundance of Streptococcus species than from residual teeth. Prevotella and Rothia species frequently reported from the oral cavity were not detected at the abutments suggesting a role as late colonizers. Different niches in the human mouth are characterized by specific groups of bacteria. Implant abutments are a very valuable approach to study dental biofilm development in vivo.

Discovery of a new genotype of Squash mosaic virus through deep sequencing of small RNAs and development of a qRT-PCR for broad spectrum detection

USDA-ARS?s Scientific Manuscript database

Squash mosaic virus (SqMV), a seed-borne virus belonging to the genus Commovirus in the family Comoviridae, could cause a serious yield loss on cucurbit crops worldwide. SqMV has a bipartite single-stranded ribonucleic acid (RNA) genome (RNA-1 and RNA-2) encapsidated separately with two capsid prote...

Nanofibrous scaffolds for the guidance of stem cell-derived neurons for auditory nerve regeneration.

PubMed

Hackelberg, Sandra; Tuck, Samuel J; He, Long; Rastogi, Arjun; White, Christina; Liu, Liqian; Prieskorn, Diane M; Miller, Ryan J; Chan, Che; Loomis, Benjamin R; Corey, Joseph M; Miller, Josef M; Duncan, R Keith

2017-01-01

Impairment of spiral ganglion neurons (SGNs) of the auditory nerve is a major cause for hearing loss occurring independently or in addition to sensory hair cell damage. Unfortunately, mammalian SGNs lack the potential for autonomous regeneration. Stem cell based therapy is a promising approach for auditory nerve regeneration, but proper integration of exogenous cells into the auditory circuit remains a fundamental challenge. Here, we present novel nanofibrous scaffolds designed to guide the integration of human stem cell-derived neurons in the internal auditory meatus (IAM), the foramen allowing passage of the spiral ganglion to the auditory brainstem. Human embryonic stem cells (hESC) were differentiated into neural precursor cells (NPCs) and seeded onto aligned nanofiber mats. The NPCs terminally differentiated into glutamatergic neurons with high efficiency, and neurite projections aligned with nanofibers in vitro. Scaffolds were assembled by seeding GFP-labeled NPCs on nanofibers integrated in a polymer sheath. Biocompatibility and functionality of the NPC-seeded scaffolds were evaluated in vivo in deafened guinea pigs (Cavia porcellus). To this end, we established an ouabain-based deafening procedure that depleted an average 72% of SGNs from apex to base of the cochleae and caused profound hearing loss. Further, we developed a surgical procedure to implant seeded scaffolds directly into the guinea pig IAM. No evidence of an inflammatory response was observed, but post-surgery tissue repair appeared to be facilitated by infiltrating Schwann cells. While NPC survival was found to be poor, both subjects implanted with NPC-seeded and cell-free control scaffolds showed partial recovery of electrically-evoked auditory brainstem thresholds. Thus, while future studies must address cell survival, nanofibrous scaffolds pose a promising strategy for auditory nerve regeneration.

Three Dimensional Collagen Scaffold Promotes Intrinsic Vascularisation for Tissue Engineering Applications

PubMed Central

Chan, Elsa C.; Kuo, Shyh-Ming; Kong, Anne M.; Morrison, Wayne A.; Dusting, Gregory J.; Mitchell, Geraldine M.

2016-01-01

Here, we describe a porous 3-dimensional collagen scaffold material that supports capillary formation in vitro, and promotes vascularization when implanted in vivo. Collagen scaffolds were synthesized from type I bovine collagen and have a uniform pore size of 80 μm. In vitro, scaffolds seeded with primary human microvascular endothelial cells suspended in human fibrin gel formed CD31 positive capillary-like structures with clear lumens. In vivo, after subcutaneous implantation in mice, cell-free collagen scaffolds were vascularized by host neovessels, whilst a gradual degradation of the scaffold material occurred over 8 weeks. Collagen scaffolds, impregnated with human fibrinogen gel, were implanted subcutaneously inside a chamber enclosing the femoral vessels in rats. Angiogenic sprouts from the femoral vessels invaded throughout the scaffolds and these degraded completely after 4 weeks. Vascular volume of the resulting constructs was greater than the vascular volume of constructs from chambers implanted with fibrinogen gel alone (42.7±5.0 μL in collagen scaffold vs 22.5±2.3 μL in fibrinogen gel alone; p<0.05, n = 7). In the same model, collagen scaffolds seeded with human adipose-derived stem cells (ASCs) produced greater increases in vascular volume than did cell-free collagen scaffolds (42.9±4.0 μL in collagen scaffold with human ASCs vs 25.7±1.9 μL in collagen scaffold alone; p<0.05, n = 4). In summary, these collagen scaffolds are biocompatible and could be used to grow more robust vascularized tissue engineering grafts with improved the survival of implanted cells. Such scaffolds could also be used as an assay model for studies on angiogenesis, 3-dimensional cell culture, and delivery of growth factors and cells in vivo. PMID:26900837

Utility of T2 mapping and dGEMRIC for evaluation of cartilage repair after allograft chondrocyte implantation in a rabbit model.

PubMed

Endo, J; Watanabe, A; Sasho, T; Yamaguchi, S; Saito, M; Akagi, R; Muramatsu, Y; Mukoyama, S; Katsuragi, J; Akatsu, Y; Fukawa, T; Okubo, T; Osone, F; Takahashi, K

2015-02-01

To investigate the effectiveness of quantitative Magnetic resonance imaging (MRI) for evaluating the quality of cartilage repair over time following allograft chondrocyte implantation using a three-dimensional scaffold for osteochondral lesions. Thirty knees from 15 rabbits were analyzed. An osteochondral defect (diameter, 4 mm; depth, 1 mm) was created on the patellar groove of the femur in both legs. The defects were filled with a chondrocyte-seeded scaffold in the right knee and an empty scaffold in the left knee. Five rabbits each were euthanized at 4, 8, and 12 weeks and their knees were examined via macroscopic inspection, histological and biochemical analysis, and quantitative MRI (T2 mapping and dGEMRIC) to assess the state of tissue repair following allograft chondrocyte implantation with a three-dimensional scaffold for osteochondral lesions. Comparatively good regenerative cartilage was observed both macroscopically and histologically. In both chondrocyte-seeded and control knees, the T2 values of repair tissues were highest at 4 weeks and showed a tendency to decrease with time. ΔR1 values of dGEMRIC also tended to decrease with time in both groups, and the mean ΔR1 was significantly lower in the CS-scaffold group than in the control group at all time points. ΔR1 = 1/r (R1post - R1pre), where r is the relaxivity of Gd-DTPA(2-), R1 = 1/T1 (longitudinal relaxation time). T2 mapping and dGEMRIC were both effective for evaluating tissue repair after allograft chondrocyte implantation. ΔR1 values of dGEMRIC represented good correlation with histologically and biochemically even at early stages after the implantation. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Dosimetric variations in permanent breast seed implant due to patient arm position.

PubMed

Watt, Elizabeth; Husain, Siraj; Sia, Michael; Brown, Derek; Long, Karen; Meyer, Tyler

2015-01-01

Planning and delivery for permanent breast seed implant (PBSI) are performed with the ipsilateral arm raised; however, changes in implant geometry can be expected because of healing and anatomical motion as the patient resumes her daily activities. The purpose of this study is to quantify the effect of ipsilateral arm position on postplan dosimetry. Twelve patients treated at the Tom Baker Cancer Centre were included in this study. Patients underwent two postimplant CT scans on the day of implant (Day 0) and two scans approximately 8 weeks later (Day 60). One scan at each time was taken with the ipsilateral arm raised, recreating the planning scan position, and the other with both arms down in a relaxed position beside the body, recreating a more realistic postimplant arm position. Postplans were completed on all four scans using deformable image registration (MIM Maestro). On the Day 0 scan, the V200 for the evaluation planning target volume was significantly increased in the arm-down position compared with the arm-up position. Lung, rib, and chest wall dose were significantly reduced at both time points. Left anterior descending coronary artery, heart, and skin dose showed no significant differences at either time point. Although some dosimetric indices show significant differences between the arm-up and arm-down positions, the magnitude of these differences is small and the values remain indicative of implant quality. Despite the delivery of the majority of dose with the arm down, it is reasonable to use CT scans taken in the arm-up position for postplanning. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Eggplant latent viroid: a friendly experimental system in the family Avsunviroidae.

PubMed

Daròs, José-Antonio

2016-10-01

Eggplant latent viroid (ELVd) is the only species of the genus Elaviroid (family Avsunviroidae). All the viroids in the family Avsunviroidae contain hammerhead ribozymes in the strands of both polarities, and are considered to replicate in the chloroplasts of infected cells. This family includes two other genera: Avsunviroid and Pelamoviroid. ELVd consists of a single-stranded, circular, non-coding RNA of 332-335 nucleotides that folds in a branched quasi-rod-like minimum free-energy conformation. RNAs of complementary polarity exist in infected cells and are considered to be replication intermediates. Plus (+) polarity is assigned arbitrarily to the strand that accumulates at a higher concentration in infected tissues. HOST: To date, ELVd has only been shown to infect eggplant (Solanum melongena L.), the species in which it was discovered. A very narrow host range seems to be a common property in members of the family Avsunviroidae. ELVd infections of eggplants are apparently symptomless. ELVd is transmitted mechanically and by seed. http://subviral.med.uottawa.ca. © 2015 BSPP and John Wiley & Sons Ltd.

SU-E-J-181: Effect of Prostate Motion On Combined Brachytherapy and External Beam Dose Based On Daily Motion of the Prostate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Narayana, V; McLaughlin, P; University of Michigan, Ann Arbor, MI

2015-06-15

Purpose: In this study, the adequacy of target expansions on the combined external beam and implant dose was examined based on the measured daily motion of the prostate. Methods: Thirty patients received an I–125 prostate implant prescribed to dose of 90Gy. This was followed by external beam to deliver a dose of 90Gyeq (external beam equivalent) to the prostate over 25 to 30 fractions. An ideal IMRT plan was developed by optimizing the external beam dose based on the delivered implant dose. The implant dose was converted to an equivalent external beam dose using the linear quadratic model. Patients weremore » set up on the treatment table by daily orthogonal imaging and aligning the marker seeds in the prostate. Orthogonal images were obtained at the end of treatment to assess prostate intrafraction motion. Based on the observed motion of the markers between the initial and final images, 5 individual plans showing the actual dose delivered to the patient were calculated. A final true dose distribution was established based on summing the implant dose and the 5 external beam plans. Dose to the prostate, seminal vesicles, lymphnodes and normal tissues, rectal wall, urethra and lower sphincter were calculated and compared to ideal. On 18 patients who were sexually active, dose to the corpus cavernosum and internal pudendal artery was also calculated. Results: The average prostate motion in 3 orthogonal directions was less than 1 mm with a standard deviation of less than +2 mm. Dose and volume parameters showed that there was no decrease in dose to the targets and a marginal decrease in dose to in normal tissues. Conclusion: Dose delivered by seed implant moves with the prostate, decreasing the impact of intrafractions dose movement on actual dose delivered. Combined brachytherapy and external beam dose delivered to the prostate was not sensitive to prostate motion.« less

Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer

PubMed Central

Belz, Jodi E.; Kumar, Rajiv; Baldwin, Paige; Ojo, Noelle Castilla; Leal, Ana S.; Royce, Darlene B.; Zhang, Di; van de Ven, Anne L.; Liby, Karen T.; Sridhar, Srinivas

2017-01-01

Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1-deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0.8 mm diameter) loaded with subclinical dose (25 or 50 µg) Talazoparib were fabricated and characterized. In vitro studies with Brca1-deficient W780 and W0069 breast cancer cells were conducted to test sensitivity to PARP inhibition. The in vivo therapeutic efficacy of Talazoparib implants was assessed following a one-time intratumoral injection in Brca1Co/Co;MMTV-Cre;p53+/- mice and compared to drug-free implants and oral gavage. Immunohistochemistry studies were performed on tumor sections using PCNA and γ-H2AX staining. Sustained release of Talazoparib was observed over 28 days in vitro. Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors. PMID:29158830

Sustained Release Talazoparib Implants for Localized Treatment of BRCA1-deficient Breast Cancer.

PubMed

Belz, Jodi E; Kumar, Rajiv; Baldwin, Paige; Ojo, Noelle Castilla; Leal, Ana S; Royce, Darlene B; Zhang, Di; van de Ven, Anne L; Liby, Karen T; Sridhar, Srinivas

2017-01-01

Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1 -deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0.8 mm diameter) loaded with subclinical dose (25 or 50 µg) Talazoparib were fabricated and characterized. In vitro studies with Brca1 -deficient W780 and W0069 breast cancer cells were conducted to test sensitivity to PARP inhibition. The in vivo therapeutic efficacy of Talazoparib implants was assessed following a one-time intratumoral injection in Brca1 Co/Co ;MMTV-Cre;p53 +/- mice and compared to drug-free implants and oral gavage. Immunohistochemistry studies were performed on tumor sections using PCNA and γ-H2AX staining. Sustained release of Talazoparib was observed over 28 days in vitro . Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors.

Nationwide Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS): first analysis on survival.

PubMed

Ito, Kazuto; Saito, Shiro; Yorozu, Atsunori; Kojima, Shinsuke; Kikuchi, Takashi; Higashide, Satoshi; Aoki, Manabu; Koga, Hirofumi; Satoh, Takefumi; Ohashi, Toshio; Nakamura, Katsumasa; Katayama, Norihisa; Tanaka, Nobumichi; Nakano, Masahiro; Shigematsu, Naoyuki; Dokiya, Takushi; Fukushima, Masanori

2018-06-22

Investigating oncological outcomes in patients registered in the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS) in terms of biochemical relapse-free survival (bRFS) by the Phoenix and the newly developed J-POPS definitions, exploration of predictive factors for bRFS, and preliminary verification of pitfalls of prostate-specific antigen (PSA) failure definitions. Between July 2005 and June 2007, 2316 clinically localized patients underwent permanent seed implantation. The primary endpoint was bRFS. One of the secondary endpoints was overall survival (OS). The median age was 69 and performance status was 0 in 99.1% of participants. The median biologically effective dose (BED) was about 180 Gy 2 . During a median follow-up of 60.0 months, 8.4 and 5.9% had PSA failure by the Phoenix and the J-POPS definitions, respectively. The 5-year bRFSs based on the Phoenix and the J-POPS definitions were 89.1 and 91.6%, respectively. The 5-year OS was 97.3%. According to multivariate analyses, only age affected bRFS based on the Phoenix definition, whereas the risk group and BED independently affected bRFS based on the J-POPS definition. A spontaneous PSA decrease was seen in 91.1% of participants after PSA failure based on the Phoenix definition alone, but in only 22.2% after PSA failure based on the J-POPS definition alone. The world's largest registration study, J-POPS, consisted of patients with longevity, and a highly quality-controlled BED resulted in excellent bRFS and OS. The high likelihood of PSA bounce by the Phoenix definition should be taken into account, especially in younger patients. NCT00534196.

Dose heterogeneity correction for low-energy brachytherapy sources using dual-energy CT images

NASA Astrophysics Data System (ADS)

Mashouf, S.; Lechtman, E.; Lai, P.; Keller, B. M.; Karotki, A.; Beachey, D. J.; Pignol, J. P.

2014-09-01

Permanent seed implant brachytherapy is currently used for adjuvant radiotherapy of early stage prostate and breast cancer patients. The current standard for calculation of dose around brachytherapy sources is based on the AAPM TG-43 formalism, which generates the dose in a homogeneous water medium. Recently, AAPM TG-186 emphasized the importance of accounting for tissue heterogeneities. We have previously reported on a methodology where the absorbed dose in tissue can be obtained by multiplying the dose, calculated by the TG-43 formalism, by an inhomogeneity correction factor (ICF). In this work we make use of dual energy CT (DECT) images to extract ICF parameters. The advantage of DECT over conventional CT is that it eliminates the need for tissue segmentation as well as assignment of population based atomic compositions. DECT images of a heterogeneous phantom were acquired and the dose was calculated using both TG-43 and TG-43 × \\text{ICF} formalisms. The results were compared to experimental measurements using Gafchromic films in the mid-plane of the phantom. For a seed implant configuration of 8 seeds spaced 1.5 cm apart in a cubic structure, the gamma passing score for 2%/2 mm criteria improved from 40.8% to 90.5% when ICF was applied to TG-43 dose distributions.

[Human stem cells from apical papilla can regenerate dentin-pulp complex].

PubMed

Xiong, Huacui; Chen, Ke; Huang, Yibin; Liu, Caiqi

2013-10-01

To regenerate dentin-pulp complex by tissue engineering with human stem cells from apical papilla cells (SCAP) as the seed cells. SCAP was separated from from normal human impacted third molars with immature roots by outgrowth culture. The cells were then cultured in the differentiation medium for 3 weeks or in normal medium for 60 days, and analyzed for mineralization potential by Alizarin red staining. The osteo/odontogenic markers including alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OC) and dentin sialoprotein (DSP) were investigated by immunofluorescence staining and reverse transcription-polymerase chain reaction. The co-cultured mixture of SCAP and HA/TCP, or HA/TCP alone was implanted subcutaneously on the back of nude mice for 8 weeks, and the implants were collected and examined by HE and immunohistochemical staining. Round alizarin red-positive nodules formed in the isolated cells after cell culture in the differentiation medium for 3 weeks or in normal medium for 60 days with positive staining for osteo/odontogenic markers. SCAP with HA/TCP could regenerate pulp-dentin complex-like tissue in nude mice. The cells near the dentin-like tissue were positive for DSP. No mineral tissue was found in mice receiving HA/TCP implantation. SCAP may serve as a promising seed cell for dentin-pulp complex tissue engineering.

Implantation of preadipocyte-loaded hyaluronic acid-based scaffolds into nude mice to evaluate potential for soft tissue engineering.

PubMed

Hemmrich, Karsten; von Heimburg, Dennis; Rendchen, Raoul; Di Bartolo, Chiara; Milella, Eva; Pallua, Norbert

2005-12-01

The reconstruction of soft tissue defects following extensive deep burns or tumor resections remains an unresolved problem in plastic and reconstructive surgery since adequate implant materials are still not available. Preadipocytes, immature precursor cells found between mature adipocytes in adipose tissue, are a potential material for soft tissue engineering since they can proliferate and differentiate into adipose tissue after transplantation. In previous studies, we identified hyaluronan benzyl ester (HYAFF 11) sponges to be promising carrier matrices. This study now evaluates, in vitro and in vivo, a new sponge architecture with pores of 400 microm either made of plain HYAFF 11 or HYAFF 11 coated with the extracellular matrix glycosaminoglycan hyaluronic acid. Human preadipocytes were isolated, seeded onto carriers and implanted into nude athymic mice. Explants harvested after 3, 8, and 12 weeks were examined for macroscopical appearance, thickness, weight, pore structure, histology, and immunohistochemistry. Compared to previous studies, we found better penetration of cells into both types of scaffolds, with more extensive formation of new vessels throughout the construct but with only minor adipose tissue. Our encouraging results contribute towards a better seeded and vascularised scaffold but also show that the enhancement of adipogenic conversion of preadipocytes remains a major task for further in vivo experiments.

Microgravity

NASA Image and Video Library

2004-04-15

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc., has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc., is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

Microgravity

NASA Image and Video Library

2004-04-15

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc. has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc. is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

Prostate Postbrachytherapy Seed Distribution: Comparison of High-Resolution, Contrast-Enhanced, T1- and T2-Weighted Endorectal Magnetic Resonance Imaging Versus Computed Tomography: Initial Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bloch, B. Nicolas; Department of Radiology, General Hospital Vienna, Medical University Vienna, Vienna; Lenkinski, Robert E.

2007-09-01

Purpose: To compare contrast-enhanced, T1-weighted, three-dimensional magnetic resonance imaging (CEMR) and T2-weighted magnetic resonance imaging (T2MR) with computed tomography (CT) for prostate brachytherapy seed location for dosimetric calculations. Methods and Materials: Postbrachytherapy prostate MRI was performed on a 1.5 Tesla unit with combined surface and endorectal coils in 13 patients. Both CEMR and T2MR used a section thickness of 3 mm. Spiral CT used a section thickness of 5 mm with a pitch factor of 1.5. All images were obtained in the transverse plane. Two readers using CT and MR imaging assessed brachytherapy seed distribution independently. The dependency of datamore » read by both readers for a specific subject was assessed with a linear mixed effects model. Results: The mean percentage ({+-} standard deviation) values of the readers for seed detection and location are presented. Of 1205 implanted seeds, CEMR, T2MR, and CT detected 91.5% {+-} 4.8%, 78.5% {+-} 8.5%, and 96.1% {+-} 2.3%, respectively, with 11.8% {+-} 4.5%, 8.5% {+-} 3.5%, 1.9% {+-} 1.0% extracapsular, respectively. Assignment to periprostatic structures was not possible with CT. Periprostatic seed assignments for CEMR and T2MR, respectively, were as follows: neurovascular bundle, 3.5% {+-} 1.6% and 2.1% {+-} 0.9%; seminal vesicles, 0.9% {+-} 1.8% and 0.3% {+-} 0.7%; periurethral, 7.1% {+-} 3.3% and 5.8% {+-} 2.9%; penile bulb, 0.6% {+-} 0.8% and 0.3% {+-} 0.6%; Denonvillier's Fascia/rectal wall, 0.5% {+-} 0.6% and 0%; and urinary bladder, 0.1% {+-} 0.3% and 0%. Data dependency analysis showed statistical significance for the type of imaging but not for reader identification. Conclusion: Both enumeration and localization of implanted seeds are readily accomplished with CEMR. Calculations with MRI dosimetry do not require CT data. Dose determinations to specific extracapsular sites can be obtained with MRI but not with CT.« less

Induction of rice mutations by high hydrostatic pressure.

PubMed

Zhang, Wei; Liu, Xuncheng; Zheng, Feng; Zeng, Songjun; Wu, Kunlin; da Silva, Jaime A Teixeira; Duan, Jun

2013-09-01

High hydrostatic pressure (HHP) is an extreme thermo-physical factor that affects the synthesis of DNA, RNA and proteins and induces mutagenesis in microorganisms. Our previous studies showed that exposure to 25-100 MPa HHP for 12 h retarded the germination and affected the viability of rice (Oryza sativa L.) seeds, increased the tolerance of rice plants to cold stress and altered gene expression patterns in germinating rice seeds. However, the mutagenic effect of HHP on rice remains unknown. In this study, exposure to 25, 50, 75 or 100 MPa for 12 h HHP could efficiently induce variation in rice plants. Furthermore, presoaking time and HHP strength during HHP treatment affected the efficiency of mutation. In addition, the Comet assay revealed that exposure to 25-100 MPa HHP for 12 h induced DNA strand breakage in germinating seeds and may have been the source of mutations. Our results suggest that HHP is a promising physical mutagen in rice breeding. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Antioxidants and bioactivities of free, esterified and insoluble-bound phenolics from berry seed meals.

PubMed

Ayoub, Maha; de Camargo, Adriano Costa; Shahidi, Fereidoon

2016-04-15

Phenolic compounds present in the free, soluble ester and insoluble-bound forms of blackberry, black raspberry and blueberry were identified and quantified using high-performance liquid chromatography-diode array detection-electrospray ionisation multistage mass spectrometry. The total phenolics, scavenging activity against hydroxyl and peroxyl radicals, the reducing power and chelating capacity were, in general, in the decreasing order of blackberry>black raspberry>blueberry. Amongst fractions, the order was insoluble-bound>esterified>free. These trends were the same as those found against copper-induced LDL-cholesterol oxidation and supercoiled plasmid DNA strand breakage inhibition induced by both peroxyl and hydroxyl radicals. Extracts were found to contain various levels of phenolic compounds that were specific to each berry seed meal type. Berry seed meals should be considered as a good source of phenolics with potential health benefits. Their full exploitation may be helpful for the food industry and consumers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Positive visualization of implanted devices with susceptibility gradient mapping using the original resolution.

PubMed

Varma, Gopal; Clough, Rachel E; Acher, Peter; Sénégas, Julien; Dahnke, Hannes; Keevil, Stephen F; Schaeffter, Tobias

2011-05-01

In magnetic resonance imaging, implantable devices are usually visualized with a negative contrast. Recently, positive contrast techniques have been proposed, such as susceptibility gradient mapping (SGM). However, SGM reduces the spatial resolution making positive visualization of small structures difficult. Here, a development of SGM using the original resolution (SUMO) is presented. For this, a filter is applied in k-space and the signal amplitude is analyzed in the image domain to determine quantitatively the susceptibility gradient for each pixel. It is shown in simulations and experiments that SUMO results in a better visualization of small structures in comparison to SGM. SUMO is applied to patient datasets for visualization of stent and prostate brachytherapy seeds. In addition, SUMO also provides quantitative information about the number of prostate brachytherapy seeds. The method might be extended to application for visualization of other interventional devices, and, like SGM, it might also be used to visualize magnetically labelled cells. Copyright © 2010 Wiley-Liss, Inc.

In vivo bioluminescence imaging of cell differentiation in biomaterials: a platform for scaffold development.

PubMed

Bagó, Juli R; Aguilar, Elisabeth; Alieva, Maria; Soler-Botija, Carolina; Vila, Olaia F; Claros, Silvia; Andrades, José A; Becerra, José; Rubio, Nuria; Blanco, Jerónimo

2013-03-01

In vivo testing is a mandatory last step in scaffold development. Agile longitudinal noninvasive real-time monitoring of stem cell behavior in biomaterials implanted in live animals should facilitate the development of scaffolds for tissue engineering. We report on a noninvasive bioluminescence imaging (BLI) procedure for simultaneous monitoring of changes in the expression of multiple genes to evaluate scaffold performance in vivo. Adipose tissue-derived stromal mensenchymal cells were dually labeled with Renilla red fluorescent protein and firefly green fluorescent protein chimeric reporters regulated by cytomegalovirus and tissue-specific promoters, respectively. Labeled cells were induced to differentiate in vitro and in vivo, by seeding in demineralized bone matrices (DBMs) and monitored by BLI. Imaging results were validated by RT-polymerase chain reaction and histological procedures. The proposed approach improves molecular imaging and measurement of changes in gene expression of cells implanted in live animals. This procedure, applicable to the simultaneous analysis of multiple genes from cells seeded in DBMs, should facilitate engineering of scaffolds for tissue repair.

In Vivo Bioluminescence Imaging of Cell Differentiation in Biomaterials: A Platform for Scaffold Development

PubMed Central

Bagó, Juli R.; Aguilar, Elisabeth; Alieva, Maria; Soler-Botija, Carolina; Vila, Olaia F.; Claros, Silvia; Andrades, José A.; Becerra, José; Rubio, Nuria

2013-01-01

In vivo testing is a mandatory last step in scaffold development. Agile longitudinal noninvasive real-time monitoring of stem cell behavior in biomaterials implanted in live animals should facilitate the development of scaffolds for tissue engineering. We report on a noninvasive bioluminescence imaging (BLI) procedure for simultaneous monitoring of changes in the expression of multiple genes to evaluate scaffold performance in vivo. Adipose tissue-derived stromal mensenchymal cells were dually labeled with Renilla red fluorescent protein and firefly green fluorescent protein chimeric reporters regulated by cytomegalovirus and tissue-specific promoters, respectively. Labeled cells were induced to differentiate in vitro and in vivo, by seeding in demineralized bone matrices (DBMs) and monitored by BLI. Imaging results were validated by RT-polymerase chain reaction and histological procedures. The proposed approach improves molecular imaging and measurement of changes in gene expression of cells implanted in live animals. This procedure, applicable to the simultaneous analysis of multiple genes from cells seeded in DBMs, should facilitate engineering of scaffolds for tissue repair. PMID:23013334

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration.

PubMed

Eap, Sandy; Keller, Laetitia; Schiavi, Jessica; Huck, Olivier; Jacomine, Leandro; Fioretti, Florence; Gauthier, Christian; Sebastian, Victor; Schwinté, Pascale; Benkirane-Jessel, Nadia

2015-01-01

New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 μm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days' implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days' implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration.

Detection and correction of patient movement in prostate brachytherapy seed reconstruction

NASA Astrophysics Data System (ADS)

Lam, Steve T.; Cho, Paul S.; Marks, Robert J., II; Narayanan, Sreeram

2005-05-01

Intraoperative dosimetry of prostate brachytherapy can help optimize the dose distribution and potentially improve clinical outcome. Evaluation of dose distribution during the seed implant procedure requires the knowledge of 3D seed coordinates. Fluoroscopy-based seed localization is a viable option. From three x-ray projections obtained at different gantry angles, 3D seed positions can be determined. However, when local anaesthesia is used for prostate brachytherapy, the patient movement during fluoroscopy image capture becomes a practical problem. If uncorrected, the errors introduced by patient motion between image captures would cause seed mismatches. Subsequently, the seed reconstruction algorithm would either fail to reconstruct or yield erroneous results. We have developed an algorithm that permits detection and correction of patient movement that may occur between fluoroscopy image captures. The patient movement is decomposed into translational shifts along the tabletop and rotation about an axis perpendicular to the tabletop. The property of spatial invariance of the co-planar imaging geometry is used for lateral movement correction. Cranio-caudal movement is corrected by analysing the perspective invariance along the x-ray axis. Rotation is estimated by an iterative method. The method can detect and correct for the range of patient movement commonly seen in the clinical environment. The algorithm has been implemented for routine clinical use as the preprocessing step for seed reconstruction.

Structural and surface changes in glassy carbon due to strontium implantation and heat treatment

NASA Astrophysics Data System (ADS)

Odutemowo, O. S.; Malherbe, J. B.; Prinsloo, L. C.; Njoroge, E. G.; Erasmus, R.; Wendler, E.; Undisz, A.; Rettenmayr, M.

2018-01-01

There are still questions around the microstructure of glassy carbon (GC), like the observation of the micropores. These were proposed to explain the low density of GC. This paper explains the effect of ion bombardment (200 keV Sr+, 1 × 1016 Sr+/cm2 at RT) on the microstructure of GC. TEM and AFM show that micropores in pristine GC are destroyed leading to densification of GC from 1.42 g/cm3 to 2.03 g/cm3. The amorphisation of glassy carbon was also not complete with graphitic strands embedded within the GC. These were relatively few, as Raman analysis showed that the Sr implantation resulted in a typical amorphous Raman spectrum. Annealing of the sample at 900 °C only resulted in a slight recovery of the GC structure. AFM and SEM analysis showed that the surface of the sample became rougher after Sr implantation. The roughness increased after the sample was annealed at 600 °C due to segregation of Sr towards the surface of the GC. SEM measurements of a sample with both implanted and un-implanted edges after annealing at 900 °C, showed that the high temperature heat treatment did not affect the surface topography of un-irradiated GC.

An experimental palladium-103 seed (OptiSeed{sup exp}) in a biocompatible polymer without a gold marker: Characterization of dosimetric parameters including the interseed effect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abboud, F.; Scalliet, P.; Vynckier, S.

Permanent implantation of {sup 125}I (iodine) or {sup 103}Pd (palladium) sources is a popular treatment option in the management of early stage prostate cancer. New sources are being developed, some of which are being marketed for different clinical applications. A new technique of adjuvant stereotactic permanent seed breast implant, similar to that used in the treatment of prostate cancer, has been proposed by [N. Jansen et al., Int. J. Radiat. Oncol. Biol. Phys. 67, 1052-1058 (2007)] with encouraging results. The presence of artifacts from the metallic seeds, however, can disturb follow-up imaging. The development of plastic seeds has reduced thesemore » artifacts. This paper presents a feasibility study of the advantages of palladium-103 seeds, encapsulated with a biocompatible polymer, for future clinical applications, and on the effect of the gold marker on the dosimetric characteristics of such seeds. Experimental palladium seeds, OptiSeed{sup exp}, were manufactured by International Brachytherapy (IBt), Seneffe, Belgium, from a biocompatible polymer, including the marker. Apart from the absence of a gold marker, the studied seed has an identical design to the OptiSeed{sup 103}[Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311-321 (2005)]. Polymer encapsulation was preferred by IBt in order to reduce the quantity of radioactive material needed for a given dose rate and to reduce the anisotropy of the radiation field around the seed. In addition, this design is intended to decrease the interseed effects that can occur as a result of the marker and the encapsulation. Dosimetric measurements were performed using LiF thermoluminescent dosimeters (1 mm{sup 3}) in solid water phantoms (WT1). Measured data were compared to Monte Carlo simulated data in solid water using the MCNP code, version 4C. Updated cross sections [Med. Phys. 30, 701-711 (2003)] were used. As the measured and calculated data were in agreement, Monte Carlo calculations were then performed in liquid water to obtain relevant dosimetric data as required by TG-43U1 recommendations. Comparison of the results with previous studies of OptiSeed{sup 103}[Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311-321 (2005)], and of InterSource{sup 103}[Appl. Radiat. Isot. 57, 805-811 (2002)] showed very good agreement for the dose rate constant and for the radial dose function. With respect to the anisotropy function, the relative dose (anisotropy value relative to 90 degree sign ) from the polymer seed at a distance of 3 cm was close to unity (105%) at 0 degree sign , whereas the relative values for the OptiSeed{sup 103} with a gold marker and the titanium-encapsulated InterSource{sup 103} seed decreased to 70% and 40%, respectively. The interseed effect from one seed was negligible and in the order of calculation uncertainty, making calculation of the dose rate distribution of the studied seeds, according to TG43U1 recommendations, more accurate and closer to reality. This feasibility study shows that due to the low energy of palladium-103, the negligible interseed effect and the reduced artifacts in postimplant medical imaging, this experimental plastic seed would be a good source for breast brachytherapy. This feasibility study was carried out in collaboration with IBt and will be continued with a study of its visibility in different tissues.« less

SU-F-T-43: Prediction of Dose Increments by Brain Metastases Resection Cavity Shrinkage Model with I-125 and Cs-131 LDR Seed Implantations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, D; Braunstein, S; Sneed, P

Purpose: This work aims to determine dose variability via a brain metastases resection cavity shrinkage model (RC-SM) with I-125 or Cs-131 LDR seed implantations. Methods: The RC-SM was developed to represent sequential volume changes of 95 consecutive brain metastases patients. All patients underwent serial surveillance MR and change in cavity volume was recorded for each patient. For the initial resection cavity, a prolate-ellipsoid cavity model was suggested and applied volume shrinkage rates to correspond to 1.7, 3.6, 5.9, 11.7, and 20.5 months after craniotomy. Extra-ring structure (6mm) was added on a surface of the resection volume and the same shrinkagemore » rates were applied. Total 31 LDR seeds were evenly distributed on the surface of the resection cavity. The Amersham 6711 I-125 seed model (Oncura, Arlington Heights, IL) and the Model Cs-1 Rev2 Cs-131 seed model (IsoRay, Richland, WA) were used for TG-43U1 dose calculation and in-house-programed 3D-volumetric dose calculation system was used for resection cavity rigid model (RC-RM) and the RC-SM dose calculation. Results: The initial resection cavity volume shrunk to 25±6%, 35±6.8%, 42±7.7%, 47±9.5%, and 60±11.6%, with respect to sequential MR images post craniotomy, and the shrinkage rate (SR) was calculated as SR=56.41Xexp(−0.2024Xt)+33.99 and R-square value was 0.98. The normal brain dose as assessed via the dose to the ring structure with the RC-SM showed 29.34% and 27.95% higher than the RC-RM, I-125 and Cs-131, respectively. The dose differences between I-125 and Cs-131 seeds within the same models, I-125 cases were 9.17% and 10.35% higher than Cs-131 cases, the RC-RM and the RC-SM, respectively. Conclusion: A realistic RC-SM should be considered during LDR brain seed implementation and post-implement planning to prevent potential overdose. The RC-SM calculation shows that Cs-131 is more advantageous in sparing normal brain as the resection cavity volume changes with the LDR seeds implementation.« less

Identifying Objects via Encased X-Ray-Fluorescent Materials - the Bar Code Inside

NASA Technical Reports Server (NTRS)

Schramm, Harry F.; Kaiser, Bruce

2005-01-01

Systems for identifying objects by means of x-ray fluorescence (XRF) of encased labeling elements have been developed. The XRF spectra of objects so labeled would be analogous to the external bar code labels now used to track objects in everyday commerce. In conjunction with computer-based tracking systems, databases, and labeling conventions, the XRF labels could be used in essentially the same manner as that of bar codes to track inventories and to record and process commercial transactions. In addition, as summarized briefly below, embedded XRF labels could be used to verify the authenticity of products, thereby helping to deter counterfeiting and fraud. A system, as described above, is called an encased core product identification and authentication system (ECPIAS). The ECPIAS concept is a modified version of that of a related recently initiated commercial development of handheld XRF spectral scanners that would identify alloys or detect labeling elements deposited on the surfaces of objects. In contrast, an ECPIAS would utilize labeling elements encased within the objects of interest. The basic ECPIAS concept is best illustrated by means of an example of one of several potential applications: labeling of cultured pearls by labeling the seed particles implanted in oysters to grow the pearls. Each pearl farmer would be assigned a unique mixture of labeling elements that could be distinguished from the corresponding mixtures of other farmers. The mixture would be either incorporated into or applied to the surfaces of the seed prior to implantation in the oyster. If necessary, the labeled seed would be further coated to make it nontoxic to the oyster. After implantation, the growth of layers of mother of pearl on the seed would encase the XRF labels, making these labels integral, permanent parts of the pearls that could not be removed without destroying the pearls themselves. The XRF labels would be read by use of XRF scanners, the spectral data outputs of which would be converted to alphanumeric data in a digital equivalent data system (DEDS), which is the subject of the previous article. These alphanumeric data would be used to track the pearls through all stages of commerce, from the farmer to the retail customer.

SU-E-T-55: Biological Equivalent Dose (BED) Comparison Between Permanent Interstitial Brachytherapy and Conventional External Beam Radiotherapy for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, X; Rahimian, J; Cosmatos, H

2014-06-01

Purpose: The goal of this research is to calculate and compare the Biological Equivalent Dose (BED) between permanent prostate Iodine-125 implant brachytherapy as monotherapy with the BED of conventional external beam radiation therapy (EBRT). Methods: A retrospective study of 605 patients treated with Iodine-125 seed implant was performed in which physician A treated 274 patients and physician B treated 331 patients. All the Brachytherapy treatment plans were created using VariSeed 8 planning system. The Iodine-125 seed source activities and loading patterns varied slightly between the two physicians. The prescription dose is 145 Gy to PTV for each patient. The BEDmore » and Tumor Control Probability (TCP) were calculated based on the TG 137 formulas. The BED for conventional EBRT of the prostate given in our institution in 2Gy per fraction for 38 fractions was calculated and compared. Results: Physician A treated 274 patients with an average BED of 123.92±0.87 Gy and an average TCP of 99.20%; Physician B treated 331 patients with an average BED of 124.87±1.12 Gy and an average TCP of 99.30%. There are no statistically significant differences (T-Test) between the BED and TCP values calculated for these two group patients.The BED of the patients undergoing conventional EBRT is calculated to be 126.92Gy. The BED of the patients treated with permanent implant brachytherapy and EBRT are comparable. Our BED and TCP values are higher than the reported values by TG 137 due to higher Iodine-125 seed activity used in our institution. Conclusion: We calculated the BED,a surrogate of the biological response to a permanent prostate brachytherapy using TG 137 formulas and recommendation. The TCP of better than 99% is calculated for these patients. A clinical outcome study of these patients correlating the BED and TCP values with PSA and Gleason Levels as well as patient survival is warranted.« less

Gamma-ray detector guidance of breast cancer therapy

NASA Astrophysics Data System (ADS)

Ravi, Ananth

2009-12-01

Breast cancer is the most common form of cancer in women. Over 75% of breast cancer patients are eligible for breast conserving therapy. Breast conserving therapy involves a lumpectomy to excise the gross tumour, followed by adjuvant radiation therapy to eradicate residual microscopic disease. Recent advances in the understanding of breast cancer biology and recurrence have presented the opportunity to improve breast conserving therapy techniques. This thesis has explored the potential of gamma-ray detecting technology to improve guidance of both surgical and adjuvant radiation therapy aspects of breast conserving therapy. The task of accurately excising the gross tumour during breast conserving surgery (BCS) is challenging, due to the limited guidance currently available to surgeons. Radioimmuno guided surgery (RIGS) has been investigated to determine its potential to delineate the gross tumour intraoperatively. The effects of varying a set of user controllable parameters on the ability of RIGS to detect and delineate model breast tumours was determined. The parameters studied were: Radioisotope, blood activity concentration, collimator height and energy threshold. The most sensitive combination of parameters was determined to be an 111Indium labelled radiopharmaceutical with a gamma-ray detecting probe collimated to a height of 5 mm and an energy threshold at the Compton backscatter peak. Using these parameters it was found that, for the breast tumour model used, the minimum tumour-to-background ratio required to delineate the tumour edge accurately was 5.2+/-0.4 at a blood activity concentration of 5 kBq/ml. Permanent breast seed implantation (PBSI) is a form of accelerated partial breast irradiation that dramatically reduces the treatment burden of adjuvant radiation therapy on patients. Unfortunately, it is currently difficult to localize the implanted brachytherapy seeds, making it difficult to perform a correction in the event that seeds have been misplaced. One method to provide intraoperative seed localization is through the use of a gamma-camera system. Monte Carlo simulations were conducted of a Cadmium Zinc Telluride (CZT) gamma-camera system and a realistic model of a breast with 3 layers of seeds distributed according to the pre-implant treatment plan of a typical patient. The simulations showed that a gamma-camera was able to localize the seeds with a maximum error of 2.0 mm within 20 seconds. An experimental prototype was designed and constructed to validate these promising Monte Carlo results. Using a 64 pixel linear array CZT detector fitted with a custom built brass collimator, images were acquired of a physical phantom similar to the model used in the Monte Carlo simulations. The experimental prototype was able to reliably detect the seeds within 30 seconds with a median error in localization of 1 mm. The results from this thesis suggest that gamma-ray detecting technology may be able to provide significant improvements in guidance of breast cancer therapies and, thus, potentially improved therapeutic outcomes.

Repair of olecranon fractures using fiberWire without metallic implants: report of two cases.

PubMed

Nimura, Akimoto; Nakagawa, Teruhiko; Wakabayashi, Yoshiaki; Sekiya, Ichiro; Okawa, Atsushi; Muneta, Takeshi

2010-10-12

Olecranon fractures are a common injury in fractures. The tension band technique for olecranon fractures yields good clinical outcomes; however, it is associated with significant complications. In many patients, implants irritate overlying soft tissues and cause pain. This is mostly due to protrusion of the proximal ends of the K-wires or by the twisted knots of the metal wire tension band. Below we described 2 cases of olecranon fractures treated with a unique technique using FiberWire without any metallic implants. Technically, the fragment was reduced, and two K-wires were inserted from the dorsal cortex of the distal segment to the tip of the olecranon. K-wire was exchanged for a suture retriever, and 2 strands of FiberWire were retrieved twice. Each of the two FiberWires was manually tensioned and knotted on the posterior surface of the olecranon. Bony unions could be achieved, and patients had no complaint of pain and skin irritation. There was only a small loss of flexion and extension in comparison with that of the contralateral side, and the patient did not feel inconvenienced in his daily life. Using the method described, difficulty due to K-wire or other metallic implants was avoided.

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

PubMed Central

Eap, Sandy; Keller, Laetitia; Schiavi, Jessica; Huck, Olivier; Jacomine, Leandro; Fioretti, Florence; Gauthier, Christian; Sebastian, Victor; Schwinté, Pascale; Benkirane-Jessel, Nadia

2015-01-01

New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 μm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days’ implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days’ implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration. PMID:25709432

An experimental palladium-103 seed (OptiSeedexp) in a biocompatible polymer without a gold marker: characterization of dosimetric parameters including the interseed effect.

PubMed

Abboud, F; Scalliet, P; Vynckier, S

2008-12-01

Permanent implantation of 125I (iodine) or 103Pd (palladium) sources is a popular treatment option in the management of early stage prostate cancer. New sources are being developed, some of which are being marketed for different clinical applications. A new technique of adjuvant stereotactic permanent seed breast implant, similar to that used in the treatment of prostate cancer, has been proposed by [N. Jansen et al., Int. J. Radiat. Oncol. Biol. Phys. 67, 1052-1058 (2007)] with encouraging results. The presence of artifacts from the metallic seeds, however, can disturb follow-up imaging. The development of plastic seeds has reduced these artifacts. This paper presents a feasibility study of the advantages of palladium-103 seeds, encapsulated with a biocompatible polymer, for future clinical applications, and on the effect of the gold marker on the dosimetric characteristics of such seeds. Experimental palladium seeds, OptiSeedexp, were manufactured by International Brachytherapy (IBt), Seneffe, Belgium, from a biocompatible polymer, including the marker. Apart from the absence of a gold marker, the studied seed has an identical design to the OptiSeed103 [Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311-321 (2005)]. Polymer encapsulation was preferred by IBt in order to reduce the quantity of radioactive material needed for a given dose rate and to reduce the anisotropy of the radiation field around the seed. In addition, this design is intended to decrease the interseed effects that can occur as a result of the marker and the encapsulation. Dosimetric measurements were performed using LiF thermoluminescent dosimeters (1 mm3) in solid water phantoms (WT1). Measured data were compared to Monte Carlo simulated data in solid water using the MCNP code, version 4C. Updated cross sections [Med. Phys. 30, 701-711 (2003)] were used. As the measured and calculated data were in agreement, Monte Carlo calculations were then performed in liquid water to obtain relevant dosimetric data as required by TG-43U1 recommendations. Comparison of the results with previous studies of OptiSeed103 [Phys. Med. Biol. 50, 1493-1504 (2005)]; [Appl. Radiat. Isot. 63, 311-321 (2005)], and of InterSource103 [Appl. Radiat. Isot. 57, 805-811 (2002)] showed very good agreement for the dose rate constant and for the radial dose function. With respect to the anisotropy function, the relative dose (anisotropy value relative to 90 degrees) from the polymer seed at a distance of 3 cm was close to unity (105%) at 0 degrees, whereas the relative values for the OptiSeed103 with a gold marker and the titanium-encapsulated InterSource103 seed decreased to 70% and 40%, respectively. The interseed effect from one seed was negligible and in the order of calculation uncertainty, making calculation of the dose rate distribution of the studied seeds, according to TG43U1 recommendations, more accurate and closer to reality. This feasibility study shows that due to the low energy of palladium-103, the negligible interseed effect and the reduced artifacts in postimplant medical imaging, this experimental plastic seed would be a good source for breast brachytherapy. This feasibility study was carried out in collaboration with IBt and will be continued with a study of its visibility in different tissues.

Fast radioactive seed localization in intraoperative cone beam CT for low-dose-rate prostate brachytherapy

NASA Astrophysics Data System (ADS)

Hu, Yu-chi; Xiong, Jian-ping; Cohan, Gilad; Zaider, Marco; Mageras, Gig; Zelefsky, Michael

2013-03-01

A fast knowledge-based radioactive seed localization method for brachytherapy was developed to automatically localize radioactive seeds in an intraoperative volumetric cone beam CT (CBCT) so that corrections, if needed, can be made during prostate implant surgery. A transrectal ultrasound (TRUS) scan is acquired for intraoperative treatment planning. Planned seed positions are transferred to intraoperative CBCT following TRUS-to-CBCT registration using a reference CBCT scan of the TRUS probe as a template, in which the probe and its external fiducial markers are pre-segmented and their positions in TRUS are known. The transferred planned seeds and probe serve as an atlas to reduce the search space in CBCT. Candidate seed voxels are identified based on image intensity. Regions are grown from candidate voxels and overlay regions are merged. Region volume and intensity variance is checked against known seed volume and intensity profile. Regions meeting the above criteria are flagged as detected seeds; otherwise they are flagged as likely seeds and sorted by a score that is based on volume, intensity profile and distance to the closest planned seed. A graphical interface allows users to review and accept or reject likely seeds. Likely seeds with approximately twice the seed volume are automatically split. Five clinical cases are tested. Without any manual correction in seed detection, the method performed the localization in 5 seconds (excluding registration time) for a CBCT scan with 512×512×192 voxels. The average precision rate per case is 99% and the recall rate is 96% for a total of 416 seeds. All false negative seeds are found with 15 in likely seeds and 1 included in a detected seed. With the new method, updating of calculations of dose distribution during the procedure is possible and thus facilitating evaluation and improvement of treatment quality.

SU-E-J-166: Sensitivity of Clinically Relevant Dosimetric Parameters to Contouring Uncertainty During Post Implant Dosimetry of Prostate Permanent Seed Implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mashouf, S; University of Toronto, Dept. of Radiation Oncology, Toronto, ON; Ravi, A

Purpose: There is a strong evidence relating post-implant dosimetry for permanent seed prostate brachytherpy to local control rates. The delineation of the prostate on CT images, however, represents a challenge as it is difficult to confidently identify the prostate borders from soft tissue surrounding it. This study aims at quantifying the sensitivity of clinically relevant dosimetric parameters to prostate contouring uncertainty. Methods: The post-implant CT images and plans for a cohort of 43 patients, who have received I–125 permanent prostate seed implant in our centre, were exported to MIM Symphony LDR brachytherapy treatment planning system (MIM Software Inc., Cleveland, OH).more » The prostate contours in post-implant CT images were expanded/contracted uniformly for margins of ±1.00mm, ±2.00mm, ±3.00mm, ±4.00mm and ±5.00mm (±0.01mm). The values for V100 and D90 were extracted from Dose Volume Histograms for each contour and compared. Results: The mean value of V100 and D90 was obtained as 92.3±8.4% and 108.4±12.3% respectively (Rx=145Gy). V100 was reduced by −3.2±1.5%, −7.2±3.0%, −12.8±4.0%, −19.0±4.8%, − 25.5±5.4% for expanded contours of prostate with margins of +1mm, +2mm, +3mm, +4mm, and +5mm, respectively, while it was increased by 1.6±1.2%, 2.4±2.4%, 2.7±3.2%, 2.9±4.2%, 2.9±5.1% for the contracted contours. D90 was reduced by −6.9±3.5%, −14.5±6.1%, −23.8±7.1%, − 33.6±8.5%, −40.6±8.7% and increased by 4.1±2.6%, 6.1±5.0%, 7.2±5.7%, 8.1±7.3% and 8.1±7.3% for the same set of contours. Conclusion: Systematic expansion errors of more than 1mm may likely render a plan sub-optimal. Conversely contraction errors may Result in labeling a plan likely as optimal. The use of MRI images to contour the prostate should results in better delineation of prostate organ which increases the predictive value of post-op plans. Since observers tend to overestimate the prostate volume on CT, compared with MRI, the impact of the contouring uncertainty on V100 and D90 fortunately, has a conservative effect of underestimating the prostate coverage.« less

Improved bone marrow stromal cell adhesion on micropatterned titanium surfaces.

PubMed

Iskandar, Maria E; Cipriano, Aaron F; Lock, Jaclyn; Gott, Shannon C; Rao, Masaru P; Liu, Huinan

2012-01-01

Implant longevity is desired for all bone replacements and fixatives. Titanium (Ti) implants fail due to lack of juxtaposed bone formation, resulting in implant loosening. Implant surface modifications have shown to affect the interactions between the implant and bone. In clinical applications, it is crucial to improve osseointegration and implant fixation at the implant and bone interface. Moreover, bone marrow derived cells play a significant role for implant and tissue integration. Therefore, the objective of this study is to investigate how surface micropatterning on Ti influences its interactions with bone marrow derived cells containing mesenchymal and hematopoietic stem cells. Bone marrow derived mesenchymal stem cells (BMSC) have the capability of differentiating into osteoblasts that contribute to bone growth, and therefore implant/bone integration. Hematopoietic stem cell derivatives are precursor cells that contribute to inflammatory response. By using all three cells naturally contained within bone marrow, we mimic the physiological environment to which an implant is exposed. Primary rat bone marrow derived cells were seeded onto Ti with surfaces composed of arrays of grooves of equal width and spacing ranging from 0.5 to 50 µm, fabricated using a novel plasma-based dry etching technique. Results demonstrated enhanced total cell adhesion on smaller micrometer-scale Ti patterns compared with larger micrometer-scale Ti patterns, after 24-hr culture. Further studies are needed to determine bone marrow derived cell proliferation and osteogenic differentiation potential on micropatterned Ti, and eventually nanopatterned Ti.

A rule of seven in Watson-Crick base-pairing of mismatched sequences.

PubMed

Cisse, Ibrahim I; Kim, Hajin; Ha, Taekjip

2012-05-13

Sequence recognition through base-pairing is essential for DNA repair and gene regulation, but the basic rules governing this process remain elusive. In particular, the kinetics of annealing between two imperfectly matched strands is not well characterized, despite its potential importance in nucleic acid-based biotechnologies and gene silencing. Here we use single-molecule fluorescence to visualize the multiple annealing and melting reactions of two untethered strands inside a porous vesicle, allowing us to precisely quantify the annealing and melting rates. The data as a function of mismatch position suggest that seven contiguous base pairs are needed for rapid annealing of DNA and RNA. This phenomenological rule of seven may underlie the requirement for seven nucleotides of complementarity to seed gene silencing by small noncoding RNA and may help guide performance improvement in DNA- and RNA-based bio- and nanotechnologies, in which off-target effects can be detrimental.

Structure-based cleavage mechanism of Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage

PubMed Central

Sheng, Gang; Zhao, Hongtu; Wang, Jiuyu; Rao, Yu; Tian, Wenwen; Swarts, Daan C.; van der Oost, John; Patel, Dinshaw J.; Wang, Yanli

2014-01-01

We report on crystal structures of ternary Thermus thermophilus Argonaute (TtAgo) complexes with 5′-phosphorylated guide DNA and a series of DNA targets. These ternary complex structures of cleavage-incompatible, cleavage-compatible, and postcleavage states solved at improved resolution up to 2.2 Å have provided molecular insights into the orchestrated positioning of catalytic residues, a pair of Mg2+ cations, and the putative water nucleophile positioned for in-line attack on the cleavable phosphate for TtAgo-mediated target cleavage by a RNase H-type mechanism. In addition, these ternary complex structures have provided insights into protein and DNA conformational changes that facilitate transition between cleavage-incompatible and cleavage-compatible states, including the role of a Glu finger in generating a cleavage-competent catalytic Asp-Glu-Asp-Asp tetrad. Following cleavage, the seed segment forms a stable duplex with the complementary segment of the target strand. PMID:24374628

Chondrocyte differentiation for auricular cartilage reconstruction using a chitosan based hydrogel.

PubMed

García-López, J; Garciadiego-Cázares, D; Melgarejo-Ramírez, Y; Sánchez-Sánchez, R; Solís-Arrieta, L; García-Carvajal, Z; Sánchez-Betancourt, J I; Ibarra, C; Luna-Bárcenas, G; Velasquillo, C

2015-12-01

Tissue engineering with the use of biodegradable and biocompatible scaffolds is an interesting option for ear repair. Chitosan-Polyvinyl alcohol-Epichlorohydrine hydrogel (CS-PVA-ECH) is biocompatible and displays appropriate mechanical properties to be used as a scaffold. The present work, studies the potential of CS-PVA-ECH scaffolds seeded with chondrocytes to develop elastic cartilage engineered-neotissues. Chondrocytes isolated from rabbit and swine elastic cartilage were independently cultured onto CS-PVA-ECH scaffolds for 20 days to form the appropriate constructs. Then, in vitro cell viability and morphology were evaluated by calcein AM and EthD-1 assays and Scanning Electron Microscopy (SEM) respectively, and the constructs were implanted in nu/nu mice for four months, in order to evaluate the neotissue formation. Histological analysis of the formed neotissues was performed by Safranin O, Toluidine blue (GAG's), Verhoeff-Van Gieson (elastic fibers), Masson's trichrome (collagen) and Von Kossa (Calcium salts) stains and SEM. Results indicate appropriate cell viability, seeded with rabbit or swine chondrocyte constructs; nevertheless, upon implantation the constructs developed neotissues with different characteristics depending on the animal species from which the seeded chondrocytes came from. Neotissues developed from swine chondrocytes were similar to auricular cartilage, while neotissues from rabbit chondrocytes were similar to hyaline cartilage and eventually they differentiate to bone. This result suggests that neotissue characteristics may be influenced by the animal species source of the chondrocytes isolated.

Effect of Different Titanium Surfaces on Maturation of Murine Bone Marrow-Derived Dendritic Cells

NASA Astrophysics Data System (ADS)

Zheng, Xiaofei; Zhou, Fengjuan; Gu, Yifei; Duan, Xiaobo; Mo, Anchun

2017-02-01

Dendritic cells (DCs) play a pivotal role in the host response to implanted biomaterials. Osseointegration of titanium (Ti) implant is an immunological and inflammatory-driven process. However, the role of DCs in this complex process is largely unknown. This study aimed to investigate the effect of different Ti surfaces on DC maturation, and evaluate its subsequent potential on osteogenic differentiation of preosteoblasts. Murine bone marrow-derived DCs were seeded on Ti disks with different surface treatments, including pretreatment (PT), sandblasted/acid-etched (SLA) and modified SLA (modSLA) surface. Compared with DCs cultured on PT and SLA surfaces, the cells seeded on modSLA surface demonstrated a more round morphology with lower expression of CD86 and MHC-II, the DC maturation markers. Those cells also secreted high levels of anti-inflammatory cytokine IL-10 and TGF-β. Notably, addition of conditioned medium (CM) from modSLA-induced DCs significantly increased the mRNA expression of Runx2 and ALP as well as ALP activity by murine preosteoblast MC3T3-E1 cells. Our data demonstrated that Ti disks with different surfaces lead to differential DCs responses. PT and SLA surfaces induce DCs mature, while DCs seeded on modSLA-Ti surface maintain an immature phenotype and exhibit a potential of promoting osteogenic differentiation of MC3T3-E1 cells.

Enhancement of tissue engineered bone formation by a low pressure system improving cell seeding and medium perfusion into a porous scaffold.

PubMed

Wang, Juyong; Asou, Yoshinori; Sekiya, Ichiro; Sotome, Shinichi; Orii, Hisaya; Shinomiya, Kenichi

2006-05-01

To obtain more extensive bone formation in composites of porous ceramics and bone marrow stromal cells (BMSCs), we hypothesized that a low-pressure system would serve to facilitate the perfusion of larger number of BMSCs into the porous scaffold, enhancing bone formation within the composites. After culturing BMSCs in osteogenic medium, porous blocks of beta-tricalcium phosphate (beta-TCP) were soaked in the cell suspension. Composites of the block and BMSCs were put immediately into a vacuum desiccator. Low pressure was applied to the low pressure group, while controls were left at atmospheric pressure. Composites were incubated in vitro or subcutaneously implanted into syngeneic rats, then analyzed biologically and histologically. In the in vitro group, cell suspension volume, cell seeding efficiency, alkaline phosphatase (ALP) activity, and DNA content in the beta-TCP blocks were significantly higher in low pressure group than in the controls. Scanning electron microscopy (SEM) demonstrated that a greater number of cells covered the central parts of the composites in the low pressure group. ALP activity in the composites was increased at 3 and 6 weeks after implantation into rats. Histomorphometric analysis revealed more uniform and extensive bone formation in the low pressure group than in the controls. The application of low pressure during the seeding of BMSCs in perfusing medium into a porous scaffold is useful for tissue-engineered bone formation.

Stem cell-based tissue-engineering for treatment of meniscal tears in the avascular zone.

PubMed

Zellner, Johannes; Hierl, Katja; Mueller, Michael; Pfeifer, Christian; Berner, Arne; Dienstknecht, Thomas; Krutsch, Werner; Geis, Sebastian; Gehmert, Sebastian; Kujat, Richard; Dendorfer, Sebastian; Prantl, Lukas; Nerlich, Michael; Angele, Peter

2013-10-01

Meniscal tears in the avascular zone have a poor self-healing potential, however partial meniscectomy predisposes the knee for early osteoarthritis. Tissue engineering with mesenchymal stem cells and a hyaluronan collagen based scaffold is a promising approach to repair meniscal tears in the avascular zone. 4 mm longitudinal meniscal tears in the avascular zone of lateral menisci of New Zealand White Rabbits were performed. The defect was left empty, sutured with a 5-0 suture or filled with a hyaluronan/collagen composite matrix without cells, with platelet rich plasma or with autologous mesenchymal stem cells. Matrices with stem cells were in part precultured in chondrogenic medium for 14 days prior to the implantation. Menisci were harvested at 6 and 12 weeks. The developed repair tissue was analyzed macroscopically, histologically and biomechanically. Untreated defects, defects treated with suture alone, with cell-free or with platelet rich plasma seeded implants showed a muted fibrous healing response. The implantation of stem cell-matrix constructs initiated fibrocartilage-like repair tissue, with better integration and biomechanical properties in the precultured stem cell-matrix group. A hyaluronan-collagen based composite scaffold seeded with mesenchymal stem cells is more effective in the repair avascular meniscal tear with stable meniscus-like tissue and to restore the native meniscus. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Effects of a hybrid micro/nanorod topography-modified titanium implant on adhesion and osteogenic differentiation in rat bone marrow mesenchymal stem cells.

PubMed

Zhang, Wenjie; Li, Zihui; Huang, Qingfeng; Xu, Ling; Li, Jinhua; Jin, Yuqin; Wang, Guifang; Liu, Xuanyong; Jiang, Xinquan

2013-01-01

Various methods have been used to modify titanium implant surfaces with the aim of achieving better osseointegration. In this study, we fabricated a clustered nanorod structure on an acid-etched, microstructured titanium plate surface using hydrogen peroxide. We also evaluated biofunctionalization of the hybrid micro/nanorod topography on rat bone marrow mesenchymal stem cells. Scanning electron microscopy and x-ray diffraction were used to investigate the surface topography and phase composition of the modified titanium plate. Rat bone marrow mesenchymal stem cells were cultured and seeded on the plate. The adhesion ability of the cells was then assayed by cell counting at one, 4, and 24 hours after cell seeding, and expression of adhesion-related protein integrin β1 was detected by immunofluorescence. In addition, a polymerase chain reaction assay, alkaline phosphatase and Alizarin Red S staining assays, and osteopontin and osteocalcin immunofluorescence analyses were used to evaluate the osteogenic differentiation behavior of the cells. The hybrid micro/nanoscale texture formed on the titanium surface enhanced the initial adhesion activity of the rat bone marrow mesenchymal stem cells. Importantly, the hierarchical structure promoted osteogenic differentiation of these cells. This study suggests that a hybrid micro/nanorod topography on a titanium surface fabricated by treatment with hydrogen peroxide followed by acid etching might facilitate osseointegration of a titanium implant in vivo.

An automated perfusion bioreactor for the streamlined production of engineered osteogenic grafts.

PubMed

Ding, Ming; Henriksen, Susan S; Wendt, David; Overgaard, Søren

2016-04-01

A computer-controlled perfusion bioreactor was developed for the streamlined production of engineered osteogenic grafts. This system automated the required bioprocesses, from the initial filling of the system through the phases of cell seeding and prolonged cell/tissue culture. Flow through chemo-optic micro-sensors allowed to non-invasively monitor the levels of oxygen and pH in the perfused culture medium throughout the culture period. To validate its performance, freshly isolated ovine bone marrow stromal cells were directly seeded on porous scaffold granules (hydroxyapatite/β-tricalcium-phosphate/poly-lactic acid), bypassing the phase of monolayer cell expansion in flasks. Either 10 or 20 days after culture, engineered cell-granule grafts were implanted in an ectopic mouse model to quantify new bone formation. After four weeks of implantation, histomorphometry showed more bone in bioreactor-generated grafts than cell-free granule controls, while bone formation did not show significant differences between 10 days and 20 days of incubation. The implanted granules without cells had no bone formation. This novel perfusion bioreactor has revealed the capability of activation larger viable bone graft material, even after shorter incubation time of graft material. This study has demonstrated the feasibility of engineering osteogenic grafts in an automated bioreactor system, laying the foundation for a safe, regulatory-compliant, and cost-effective manufacturing process. © 2015 Wiley Periodicals, Inc.

Mesenchymal stem cell-based repair of articular cartilage with polyglycolic acid-hydroxyapatite biphasic scaffold.

PubMed

Zhou, X Z; Leung, V Y; Dong, Q R; Cheung, K M; Chan, D; Lu, W W

2008-06-01

This study investigates the capacity of a composite scaffold composed of polyglycolic acid-hydroxyapatite (PGA-HA) and autologous mesenchymal stem cells (MSCs) to promote repair of osteochondral defects. MSCs from culture-expanded rabbits were seeded onto a PGA and HA scaffold. After a 72-hour co-culture period, the cell-adhered PGA and HA were joined together, forming an MSCs-PGA-HA composite. Full-thickness cartilage defects in the intercondylar fossa of the femur were then implanted with the MSC-PGA-HA composite, the PGA-HA scaffold only, or they were left empty (n=20). Animals were sacrificed 16 or 32 weeks after surgery and the gross appearance of the defects was evaluated. The specimens were examined histologically for morphologic features, and stained immunohistochemically for type 2 collagen. Specimens of the MSCs-PGA-HA composite implantation group demonstrated hyaline cartilage and a complete subchondral bone formation. At 16 weeks post-implantation, significant integration of the newly formed tissue with surrounding normal cartilage and subchondral bone was observed when compared to the two control groups. At 32 weeks, no sign of progressive degeneration of the newly formed tissue was found. A significant difference in histological grading score was found compared with the control groups. The novel MSCs-seeded, PGA-HA biphasic graft facilitated both articular cartilage and subchondral bone regeneration in an animal model and might serve as a new approach for clinical applications.

Cell Culturing of Cytoskeleton

NASA Technical Reports Server (NTRS)

2004-01-01

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc., has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc., is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

Cell Culturing of Cytoskeleton

NASA Technical Reports Server (NTRS)

2004-01-01

Biomedical research offers hope for a variety of medical problems, from diabetes to the replacement of damaged bone and tissues. Bioreactors, which are used to grow cells and tissue cultures, play a major role in such research and production efforts. Cell culturing, such as this bone cell culture, is an important part of biomedical research. The BioDyn payload includes a tissue engineering investigation. The commercial affiliate, Millenium Biologix, Inc. has been conducting bone implant experiments to better understand how synthetic bone can be used to treat bone-related illnesses and bone damaged in accidents. On STS-95, the BioDyn payload will include a bone cell culture aimed to help develop this commercial synthetic bone product. Millenium Biologix, Inc. is exploring the potential for making human bone implantable materials by seeding its proprietary artificial scaffold material with human bone cells. The product of this tissue engineering experiment using the Bioprocessing Modules (BPMs) on STS-95 is space-grown bone implants, which could have potential for dental implants, long bone grafts, and coating for orthopedic implants such as hip replacements.

Convergent transmission of RNAi guide-target mismatch information across Argonaute internal allosteric network.

PubMed

Joseph, Thomas T; Osman, Roman

2012-01-01

In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA) is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC) that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand "seed region" have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the cumulative effects of a large number of internal allosteric pathways.

Convergent Transmission of RNAi Guide-Target Mismatch Information across Argonaute Internal Allosteric Network

PubMed Central

Joseph, Thomas T.; Osman, Roman

2012-01-01

In RNA interference, a guide strand derived from a short dsRNA such as a microRNA (miRNA) is loaded into Argonaute, the central protein in the RNA Induced Silencing Complex (RISC) that silences messenger RNAs on a sequence-specific basis. The positions of any mismatched base pairs in an miRNA determine which Argonaute subtype is used. Subsequently, the Argonaute-guide complex binds and silences complementary target mRNAs; certain Argonautes cleave the target. Mismatches between guide strand and the target mRNA decrease cleavage efficiency. Thus, loading and silencing both require that signals about the presence of a mismatched base pair are communicated from the mismatch site to effector sites. These effector sites include the active site, to prevent target cleavage; the binding groove, to modify nucleic acid binding affinity; and surface allosteric sites, to control recruitment of additional proteins to form the RISC. To examine how such signals may be propagated, we analyzed the network of internal allosteric pathways in Argonaute exhibited through correlations of residue-residue interactions. The emerging network can be described as a set of pathways emanating from the core of the protein near the active site, distributed into the bulk of the protein, and converging upon a distributed cluster of surface residues. Nucleotides in the guide strand “seed region” have a stronger relationship with the protein than other nucleotides, concordant with their importance in sequence selectivity. Finally, any of several seed region guide-target mismatches cause certain Argonaute residues to have modified correlations with the rest of the protein. This arises from the aggregation of relatively small interaction correlation changes distributed across a large subset of residues. These residues are in effector sites: the active site, binding groove, and surface, implying that direct functional consequences of guide-target mismatches are mediated through the cumulative effects of a large number of internal allosteric pathways. PMID:23028290

Laser Sintered Porous Ti-6Al-4V Implants Stimulate Vertical Bone Growth.

PubMed

Cheng, Alice; Cohen, David J; Kahn, Adrian; Clohessy, Ryan M; Sahingur, Kaan; Newton, Joseph B; Hyzy, Sharon L; Boyan, Barbara D; Schwartz, Zvi

2017-08-01

The objective of this study was to examine the ability of 3D implants with trabecular-bone-inspired porosity and micro-/nano-rough surfaces to enhance vertical bone ingrowth. Porous Ti-6Al-4V constructs were fabricated via laser-sintering and processed to obtain micro-/nano-rough surfaces. Male and female human osteoblasts were seeded on constructs to analyze cell morphology and response. Implants were then placed on rat calvaria for 10 weeks to assess vertical bone ingrowth, mechanical stability and osseointegration. All osteoblasts showed higher levels of osteocalcin, osteoprotegerin, vascular endothelial growth factor and bone morphogenetic protein 2 on porous constructs compared to solid laser-sintered controls. Porous implants placed in vivo resulted in an average of 3.1 ± 0.6 mm 3 vertical bone growth and osseointegration within implant pores and had significantly higher pull-out strength values than solid implants. New bone formation and pull-out strength was not improved with the addition of demineralized bone matrix putty. Scanning electron images and histological results corroborated vertical bone growth. This study indicates that Ti-6Al-4V implants fabricated by additive manufacturing to have porosity based on trabecular bone and post-build processing to have micro-/nano-surface roughness can support vertical bone growth in vivo, and suggests that these implants may be used clinically to increase osseointegration in challenging patient cases.

Monte Carlo simulation of radiation transport and dose deposition from locally released gold nanoparticles labeled with 111In, 177Lu or 90Y incorporated into tissue implantable depots

NASA Astrophysics Data System (ADS)

Lai, Priscilla; Cai, Zhongli; Pignol, Jean-Philippe; Lechtman, Eli; Mashouf, Shahram; Lu, Yijie; Winnik, Mitchell A.; Jaffray, David A.; Reilly, Raymond M.

2017-11-01

Permanent seed implantation (PSI) brachytherapy is a highly conformal form of radiation therapy but is challenged with dose inhomogeneity due to its utilization of low energy radiation sources. Gold nanoparticles (AuNP) conjugated with electron emitting radionuclides have recently been developed as a novel form of brachytherapy and can aid in homogenizing dose through physical distribution of radiolabeled AuNP when injected intratumorally (IT) in suspension. However, the distribution is unpredictable and precise placement of many injections would be difficult. Previously, we reported the design of a nanoparticle depot (NPD) that can be implanted using PSI techniques and which facilitates controlled release of AuNP. We report here the 3D dose distribution resulting from a NPD incorporating AuNP labeled with electron emitters (90Y, 177Lu, 111In) of different energies using Monte Carlo based voxel level dosimetry. The MCNP5 Monte Carlo radiation transport code was used to assess differences in dose distribution from simulated NPD and conventional brachytherapy sources, positioned in breast tissue simulating material. We further compare these dose distributions in mice bearing subcutaneous human breast cancer xenografts implanted with 177Lu-AuNP NPD, or injected IT with 177Lu-AuNP in suspension. The radioactivity distributions were derived from registered SPECT/CT images and time-dependent dose was estimated. Results demonstrated that the dose distribution from NPD reduced the maximum dose 3-fold when compared to conventional seeds. For simulated NPD, as well as NPD implanted in vivo, 90Y delivered the most homogeneous dose distribution. The tumor radioactivity in mice IT injected with 177Lu-AuNP redistributed while radioactivity in the NPD remained confined to the implant site. The dose distribution from radiolabeled AuNP NPD were predictable and concentric in contrast to IT injected radiolabeled AuNP, which provided irregular and temporally variant dose distributions. The use of NPD may serve as an intermediate between PSI and radiation delivered by radiolabeled AuNP by providing a controlled method to improve delivery of prescribed doses as well as homogenize dose from low penetrating electron sources.

Casting inorganic structures with DNA molds.

PubMed

Sun, Wei; Boulais, Etienne; Hakobyan, Yera; Wang, Wei Li; Guan, Amy; Bathe, Mark; Yin, Peng

2014-11-07

We report a general strategy for designing and synthesizing inorganic nanostructures with arbitrarily prescribed three-dimensional shapes. Computationally designed DNA strands self-assemble into a stiff "nanomold" that contains a user-specified three-dimensional cavity and encloses a nucleating gold "seed." Under mild conditions, this seed grows into a larger cast structure that fills and thus replicates the cavity. We synthesized a variety of nanoparticles with 3-nanometer resolution: three distinct silver cuboids with three independently tunable dimensions, silver and gold nanoparticles with diverse cross sections, and composite structures with homo- and heterogeneous components. The designer equilateral silver triangular and spherical nanoparticles exhibited plasmonic properties consistent with electromagnetism-based simulations. Our framework is generalizable to more complex geometries and diverse inorganic materials, offering a range of applications in biosensing, photonics, and nanoelectronics. Copyright © 2014, American Association for the Advancement of Science.

Tissue-engineered composite scaffold of poly(lactide-co-glycolide) and hydroxyapatite nanoparticles seeded with autologous mesenchymal stem cells for bone regeneration*

PubMed Central

Zhang, Bing; Zhang, Pei-biao; Wang, Zong-liang; Lyu, Zhong-wen; Wu, Han

2017-01-01

Objective: A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapatite (g-HA)/poly(lactide-co-glycolide) (PLGA) carried with autologous mesenchymal stem cells (MSCs) and bone morphogenetic protein-2 (BMP-2) was assessed for the therapy of critical bone defects. At the same time, tissue response and in vivo mineralization of tissue-engineered implants were investigated. Methods: A composite scaffold of PLGA and g-HA was fabricated by the solvent casting and particulate-leaching method. The tissue-engineered implants were prepared by seeding the scaffolds with autologous bone marrow MSCs in vitro. Then, mineralization and osteogenesis were observed by intramuscular implantation, as well as the repair of the critical radius defects in rabbits. Results: After eight weeks post-surgery, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) revealed that g-HA/PLGA had a better interface of tissue response and higher mineralization than PLGA. Apatite particles were formed and varied both in macropores and micropores of g-HA/PLGA. Computer radiographs and histological analysis revealed that there were more and more quickly formed new bone formations and better fusion in the bone defect areas of g-HA/PLGA at 2–8 weeks post-surgery. Typical bone synostosis between the implant and bone tissue was found in g-HA/PLGA, while only fibrous tissues formed in PLGA. Conclusions: The incorporation of g-HA mainly improved mineralization and bone formation compared with PLGA. The application of MSCs can enhance bone formation and mineralization in PLGA scaffolds compared with cell-free scaffolds. Furthermore, it can accelerate the absorption of scaffolds compared with composite scaffolds. PMID:29119734

Tissue-engineered composite scaffold of poly(lactide-co-glycolide) and hydroxyapatite nanoparticles seeded with autologous mesenchymal stem cells for bone regeneration.

PubMed

Zhang, Bing; Zhang, Pei-Biao; Wang, Zong-Liang; Lyu, Zhong-Wen; Wu, Han

A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapatite (g-HA)/ poly(lactide-co-glycolide) (PLGA) carried with autologous mesenchymal stem cells (MSCs) and bone morphogenetic protein-2 (BMP-2) was assessed for the therapy of critical bone defects. At the same time, tissue response and in vivo mineralization of tissue-engineered implants were investigated. A composite scaffold of PLGA and g-HA was fabricated by the solvent casting and particulate-leaching method. The tissue-engineered implants were prepared by seeding the scaffolds with autologous bone marrow MSCs in vitro. Then, mineralization and osteogenesis were observed by intramuscular implantation, as well as the repair of the critical radius defects in rabbits. After eight weeks post-surgery, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) revealed that g-HA/PLGA had a better interface of tissue response and higher mineralization than PLGA. Apatite particles were formed and varied both in macropores and micropores of g-HA/PLGA. Computer radiographs and histological analysis revealed that there were more and more quickly formed new bone formations and better fusion in the bone defect areas of g-HA/PLGA at 2-8 weeks post-surgery. Typical bone synostosis between the implant and bone tissue was found in g-HA/PLGA, while only fibrous tissues formed in PLGA. The incorporation of g-HA mainly improved mineralization and bone formation compared with PLGA. The application of MSCs can enhance bone formation and mineralization in PLGA scaffolds compared with cell-free scaffolds. Furthermore, it can accelerate the absorption of scaffolds compared with composite scaffolds.

Fabrication of multi-well chips for spheroid cultures and implantable constructs through rapid prototyping techniques.

PubMed

Lopa, Silvia; Piraino, Francesco; Kemp, Raymond J; Di Caro, Clelia; Lovati, Arianna B; Di Giancamillo, Alessia; Moroni, Lorenzo; Peretti, Giuseppe M; Rasponi, Marco; Moretti, Matteo

2015-07-01

Three-dimensional (3D) culture models are widely used in basic and translational research. In this study, to generate and culture multiple 3D cell spheroids, we exploited laser ablation and replica molding for the fabrication of polydimethylsiloxane (PDMS) multi-well chips, which were validated using articular chondrocytes (ACs). Multi-well ACs spheroids were comparable or superior to standard spheroids, as revealed by glycosaminoglycan and type-II collagen deposition. Moreover, the use of our multi-well chips significantly reduced the operation time for cell seeding and medium refresh. Exploiting a similar approach, we used clinical-grade fibrin to generate implantable multi-well constructs allowing for the precise distribution of multiple cell types. Multi-well fibrin constructs were seeded with ACs generating high cell density regions, as shown by histology and cell fluorescent staining. Multi-well constructs were compared to standard constructs with homogeneously distributed ACs. After 7 days in vitro, expression of SOX9, ACAN, COL2A1, and COMP was increased in both constructs, with multi-well constructs expressing significantly higher levels of chondrogenic genes than standard constructs. After 5 weeks in vivo, we found that despite a dramatic size reduction, the cell distribution pattern was maintained and glycosaminoglycan content per wet weight was significantly increased respect to pre-implantation samples. In conclusion, multi-well chips for the generation and culture of multiple cell spheroids can be fabricated by low-cost rapid prototyping techniques. Furthermore, these techniques can be used to generate implantable constructs with defined architecture and controlled cell distribution, allowing for in vitro and in vivo investigation of cell interactions in a 3D environment. © 2015 Wiley Periodicals, Inc.

Seed Transmission of Soybean vein necrosis virus: The First Tospovirus Implicated in Seed Transmission.

PubMed

Groves, Carol; German, Thomas; Dasgupta, Ranjit; Mueller, Daren; Smith, Damon L

2016-01-01

Soybean vein necrosis virus (SVNV; genus Tospovirus; Family Bunyaviridae) is a negative-sense single-stranded RNA virus that has been detected across the United States and in Ontario, Canada. In 2013, a seed lot of a commercial soybean variety (Glycine max) with a high percentage of discolored, deformed and undersized seed was obtained. A random sample of this seed was planted in a growth room under standard conditions. Germination was greater than 90% and the resulting seedlings looked normal. Four composite samples of six plants each were tested by reverse transcription polymerase chain reaction (RT-PCR) using published primers complimentary to the S genomic segment of SVNV. Two composite leaflet samples retrieved from seedlings yielded amplicons with a size and sequence predictive of SVNV. Additional testing of twelve arbitrarily selected individual plants resulted in the identification of two SVNV positive plants. Experiments were repeated by growing seedlings from the same seed lot in an isolated room inside a thrips-proof cage to further eliminate any external source of infection. Also, increased care was taken to reduce any possible PCR contamination. Three positive plants out of forty-eight were found using these measures. Published and newly designed primers for the L and M RNAs of SVNV were also used to test the extracted RNA and strengthen the diagnosis of viral infection. In experiments, by three scientists, in two different labs all three genomic RNAs of SVNV were amplified in these plant materials. RNA-seq analysis was also conducted using RNA extracted from a composite seedling sample found to be SVNV-positive and a symptomatic sample collected from the field. This analysis revealed both sense and anti-sense reads from all three gene segments in both samples. We have shown that SVNV can be transmitted in seed to seedlings from an infected seed lot at a rate of 6%. To our knowledge this is the first report of seed-transmission of a Tospovirus.

Role of anthropometric data in the prediction of 4-stranded hamstring graft size in anterior cruciate ligament reconstruction.

PubMed

Ho, Sean Wei Loong; Tan, Teong Jin Lester; Lee, Keng Thiam

2016-03-01

To evaluate whether pre-operative anthropometric data can predict the optimal diameter and length of hamstring tendon autograft for anterior cruciate ligament (ACL) reconstruction. This was a cohort study that involved 169 patients who underwent single-bundle ACL reconstruction (single surgeon) with 4-stranded MM Gracilis and MM Semi-Tendinosus autografts. Height, weight, body mass index (BMI), gender, race, age and -smoking status were recorded pre-operatively. Intra-operatively, the diameter and functional length of the 4-stranded autograft was recorded. Multiple regression analysis was used to determine the relationship between the anthropometric measurements and the length and diameter of the implanted autografts. The strongest correlation between 4-stranded hamstring autograft diameter was height and weight. This correlation was stronger in females than males. BMI had a moderate correlation with the diameter of the graft in females. Females had a significantly smaller graft both in diameter and length when compared with males. Linear regression models did not show any significant correlation between hamstring autograft length with height and weight (p>0.05). Simple regression analysis demonstrated that height and weight can be used to predict hamstring graft diameter. The following regression equation was obtained for females: Graft diameter=0.012+0.034*Height+0.026*Weight (R2=0.358, p=0.004) The following regression equation was obtained for males: Graft diameter=5.130+0.012*Height+0.007*Weight (R2=0.086, p=0.002). Pre-operative anthropometric data has a positive correlation with the diameter of 4 stranded hamstring autografts but no significant correlation with the length. This data can be utilised to predict the autograft diameter and may be useful for pre-operative planning and patient counseling for graft selection.

Use of Multiple Operatories in Dental Care Delivery.

DTIC Science & Technology

1982-02-01

07212 Repair Traumatic Wounds, Complex Under 5cm 2.6 07213 Repair Traumatic Wounds, Complex Over 5cm 5.3 07260 Cleft Palate Repair 10.6 07265 Cleft Lip ...Facial Prosthesis 18.5 05940 Implants 16.8 05950 Maxillary Inclined Plane or Occlusal Table 19.4 05955 Mandibular Guide Flange 16.8 05960 Palatal Lift...Passive Lingual or Palatal Wire 1.2 08446 Face Bow, J Hooks, Clinical Cup 1.2 08447 Active Lingual or Palatal Wire 1.2 08448 Multi-Stranded Wire 0.6 08510

125I Brachytherapy in Locally Advanced Nonsmall Cell Lung Cancer After Progression of Concurrent Radiochemotherapy

PubMed Central

Xiang, Zhanwang; Li, Guohong; Liu, Zhenyin; Huang, Jinhua; Zhong, Zhihui; Sun, Lin; Li, Chuanxing; Zhang, Funjun

2015-01-01

Abstract To investigate the safety and effectiveness of computed tomography (CT)-guided 125I seed implantation for locally advanced nonsmall cell lung cancer (NSCLC) after progression of concurrent radiochemotherapy (CCRT). We reviewed 78 locally advanced NSCLC patients who had each one cycle of first-line CCRT but had progressive disease identified from January 2006 to February 2015 at our institution. A total of 37 patients with 44 lesions received CT-guided percutaneous 125I seed implantation and second-line chemotherapy (group A), while 41 with 41 lesions received second-line chemotherapy (group B). Patients in group A and B received a total of 37 and 41 first cycle of CCRT treatment. The median follow-up was 19 (range 3–36) months. After the second treatment, the total response rate (RR) in tumor response accounted for 63.6% in group A, which was significantly higher than that of group B (41.5%) (P = 0.033). The median progression-free survival time (PFST) was 8.00 ± 1.09 months and 5.00 ± 0.64 months in groups A and B (P = 0.011). The 1-, 2-, and 3-year overall survival (OS) rates for group A were 56.8%, 16.2%, and 2.7%, respectively. For group B, OS rates were 36.6%, 9.8%, and 2.4%, respectively. The median OS time was 14.00 ± 1.82 months and 10.00 ± 1.37 months for groups A and B, respectively (P = 0.059). Similar toxicity reactions were found in both groups. Tumor-related clinical symptoms were significantly reduced and the patients’ quality of life was obviously improved. CT-guided 125I seed implantation proved to be potentially beneficial in treating localized advanced NSCLC; it achieved good local control rates and relieved clinical symptoms without increasing side effects. PMID:26656370

A Carbon Nanotube Reporter of miRNA Hybridization Events In Vivo

PubMed Central

Harvey, Jackson D.; Jena, Prakrit V.; Baker, Hanan A.; Zerze, Gül H.; Williams, Ryan M.; Galassi, Thomas V.; Roxbury, Daniel; Mittal, Jeetain

2017-01-01

MicroRNAs and other small oligonucleotides in biofluids are promising disease biomarkers, yet conventional assays require complex processing steps that are unsuitable for point-of-care testing or for implantable or wearable sensors. Single-walled carbon nanotubes are an ideal material for implantable sensors, owing to their emission in the near-infrared spectral region, photostability and exquisite sensitivity. Here, we report an engineered carbon-nanotube-based sensor capable of real-time optical quantification of hybridization events of microRNA and other oligonucleotides. The mechanism of the sensor arises from competitive effects between displacement of both oligonucleotide charge groups and water from the nanotube surface, which result in a solvatochromism-like response. The sensor, which allows for detection via single-molecule sensor elements and for multiplexing by using multiple nanotube chiralities, can monitor toehold-based strand-displacement events, which reverse the sensor response and regenerate the sensor complex. We also show that the sensor functions in whole urine and serum, and can non-invasively measure DNA and microRNA after implantation in live mice. PMID:28845337

A Carbon Nanotube Reporter of miRNA Hybridization Events In Vivo.

PubMed

Harvey, Jackson D; Jena, Prakrit V; Baker, Hanan A; Zerze, Gül H; Williams, Ryan M; Galassi, Thomas V; Roxbury, Daniel; Mittal, Jeetain; Heller, Daniel A

2017-01-01

MicroRNAs and other small oligonucleotides in biofluids are promising disease biomarkers, yet conventional assays require complex processing steps that are unsuitable for point-of-care testing or for implantable or wearable sensors. Single-walled carbon nanotubes are an ideal material for implantable sensors, owing to their emission in the near-infrared spectral region, photostability and exquisite sensitivity. Here, we report an engineered carbon-nanotube-based sensor capable of real-time optical quantification of hybridization events of microRNA and other oligonucleotides. The mechanism of the sensor arises from competitive effects between displacement of both oligonucleotide charge groups and water from the nanotube surface, which result in a solvatochromism-like response. The sensor, which allows for detection via single-molecule sensor elements and for multiplexing by using multiple nanotube chiralities, can monitor toehold-based strand-displacement events, which reverse the sensor response and regenerate the sensor complex. We also show that the sensor functions in whole urine and serum, and can non-invasively measure DNA and microRNA after implantation in live mice.

Implantable chemothermal brachytherapy seeds: A synergistic approach to brachytherapy using polymeric dual drug delivery and hyperthermia for malignant solid tumor ablation.

PubMed

Aguilar, Ludwig Erik; Thomas, Reju George; Moon, Myeong Ju; Jeong, Yong Yeon; Park, Chan Hee; Kim, Cheol Sang

2018-08-01

Chemothermal brachytherapy seeds have been developed using a combination of polymeric dual drug chemotherapy and alternating magnetic field induced hyperthermia. The synergistic effect of chemotherapy and hyperthermia brachytherapy has been investigated in a way that has never been performed before, with an in-depth analysis of the cancer cell inhibition property of the new system. A comprehensive in vivo study on athymic mice model with SCC7 tumor has been conducted to determine optimal arrays and specifications of the chemothermal seeds. Dual drug chemotherapy has been achieved via surface deposition of polydopamine that carries bortezomib, and also via loading an acidic pH soluble hydrogel that contains 5-Fluorouracil inside the chemothermal seed; this increases the drug loading capacity of the chemothermal seed, and creates dual drug synergism. An external alternating magnetic field has been utilized to induce hyperthermia conditions, using the inherent ferromagnetic property of the nitinol alloy used as the seed casing. The materials used in this study were fully characterized using FESEM, H 1 NMR, FT-IR, and XPS to validate their properties. This new approach to experimental cancer treatment is a pilot study that exhibits the potential of thermal brachytherapy and chemotherapy as a combined treatment modality. Copyright © 2018 Elsevier B.V. All rights reserved.

PA1b, an insecticidal protein extracted from pea seeds (Pisum sativum): 1H-2-D NMR study and molecular modeling.

PubMed

Jouvensal, Laurence; Quillien, Laurence; Ferrasson, Eric; Rahbé, Yvan; Guéguen, Jacques; Vovelle, Françoise

2003-10-21

PA1b (pea albumin 1, subunit b) is a 37-amino acid cysteine-rich plant defense protein isolated from pea seeds (Pisum sativum). It induces short-term mortality in several pests, among which the cereal weevils Sitophilus sp. (Sitophilus oryzae, Sitophilus granarius, and Sitophilus zeamais) that are a major nuisance for stored cereals, all over the world. As such, PA1b is the first genuine protein phytotoxin specifically toxic to insects, which makes it a promising tool for seed weevil damage control. We have determined the 3-D solution structure of PA1b, using 2-D homonuclear proton NMR methods and molecular modeling. The primary sequence of the protein does not share similarities with other known toxins. It includes six cysteines forming three disulfide bridges. However, because of PA1b resistance to protease cleavage, conventional methods failed to establish the connectivity pattern. Our first attempts to assign the disulfide network from NOE data alone remained unsuccessful due to the tight packing of the cysteine residues within the core of the molecule. Yet, the use of ambiguous disulfide restraints within ARIA allowed us to establish that PA1b belongs to the inhibitor cystine-knot family. It exhibits the structural features that are characteristic of the knottin fold, namely, a triple-stranded antiparallel beta-sheet with a long flexible loop connecting the first to the second strand and a series of turns. A comparison of the structural properties of PA1b with that of structurally related proteins adopting a knottin fold and exhibiting a diverse range of biological activities shows that the electrostatic and lipophilic potentials at the surface of PA1b are very close to those found for the spider toxin ACTX-Hi:OB4219, thereby suggesting activity on ion channels.

Nucleases activities during French bean leaf aging and dark-induced senescence.

PubMed

Lambert, Rocío; Quiles, Francisco Antonio; Gálvez-Valdivieso, Gregorio; Piedras, Pedro

2017-11-01

During leaf senescence resources are managed, with nutrients mobilized from older leaves to new sink tissues. The latter implies a dilemma in terms of resource utilization, the leaf senescence should increase seed quality whereas delay in senescence should improve the seed yield. Increased knowledge about nutrient recycling during leaf senescence could lead to advances in agriculture and improved seed quality. Macromolecules mobilized during leaf senescence include proteins and nucleic acids. Although nucleic acids have been less well studied than protein degradation, they are possible reservoirs of nitrogen and phosphorous. The present study investigated nuclease activities and gene expression patterns of five members of the S1/P1 family in French bean (Phaseolus vulgaris L. cv.)Page: 2 during leaf senescence. An in-gel assay was used to detect nuclease activity during natural and dark-induced senescence, with single-stranded DNA (ssDNA) used as a substrate. The results revealed two nucleases (glycoproteins), with molecular masses of 34 and 39kDa in the senescent leaves. The nuclease activities were higher at a neutral than at an acidic pH. EDTA treatment inhibited the activities of the nucleases, and the addition of zinc resulted in the recovery of these activities. Both the 34 and 39kDa nucleases were able to use RNA and double-stranded DNA (dsDNA) as substrates, although their activities were low when dsDNA was used as a substrate. In addition, two ribonucleases with molecular masses of 14 and 16kDa, both of which could only utilize RNA as a substrate, were detected in the senescent leaves. Two members of the S1/P1 family, PVN2 and PVN5, were expressed under the experimental conditions, suggesting that these two genes were involved in senescence. The nuclease activity of the glycoproteins and gene expression were similar under both natural senescence and dark-induced senescence conditions. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

WE-DE-201-12: Thermal and Dosimetric Properties of a Ferrite-Based Thermo-Brachytherapy Seed

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warrell, G; Shvydka, D; Parsai, E I

Purpose: The novel thermo-brachytherapy (TB) seed provides a simple means of adding hyperthermia to LDR prostate permanent implant brachytherapy. The high blood perfusion rate (BPR) within the prostate motivates the use of the ferrite and conductive outer layer design for the seed cores. We describe the results of computational analyses of the thermal properties of this ferrite-based TB seed in modelled patient-specific anatomy, as well as studies of the interseed and scatter (ISA) effect. Methods: The anatomies (including the thermophysical properties of the main tissue types) and seed distributions of 6 prostate patients who had been treated with LDR brachytherapymore » seeds were modelled in the finite element analysis software COMSOL, using ferrite-based TB and additional hyperthermia-only (HT-only) seeds. The resulting temperature distributions were compared to those computed for patient-specific seed distributions, but in uniform anatomy with a constant blood perfusion rate. The ISA effect was quantified in the Monte Carlo software package MCNP5. Results: Compared with temperature distributions calculated in modelled uniform tissue, temperature distributions in the patient-specific anatomy were higher and more heterogeneous. Moreover, the maximum temperature to the rectal wall was typically ∼1 °C greater for patient-specific anatomy than for uniform anatomy. The ISA effect of the TB and HT-only seeds caused a reduction in D90 similar to that found for previously-investigated NiCu-based seeds, but of a slightly smaller magnitude. Conclusion: The differences between temperature distributions computed for uniform and patient-specific anatomy for ferrite-based seeds are significant enough that heterogeneous anatomy should be considered. Both types of modelling indicate that ferrite-based seeds provide sufficiently high and uniform hyperthermia to the prostate, without excessively heating surrounding tissues. The ISA effect of these seeds is slightly less than that for the previously-presented NiCu-based seeds.« less

Tissue-engineered bone with 3-dimensionally printed β-tricalcium phosphate and polycaprolactone scaffolds and early implantation: an in vivo pilot study in a porcine mandible model.

PubMed

Konopnicki, Sandra; Sharaf, Basel; Resnick, Cory; Patenaude, Adam; Pogal-Sussman, Tracy; Hwang, Kyung-Gyun; Abukawa, Harutsugi; Troulis, Maria J

2015-05-01

Deep bone penetration into implanted scaffolds remains a challenge in tissue engineering. The purpose of this study was to evaluate bone penetration depth within 3-dimensionally (3D) printed β-tricalcium phosphate (β-TCP) and polycaprolactone (PCL) scaffolds, seeded with porcine bone marrow progenitor cells (pBMPCs), and implanted early in vivo. Scaffolds were 3D printed with 50% β-TCP and 50% PCL. The pBMPCs were harvested, isolated, expanded, and differentiated into osteoblasts. Cells were seeded into the scaffolds and constructs were incubated in a rotational oxygen-permeable bioreactor system for 14 days. Six 2- × 2-cm defects were created in each mandible (N = 2 minipigs). In total, 6 constructs were placed within defects and 6 defects were used as controls (unseeded scaffolds, n = 3; empty defects, n = 3). Eight weeks after surgery, specimens were harvested and analyzed by hematoxylin and eosin (H&E), 4',6-diamidino-2-phenylindole (DAPI), and CD31 staining. Analysis included cell counts, bone penetration, and angiogenesis at the center of the specimens. All specimens (N = 12) showed bone formation similar to native bone at the periphery. Of 6 constructs, 4 exhibited bone formation in the center. Histomorphometric analysis of the H&E-stained sections showed an average of 22.1% of bone in the center of the constructs group compared with 1.87% in the unseeded scaffolds (P < .05). The 2 remaining constructs, which did not display areas of mature bone in the center, showed massive cell penetration depth by DAPI staining, with an average of 2,109 cells/0.57 mm(2) in the center compared with 1,114 cells/0.57 mm(2) in the controls (P < .05). CD31 expression was greater in the center of the constructs compared with the unseeded scaffolds (P < .05). 3D printed β-TCP and PCL scaffolds seeded with pBMPCs and implanted early into porcine mandibular defects display good bone penetration depth. Further study with a larger sample and larger bone defects should be performed before human applications. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Hard, soft tissue and in vitro cell response to porous nickel-titanium: a biocompatibility evaluation.

PubMed

Rhalmi, S; Odin, M; Assad, M; Tabrizian, M; Rivard, C H; Yahia, L H

1999-01-01

Porous nickel-titanium (NiTi) alloys have demonstrated bone attachment as well as tissue ingrowth in the past. However, very few studies have compared porous NiTi soft and hard tissue reactions, and in vitro cell response. We therefore have evaluated the general muscle and bone reaction to porous nickel-titanium. The latter material was implanted in rabbit tibias and back muscle, and assessed after three, six and twelve weeks of implantation. Porous NiTi specimens did not cause any adverse effect regardless of both implantation site and post-surgery recovery time. Muscle tissue exhibited thin tightly adherent fibrous capsules with fibers penetrating into implant pores. We observed that attachment strength of the soft tissue to the porous implant seemed to increase with post-implantation time. Bone tissue demonstrated good healing of the osteotomy. There was bone remodeling characterized by osteoclastic and osteoblastic activity in the cortex. This general good in vivo biocompatibility with muscle and bone tissue corresponded very well with the in vitro cell culture results we obtained. Fibroblasts seeded on porous nickel-titanium sheets managed to grow into the pores and all around specimen edges showing an another interesting cytocompatibility behavior. These results indicate good biocompatibility acceptance of porous nickel-titanium and are very promising towards eventual NiTi medical device approbation.

Monte Carlo calculated doses to treatment volumes and organs at risk for permanent implant lung brachytherapy

NASA Astrophysics Data System (ADS)

Sutherland, J. G. H.; Furutani, K. M.; Thomson, R. M.

2013-10-01

Iodine-125 (125I) and Caesium-131 (131Cs) brachytherapy have been used with sublobar resection to treat stage I non-small cell lung cancer and other radionuclides, 169Yb and 103Pd, are considered for these treatments. This work investigates the dosimetry of permanent implant lung brachytherapy for a range of source energies and various implant sites in the lung. Monte Carlo calculated doses are calculated in a patient CT-derived computational phantom using the EGsnrc user-code BrachyDose. Calculations are performed for 103Pd, 125I, 131Cs seeds and 50 and 100 keV point sources for 17 implant positions. Doses to treatment volumes, ipsilateral lung, aorta, and heart are determined and compared to those determined using the TG-43 approach. Considerable variation with source energy and differences between model-based and TG-43 doses are found for both treatment volumes and organs. Doses to the heart and aorta generally increase with increasing source energy. TG-43 underestimates the dose to the heart and aorta for all implants except those nearest to these organs where the dose is overestimated. Results suggest that model-based dose calculations are crucial for selecting prescription doses, comparing clinical endpoints, and studying radiobiological effects for permanent implant lung brachytherapy.

Influence of bone marrow-derived mesenchymal stem cells pre-implantation differentiation approach on periodontal regeneration in vivo.

PubMed

Cai, Xinjie; Yang, Fang; Yan, Xiangzhen; Yang, Wanxun; Yu, Na; Oortgiesen, Daniel A W; Wang, Yining; Jansen, John A; Walboomers, X Frank

2015-04-01

The implantation of bone marrow-derived mesenchymal stem cells (MSCs) has previously been shown successful to achieve periodontal regeneration. However, the preferred pre-implantation differentiation strategy (e.g. maintenance of stemness, osteogenic or chondrogenic induction) to obtain optimal periodontal regeneration is still unknown. This in vivo study explored which differentiation approach is most suitable for periodontal regeneration. Mesenchymal stem cells were obtained from Fischer rats and seeded onto poly(lactic-co-glycolic acid)/poly(ɛ-caprolactone) electrospun scaffolds, and then pre-cultured under different in vitro conditions: (i) retention of multilineage differentiation potential; (ii) osteogenic differentiation approach; and (iii) chondrogenic differentiation approach. Subsequently, the cell-scaffold constructs were implanted into experimental periodontal defects of Fischer rats, with empty scaffolds as controls. After 6 weeks of implantation, histomorphometrical analyses were applied to evaluate the regenerated periodontal tissues. The chondrogenic differentiation approach showed regeneration of alveolar bone and ligament tissues. The retention of multilineage differentiation potential supported only ligament regeneration, while the osteogenic differentiation approach boosted alveolar bone regeneration. Chondrogenic differentiation of MSCs before implantation is a useful strategy for regeneration of alveolar bone and periodontal ligament, in the currently used rat model. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Enhancing surface properties of breast implants by using electrospun silk fibroin.

PubMed

Valencia-Lazcano, A A; Román-Doval, R; De La Cruz-Burelo, E; Millán-Casarrubias, E J; Rodríguez-Ortega, A

2017-08-24

In the present study, a new electrospun silk fibroin coating of silicone breast implants with improved biocompatibility and mechanical properties was obtained. Fibrous scaffolds were produced by electrospinning a solution containing silk fibroin, derived from Bombyx mori cocoons, and polyethylene oxide (PEO) to be used as a coating of breast implants. A randomly oriented structure of fibroin/PEO was electrospun on implants as assessed by SEM analysis, roughness measurements and ATR-FTIR spectroscopy. The scaffold showed 0.25 µm diameter fibres, 0.76 µm size superficial pores, arithmetic roughness of 0.632 ± 0.12 µm and texture aspect ratio of 0.893 ± 0.04. ATR-FTIR spectroscopy demonstrates the presence of PEO and fibroin in the coating. The mechanical characterisation of the implants before and after being coated with fibroin/PEO demonstrated that the fibroin/PEO scaffold contributes to the increase in the elastic modulus from 0.392 ± 0.02 to 0.560 ± 0.03 MPa and to a more elastic behaviour of the breast implants. Using the fibroin/PEO coating, human fibroblasts seeded on this matrix increased viability up to 30% compared to conventional breast implants. Electrospun silk fibroin could represent a clinically compatible, viable form to coat breast implants. Low cytotoxicity by the fibroin coating and its physico-chemical and mechanical properties may find application in improving breast implants biocompatibility. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

Optimization of L(+)-Lactic Acid Fermentation Without Neutralisation of Rhizopus Oryzae Mutant RK02 by Low-Energy Ion Implantation

NASA Astrophysics Data System (ADS)

Li, Wen; Wang, Tao; Yang, Yingge; Liu, Dan; Fan, Yonghong; Wang, Dongmei; Yang, Qian; Yao, Jianming; Zheng, Zhiming; Yu, Zengliang

2008-04-01

In order to get an industrial strain which can yield a high concentration of lactic acid for ISPR (in situ product removal), the original strain Rhizopus oryzae RE3303 was mutated by low-energy ion beam implantation. A mutant RK02 was screened, and the factors such as the substrate concentration, nitrogen source concentration, inoculum size, seed age, aeration and temperature that affect the production of lactic acid were studied in detail. Under optimal conditions, the maximum concentration of L(+)-lactic acid reached 34.85 g/L after 30 h shake-flask cultivation without adding any neutralisation (5% Glucose added), which was a 146% increase in lactic acid production after ion implantation compared with the original strain. It was also shown that RK02 can be used in ISPR to reduce the number of times of separation.

In vivo performance of an acellular disc-like angle ply structure (DAPS) for total disc replacement in a small animal model.

PubMed

Martin, John T; Kim, Dong Hwa; Milby, Andrew H; Pfeifer, Christian G; Smith, Lachlan J; Elliott, Dawn M; Smith, Harvey E; Mauck, Robert L

2017-01-01

Total intervertebral disc replacement with a biologic engineered disc may be an alternative to spinal fusion for treating end-stage disc disease. In previous work, we developed disc-like angle ply structures (DAPS) that replicate the structure and function of the native disc and a rat tail model to evaluate DAPS in vivo. Here, we evaluated a strategy in which, after in vivo implantation, endogenous cells could colonize the acellular DAPS and form an extracellular matrix organized by the DAPS topographical template. To do so, acellular DAPS were implanted into the caudal spines of rats and evaluated over 12 weeks by mechanical testing, histology, and microcomputed tomography. An external fixation device was used to stabilize the implant site and various control groups were included to evaluate the effect of immobilization. There was robust tissue formation within the DAPS after implantation and compressive mechanical properties of the implant matched that of the native motion segment. Immobilization provided a stable site for fibrous tissue formation after either a discectomy or a DAPS implantation, but bony fusion eventually resulted, with segments showing intervertebral bridging after long-term implantation, a process that was accelerated by the implanted DAPS. Thus, while compressive mechanical properties were replicated after DAPS implantation, methods to actively prevent fusion must be developed. Future work will focus on limiting fusion by remobilizing the motion segment after a period of integration, delivering pro-chondrogenic factors, and pre-seeding DAPS with cells prior to implantation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:23-31, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Understanding the effect of locked nucleic acid and 2'-O-methyl modification on the hybridization thermodynamics of a miRNA-mRNA pair in the presence and absence of AfPiwi protein.

PubMed

Kumar, Santosh; Mapa, Koyeli; Maiti, Souvik

2014-03-18

miRNAs are some of the key epigenetic regulators of gene expression. They act through hybridization with their target mRNA and modulate the level of respective proteins via different mechanisms. Various cancer conditions are known to be associated with up- and downregulation of the oncogenic and tumor suppressor miRNAs, respectively. The levels of aberrantly expressed oncogenic miRNAs can be downregulated in different ways. Similarly, restoration of tumor suppressor miRNAs to their normal levels can be achieved using miRNA mimics. However, the use of miRNA mimics is limited by their reduced biostability and function. We have studied the hybridization thermodynamics of the miRNA 26a (11-mer, including the seed sequence) guide strand with the mRNA (11-mer) target strand in the absence and presence of AfPiwi protein. We have also inserted locked nucleic acids (LNAs) and 2'-O-methyl-modified nucleotides into the guide strand, in a walk-through manner, to assess their effect on the binding efficiency between guide and target RNA. Insertion of LNA and 2'-O-methyl-modified nucleotides into the guide strand helped to strengthen the binding affinity irrespective of the position of insertion. However, in the presence of AfPiwi protein, these modifications reduced the binding affinity to different extents depending on the position of insertion. Insertion of a modification leads to an increase in the enthalpic contribution with an increased unfavorable entropic contribution, which negatively compensates for the higher favorable enthalpy.

WE-A-17A-09: Exploiting Electromagnetic Technologies for Real-Time Seed Drop Position Validation in Permanent Implant Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Racine, E; Hautvast, G; Binnekamp, D

Purpose: To report on preliminary results validating the performance of a specially designed LDR brachytherapy needle prototype possessing both electromagnetic (EM) tracking and seed drop detection abilities. Methods: An EM hollow needle prototype has been designed and constructed in collaboration with research partner Philips Healthcare. The needle possesses conventional 3D tracking capabilities, along with a novel seed drop detection mechanism exploiting local changes of electromagnetic properties generated by the passage of seeds in the needle's embedded sensor coils. These two capabilities are exploited by proprietary engineering and signal processing techniques to generate seed drop position estimates in real-time treatment delivery.more » The electromagnetic tracking system (EMTS) used for the experiment is the NDI Aurora Planar Field Generator. The experiment consisted of dropping a total of 35 seeds in a prismatic agarose phantom, and comparing the 3D seed drop positions of the EMTS to those obtained by an image analysis of subsequent micro-CT scans. Drop position error computations and statistical analysis were performed after a 3D registration of the two seed distributions. Results: Of the 35 seeds dropped in the phantom, 32 were properly detected by the needle prototype. Absolute drop position errors among the detected seeds ranged from 0.5 to 4.8 mm with mean and standard deviation values of 1.6 and 0.9 mm, respectively. Error measurements also include undesirable and uncontrollable effects such as seed motion upon deposition. The true accuracy performance of the needle prototype is therefore underestimated. Conclusion: This preliminary study demonstrates the potential benefits of EM technologies in detecting the passage of seeds in a hollow needle as a means of generating drop position estimates in real-time treatment delivery. Such tools could therefore represent a potentially interesting addition to existing brachytherapy protocols for rapid dosimetry validation. Equipments and fundings for this project were provided by Philips Medical.« less

Rectourethral fistula following LDR brachytherapy.

PubMed

Borchers, Holger; Pinkawa, Michael; Donner, Andreas; Wolter, Timm P; Pallua, Norbert; Eble, Michael J; Jakse, Gerhard

2009-01-01

Modern LDR brachytherapy has drastically reduced rectal toxicity and decreased the occurrence of rectourethral fistulas to <0.5% of patients. Therefore, symptoms of late-onset sequelae are often ignored initially. These fistulas cause severe patient morbidity and require interdisciplinary treatment. We report on the occurrence and management of a rectourethral fistula which occurred 4 years after (125)I seed implantation. Copyright 2009 S. Karger AG, Basel.

An NTCP Analysis of Urethral Complications from Low Doserate Mono- and Bi-Radionuclide Brachytherapy.

PubMed

Nuttens, V E; Nahum, A E; Lucas, S

2011-01-01

Urethral NTCP has been determined for three prostates implanted with seeds based on (125)I (145 Gy), (103)Pd (125 Gy), (131)Cs (115 Gy), (103)Pd-(125)I (145 Gy), or (103)Pd-(131)Cs (115 Gy or 130 Gy). First, DU(20), meaning that 20% of the urhral volume receive a dose of at least DU(20), is converted into an I-125 LDR equivalent DU(20) in order to use the urethral NTCP model. Second, the propagation of uncertainties through the steps in the NTCP calculation was assessed in order to identify the parameters responsible for large data uncertainties. Two sets of radiobiological parameters were studied. The NTCP results all fall in the 19%-23% range and are associated with large uncertainties, making the comparison difficult. Depending on the dataset chosen, the ranking of NTCP values among the six seed implants studied changes. Moreover, the large uncertainties on the fitting parameters of the urethral NTCP model result in large uncertainty on the NTCP value. In conclusion, the use of NTCP model for permanent brachytherapy is feasible but it is essential that the uncertainties on the parameters in the model be reduced.

[Reconstruction of penile function with tissue engineering techniques].

PubMed

Song, Lu-jie; Pan, Lian-jun; Xu, Yue-min

2007-04-01

Tissue engineering techniques, with their potential applied value for penile reconstruction, are of special interest for andrologists. The purpose of this review is to appraise the recent development and publications in this field. In the past few years, great efforts have been made to develop corpus cavernosum tissues by combining smooth muscle and endothelial cells seeded on biodegradable polyglycolic acid polymer (PGA) or acellular corporal collagen matrices scaffolds. Animal experiment demonstrated that the engineered corpus cavernosum achieved adequate structural and functional parameters. Engineered cartilage rods as an alternative for the current clinical standard of semirigid or inflatable penile implants could be created by seeding chondrocyte cylindrical PGA. A series of studies showed that, compared to commercially available silicone implants, the engineered rods were flexible, elastic and stable. Besides, a variety of decellularized biological materials have been used as grafts not only for substitution of tunica albuginea but also for penile enhancement, with promising results. For treating erectile dysfunction, a new approach to recovering erectile function by cell-based therapy could be the injection of functional cells into corpus cavernosum, which seemed to be promising when combined with cell manipulation by gene therapy prior to cell transfer.

Poster - Thur Eve - 06: Comparison of an open source genetic algorithm to the commercially used IPSA for generation of seed distributions in LDR prostate brachytherapy.

PubMed

McGeachy, P; Khan, R

2012-07-01

In early stage prostate cancer, low dose rate (LDR) prostate brachytherapy is a favorable treatment modality, where small radioactive seeds are permanently implanted throughout the prostate. Treatment centres currently rely on a commercial optimization algorithm, IPSA, to generate seed distributions for treatment plans. However, commercial software does not allow the user access to the source code, thus reducing the flexibility for treatment planning and impeding any implementation of new and, perhaps, improved clinical techniques. An open source genetic algorithm (GA) has been encoded in MATLAB to generate seed distributions for a simplified prostate and urethra model. To assess the quality of the seed distributions created by the GA, both the GA and IPSA were used to generate seed distributions for two clinically relevant scenarios and the quality of the GA distributions relative to IPSA distributions and clinically accepted standards for seed distributions was investigated. The first clinically relevant scenario involved generating seed distributions for three different prostate volumes (19.2 cc, 32.4 cc, and 54.7 cc). The second scenario involved generating distributions for three separate seed activities (0.397 mCi, 0.455 mCi, and 0.5 mCi). Both GA and IPSA met the clinically accepted criteria for the two scenarios, where distributions produced by the GA were comparable to IPSA in terms of full coverage of the prostate by the prescribed dose, and minimized dose to the urethra, which passed straight through the prostate. Further, the GA offered improved reduction of high dose regions (i.e hot spots) within the planned target volume. © 2012 American Association of Physicists in Medicine.

Grave fraudulence in medical device research: a narrative review of the PIN seeding study for the Pinnacle hip system.

PubMed

Steffen, Joan E; Fassler, Ella A; Reardon, Kevin J; Egilman, David S

2018-01-01

In 2001, DePuy, a wholly-owned subsidiary of Johnson & Johnson (J&J/DePuy), initiated a seeding study called the "Multi-center, Prospective, Clinical Evaluation of Pinnacle Acetabular Implants in Total Hip Arthroplasty" (PIN Study). J&J/DePuy designed this study to develop new business opportunities during the launch of their Pinnacle Hip System (PHS) and generate survivorship data for marketing. This article, the first review of a seeding trial for a medical device, examines internal company documents relating to the PIN Study; the analysis herein focuses on the integrity of J&J/DePuy's research practices in conception, implementation, and analysis. J&J/DePuy violated the study protocol and manipulated data; consented participants in violation of standards protecting human subjects; and did not secure Institutional Review Board approval for all study sites. J&J/DePuy used PIN Study results as the "fundamental selling point" for the PHS. Medical device seeding trials are distinct from previously-documented pharmaceutical seeding trials because companies can profit directly from device sales and because these studies may be the first clinical evaluation of the device (as was the case for the PIN Study). Seeding trials are malleable marketing projects, not rigorous scientific studies. Regulatory bodies, physicians, and others should be vigilant for persuasive marketing accounts disguised as science.

Synergistic effects of micropatterned biodegradable conduits and Schwann cells on sciatic nerve regeneration

NASA Astrophysics Data System (ADS)

Rutkowski, Gregory E.; Miller, Cheryl A.; Jeftinija, Srdija; Mallapragada, Surya K.

2004-09-01

This paper describes a novel biodegradable conduit that provides a combination of physical, chemical and biological cues at the cellular level to facilitate peripheral nerve regeneration. The conduit consists of a porous poly(D,L-lactic acid) (PDLLA) tubular support structure with a micropatterned inner lumen. Schwann cells were pre-seeded into the lumen to provide additional trophic support. Conduits with micropatterned inner lumens pre-seeded with Schwann cells (MS) were fabricated and compared with three types of conduits used as controls: M (conduits with micropatterned inner lumens without pre-seeded Schwann cells), NS (conduits without micropatterned inner lumens pre-seeded with Schwann cells) and N (conduits without micropatterned inner lumens, without pre-seeded Schwann cells). The conduits were implanted in rats with 1 cm sciatic nerve transections and the regeneration and functional recovery were compared in the four different cases. The number or size of regenerated axons did not vary significantly among the different conduits. The time of recovery, and the sciatic function index, however, were significantly enhanced using the MS conduits, based on qualitative observations as well as quantitative measurements using walking track analysis. This demonstrates that biodegradable micropatterned conduits pre-seeded with Schwann cells that provide a combination of physical, chemical and biological guidance cues for regenerating axons at the cellular level offer a better alternative for repairing sciatic nerve transactions than conventional biodegradable conduits.

Evaluation of the effect of prostate volume change on tumor control probability in LDR brachytherapy.

PubMed

Knaup, Courtney; Mavroidis, Panayiotis; Stathakis, Sotirios; Smith, Mark; Swanson, Gregory; Papanikolaou, Niko

2011-09-01

This study evaluates low dose-rate brachytherapy (LDR) prostate plans to determine the biological effect of dose degradation due to prostate volume changes. In this study, 39 patients were evaluated. Pre-implant prostate volume was determined using ultrasound. These images were used with the treatment planning system (Nucletron Spot Pro 3.1(®)) to create treatment plans using (103)Pd seeds. Following the implant, patients were imaged using CT for post-implant dosimetry. From the pre and post-implant DVHs, the biologically equivalent dose and the tumor control probability (TCP) were determined using the biologically effective uniform dose. The model used RBE = 1.75 and α/β = 2 Gy. The prostate volume changed between pre and post implant image sets ranged from -8% to 110%. TCP and the mean dose were reduced up to 21% and 56%, respectively. TCP is observed to decrease as the mean dose decreases to the prostate. The post-implant tumor dose was generally observed to decrease, compared to the planned dose. A critical uniform dose of 130 Gy was established. Below this dose, TCP begins to fall-off. It was also determined that patients with a small prostates were more likely to suffer TCP decrease. The biological effect of post operative prostate growth due to operative trauma in LDR was evaluated using the concept. The post-implant dose was lower than the planned dose due to an increase of prostate volume post-implant. A critical uniform dose of 130 Gy was determined, below which TCP begun to decline.

Deuterium permeation behaviors in tungsten implanted with nitrogen

NASA Astrophysics Data System (ADS)

Liang, Chuan-hui; Wang, Dongping; Jin, Wei; Lou, Yuanfu; Wang, Wei; Ye, Xiaoqiu; Chen, Chang-an; Liu, Kezhao; Xu, Haiyan; Wang, Xiaoying; Kleyn, Aart W.

2018-07-01

Surface modification of tungsten due to the cooling species nitrogen seeded in the divertor region, i.e., by nitrogen ion implantation or re-deposition, is considered to affect the permeation behavior of H isotopes. This work focuses on the effect of nitrogen ion implantation into tungsten (W-N) on the deuterium gas-driven permeation behavior. For comparison, both permeation in tungsten implanted with W ion (W-W) and without implantation (pristine W) are studied. These three samples were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photo-electron spectroscopy (XPS). The SEM results revealed that the W-W sample has various voids on the surface, and the W-N sample has a rough surface with pretty fine microstructures. These are different from the pristine W sample with a smooth and compact surface. The XRD patterns show the disappearance of crystallinity on both W-W and W-N sample surfaces. It indicates that the ion implantation process results in an almost complete conversion from crystalline to amorphous in the sample surfaces. The sputter-depth profiling XPS spectra show that the implanted nitrogen prefers to form a 140 nm thick tungsten nitride layer. In permeation experiments, it was found that the D permeability is temperature dependent. Interestingly, the W-N sample presented a lower D permeability than the W-W sample, but higher than the pristine W sample. Such behavior implies that tungsten nitride acts as a permeation barrier, while defects created by ions implantation can promote permeability. The possible permeation mechanism correlated with sample surface composition and microstructure is consequently discussed in this work.

The Recent Revolution in the Design and Manufacture of Cranial Implants: Modern Advancements and Future Directions

PubMed Central

Bonda, David J.; Manjila, Sunil; Selman, Warren R.; Dean, David

2015-01-01

Large format (i.e., > 25 cm2) cranioplasty is a challenging procedure not only from a cosmesis standpoint, but also in terms of ensuring that the patient's brain will be well-protected from direct trauma. Until recently, when a patient's own cranial flap was unavailable, these goals were unattainable. Recent advances in implant Computer Aided Design and 3-D printing are leveraging other advances in regenerative medicine. It is now possible to 3-D-print patient-specific implants from a variety of polymer, ceramic, or metal components. A skull template may be used to design the external shape of an implant that will become well integrated in the skull, while also providing beneficial distribution of mechanical force distribution in the event of trauma. Furthermore, an internal pore geometry can be utilized to facilitate the seeding of banked allograft cells. Implants may be cultured in a bioreactor along with recombinant growth factors to produce implants coated with bone progenitor cells and extracellular matrix that appear to the body as a graft, albeit a tissue-engineered graft. The growth factors would be left behind in the bioreactor and the graft would resorb as new host bone invades the space and is remodeled into strong bone. As we describe in this review, such advancements will lead to optimal replacement of cranial defects that are both patient-specific and regenerative. PMID:26171578

An in vitro verification of strength estimation for moving an 125I source during implantation in brachytherapy.

PubMed

Tanaka, Kenichi; Kajimoto, Tsuyoshi; Hayashi, Takahiro; Asanuma, Osamu; Hori, Masakazu; Kamo, Ken-Ichi; Sumida, Iori; Takahashi, Yutaka; Tateoka, Kunihiko; Bengua, Gerard; Sakata, Koh-Ichi; Endo, Satoru

2018-04-11

This study aims to demonstrate the feasibility of a method for estimating the strength of a moving brachytherapy source during implantation in a patient. Experiments were performed under the same conditions as in the actual treatment, except for one point that the source was not implanted into a patient. The brachytherapy source selected for this study was 125I with an air kerma strength of 0.332 U (μGym2h-1), and the detector used was a plastic scintillator with dimensions of 10 cm × 5 cm × 5 cm. A calibration factor to convert the counting rate of the detector to the source strength was measured and then the accuracy of the proposed method was investigated for a manually driven source. The accuracy was found to be under 10% when the shielding effect of additional needles for implantation at other positions was corrected, and about 30% when the shielding was not corrected. Even without shielding correction, the proposed method can detect dead/dropped source, implantation of a source with the wrong strength, and a mistake in the number of the sources implanted. Furthermore, when the correction was applied, the achieved accuracy came close to within 7% required to find the Oncoseed 6711 (125I seed with unintended strength among the commercially supplied values of 0.392, 0.462 and 0.533 U).

Corrosion analysis of NiCu and PdCo thermal seed alloys used as interstitial hyperthermia implants.

PubMed

Paulus, J A; Parida, G R; Tucker, R D; Park, J B

1997-12-01

Ferromagnetic materials with low Curie temperatures are being investigated for use as interstitial implants for fractionated hyperthermia treatment of prostatic disease. Previous investigations of the system have utilized alloys, such as NiCu, with inadequate corrosion resistance, requiring the use of catheters for removal of the implants following treatment or inert surface coatings which may interfere with thermal characteristics of the implants. We are evaluating a palladium-cobalt (PdCo) binary alloy which is very similar to high palladium alloys used in dentistry. Electrochemical corrosion tests and immersion tests at 37 degrees C for both NiCu and PdCo alloy samples in mammalian Ringer's solution were performed. Long-term corrosion rates are 5.8 x 10(-5) microm per year (NiCu) and 7.7 x 10(-8) microm per year (PdCo) from average immersion test results, indicating higher corrosion resistance of PdCo (P < 0.02); immersion corrosion rates were much lower than initial corrosion rates found electrochemically. Both alloys had significantly lower corrosion rates than standard surgical implant rates of 0.04 microm per year (P < 0.001 for both alloys). Scanning electron microscopy illustrates changes in the NiCu alloy surface due to pitting corrosion; no difference is observed for PdCo. The data indicate that the PdCo alloy may be suitable as a long-term implant for use in fractionated hyperthermia.

Chitosan inhibits platelet-mediated clot retraction, increases platelet-derived growth factor release, and increases residence time and bioactivity of platelet-rich plasma in vivo.

PubMed

Deprés-Tremblay, Gabrielle; Chevrier, Anik; Tran-Khanh, Nicolas; Nelea, Monica; Buschmann, Michael D

2017-11-10

Platelet-rich plasma (PRP) has been used to treat different orthopedic conditions, however, the clinical benefits of using PRP remain uncertain. Chitosan (CS)-PRP implants have been shown to improve meniscus, rotator cuff and cartilage repair in pre-clinical models. The purpose of this current study was to investigate in vitro and in vivo mechanisms of action of CS-PRP implants. Freeze-dried formulations containing 1% (w/v) CS (80% degree of deacetylation and number average molar mass 38 kDa), 1% (w/v) trehalose as a lyoprotectant and 42.2 mM calcium chloride as a clot activator were solubilized in PRP. Gravimetric measurements and molecular/cellular imaging studies revealed that clot retraction is inhibited in CS-PRP hybrid clots through physical coating of platelets, blood cells and fibrin strands by chitosan, which interferes with platelet aggregation and platelet-mediated clot retraction. Flow cytometry and ELISA assays revealed that platelets are activated and granules secreted in CS-PRP hybrid clots and that cumulative release of platelet-derived growth factor (PDGF-AB) and epidermal growth factor is higher from CS-PRP hybrid clots compared to PRP clots in vitro. Finally, CS-PRP implants resided for up to 6 weeks in a subcutaneous implantation model and induced cell recruitment and granulation tissue synthesis, confirming greater residency and bioactivity compared to PRP in vivo.

Bioreactor culture duration of engineered constructs influences bone formation by mesenchymal stem cells.

PubMed

Mitra, Debika; Whitehead, Jacklyn; Yasui, Osamu W; Leach, J Kent

2017-11-01

Perfusion culture of mesenchymal stem cells (MSCs) seeded in biomaterial scaffolds provides nutrients for cell survival, enhances extracellular matrix deposition, and increases osteogenic cell differentiation. However, there is no consensus on the appropriate perfusion duration of cellular constructs in vitro to boost their bone forming capacity in vivo. We investigated this phenomenon by culturing human MSCs in macroporous composite scaffolds in a direct perfusion bioreactor and compared their response to scaffolds in continuous dynamic culture conditions on an XYZ shaker. Cell seeding in continuous perfusion bioreactors resulted in more uniform MSC distribution than static seeding. We observed similar calcium deposition in all composite scaffolds over 21 days of bioreactor culture, regardless of pore size. Compared to scaffolds in dynamic culture, perfused scaffolds exhibited increased DNA content and expression of osteogenic markers up to 14 days in culture that plateaued thereafter. We then evaluated the effect of perfusion culture duration on bone formation when MSC-seeded scaffolds were implanted in a murine ectopic site. Human MSCs persisted in all scaffolds at 2 weeks in vivo, and we observed increased neovascularization in constructs cultured under perfusion for 7 days relative to those cultured for 1 day within each gender. At 8 weeks post-implantation, we observed greater bone volume fraction, bone mineral density, tissue ingrowth, collagen density, and osteoblastic markers in bioreactor constructs cultured for 14 days compared to those cultured for 1 or 7 days, and acellular constructs. Taken together, these data demonstrate that culturing MSCs under perfusion culture for at least 14 days in vitro improves the quantity and quality of bone formation in vivo. This study highlights the need for optimizing in vitro bioreactor culture duration of engineered constructs to achieve the desired level of bone formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intra-operative 3D guidance and edema detection in prostate brachytherapy using a non-isocentric C-arm

PubMed Central

Jain, A.; Deguet, A.; Iordachita, I.; Chintalapani, G.; Vikal, S.; Blevins, J.; Le, Y.; Armour, E.; Burdette, C.; Song, D.; Fichtinger, G.

2015-01-01

Purpose Brachytherapy (radioactive seed insertion) has emerged as one of the most effective treatment options for patients with prostate cancer, with the added benefit of a convenient outpatient procedure. The main limitation in contemporary brachytherapy is faulty seed placement, predominantly due to the presence of intra-operative edema (tissue expansion). Though currently not available, the capability to intra-operatively monitor the seed distribution, can make a significant improvement in cancer control. We present such a system here. Methods Intra-operative measurement of edema in prostate brachytherapy requires localization of inserted radioactive seeds relative to the prostate. Seeds were reconstructed using a typical non-isocentric C-arm, and exported to a commercial brachytherapy treatment planning system. Technical obstacles for 3D reconstruction on a non-isocentric C-arm include pose-dependent C-arm calibration; distortion correction; pose estimation of C-arm images; seed reconstruction; and C-arm to TRUS registration. Results In precision-machined hard phantoms with 40–100 seeds and soft tissue phantoms with 45–87 seeds, we correctly reconstructed the seed implant shape with an average 3D precision of 0.35 mm and 0.24 mm, respectively. In a DoD Phase-1 clinical trial on six patients with 48–82 planned seeds, we achieved intra-operative monitoring of seed distribution and dosimetry, correcting for dose inhomogeneities by inserting an average of over four additional seeds in the six enrolled patients (minimum 1; maximum 9). Additionally, in each patient, the system automatically detected intra-operative seed migration induced due to edema (mean 3.84 mm, STD 2.13 mm, Max 16.19 mm). Conclusions The proposed system is the first of a kind that makes intra-operative detection of edema (and subsequent re-optimization) possible on any typical non-isocentric C-arm, at negligible additional cost to the existing clinical installation. It achieves a significantly more homogeneous seed distribution, and has the potential to affect a paradigm shift in clinical practice. Large scale studies and commercialization are currently underway. PMID:21168357

A feasibility study for in vitro evaluation of fixation between prosthesis and bone with bone marrow-derived mesenchymal stem cells.

PubMed

Morita, Yusuke; Yamasaki, Kenichi; Hattori, Koji

2010-10-01

It is difficult to quantitatively evaluate adhesive strength between an implant and the neighboring bone using animal experiments, because the degree of fixation of an implant depends on differences between individuals and the clearance between the material and the bone resulting from surgical technique. A system was designed in which rat bone marrow cells were used to quantitatively evaluate the adhesion between titanium alloy plates and bone plates in vitro. Three kinds of surface treatment were used: a sand-blasted surface, a titanium-sprayed surface and a titanium-sprayed surface coated with hydroxyapatite. Bone marrow cells obtained from rat femora were seeded on the titanium alloy plates, and the cells were cultured between the titanium alloy plates and the bone plates sliced from porcine ilium for 2 weeks. After cultivation, adhesive strength was measured using a tensile test, after which DNA amount and Alkaline phosphatase activity were measured. The seeded cells accelerated adhesion of the titanium alloy plate to the bone plate. Adhesive strength of the titanium-sprayed surface was lower than that of the sand-blasted surface because of lower initial contact area, although there was no difference in Alkaline phosphatase activity between two surface treatments. A hydroxyapatite coating enhanced adhesive strength between the titanium alloy palate and the bone plate, as well as enhancing osteogenic differentiation of bone marrow cells. It is believed that this novel experimental method can be used to simultaneously evaluate the osteogenic differentiation and the adhesive strength of an implant during in vitro cultivation. 2010 Elsevier Ltd. All rights reserved.

An allogenic cell-based implant for meniscal lesions.

PubMed

Weinand, Christian; Peretti, Giuseppe M; Adams, Samuel B; Bonassar, Lawrence J; Randolph, Mark A; Gill, Thomas J

2006-11-01

Meniscal tears in the avascular zones do not heal. Although tissue-engineering approaches using cells seeded onto scaffolds could expand the indication for meniscal repair, harvesting autologous cells could cause additional trauma to the patient. Allogenic cells, however, could provide an unlimited amount of cells. Allogenic cells from 2 anatomical sources can repair lesions in the avascular region of the meniscus. Controlled laboratory study. Both autologous and allogenic chondrocytes were seeded onto a Vicryl mesh scaffold and sutured into a bucket-handle lesion created in the medial menisci of 17 swine. Controls consisted of 3 swine knees treated with unseeded implants and controls from a previous experiment in which 4 swine were treated with suture only and 4 with no treatment. Menisci were harvested after 12 weeks and evaluated histologically for new tissue and percentage of interface healing surface; they were also evaluated statistically. The lesions were closed in 15 of 17 menisci. None of the control samples demonstrated healing. Histologic analysis of sequential cuts through the lesion showed formation of new scar-like tissue in all experimental samples. One of 8 menisci was completely healed in the allogenic group and 2 of 9 in the autologous group; the remaining samples were partially healed in both groups. No statistically significant differences in the percentage of healing were observed between the autologous and allogenic cell-based implants. Use of autologous and allogenic chondrocytes delivered via a biodegradable mesh enhanced healing of avascular meniscal lesions. This study demonstrates the potential of a tissue-engineered cellular repair of the meniscus using autologous and allogenic chondrocytes.

Development of virtual patient models for permanent implant brachytherapy Monte Carlo dose calculations: interdependence of CT image artifact mitigation and tissue assignment.

PubMed

Miksys, N; Xu, C; Beaulieu, L; Thomson, R M

2015-08-07

This work investigates and compares CT image metallic artifact reduction (MAR) methods and tissue assignment schemes (TAS) for the development of virtual patient models for permanent implant brachytherapy Monte Carlo (MC) dose calculations. Four MAR techniques are investigated to mitigate seed artifacts from post-implant CT images of a homogeneous phantom and eight prostate patients: a raw sinogram approach using the original CT scanner data and three methods (simple threshold replacement (STR), 3D median filter, and virtual sinogram) requiring only the reconstructed CT image. Virtual patient models are developed using six TAS ranging from the AAPM-ESTRO-ABG TG-186 basic approach of assigning uniform density tissues (resulting in a model not dependent on MAR) to more complex models assigning prostate, calcification, and mixtures of prostate and calcification using CT-derived densities. The EGSnrc user-code BrachyDose is employed to calculate dose distributions. All four MAR methods eliminate bright seed spot artifacts, and the image-based methods provide comparable mitigation of artifacts compared with the raw sinogram approach. However, each MAR technique has limitations: STR is unable to mitigate low CT number artifacts, the median filter blurs the image which challenges the preservation of tissue heterogeneities, and both sinogram approaches introduce new streaks. Large local dose differences are generally due to differences in voxel tissue-type rather than mass density. The largest differences in target dose metrics (D90, V100, V150), over 50% lower compared to the other models, are when uncorrected CT images are used with TAS that consider calcifications. Metrics found using models which include calcifications are generally a few percent lower than prostate-only models. Generally, metrics from any MAR method and any TAS which considers calcifications agree within 6%. Overall, the studied MAR methods and TAS show promise for further retrospective MC dose calculation studies for various permanent implant brachytherapy treatments.

The junction between hyaline cartilage and engineered cartilage in rabbits.

PubMed

Komura, Makoto; Komura, Hiroko; Otani, Yushi; Kanamori, Yutaka; Iwanaka, Tadashi; Hoshi, Kazuto; Tsuyoshi, Takato; Tabata, Yasuhiko

2013-06-01

Tracheoplasty using costal cartilage grafts to enlarge the tracheal lumen was performed to treat congenital tracheal stenosis. Fibrotic granulomatous tissue was observed at the edge of grafted costal cartilage. We investigated the junction between the native hyaline cartilage and the engineered cartilage plates that were generated by auricular chondrocytes for fabricating the airway. Controlled, prospecive study. In group 1, costal cartilage from New Zealand white rabbits was collected and implanted into a space created in the cervical trachea. In group 2, chondrocytes from auricular cartilages were seeded on absorbable scaffolds. These constructs were implanted in the subcutaneous space. Engineered cartilage plates were then implanted into the trachea after 3 weeks of implantation of the constructs. The grafts in group 1 and 2 were retrieved after 4 weeks. In group 1, histological studies of the junction between the native hyaline cartilage and the implanted costal cartilage demonstrated chondrogenic tissue in four anastomoses sides out of the 10 examined. In group 2, the junction between the native trachea and the engineered cartilage showed neocartilage tissue in nine anastomoses sides out of 10. Engineered cartilage may be beneficial for engineered airways, based on the findings of the junction between the native and engineered grafts. Copyright © 2012 The American Laryngological, Rhinological and Otological Society, Inc.

A novel imaging approach for prostate cancer is tested in new clinical trial | Center for Cancer Research

Cancer.gov

Prostate cancer patients who have failed standard radiation therapy have the options of surgery, radioactive seed implantation or cryoablation. Deborah Citrin, M.D., of the Radiation Oncology Branch is leading a study of stereotactic body radiation therapy (SBRT) to treat prostate cancer that has recurred locally after standard radiation therapy. The goal of this study is to

Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer.

PubMed

Yang, Ruijie; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang

2016-01-01

To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D90 of 34Gy in 8.5Gy per fraction, and 145Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2Gy per fraction, EQD2) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The Dmean (EQD2) of rectum decreased 22.36Gy in HDR and 17.01Gy in LDR from 30.24Gy in VMAT, respectively. The Dmean (EQD2) of bladder decreased 6.91Gy in HDR and 2.53Gy in LDR from 13.46Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD2) was 80.26, 70.23, and 104.91Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Ruijie, E-mail: ruijyang@yahoo.com; Zhao, Nan; Liao, Anyan

To investigate the dosimetric and radiobiological differences among volumetric modulated arc therapy (VMAT), high-dose rate (HDR) brachytherapy, and low-dose rate (LDR) permanent seeds implant for localized prostate cancer. A total of 10 patients with localized prostate cancer were selected for this study. VMAT, HDR brachytherapy, and LDR permanent seeds implant plans were created for each patient. For VMAT, planning target volume (PTV) was defined as the clinical target volume plus a margin of 5 mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78 Gy in 39 fractions were prescribed for PTV. For HDR andmore » LDR plans, the dose prescription was D{sub 90} of 34 Gy in 8.5 Gy per fraction, and 145 Gy to clinical target volume, respectively. The dose and dose volume parameters were evaluated for target, organs at risk, and normal tissue. Physical dose was converted to dose based on 2-Gy fractions (equivalent dose in 2 Gy per fraction, EQD{sub 2}) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The D{sub mean} (EQD{sub 2}) of rectum decreased 22.36 Gy in HDR and 17.01 Gy in LDR from 30.24 Gy in VMAT, respectively. The D{sub mean} (EQD{sub 2}) of bladder decreased 6.91 Gy in HDR and 2.53 Gy in LDR from 13.46 Gy in VMAT. For the femoral heads and normal tissue, the mean doses were also significantly reduced in both HDR and LDR compared with VMAT. For the urethra, the mean dose (EQD{sub 2}) was 80.26, 70.23, and 104.91 Gy in VMAT, HDR, and LDR brachytherapy, respectively. For localized prostate cancer, both HDR and LDR brachytherapy were clearly superior in the sparing of rectum, bladder, femoral heads, and normal tissue compared with VMAT. HDR provided the advantage in sparing of urethra compared with VMAT and LDR.« less

SU-E-J-232: Feasibility of MRI-Based Preplan On Low Dose Rate Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Y; Tward, J; Rassiah-Szegedi, P

Purpose: To investigate the feasibility of using MRI-based preplan for low dose rate prostate brachytherapy. Methods: 12 patients who received transrectal ultrasound (TRUS) guided prostate brachytherapy with Pd-103 were retrospectively studied. Our care-standard of the TRUS-based preplan served as the control. One or more prostate T2-weighted wide and/or narrow-field of view MRIs obtained within the 3 months prior to the implant were imported into the MIM Symphony software v6.3 (MIM Software Inc., Cleveland, OH) for each patient. In total, 37 MRI preplans (10 different image sequences with average thickness of 4.8mm) were generated. The contoured prostate volume and the seedmore » counts required to achieve adequate dosimetric coverage from TRUS and MRI preplans were compared for each patient. The effects of different MRI sequences and image thicknesses were also investigated statistically using Student’s t-test. Lastly, the nomogram from the MRI preplan and TRUS preplan from our historical treatment data were compared. Results: The average prostate volume contoured on the TRUS and MRI were 26.6cc (range: 12.6∼41.3cc), and 27.4 cc (range: 14.3∼50.0cc), respectively. Axial MRI thicknesses (range: 3.5∼8.1mm) did not significantly affect the contoured volume or the number of seeds required on the preplan (R2 = 0.0002 and 0.0012, respectively). Four of the MRI sequences (AX-T2, AX-T2-Whole-Pelvis, AX-T2-FSE, and AXIALT2- Hi-Res) showed statistically significant better prostate volume agreement with TRUS than the other seven sequences (P <0.01). Nomogram overlay between the MRI and TRUS preplans showed good agreement; indicating volumes contoured on MRI preplan scan reliably predict how many seeds are needed for implant. Conclusion: Although MRI does not allow for determination of the actual implant geometry, it can give reliable volumes for seed ordering purposes. Our future work will investigate if MRI is sufficient to reliably replace TRUS preplanning in patients where preplan TRUS may be technically challenging.« less

Amide linkages mimic phosphates in RNA interactions with proteins and are well tolerated in the guide strand of short interfering RNAs

PubMed Central

Mutisya, Daniel; Hardcastle, Travis; Cheruiyot, Samwel K.; Pallan, Pradeep S.; Kennedy, Scott D.; Egli, Martin; Kelley, Melissa L.; Smith, Anja van Brabant

2017-01-01

Abstract While the use of RNA interference (RNAi) in molecular biology and functional genomics is a well-established technology, in vivo applications of synthetic short interfering RNAs (siRNAs) require chemical modifications. We recently found that amides as non-ionic replacements for phosphodiesters may be useful modifications for optimization of siRNAs. Herein, we report a comprehensive study of systematic replacement of a single phosphate with an amide linkage throughout the guide strand of siRNAs. The results show that amides are surprisingly well tolerated in the seed and central regions of the guide strand and increase the silencing activity when placed between nucleosides 10 and 12, at the catalytic site of Argonaute. A potential explanation is provided by the first crystal structure of an amide-modified RNA–DNA with Bacillus halodurans RNase H1. The structure reveals how small changes in both RNA and protein conformation allow the amide to establish hydrogen bonding interactions with the protein. Molecular dynamics simulations suggest that these alternative binding modes may compensate for interactions lost due to the absence of a phosphodiester moiety. Our results suggest that an amide can mimic important hydrogen bonding interactions with proteins required for RNAi activity and may be a promising modification for optimization of biological properties of siRNAs. PMID:28854734

Amide linkages mimic phosphates in RNA interactions with proteins and are well tolerated in the guide strand of short interfering RNAs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mutisya, Daniel; Hardcastle, Travis; Cheruiyot, Samwel K.

While the use of RNA interference (RNAi) in molecular biology and functional genomics is a well-established technology, in vivo applications of synthetic short interfering RNAs (siRNAs) require chemical modifications. We recently found that amides as non-ionic replacements for phosphodiesters may be useful modifications for optimization of siRNAs. Herein, we report a comprehensive study of systematic replacement of a single phosphate with an amide linkage throughout the guide strand of siRNAs. The results show that amides are surprisingly well tolerated in the seed and central regions of the guide strand and increase the silencing activity when placed between nucleosides 10 andmore » 12, at the catalytic site of Argonaute. A potential explanation is provided by the first crystal structure of an amide-modified RNA–DNA with Bacillus halodurans RNase H1. The structure reveals how small changes in both RNA and protein conformation allow the amide to establish hydrogen bonding interactions with the protein. Molecular dynamics simulations suggest that these alternative binding modes may compensate for interactions lost due to the absence of a phosphodiester moiety. Our results suggest that an amide can mimic important hydrogen bonding interactions with proteins required for RNAi activity and may be a promising modification for optimization of biological properties of siRNAs.« less

The difference of scoring dose to water or tissues in Monte Carlo dose calculations for low energy brachytherapy photon sources.

PubMed

Landry, Guillaume; Reniers, Brigitte; Pignol, Jean-Philippe; Beaulieu, Luc; Verhaegen, Frank

2011-03-01

The goal of this work is to compare D(m,m) (radiation transported in medium; dose scored in medium) and D(w,m) (radiation transported in medium; dose scored in water) obtained from Monte Carlo (MC) simulations for a subset of human tissues of interest in low energy photon brachytherapy. Using low dose rate seeds and an electronic brachytherapy source (EBS), the authors quantify the large cavity theory conversion factors required. The authors also assess whether ap plying large cavity theory utilizing the sources' initial photon spectra and average photon energy induces errors related to spatial spectral variations. First, ideal spherical geometries were investigated, followed by clinical brachytherapy LDR seed implants for breast and prostate cancer patients. Two types of dose calculations are performed with the GEANT4 MC code. (1) For several human tissues, dose profiles are obtained in spherical geometries centered on four types of low energy brachytherapy sources: 125I, 103Pd, and 131Cs seeds, as well as an EBS operating at 50 kV. Ratios of D(w,m) over D(m,m) are evaluated in the 0-6 cm range. In addition to mean tissue composition, compositions corresponding to one standard deviation from the mean are also studied. (2) Four clinical breast (using 103Pd) and prostate (using 125I) brachytherapy seed implants are considered. MC dose calculations are performed based on postimplant CT scans using prostate and breast tissue compositions. PTV D90 values are compared for D(w,m) and D(m,m). (1) Differences (D(w,m)/D(m,m)-1) of -3% to 70% are observed for the investigated tissues. For a given tissue, D(w,m)/D(m,m) is similar for all sources within 4% and does not vary more than 2% with distance due to very moderate spectral shifts. Variations of tissue composition about the assumed mean composition influence the conversion factors up to 38%. (2) The ratio of D90(w,m) over D90(m,m) for clinical implants matches D(w,m)/D(m,m) at 1 cm from the single point sources, Given the small variation with distance, using conversion factors based on the emitted photon spectrum (or its mean energy) of a given source introduces minimal error. The large differences observed between scoring schemes underline the need for guidelines on choice of media for dose reporting. Providing such guidelines is beyond the scope of this work.

A controlled double-duration inducible gene expression system for cartilage tissue engineering.

PubMed

Ma, Ying; Li, Junxiang; Yao, Yi; Wei, Daixu; Wang, Rui; Wu, Qiong

2016-05-25

Cartilage engineering that combines competent seeding cells and a compatible scaffold is increasingly gaining popularity and is potentially useful for the treatment of various bone and cartilage diseases. Intensive efforts have been made by researchers to improve the viability and functionality of seeding cells of engineered constructs that are implanted into damaged cartilage. Here, we designed an integrative system combining gene engineering and the controlled-release concept to solve the problems of both seeding cell viability and functionality through precisely regulating the anti-apoptotic gene bcl-2 in the short-term and the chondrogenic master regulator Sox9 in the long-term. Both in vitro and in vivo experiments demonstrated that our system enhances the cell viability and chondrogenic effects of the engineered scaffold after introduction of the system while restricting anti-apoptotic gene expression to only the early stage, thereby preventing potential oncogenic and overdose effects. Our system was designed to be modular and can also be readily adapted to other tissue engineering applications with minor modification.

Tissue-engineered vascular grafts for use in the treatment of congenital heart disease: from the bench to the clinic and back again.

PubMed

Patterson, Joseph T; Gilliland, Thomas; Maxfield, Mark W; Church, Spencer; Naito, Yuji; Shinoka, Toshiharu; Breuer, Christopher K

2012-05-01

Since the first tissue-engineered vascular graft (TEVG) was implanted in a child over a decade ago, growth in the field of vascular tissue engineering has been driven by clinical demand for improved vascular prostheses with performance and durability similar to an autologous blood vessel. Great strides were made in pediatric congenital heart surgery using the classical tissue engineering paradigm, and cell seeding of scaffolds in vitro remained the cornerstone of neotissue formation. Our second-generation bone marrow cell-seeded TEVG diverged from tissue engineering dogma with a design that induces the recipient to regenerate vascular tissue in situ. New insights suggest that neovessel development is guided by cell signals derived from both seeded cells and host inflammatory cells that infiltrate the graft. The identification of these signals and the regulatory interactions that influence cell migration, phenotype and extracellular matrix deposition during TEVG remodeling are yielding a next-generation TEVG engineered to guide neotissue regeneration without the use of seeded cells. These developments represent steady progress towards our goal of an off-the-shelf tissue-engineered vascular conduit for pediatric congenital heart surgery.

Preliminary experimental investigation of in vivo magnetic manipulation: results and potential application in hyperthermia.

PubMed

Grady, M S; Howard, M A; Molloy, J A; Ritter, R C; Quate, E G; Gillies, G T

1989-01-01

The first in vivo experiments in support of a new technique for delivering stereotaxic hyperthermia have been conducted at the Experimental Surgery Facility of the University of Virginia's Medical Center. We call this technique the "Video Tumor Fighter." In each of twelve trials a single, small permanent magnet or train of small permanent magnets was implanted on the brain surface of adult canine models. In three of the trials, this "seed" (typically 6-mm diameter X 6-mm long) was moved by magnetic manipulation to different locations within the brain. In two other trials, the seed moved along the interface between the brain and the inner vault of the skull. The noncontact magnetic manipulation was accomplished by coupling the permanently magnetized seed to the large dc magnetic field gradient created by a water-cooled coil surrounding the animal's head. The seed's motions were monitored with x-ray fluoroscopy; its rate of movement was found to be approximately 0.8 mm s-1. The forces required to produce these motions were on the order of 0.07 N. We document here the instrumentation used in these trials, describe the experimental procedures employed, and discuss the technical aspects of the results.

Engineering functional and histological regeneration of vascularized skeletal muscle.

PubMed

Gilbert-Honick, Jordana; Iyer, Shama R; Somers, Sarah M; Lovering, Richard M; Wagner, Kathryn; Mao, Hai-Quan; Grayson, Warren L

2018-05-01

Tissue engineering strategies to treat patients with volumetric muscle loss (VML) aim to recover the structure and contractile function of lost muscle tissue. Here, we assessed the capacity of novel electrospun fibrin hydrogel scaffolds seeded with murine myoblasts to regenerate the structure and function of damaged muscle within VML defects to the mouse tibialis anterior muscle. The electrospun fibrin scaffolds provide pro-myogenic alignment and stiffness cues, myomimetic hierarchical structure, suturability, and scale-up capabilities. Myoblast-seeded scaffolds enabled remarkable muscle regeneration with high myofiber and vascular densities after 2 and 4 weeks, mimicking that of native skeletal muscle, while acellular scaffolds lacked muscle regeneration. Both myoblast-seeded and acellular scaffolds fully recovered muscle contractile function to uninjured values after 2 and 4 weeks. Electrospun scaffolds pre-vascularized with co-cultured human endothelial cells and human adipose-derived stem cells implanted into VML defects for 2 weeks anastomosed with host vasculature and were perfused with host red blood cells. These data demonstrate the significant potential of electrospun fibrin scaffolds seeded with myoblasts to fully regenerate the structure and function of volumetric muscle defects and these scaffolds offer a promising treatment option for patients with VML. Copyright © 2018 Elsevier Ltd. All rights reserved.

In Vitro Endothelialization of Biodegradable Vascular Grafts Via Endothelial Progenitor Cell Seeding and Maturation in a Tubular Perfusion System Bioreactor.

PubMed

Melchiorri, Anthony J; Bracaglia, Laura G; Kimerer, Lucas K; Hibino, Narutoshi; Fisher, John P

2016-07-01

A critical challenge to the success of biodegradable vascular grafts is the establishment of a healthy endothelium. To establish this monolayer of endothelial cells (ECs), a variety of techniques have been developed, including cell seeding. Vascular grafts may be seeded with relevant cell types and allowed to mature before implantation. Due to the low proliferative ability of adult ECs and issues with donor site morbidity, there has been increasing interest in using endothelial progenitor cells (EPCs) for vascular healing procedures. In this work, we combined the proliferative and differentiation capabilities of a commercial cell line of early EPCs with an established bioreactor system to support the maturation of cell-seeded vascular grafts. All components of the vascular graft and bioreactor setup are commercially available and allow for complete customization of the scaffold and culturing system. This bioreactor setup enables the control of flow through the graft, imparting fluid shear stress on EPCs and affecting cellular proliferation and differentiation. Grafts cultured with EPCs in the bioreactor system demonstrated greatly increased cell populations and neotissue formation compared with grafts seeded and cultured in a static system. Increased expression of markers for mature endothelial tissues were also observed in bioreactor-cultured EPC-seeded grafts. These findings suggest the distinct advantages of a customizable bioreactor setup for the proliferation and maturation of EPCs. Such a strategy may be beneficial for utilizing EPCs in vascular tissue engineering applications.

Evaluating 3D bone tissue engineered constructs with different seeding densities using the alamarBlue assay and the effect on in vivo bone formation.

PubMed

Wilson, C E; Dhert, W J A; Van Blitterswijk, C A; Verbout, A J; De Bruijn, J D

2002-12-01

Bone tissue engineering using patient derived cells seeded onto porous scaffolds has gained much attention in recent years. Evaluating the viability of these 3D constructs is an essential step in optimizing the process. The alamarBlue (aB) assay was evaluated for its potential to follow in vitro cell proliferation on architecturally standardized hydroxyapatite scaffolds. The impact of the aB assayed and seeding density on subsequent in vivo bone formation was investigated. Twelve scaffolds were seeded with various densities from 250 to 2.5x10(6) cells/scaffold and assay by aB at 5 time points during the 7-day culture period. Twelve additional scaffolds were seeded with 2.5x10(5) cells/scaffold. Two control and 2 aB treated scaffolds were subcutaneously implanted into each of 6 nude mice for 6 weeks. Four observers ranked bone formation using a pair wise comparison of histological sections form each mouse. The aB assay successfully followed cell proliferation, however, the diffusion kinetics of the 3D constructs must be considered. The influence of in vitro aB treatment on subsequent in vivo bone formation cannot be ruled out but was not shown to be significant in the current study. The aB assay appears to be quite promising for evaluating a maximum or end-point viability of 3D tissue engineered constructs. Finally, higher seeding densities resulted in more observed bone formation.

In vivo photoacoustic imaging of prostate brachytherapy seeds

NASA Astrophysics Data System (ADS)

Lediju Bell, Muyinatu A.; Kuo, Nathanael P.; Song, Danny Y.; Kang, Jin; Boctor, Emad M.

2014-03-01

We conducted an approved canine study to investigate the in vivo feasibility of photoacoustic imaging for intraoperative updates to brachytherapy treatment plans. Brachytherapy seeds coated with black ink were inserted into the canine prostate using methods similar to a human procedure. A transperineal, interstitial, fiber optic light delivery method, coupled to a 1064 nm laser, was utilized to irradiate the prostate and the resulting acoustic waves were detected with a transrectal ultrasound probe. The fiber was inserted into a high dose rate (HDR) brachytherapy needle that acted as a light-diffusing sheath, enabling radial light delivery from the tip of the fiber inside the sheath. The axis of the fiber was located at a distance of 4-9 mm from the long axis of the cylindrical seeds. Ultrasound images acquired with the transrectal probe and post-operative CT images of the implanted seeds were analyzed to confirm seed locations. In vivo limitations with insufficient light delivery within the ANSI laser safety limit (100 mJ/cm2) were overcome by utilizing a short-lag spatial coherence (SLSC) beamformer, which provided average seed contrasts of 20-30 dB for energy densities ranging 8-84 mJ/cm2. The average contrast was improved by up to 20 dB with SLSC beamforming compared to conventional delay-and-sum beamforming. There was excellent agreement between photoacoustic, ultrasound, and CT images. Challenges included visualization of photoacoustic artifacts that corresponded with locations of the optical fiber and hyperechoic tissue structures.

Nanosurface design of dental implants for improved cell growth and function

NASA Astrophysics Data System (ADS)

Pan, Hsu-An; Hung, Yao-Ching; Chiou, Jin-Chern; Tai, Shih-Ming; Chen, Hsin-Hung; Huang, G. Steven

2012-08-01

A strategy was proposed for the topological design of dental implants based on an in vitro survey of optimized nanodot structures. An in vitro survey was performed using nanodot arrays with dot diameters ranging from 10 to 200 nm. MG63 osteoblasts were seeded on nanodot arrays and cultured for 3 days. Cell number, percentage undergoing apoptotic-like cell death, cell adhesion and cytoskeletal organization were evaluated. Nanodots with a diameter of approximately 50 nm enhanced cell number by 44%, minimized apoptotic-like cell death to 2.7%, promoted a 30% increase in microfilament bundles and maximized cell adhesion with a 73% increase in focal adhesions. An enhancement of about 50% in mineralization was observed, determined by von Kossa staining and by Alizarin Red S staining. Therefore, we provide a complete range of nanosurfaces for growing osteoblasts to discriminate their nanoscale environment. Nanodot arrays present an opportunity to positively and negatively modulate cell behavior and maturation. Our results suggest a topological approach which is beneficial for the design of dental implants.

Preparation of graphene on Cu foils by ion implantation with negative carbon clusters

NASA Astrophysics Data System (ADS)

Li, Hui; Shang, Yan-Xia; Zhang, Zao-Di; Wang, Ze-Song; Zhang, Rui; Fu, De-Jun

2015-01-01

We report on few-layer graphene synthesized on Cu foils by ion implantation using negative carbon cluster ions, followed by annealing at 950 °C in vacuum. Raman spectroscopy reveals IG/I2D values varying from 1.55 to 2.38 depending on energy and dose of the cluster ions, indicating formation of multilayer graphene. The measurements show that the samples with more graphene layers have fewer defects. This is interpreted by graphene growth seeded by the first layers formed via outward diffusion of C from the Cu foil, though nonlinear damage and smoothing effects also play a role. Cluster ion implantation overcomes the solubility limit of carbon in Cu, providing a technique for multilayer graphene synthesis. Project supported by the National Natural Science Foundation of China (Grant Nos. 11105100, 11205116, and 11375135) and the State Key Laboratory of Advanced Welding and Joining, Harbin Institute of Technology, China (Grant No. AWJ-M13-03).

Hybrid titanium/biodegradable polymer implants with an hierarchical pore structure as a means to control selective cell movement.

PubMed

Vrana, Nihal Engin; Dupret, Agnès; Coraux, Christelle; Vautier, Dominique; Debry, Christian; Lavalle, Philippe

2011-01-01

In order to improve implant success rate, it is important to enhance their responsiveness to the prevailing conditions following implantation. Uncontrolled movement of inflammatory cells and fibroblasts is one of these in vivo problems and the porosity properties of the implant have a strong effect on these. Here, we describe a hybrid system composed of a macroporous titanium structure filled with a microporous biodegradable polymer. This polymer matrix has a distinct porosity gradient to accommodate different cell types (fibroblasts and epithelial cells). The main clinical application of this system will be the prevention of restenosis due to excessive fibroblast migration and proliferation in the case of tracheal implants. A microbead-based titanium template was filled with a porous Poly (L-lactic acid) (PLLA) body by freeze-extraction method. A distinct porosity difference was obtained between the inner and outer surfaces of the implant as characterized by image analysis and Mercury porosimetry (9.8±2.2 µm vs. 36.7±11.4 µm, p≤0.05). On top, a thin PLLA film was added to optimize the growth of epithelial cells, which was confirmed by using human respiratory epithelial cells. To check the control of fibroblast movement, PKH26 labeled fibroblasts were seeded onto Titanium and Titanium/PLLA implants. The cell movement was quantified by confocal microscopy: in one week cells moved deeper in Ti samples compared to Ti/PLLA. In vitro experiments showed that this new implant is effective for guiding different kind of cells it will contact upon implantation. Overall, this system would enable spatial and temporal control over cell migration by a gradient ranging from macroporosity to nanoporosity within a tracheal implant. Moreover, mechanical properties will be dependent mainly on the titanium frame. This will make it possible to create a polymeric environment which is suitable for cells without the need to meet mechanical requirements with the polymeric structure.

Hybrid Titanium/Biodegradable Polymer Implants with an Hierarchical Pore Structure as a Means to Control Selective Cell Movement

PubMed Central

Vrana, Nihal Engin; Dupret, Agnès; Coraux, Christelle; Vautier, Dominique; Debry, Christian; Lavalle, Philippe

2011-01-01

In order to improve implant success rate, it is important to enhance their responsiveness to the prevailing conditions following implantation. Uncontrolled movement of inflammatory cells and fibroblasts is one of these in vivo problems and the porosity properties of the implant have a strong effect on these. Here, we describe a hybrid system composed of a macroporous titanium structure filled with a microporous biodegradable polymer. This polymer matrix has a distinct porosity gradient to accommodate different cell types (fibroblasts and epithelial cells). The main clinical application of this system will be the prevention of restenosis due to excessive fibroblast migration and proliferation in the case of tracheal implants. Methodology/Principal Findings A microbead-based titanium template was filled with a porous Poly (L-lactic acid) (PLLA) body by freeze-extraction method. A distinct porosity difference was obtained between the inner and outer surfaces of the implant as characterized by image analysis and Mercury porosimetry (9.8±2.2 µm vs. 36.7±11.4 µm, p≤0.05). On top, a thin PLLA film was added to optimize the growth of epithelial cells, which was confirmed by using human respiratory epithelial cells. To check the control of fibroblast movement, PKH26 labeled fibroblasts were seeded onto Titanium and Titanium/PLLA implants. The cell movement was quantified by confocal microscopy: in one week cells moved deeper in Ti samples compared to Ti/PLLA. Conclusions In vitro experiments showed that this new implant is effective for guiding different kind of cells it will contact upon implantation. Overall, this system would enable spatial and temporal control over cell migration by a gradient ranging from macroporosity to nanoporosity within a tracheal implant. Moreover, mechanical properties will be dependent mainly on the titanium frame. This will make it possible to create a polymeric environment which is suitable for cells without the need to meet mechanical requirements with the polymeric structure. PMID:21637824

SU-G-IeP1-01: A Novel MRI Post-Processing Algorithm for Visualization of the Prostate LDR Brachytherapy Seeds and Calcifications Based On B0 Field Inhomogeneity Correction and Hough Transform

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nosrati, R; Sunnybrook Health Sciences Centre, Toronto, Ontario; Soliman, A

Purpose: This study aims at developing an MRI-only workflow for post-implant dosimetry of the prostate LDR brachytherapy seeds. The specific goal here is to develop a post-processing algorithm to produce positive contrast for the seeds and prostatic calcifications and differentiate between them on MR images. Methods: An agar-based phantom incorporating four dummy seeds (I-125) and five calcifications of different sizes (from sheep cortical bone) was constructed. Seeds were placed arbitrarily in the coronal plane. The phantom was scanned with 3T Philips Achieva MR scanner using an 8-channel head coil array. Multi-echo turbo spin echo (ME-TSE) and multi-echo gradient recalled echomore » (ME-GRE) sequences were acquired. Due to minimal susceptibility artifacts around seeds, ME-GRE sequence (flip angle=15; TR/TE=20/2.3/2.3; resolution=0.7×0.7×2mm3) was further processed.The induced field inhomogeneity due to the presence of titaniumencapsulated seeds was corrected using a B0 field map. B0 map was calculated using the ME-GRE sequence by calculating the phase difference at two different echo times. Initially, the product of the first echo and B0 map was calculated. The features corresponding to the seeds were then extracted in three steps: 1) the edge pixels were isolated using “Prewitt” operator; 2) the Hough transform was employed to detect ellipses approximately matching the dimensions of the seeds and 3) at the position and orientation of the detected ellipses an ellipse was drawn on the B0-corrected image. Results: The proposed B0-correction process produced positive contrast for the seeds and calcifications. The Hough transform based on Prewitt edge operator successfully identified all the seeds according to their ellipsoidal shape and dimensions in the edge image. Conclusion: The proposed post-processing algorithm successfully visualized the seeds and calcifications with positive contrast and differentiates between them according to their shapes. Further assessments on more realistic phantoms and patient study are required to validate the outcome.« less

Ex-vivo transduced autologous skin fibroblasts expressing human Lim Mineralization Protein-3 efficiently form new bone in animal models

PubMed Central

Lattanzi, Wanda; Parrilla, Claudio; Fetoni, Annarita; Logroscino, Giandomenico; Straface, Giuseppe; Pecorini, Giovanni; Stigliano, Egidio; Tampieri, Anna; Bedini, Rossella; Pecci, Raffaella; Michetti, Fabrizio; Gambotto, Andrea; Robbins, Paul D.; Pola, Enrico

2012-01-01

Local gene transfer of the human LIM Mineralization Protein (LMP), a novel intracellular positive regulator of the osteoblast differentiation program, can induce efficient bone formation in rodents. In order to develop a clinically relevant gene therapy approach to facilitate bone healing, we have used primary dermal fibroblasts transduced ex vivo with Ad.LMP3 and seeded on an hydroxyapatite/collagen matrix prior to autologous implantation. Here we demonstrate that genetically modified autologous dermal fibroblasts expressing Ad.LMP-3 are able to induce ectopic bone formation following implantation of the matrix into the mouse triceps and paravertebral muscles. Moreover, implantation of the Ad.LMP-3-modified dermal fibroblasts into a rat mandibular bone critical size defect model results in efficient healing as determined by X-ray, histology and three dimensional micro computed tomography (3DμCT). These results demonstrate the effectiveness of the non-secreted intracellular osteogenic factor LMP-3, in inducing bone formation in vivo. Moreover, the utilization of autologous dermal fibroblasts implanted on a biomaterial represents a promising approach for possible future clinical applications aimed at inducing new bone formation. PMID:18633445

Expression of lectin genes during seed development in normal and phytohemagglutinin-deficient cultivars of Phaseolus vulgaris.

PubMed

Staswick, P; Chrispeels, M J

1984-01-01

Phytohemagglutinin (PHA), the major lectin of the common bean Phaseolus vulgaris, is synthesized during the development of the seeds. In most cultivars PHA makes up 5-10% of the total seed protein, but certain cultivars do not contain PHA. In vivo labeling of a normal cultivar (Greensleeves) and a PHA-minus cultivar (Pinto 111) showed that PHA was not synthesized in the PHA-minus cultivar. To find out whether the lack of synthesis was due to the absence of mRNA for PHA, recombinant cDNA clones for PHA were obtained. Total poly(A)+ RNA was isolated from cotyledons of developing seeds of Greensleeves and used to direct cDNA synthesis. The double stranded cDNA was cloned in pUC8 and transformants of Escherichia coli screened with pPVL134, a recombinant plasmid which contains the complete coding sequence for a PHA-like protein. Two weakly hybridizing clones (pSC1 and pSC2) were selected. Hybrid selection experiments showed that these two clones selected mRNAs which could be translated into polypeptides identical in size to PHA and recognized by antibodies to PHA. The recombinant pPVL134 selected mRNA which translated into polypeptides which were slightly smaller than those of PHA, and poorly recognized by antibodies to PHA. The recombinant clones were used to demonstrate that the genes for PHA and for the PHA-like protein are under temporal control during seed development. The cultivar Pinto 111, which has no detectable PHA, also has greatly reduced levels of mRNA for PHA. However, the gene for the PHA-like protein encoded by pPVL134 is expressed to the same degree in the cultivars Greensleeves and Pinto 111.

SEED: a tool for disseminating systematic review data into Wikipedia.

PubMed

Schmidt, Lena; Friedel, Johannes; Adams, Clive E

2017-10-17

Wikipedia, the free-content online encyclopaedia, contains many heavily accessed pages relating to healthcare. Cochrane systematic reviews contain much high-grade evidence but dissemination into Wikipedia has been slow. New skills are needed to both translate and relocate data from Cochrane reviews to implant into Wikipedia pages. This letter introduces a programme to greatly simplify the process of disseminating the summary of findings of Cochrane reviews into Wikipedia pages.

Implantation of In Vitro Tissue Engineered Muscle Repair Constructs and Bladder Acellular Matrices Partially Restore In Vivo Skeletal Muscle Function in a Rat Model of Volumetric Muscle Loss Injury

DTIC Science & Technology

2014-01-01

thickness abdominal wall defects. Tissue Eng 12, 1929, 2006. 7. Gamba, P.G., Conconi, M.T., Lo Piccolo, R., Zara , G., Spi nazzi, R., and Parnigotto... Zara , G., Sabatti, M., Marzaro, M., et al. Homologous muscle acellular matrix seeded with autologous myoblasts as a tissue engineering approach to

Human mesenchymal stem cell behavior on femtosecond laser-textured Ti-6Al-4V surfaces.

PubMed

Cunha, Alexandre; Zouani, Omar Farouk; Plawinski, Laurent; Botelho do Rego, Ana Maria; Almeida, Amélia; Vilar, Rui; Durrieu, Marie-Christine

2015-01-01

The aim of the present work was to investigate ultrafast laser surface texturing as a surface treatment of Ti-6Al-4V alloy dental and orthopedic implants to improve osteoblastic commitment of human mesenchymal stem cells (hMSCs). Surface texturing was carried out by direct writing with an Yb:KYW chirped-pulse regenerative amplification laser system with a central wavelength of 1030 nm and a pulse duration of 500 fs. The surface topography and chemical composition were investigated by scanning electron microscopy and x-ray photoelectron spectroscopy, respectively. Three types of surface textures with potential interest to improve implant osseointegration can be produced by this method: laser-induced periodic surface structures (LIPSSs); nanopillars (NPs); and microcolumns covered with LIPSSs, forming a bimodal roughness distribution. The potential of the laser treatment in improving hMSC differentiation was assessed by in vitro study of hMSCs spreading, adhesion, elongation and differentiation using epifluorescence microscopy at different times after cell seeding, after specific stainings and immunostainings. Cell area and focal adhesion area were lower on the laser-textured surfaces than on a polished reference surface. Obviously, the laser-textured surfaces have an impact on cell shape. Osteoblastic commitment was observed independently of the surface topography after 2 weeks of cell seeding. When the cells were cultured (after 4 weeks of seeding) in osteogenic medium, LIPSS- and NP- textured surfaces enhanced matrix mineralization and bone-like nodule formation as compared with polished and microcolumn-textured surfaces. The present work shows that surface nanotextures consisting of LIPSSs and NPs can, potentially, improve hMSC differentiation into an osteoblastic lineage.

Structural determinants of miRNAs for RISC loading and slicer-independent unwinding.

PubMed

Kawamata, Tomoko; Seitz, Hervé; Tomari, Yukihide

2009-09-01

MicroRNAs (miRNAs) regulate expression of their target mRNAs through the RNA-induced silencing complex (RISC), which contains an Argonaute (Ago) family protein as a core component. In Drosophila melanogaster, miRNAs are generally sorted into Ago1-containing RISC (Ago1-RISC). We established a native gel system that can biochemically dissect the Ago1-RISC assembly pathway. We found that miRNA-miRNA* duplexes are loaded into Ago1 as double-stranded RNAs in an ATP-dependent fashion. In contrast, unexpectedly, unwinding of miRNA-miRNA* duplexes is a passive process that does not require ATP or slicer activity of Ago1. Central mismatches direct miRNA-miRNA* duplexes into pre-Ago1-RISC, whereas mismatches in the seed or guide strand positions 12-15 promote conversion of pre-Ago1-RISC into mature Ago1-RISC. Our findings show that unwinding of miRNAs is a precise mirror-image process of target recognition, and both processes reflect the unique geometry of RNAs in Ago proteins.

Induction of human umbilical cord mesenchymal stem cells into tissue-forming cells in a murine model: implications for pelvic floor reconstruction.

PubMed

Ding, Jing; Han, Qin; Deng, Mou; Song, Xiao-Chen; Chen, Chun; Ai, Fang-Fang; Zhu, Lan; Zhao, Robert Chun-Hua

2018-06-01

HUMSCs were isolated, differentiated and characterized in vitro. Both HUMSCs and smooth muscle cells differentiated from HUMSCs were used to fabricate tissue-engineered fascia equivalents. Forty-eight mature female Sprague Dawley rats were randomly assigned to four groups: group A (GynemeshTMPS, n = 12), group B (GynemeshTMPS + HUMSCs; n = 12), group C (GynemeshTMPS + smooth muscle cells differentiated from HUMSCs; n = 12) and group D (GynemeshTMPS + HUMSCs + smooth muscle cells differentiated from HUMSCs; n = 12). The posterior vaginal wall was incised from the introitus and the mesh was then implanted. Three implants of each type were tested at 1, 4, 8 and 12 weeks. Fibrotic remodeling, inflammation, vascularization and tissue regeneration were histologically assessed. The levels of type I and type III collagen were determined. There was no difference in fibrotic remodeling between cell-seeded and unseeded meshes at any time (p > 0.05). At 12 weeks, there did not appear to be fewer inflammatory cells around the filament bundles in the mesh with cells compared with the mesh alone (P > 0.05). Group D showed a trend toward better vascularization at 12 weeks compared with group A (P < 0.05). Twelve weeks after implantation, a thin layer of new tissue growth covered the unseeded scaffold and a thicker layer covered the cell-seeded scaffold (P < 0.05). No significant difference in the ratio of collagen type I/III could be detected among the different groups after 12 weeks (P > 0.05). HUMSCs with differentiated smooth muscle cells might have a potential role in fascia tissue engineering to repair POP in the future.

LDR brachytherapy: can low dose rate hypersensitivity from the "inverse" dose rate effect cause excessive cell killing to peripherial connective tissues and organs?

PubMed

Leonard, B E; Lucas, A C

2009-02-01

Examined here are the possible effects of the "inverse" dose rate effect (IDRE) on low dose rate (LDR) brachytherapy. The hyper-radiosensitivity and induced radioresistance (HRS/IRR) effect benefits cell killing in radiotherapy, and IDRE and HRS/IRR seem to be generated from the same radioprotective mechanisms. We have computed the IDRE excess cell killing experienced in LDR brachytherapy using permanent seed implants. We conclude, firstly, that IDRE is a dose rate-dependent manifestation of HRS/IRR. Secondly, the presence of HRS/IRR or IDRE in a cell species or tissue must be determined by direct dose-response measurements. Thirdly, a reasonable estimate is that 50-80% of human adjoining connective and organ tissues experience IDRE from permanent implanted LDR brachytherapy. If IDRE occurs for tissues at point A for cervical cancer, the excess cell killing will be about a factor of 3.5-4.0 if the initial dose rate is 50-70 cGy h(-1). It is greater for adjacent tissues at lower dose rates and higher for lower initial dose rates at point A. Finally, higher post-treatment complications are observed in LDR brachytherapy, often for unknown reasons. Some of these are probably a result of IDRE excess cell killing. Measurements of IDRE need be performed for connective and adjacent organ tissues, i.e. bladder, rectum, urinary tract and small bowels. The measured dose rate-dependent dose responses should extended to <10 cGy h(-1) and involve multiple patients to detect patient variability. Results may suggest a preference for high dose rate brachytherapy or LDR brachytherapy without permanent retention of the implant seeds (hence the dose rates in peripheral tissues and organs remain above IDRE thresholds).

Parameters predicting for prostate specific antigen response rates at one year post low-dose-rate intraoperative prostate brachytherapy

PubMed Central

Meyer, Tyler; Sia, Michael; Angyalfi, Steve; Husain, Siraj

2017-01-01

Purpose To develop a model for prostate specific antigen (PSA) values at one year among patients treated with intraoperatively planned 125I prostate brachytherapy (IOPB). Material and methods Four hundred and deven patients treated with IOPB for prostate adenocarcinoma were divided into four groups: those with PSA values ≥ 3 ng/ml; < 3 and ≥ 2; < 2 and ≥ 1 or PSA < 1 between 10.5 and 14.5 months post implantation (1yPSA). Ordinal regression analysis was then performed between patient, tumor, and treatment characteristics. 1yPSA values were also compared with toxicity outcomes. Results Median 1yPSA was 0.77 (0.04-17.36). Thirty-two patients (8%) had a PSA ≥ 3; 35 (9%) had PSA < 3, ≥ 2; 87 (21%) had PSA < 2, ≥ 1, and most patients 254 (62%) had PSA < 1. PSA response was independent of gland volume, Gleason score, clinical stage, seed activity, V90, V200, D90, or number of needles and seeds used. Older patients had significantly lower 1yPSA; median ages 65.1 (46.5-81.0), 62.1 (50.4-79.5), 60.5 (47.1-80.3), and 58.1 (45.1-74.2) years for each of the 1yPSA groups respectively (p < 0.001). Also, both implant V150 (p < 0.001) and initial PSA values (p = 0.04) were predictive of 1yPSA values. There was no correlation between 1yPSA values and toxicity encountered. Conclusions PSA response at 1 year post IOPB appears to be dependent on patient age, initial PSA, and implant V150. Our results provide reassurance that parameters other than biochemical failure influence 1yPSA values. PMID:28533796

Transarterial chemoembolization plus iodine-125 implantation for hepatocellular carcinoma: a systematic review and meta-analysis.

PubMed

Zhu, Ze-Xin; Wang, Xiao-Xue; Yuan, Ke-Fei; Huang, Ji-Wei; Zeng, Yong

2018-05-17

Hepatocellular carcinoma (HCC) is the most common malignancy in liver. Transarterial chemoembolization (TACE) is recommended as an effective treatment in advanced HCC patients. Recent studies showed iodine-125 seed (a low-energy radionuclide) can provide long-term local control and increase survival for HCC patients. The aim of the study was to evaluate the outcome of TACE plus iodine-125 seed in comparison with TACE alone for HCC. A comprehensive search of studies among PubMed, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews was conducted with published date from the earliest to January 10th, 2018. No language restrictions were applied, while only prospective randomized controlled trials (RCTs) or non-randomized controlled trials (non-RCTs) were eligible for a full-text review. The primary outcome was overall survival (OS), response rate (the rate of partial atrophy or complete clearance of the tumor lesion) and adverse events (AEs). The odds ratios (ORs) were combined using either fixed-effects model or random-effects model. All statistical analyses were performed using the Stata 12.0 software. 9 studies were included, involving 894 patients. Among them, 473 patients received combined therapy of TACE plus iodine-125 implantation, compared with 421 patients with TACE alone. Patients receiving combined therapy of TACE plus iodine-125 showed significantly improvement in 1-year OS (OR = 4.47, 95% confidence intervals (CI): 2.97-6.73; P < 0.001), 2-year OS (OR = 4.72, 95% CI: 2.63-8.47; P < 0.001). No significant publication bias was observed in any of the measured outcomes. Based on these findings, TACE plus iodine-125 implantation achieves better clinical efficacy compared with TACE alone in the treatment of HCC. Copyright © 2018. Published by Elsevier Ltd.

Assessment of an aqueous seed extract of Parkia clappertoniana on reproductive performance and toxicity in rodents.

PubMed

Boye, Alex; Boampong, Victor Addai; Takyi, Nutifafa; Martey, Orleans

2016-06-05

The seeds of Parkia clappertoniana Keay (Family: Fabaceae) are extensively used in food in the form of a local condiment called 'Dawadawa' in Ghana and consumed by all class of people including sensitive groups such as pregnant women and children. Also, crudely pounded preparations of P. clappertoniana seeds are used as labor inducing agent in farm animals by local farmers across northern Ghana where nomadism is the livelihood of most indigenes. Ecologically, P. clappertoniana is extensively distributed across the savannah ecological zone of many African countries where just like Ghana it enjoys ethnobotanical usage. Although, many studies have investigated some aspects of the pharmacological activity of P. clappertoniana, none of these studies focused on the reproductive system, particularly its effects on reproductive performance and toxicity. To contribute, this study assessed the effect of aqueous seed extract of P. clappertoniana (PCE) on reproductive performance and toxicity in Sprague-Dawley rats and ICR mice. After preparation of PCE, it was then tested on rodents at different gestational and developmental windows (1-7, 8-14, and 15-term gestational days) to assess the following: mating behavior, implantation rate, maternal and developmental toxicities. Generally, animals were randomly grouped into five and treated as follows: normal saline group (5ml/kg po), cytotec (misoprostol) group (200mg/kg po), folic acid group (5mg/kg po), and PCE groups (100, 200, and 500mg/kg po), however, these groupings were varied to suit the specific requirements of some parameters. For acute toxicity, animals were orally administered PCE (3 and 5g/kg for mice and rats respectively). PCE-treated rats showed improved mating behavior compared to control rats. PCE improved implantation rate compared to misoprostol-treated rats. On the average, PCE-treated rats delivered termed live pubs at 21 days compared to that of folic acid-treated rats at 23 days. Also, PCE-treated rats showed no observable maternal and developmental toxicities compared to folic acid and control rats. PCE (3-5g/kg po) was orally tolerated in rodents. Oral administration of Parkia clappertoniana seed extract improves reproductive performance in rodents with no observable maternal and developmental toxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Zinc-ion implanted and deposited titanium surfaces reduce adhesion of Streptococccus mutans

NASA Astrophysics Data System (ADS)

Xu, Juan; Ding, Gang; Li, Jinlu; Yang, Shenhui; Fang, Bisong; Sun, Hongchen; Zhou, Yanmin

2010-10-01

While titanium (Ti) is a commonly used dental implant material with advantageous biocompatible and mechanical properties, native Ti surfaces do not have the ability to prevent bacterial colonization. The objective of this study was to evaluate the chemical composition and bacterial adhesive properties of zinc (Zn) ion implanted and deposited Ti surfaces (Zn-PIIID-Ti) as potential dental implant materials. Surfaces of pure Ti (cp-Ti) were modified with increasing concentrations of Zn using plasma immersion ion implantation and deposition (PIIID), and elemental surface compositions were characterized by X-ray photoelectron spectrometry (XPS). To evaluate bacterial responses, Streptococcus mutans were seeded onto the modifiedTi surfaces for 48 h and subsequently observed by scanning electron microscopy. Relative numbers of bacteria on each surface were assessed by collecting the adhered bacteria, reculturing and counting colony forming units after 48 h on bacterial grade plates. Ti, oxygen and carbon elements were detected on all surfaces by XPS. Increased Zn signals were detected on Zn-PIIID-Ti surfaces, correlating with an increase of Zn-deposition time. Substantial numbers of S. mutans adhered to cp-Ti samples, whereas bacterial adhesion on Zn-PIIID-Ti surfaces signficantly decreased as the Zn concentration increased ( p < 0.01). In conclusion, PIIID can successfully introduce Zn onto a Ti surface, forming a modified surface layer bearing Zn ions that consequently deter adhesion of S. mutans, a common bacterium in the oral environment.

Osteogenic potential of human adipose-tissue-derived mesenchymal stromal cells cultured on 3D-printed porous structured titanium.

PubMed

Lewallen, Eric A; Jones, Dakota L; Dudakovic, Amel; Thaler, Roman; Paradise, Christopher R; Kremers, Hilal M; Abdel, Matthew P; Kakar, Sanjeev; Dietz, Allan B; Cohen, Robert C; Lewallen, David G; van Wijnen, Andre J

2016-05-01

Integration of porous metal prosthetics, which restore form and function of irreversibly damaged joints, into remaining healthy bone is critical for implant success. We investigated the biological properties of adipose-tissue-derived mesenchymal stromal/stem cells (AMSCs) and addressed their potential to alter the in vitro microenvironment of implants. We employed human AMSCs as a practical source for musculoskeletal applications because these cells can be obtained in large quantities, are multipotent, and have trophic paracrine functions. AMSCs were cultured on surgical-grade porous titanium disks as a model for orthopedic implants. We monitored cell/substrate attachment, cell proliferation, multipotency, and differentiation phenotypes of AMSCs upon osteogenic induction. High-resolution scanning electron microscopy and histology revealed that AMSCs adhere to the porous metallic surface. Compared to standard tissue culture plastic, AMSCs grown in the porous titanium microenvironment showed differences in temporal expression for genes involved in cell cycle progression (CCNB2, HIST2H4), extracellular matrix production (COL1A1, COL3A1), mesenchymal lineage identity (ACTA2, CD248, CD44), osteoblastic transcription factors (DLX3, DLX5, ID3), and epigenetic regulators (EZH1, EZH2). We conclude that metal orthopedic implants can be effectively seeded with clinical-grade stem/stromal cells to create a pre-conditioned implant. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of Regenerative Tissue Quality following Matrix-Associated Cell Implantation Using Amplified Chondrocytes Compared to Synovium-Derived Stem Cells in a Rabbit Model for Cartilage Lesions.

PubMed

Schmal, Hagen; Kowal, Justyna M; Kassem, Moustapha; Seidenstuecker, Michael; Bernstein, Anke; Böttiger, Katharina; Xiong, Tanshiyue; Südkamp, Norbert P; Kubosch, Eva J

2018-01-01

Known problems of the autologous chondrocyte implantation motivate the search for cellular alternatives. The aim of the study was to test the potential of synovium-derived stem cells (SMSC) to regenerate cartilage using a matrix-associated implantation. In an osteochondral defect model of the medial femoral condyle in a rabbit, a collagen membrane was seeded with either culture-expanded allogenic chondrocytes or SMSC and then transplanted into the lesion. A tailored piece synovium served as a control. Rabbit SMSC formed typical cartilage in vitro. Macroscopic evaluation of defect healing and the thickness of the regenerated tissue did not reveal a significant difference between the intervention groups. However, instantaneous and shear modulus, reflecting the biomechanical strength of the repair tissue, was superior in the implantation group using allogenic chondrocytes ( p < 0.05). This correlated with a more chondrogenic structure and higher proteoglycan expression, resulting in a lower OARSI score ( p < 0.05). The repair tissue of all groups expressed comparable amounts of the collagen types I, II, and X. Cartilage regeneration following matrix-associated implantation using allogenic undifferentiated synovium-derived stem cells in a defect model in rabbits showed similar macroscopic results and collagen composition compared to amplified chondrocytes; however, biomechanical characteristics and histological scoring were inferior.

Plasma Electrolytic Oxidation of Titanium Implant Surfaces: Microgroove-Structures Improve Cellular Adhesion and Viability.

PubMed

Hartjen, Philip; Hoffmann, Alexia; Henningsen, Anders; Barbeck, Mike; Kopp, Alexander; Kluwe, Lan; Precht, Clarissa; Quatela, Olivia; Gaudin, Robert; Heiland, Max; Friedrich, Reinhard E; Knipfer, Christian; Grubeanu, Daniel; Smeets, Ralf; Jung, Ole

2018-01-01

Plasma electrolytic oxidation (PEO) is an established electrochemical treatment technique that can be used for surface modifications of metal implants. In this study we to treated titanium implants with PEO, to examine the resulting microstructure and to characterize adhesion and viability of cells on the treated surfaces. Our aim was to identify an optimal surface-modification for titanium implants in order to improve soft-tissue integration. Three surface-variants were generated on titanium alloy Ti6Al4V by PEO-treatment. The elemental composition and the microstructures of the surfaces were characterized using energy dispersive X-ray spectroscopy, scanning electron microscopy and profilometry. In vitro cytocompatibility of the surfaces was assessed by seeding L929 fibroblasts onto them and measuring the adhesion, viability and cytotoxicity of cells by means of live/dead staining, XTT assay and LDH assay. Electron microscopy and profilometry revealed that the PEO-surface variants differed largely in microstructure/topography, porosity and roughness from the untreated control material as well as from one another. Roughness was generally increased after PEO-treatment. In vitro, PEO-treatment led to improved cellular adhesion and viability of cells accompanied by decreased cytotoxicity. PEO-treatment provides a promising strategy to improve the integration of titanium implants with surrounding tissues. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Comparison of Regenerative Tissue Quality following Matrix-Associated Cell Implantation Using Amplified Chondrocytes Compared to Synovium-Derived Stem Cells in a Rabbit Model for Cartilage Lesions

PubMed Central

Kowal, Justyna M.; Seidenstuecker, Michael; Bernstein, Anke; Böttiger, Katharina; Xiong, Tanshiyue; Südkamp, Norbert P.

2018-01-01

Known problems of the autologous chondrocyte implantation motivate the search for cellular alternatives. The aim of the study was to test the potential of synovium-derived stem cells (SMSC) to regenerate cartilage using a matrix-associated implantation. In an osteochondral defect model of the medial femoral condyle in a rabbit, a collagen membrane was seeded with either culture-expanded allogenic chondrocytes or SMSC and then transplanted into the lesion. A tailored piece synovium served as a control. Rabbit SMSC formed typical cartilage in vitro. Macroscopic evaluation of defect healing and the thickness of the regenerated tissue did not reveal a significant difference between the intervention groups. However, instantaneous and shear modulus, reflecting the biomechanical strength of the repair tissue, was superior in the implantation group using allogenic chondrocytes (p < 0.05). This correlated with a more chondrogenic structure and higher proteoglycan expression, resulting in a lower OARSI score (p < 0.05). The repair tissue of all groups expressed comparable amounts of the collagen types I, II, and X. Cartilage regeneration following matrix-associated implantation using allogenic undifferentiated synovium-derived stem cells in a defect model in rabbits showed similar macroscopic results and collagen composition compared to amplified chondrocytes; however, biomechanical characteristics and histological scoring were inferior. PMID:29765410

Periodontal regeneration with stem cells-seeded collagen-hydroxyapatite scaffold.

PubMed

Liu, Zeping; Yin, Xing; Ye, Qingsong; He, Wulin; Ge, Mengke; Zhou, Xiaofu; Hu, Jing; Zou, Shujuan

2016-07-01

Re-establishing compromised periodontium to its original structure, properties and function is demanding, but also challenging, for successful orthodontic treatment. In this study, the periodontal regeneration capability of collagen-hydroxyapatite scaffolds, seeded with bone marrow stem cells, was investigated in a canine labial alveolar bone defect model. Bone marrow stem cells were isolated, expanded and characterized. Porous collagen-hydroxyapatite scaffold and cross-linked collagen-hydroxyapatite scaffold were prepared. Attachment, migration, proliferation and morphology of bone marrow stem cells, co-cultured with porous collagen-hydroxyapatite or cross-linked collagen-hydroxyapatite, were evaluated in vitro. The periodontal regeneration capability of collagen-hydroxyapatite scaffold with or without bone marrow stem cells was tested in six beagle dogs, with each dog carrying one sham-operated site as healthy control, and three labial alveolar bone defects untreated to allow natural healing, treated with bone marrow stem cells - collagen-hydroxyapatite scaffold implant or collagen-hydroxyapatite scaffold implant, respectively. Animals were euthanized at 3 and 6 months (3 animals per group) after implantation and the resected maxillary and mandibular segments were examined using micro-computed tomography scan, H&E staining, Masson's staining and histometric evaluation. Bone marrow stem cells were successfully isolated and demonstrated self-renewal and multi-potency in vitro. The porous collagen-hydroxyapatite and cross-linked collagen-hydroxyapatite had average pore sizes of 415 ± 20 µm and 203 ± 18 µm and porosity of 69 ± 0.5% and 50 ± 0.2%, respectively. The attachment, proliferation and migration of bone marrow stem cells were satisfactory on both porous collagen-hydroxyapatite and cross-linked collagen-hydroxyapatite scaffolds. Implantation of bone marrow stem cells - collagen-hydroxyapatite or collagen-hydroxyapatite scaffold in beagle dogs with experimental periodontal defects resulted in significantly enhanced periodontal regeneration characterized by formation of new bone, periodontal ligament and cementum, compared with the untreated defects, as evidenced by histological and micro-computed tomography examinations. The prepared collagen-hydroxyapatite scaffolds possess favorable bio-compatibility. The bone marrow stem cells - collagen-hydroxyapatite and collagen-hydroxyapatite scaffold - induced periodontal regeneration, with no aberrant events complicating the regenerative process. Further research is necessary to improve the bone marrow stem cells behavior in collagen-hydroxyapatite scaffolds after implantation. © The Author(s) 2016.

Oxygen mapping: Probing a novel seeding strategy for bone tissue engineering.

PubMed

Westphal, Ines; Jedelhauser, Claudia; Liebsch, Gregor; Wilhelmi, Arnd; Aszodi, Attila; Schieker, Matthias

2017-04-01

Bone tissue engineering (BTE) utilizing biomaterial scaffolds and human mesenchymal stem cells (hMSCs) is a promising approach for the treatment of bone defects. The quality of engineered tissue is crucially affected by numerous parameters including cell density and the oxygen supply. In this study, a novel oxygen-imaging sensor was introduced to monitor the oxygen distribution in three dimensional (3D) scaffolds in order to analyze a new cell-seeding strategy. Immortalized hMSCs, pre-cultured in a monolayer for 30-40% or 70-80% confluence, were used to seed demineralized bone matrix (DBM) scaffolds. Real-time measurements of oxygen consumption in vitro were simultaneously performed by the novel planar sensor and a conventional needle-type sensor over 24 h. Recorded oxygen maps of the novel planar sensor revealed that scaffolds, seeded with hMSCs harvested at lower densities (30-40% confluence), exhibited rapid exponential oxygen consumption profile. In contrast, harvesting cells at higher densities (70-80% confluence) resulted in a very slow, almost linear, oxygen decrease due to gradual achieving the stationary growth phase. In conclusion, it could be shown that not only the seeding density on a scaffold, but also the cell density at the time point of harvest is of major importance for BTE. The new cell seeding strategy of harvested MSCs at low density during its log phase could be a useful strategy for an early in vivo implantation of cell-seeded scaffolds after a shorter in vitro culture period. Furthermore, the novel oxygen imaging sensor enables a continuous, two-dimensional, quick and convenient to handle oxygen mapping for the development and optimization of tissue engineered scaffolds. Biotechnol. Bioeng. 2017;114: 894-902. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The challenge of staphylococcal pacemaker endocarditis in a patient with transposition of the great arteries endocarditis in congenital heart disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ch'ng, Julie; Chan, William; Lee, Paul

2003-06-01

Staphylococcus aureus is a leading cause of septicaemia and infective endocarditis. The overall incidence of staphylococcal bacteraemia is increasing, contributing to 16% of all hospital-acquired bacteraemias. The use of cardiac pacemakers has revolutionized the management of rhythm disturbances, yet this has also resulted in a group of patients at risk of pacemaker lead endocarditis and seeding in the range of 1% to 7%. We describe a 26-year-old man with transposition of the great arteries who had a pacemaker implanted and presented with S. aureus septicaemia 2 years postpacemaker implantation and went on to develop pacemaker lead endocarditis. This report illustratesmore » the risk of endocarditis in the population with congenital heart disease and an intracardiac device.« less

Ready to Use Tissue Construct for Military Bone & Cartilage Trauma

DTIC Science & Technology

2013-10-01

scaffolds composed of 90% poly-caprolactone (PCL) and 10% hydroxyapatite (HA) by weight (PCL+HA) without any seeding with either canine MSC or biologic...ligaments of the 5 knee. The implant consisted of a two layer Polycarprolacton (PCL) mixed with 10% hydroxyapatite (HA) scaffold with a 500 μm top...denoted by arrows, are apparent on both tibiae. Ratios of the biomechanical test parameters (experimental/control) in terms of percentage for

Phase I Trial of Adenovirus-Mediated IL-12 Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following Therapy

DTIC Science & Technology

2005-10-01

salvage seed implant, cryotherapy ) or who have a rising PSA while on hormone therapy for locally advanced prostate cancer are as follows: a. A...Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following Therapy PRINCIPAL INVESTIGATOR: Simon J. Hall, MD...CONTRACT NUMBER Phase I Trial of Adenovirus-Mediated IL-12 Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following

Amide linkages mimic phosphates in RNA interactions with proteins and are well tolerated in the guide strand of short interfering RNAs.

PubMed

Mutisya, Daniel; Hardcastle, Travis; Cheruiyot, Samwel K; Pallan, Pradeep S; Kennedy, Scott D; Egli, Martin; Kelley, Melissa L; Smith, Anja van Brabant; Rozners, Eriks

2017-08-21

While the use of RNA interference (RNAi) in molecular biology and functional genomics is a well-established technology, in vivo applications of synthetic short interfering RNAs (siRNAs) require chemical modifications. We recently found that amides as non-ionic replacements for phosphodiesters may be useful modifications for optimization of siRNAs. Herein, we report a comprehensive study of systematic replacement of a single phosphate with an amide linkage throughout the guide strand of siRNAs. The results show that amides are surprisingly well tolerated in the seed and central regions of the guide strand and increase the silencing activity when placed between nucleosides 10 and 12, at the catalytic site of Argonaute. A potential explanation is provided by the first crystal structure of an amide-modified RNA-DNA with Bacillus halodurans RNase H1. The structure reveals how small changes in both RNA and protein conformation allow the amide to establish hydrogen bonding interactions with the protein. Molecular dynamics simulations suggest that these alternative binding modes may compensate for interactions lost due to the absence of a phosphodiester moiety. Our results suggest that an amide can mimic important hydrogen bonding interactions with proteins required for RNAi activity and may be a promising modification for optimization of biological properties of siRNAs. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

The effect of incorporation of SDF-1alpha into PLGA scaffolds on stem cell recruitment and the inflammatory response.

PubMed

Thevenot, Paul T; Nair, Ashwin M; Shen, Jinhui; Lotfi, Parisa; Ko, Cheng-Yu; Tang, Liping

2010-05-01

Despite significant advances in the understanding of tissue responses to biomaterials, most implants are still plagued by inflammatory responses which can lead to fibrotic encapsulation. This is of dire consequence in tissue engineering, where seeded cells and bioactive components are separated from the native tissue, limiting the regenerative potential of the design. Additionally, these interactions prevent desired tissue integration and angiogenesis, preventing functionality of the design. Recent evidence supports that mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC) can have beneficial effects which alter the inflammatory responses and improve healing. The purpose of this study was to examine whether stem cells could be targeted to the site of biomaterial implantation and whether increasing local stem cell responses could improve the tissue response to PLGA scaffold implants. Through incorporation of SDF-1alpha through factor adsorption and mini-osmotic pump delivery, the host-derived stem cell response can be improved resulting in 3X increase in stem cell populations at the interface for up to 2 weeks. These interactions were found to significantly alter the acute mast cell responses, reducing the number of mast cells and degranulated mast cells near the scaffold implants. This led to subsequent downstream reduction in the inflammatory cell responses, and through altered mast cell activation and stem cell participation, increased angiogenesis and decreased fibrotic responses to the scaffold implants. These results support that enhanced recruitment of autologous stem cells can improve the tissue responses to biomaterial implants through modifying/bypassing inflammatory cell responses and jumpstarting stem cell participation in healing at the implant interface. Copyright 2010 Elsevier Ltd. All rights reserved.

Platelet-rich plasma enhances the integration of bioengineered cartilage with native tissue in an in vitro model.

PubMed

Sermer, Corey; Kandel, Rita; Anderson, Jesse; Hurtig, Mark; Theodoropoulos, John

2018-02-01

Current therapies for cartilage repair can be limited by an inability of the repair tissue to integrate with host tissue. Thus, there is interest in developing approaches to enhance integration. We have previously shown that platelet-rich plasma (PRP) improves cartilage tissue formation. This raised the question as to whether PRP could promote cartilage integration. Chondrocytes were isolated from cartilage harvested from bovine joints, seeded on a porous bone substitute and grown in vitro to form an osteochondral-like implant. After 7 days, the biphasic construct was soaked in PRP for 30 min before implantation into the core of a donut-shaped biphasic explant of native cartilage and bone. Controls were not soaked in PRP. The implant-explant construct was cultured for 2-4 weeks. PRP-soaked bioengineered implants integrated with host tissue in 73% of samples, whereas controls only integrated in 19% of samples. The integration strength, as determined by a push-out test, was significantly increased in the PRP-soaked implant group (219 ± 35.4 kPa) compared with controls (72.0 ± 28.5 kPa). This correlated with an increase in glycosaminoglycan and collagen accumulation in the region of integration in the PRP-treated implant group, compared with untreated controls. Immunohistochemical studies revealed that the integration zone contained collagen type II and aggrecan. The cells at the zone of integration in the PRP-soaked group had a 3.5-fold increase in matrix metalloproteinase-13 gene expression compared with controls. These results suggest that PRP-soaked bioengineered cartilage implants may be a better approach for cartilage repair due to enhanced integration. Copyright © 2017 John Wiley & Sons, Ltd.

The Effect of Incorporation of SDF-1α into PLGA Scaffolds on Stem Cell Recruitment and the Inflammatory Response

PubMed Central

Thevenot, Paul; Nair, Ashwin; Shen, Jinhui; Lotfi, Parisa; Ko, Cheng Yu; Tang, Liping

2010-01-01

Despite significant advances in the understanding of tissue responses to biomaterials, most implants are still plagued by inflammatory responses which can lead to fibrotic encapsulation. This is of dire consequence in tissue engineering, where seeded cells and bioactive components are separated from the native tissue, limiting the regenerative potential of the design. Additionally, these interactions prevent desired tissue integration and angiogenesis, preventing functionality of the design. Recent evidence supports that mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC) can have beneficial effects which alter the inflammatory responses and improve healing. The purpose of this study was to examine whether stem cells could be targeted to the site of biomaterial implantation and whether increasing local stem cell responses could improve the tissue response to PLGA scaffold implants. Through incorporation of SDF-1α through factor adsorption and mini-osmotic pump delivery, the host-derived stem cell response can be improved resulting in 3X increase in stem cell populations at the interface for up to 2 weeks. These interactions were found to significantly alter the acute mast cell responses, reducing the number of mast cells and degranulated mast cells near the scaffold implants. This led to subsequent downstream reduction in the inflammatory cell responses, and through altered mast cell activation and stem cell participation, increased angiogenesis and decreased fibrotic responses to the scaffold implants. These results support that enhanced recruitment of autologous stem cells can improve the tissue responses to biomaterial implants through modifying/bypassing inflammatory cell responses and jumpstarting stem cell participation in healing at the implant interface. PMID:20185171

Evaluation of a Proposed Biodegradable 188Re Source for Brachytherapy Application

PubMed Central

Khorshidi, Abdollah; Ahmadinejad, Marjan; Hamed Hosseini, S.

2015-01-01

Abstract This study aimed to evaluate dosimetric characteristics based on Monte Carlo (MC) simulations for a proposed beta emitter bioglass 188Re seed for internal radiotherapy applications. The bioactive glass seed has been developed using the sol-gel technique. The simulations were performed for the seed using MC radiation transport code to investigate the dosimetric factors recommended by the AAPM Task Group 60 (TG-60). Dose distributions due to the beta and photon radiation were predicted at different radial distances surrounding the source. The dose rate in water at the reference point was calculated to be 7.43 ± 0.5 cGy/h/μCi. The dosimetric factors consisting of the reference point dose rate, D(r0,θ0), the radial dose function, g(r), the 2-dimensional anisotropy function, F(r,θ), the 1-dimensional anisotropy function, φan(r), and the R90 quantity were estimated and compared with several available beta-emitting sources. The element 188Re incorporated in bioactive glasses produced by the sol-gel technique provides a suitable solution for producing new materials for seed implants applied to brachytherapy applications in prostate and liver cancers treatment. Dose distribution of 188Re seed was greater isotropic than other commercially attainable encapsulated seeds, since it has no end weld to attenuate radiation. The beta radiation-emitting 188Re source provides high doses of local radiation to the tumor tissue and the short range of the beta particles limit damage to the adjacent normal tissue. PMID:26181543

Practical considerations for maximizing heat production in a novel thermobrachytherapy seed prototype

PubMed Central

Gautam, Bhoj; Warrell, Gregory; Shvydka, Diana; Subramanian, Manny; Ishmael Parsai, E.

2014-01-01

Purpose: A combination of hyperthermia and radiation in the treatment of cancer has been proven to provide better tumor control than radiation administered as a monomodality, without an increase in complications or serious toxicities. Moreover, concurrent administration of hyperthermia and radiation displays synergistic enhancement, resulting in greater tumor cell killing than hyperthermia and radiation delivered separately. The authors have designed a new thermobrachytherapy (TB) seed, which serves as a source of both radiation and heat for concurrent brachytherapy and hyperthermia treatments when implanted in solid tumors. This innovative seed, similar in size and geometry to conventional seeds, will have self-regulating thermal properties. Methods: The new seed's geometry is based on the standard BEST Model 2301 125I seed, resulting in very similar dosimetric properties. The TB seed generates heat when placed in an oscillating magnetic field via induction heating of a ferromagnetic Ni–Cu alloy core that replaces the tungsten radiographic marker of the standard Model 2301. The alloy composition is selected to undergo a Curie transition near 50 °C, drastically decreasing power production at higher temperatures and providing for temperature self-regulation. Here, the authors present experimental studies of the magnetic properties of Ni–Cu alloy material, the visibility of TB seeds in radiographic imaging, and the ability of seed prototypes to uniformly heat tissue to a desirable temperature. Moreover, analyses are presented of magnetic shielding and thermal expansion of the TB seed, as well as matching of radiation dose to temperature distributions for a short interseed distance in a given treatment volume. Results: Annealing the Ni–Cu alloy has a significant effect on its magnetization properties, increasing the sharpness of the Curie transition. The TB seed preserves the radiographic properties of the BEST 2301 seed in both plain x rays and CT images, and a preliminary experiment demonstrates thermal self-regulation and adequate heating of a tissue-mimicking phantom by seed prototypes. The effect of self-shielding of the seed against the external magnetic field is small, and only minor thermal stress is induced in heating of the seeds from room temperature to well above the seed operating temperature. With proper selection of magnetic field parameters, the thermal dose distribution of an arrangement of TB and hyperthermia-only seeds may be made to match with its radiation dose distribution. Conclusions: The presented analyses address several practical considerations for manufacturing of the proposed TB seeds and identify critical issues for the prototype implementation. The authors’ preliminary experiments demonstrate close agreement with the modeling results, confirming the feasibility of combining sources of heat and radiation into a single thermobrachytherapy seed. PMID:24506651

Practical considerations for maximizing heat production in a novel thermobrachytherapy seed prototype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gautam, Bhoj; Warrell, Gregory; Shvydka, Diana

2014-02-15

Purpose: A combination of hyperthermia and radiation in the treatment of cancer has been proven to provide better tumor control than radiation administered as a monomodality, without an increase in complications or serious toxicities. Moreover, concurrent administration of hyperthermia and radiation displays synergistic enhancement, resulting in greater tumor cell killing than hyperthermia and radiation delivered separately. The authors have designed a new thermobrachytherapy (TB) seed, which serves as a source of both radiation and heat for concurrent brachytherapy and hyperthermia treatments when implanted in solid tumors. This innovative seed, similar in size and geometry to conventional seeds, will have self-regulatingmore » thermal properties. Methods: The new seed's geometry is based on the standard BEST Model 2301{sup 125}I seed, resulting in very similar dosimetric properties. The TB seed generates heat when placed in an oscillating magnetic field via induction heating of a ferromagnetic Ni–Cu alloy core that replaces the tungsten radiographic marker of the standard Model 2301. The alloy composition is selected to undergo a Curie transition near 50 °C, drastically decreasing power production at higher temperatures and providing for temperature self-regulation. Here, the authors present experimental studies of the magnetic properties of Ni–Cu alloy material, the visibility of TB seeds in radiographic imaging, and the ability of seed prototypes to uniformly heat tissue to a desirable temperature. Moreover, analyses are presented of magnetic shielding and thermal expansion of the TB seed, as well as matching of radiation dose to temperature distributions for a short interseed distance in a given treatment volume. Results: Annealing the Ni–Cu alloy has a significant effect on its magnetization properties, increasing the sharpness of the Curie transition. The TB seed preserves the radiographic properties of the BEST 2301 seed in both plain x rays and CT images, and a preliminary experiment demonstrates thermal self-regulation and adequate heating of a tissue-mimicking phantom by seed prototypes. The effect of self-shielding of the seed against the external magnetic field is small, and only minor thermal stress is induced in heating of the seeds from room temperature to well above the seed operating temperature. With proper selection of magnetic field parameters, the thermal dose distribution of an arrangement of TB and hyperthermia-only seeds may be made to match with its radiation dose distribution. Conclusions: The presented analyses address several practical considerations for manufacturing of the proposed TB seeds and identify critical issues for the prototype implementation. The authors’ preliminary experiments demonstrate close agreement with the modeling results, confirming the feasibility of combining sources of heat and radiation into a single thermobrachytherapy seed.« less

Practical considerations for maximizing heat production in a novel thermobrachytherapy seed prototype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gautam, Bhoj; Warrell, Gregory; Shvydka, Diana

Purpose: A combination of hyperthermia and radiation in the treatment of cancer has been proven to provide better tumor control than radiation administered as a monomodality, without an increase in complications or serious toxicities. Moreover, concurrent administration of hyperthermia and radiation displays synergistic enhancement, resulting in greater tumor cell killing than hyperthermia and radiation delivered separately. The authors have designed a new thermobrachytherapy (TB) seed, which serves as a source of both radiation and heat for concurrent brachytherapy and hyperthermia treatments when implanted in solid tumors. This innovative seed, similar in size and geometry to conventional seeds, will have self-regulatingmore » thermal properties. Methods: The new seed's geometry is based on the standard BEST Model 2301{sup 125}I seed, resulting in very similar dosimetric properties. The TB seed generates heat when placed in an oscillating magnetic field via induction heating of a ferromagnetic Ni–Cu alloy core that replaces the tungsten radiographic marker of the standard Model 2301. The alloy composition is selected to undergo a Curie transition near 50 °C, drastically decreasing power production at higher temperatures and providing for temperature self-regulation. Here, the authors present experimental studies of the magnetic properties of Ni–Cu alloy material, the visibility of TB seeds in radiographic imaging, and the ability of seed prototypes to uniformly heat tissue to a desirable temperature. Moreover, analyses are presented of magnetic shielding and thermal expansion of the TB seed, as well as matching of radiation dose to temperature distributions for a short interseed distance in a given treatment volume. Results: Annealing the Ni–Cu alloy has a significant effect on its magnetization properties, increasing the sharpness of the Curie transition. The TB seed preserves the radiographic properties of the BEST 2301 seed in both plain x rays and CT images, and a preliminary experiment demonstrates thermal self-regulation and adequate heating of a tissue-mimicking phantom by seed prototypes. The effect of self-shielding of the seed against the external magnetic field is small, and only minor thermal stress is induced in heating of the seeds from room temperature to well above the seed operating temperature. With proper selection of magnetic field parameters, the thermal dose distribution of an arrangement of TB and hyperthermia-only seeds may be made to match with its radiation dose distribution. Conclusions: The presented analyses address several practical considerations for manufacturing of the proposed TB seeds and identify critical issues for the prototype implementation. The authors’ preliminary experiments demonstrate close agreement with the modeling results, confirming the feasibility of combining sources of heat and radiation into a single thermobrachytherapy seed.« less

Experimental and Monte Carlo measurements of dose perturbation around a non-radioactive brachytherapy seed in external beam radiotherapy

NASA Astrophysics Data System (ADS)

Steinman, James P.

I-125 seeds used in permanent prostate brachytherapy are composed of high-Z metals and may number from 40 to over 100 in a typical implant. If any supplemental external beam treatment is administered afterward (as for salvaging failed brachytherapy treatment), it is possible that the seeds may cause substantial dose perturbation which will depend on numerous factors (photon energy, depth, field size, number of seeds, etc.) and this effect needs to be thoroughly investigated. Film measurements were primarily done using Kodak XV2 layered above and below a non-radioactive I-125 seed placed in a groove on a Lucite plate with 5 cm buildup and 10 cm backscatter added at 95 cm SSD. The phantom was irradiated with and without seed with 6 MV photons for a 1 x 1 cm2 field size. Monte Carlo simulations were carried out using DOSXYZnrc using the same parameters and compared with Gafchromic EBT2 film. Other comparisons looked at changing energy, depth, and field size in both with and without seeds configuration. This study was further extended to include metals of various Z of the seed's dimensions and also looked into effect of 3 seeds spaced 0.5 cm vertically. Another measurement was done using two opposing fields using single as well as 3 seed configuration to see whether the dose enhancement and attenuation cancel out in multi-field treatments which is the norm clinically in a prostate treatment. For a single I-125 seed, on XV film a localized dose enhancement of 6.3% upstream and -10.9% downstream was noticed. With three seeds, this effect did not change. With two opposing fields, a cold spot around the seed of ~3% was noticed from film measurements. Increasing energy and field size decreased the effect while increase in Z of material greatly increased the effect. Increasing depth appeared to have no effect. DOSXYZnrc and EBT2 film verified maximum dose enhancement of +15% upstream and -20% downstream of the I-125 seed surface. In general, the range of the effect was limited to ~2 mm upstream and ~5 mm downstream with reference to the seed surface in relation to the incident photon beam. As with other heterogeneities in a human body, the dose perturbation due to I-125 seeds in external beam radiotherapy depends on incident beam energy, field size, and the composition of the seed. However, unlike other heterogeneities, no depth dependence of the seed in the material was noted. With multiple seeds spaced apart and multiple fields normally used in prostate treatment, the dose perturbation due to them may not be clinically significant.

Interpreting sperm DNA damage in a diverse range of mammalian sperm by means of the two-tailed comet assay

PubMed Central

Cortés-Gutiérrez, Elva I.; López-Fernández, Carmen; Fernández, José Luis; Dávila-Rodríguez, Martha I.; Johnston, Stephen D.; Gosálvez, Jaime

2014-01-01

Key Concepts The two-dimensional Two-Tailed Comet assay (TT-comet) protocol is a valuable technique to differentiate between single-stranded (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell.Protein lysis inherent with the TT-comet protocol accounts for differences in sperm protamine composition at a species-specific level to produce reliable visualization of sperm DNA damage.Alkaline treatment may break the sugar–phosphate backbone in abasic sites or at sites with deoxyribose damage, transforming these lesions into DNA breaks that are also converted into ssDNA. These lesions are known as Alkali Labile Sites “ALSs.”DBD–FISH permits the in situ visualization of DNA breaks, abasic sites or alkaline-sensitive DNA regions.The alkaline comet single assay reveals that all mammalian species display constitutive ALS related with the requirement of the sperm to undergo transient changes in DNA structure linked with chromatin packing.Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome.The TT is a valuable tool for identifying SSBs or DSBs in sperm cells with DNA fragmentation and can be therefore used for the purposes of fertility assessment. Sperm DNA damage is associated with fertilization failure, impaired pre-and post- embryo implantation and poor pregnancy outcome. A series of methodologies to assess DNA damage in spermatozoa have been developed but most are unable to differentiate between single-stranded DNA breaks (SSBs) and double-stranded DNA breaks (DSBs) on the same sperm cell. The two-dimensional Two-Tailed Comet assay (TT-comet) protocol highlighted in this review overcomes this limitation and emphasizes the importance in accounting for the difference in sperm protamine composition at a species-specific level for the appropriate preparation of the assay. The TT-comet is a modification of the original comet assay that uses a two dimensional electrophoresis to allow for the simultaneous evaluation of DSBs and SSBs in mammalian spermatozoa. Here we have compiled a retrospective overview of how the TT-comet assay has been used to investigate the structure and function of sperm DNA across a diverse range of mammalian species (eutheria, metatheria, and prototheria). When conducted as part of the TT-comet assay, we illustrate (a) how the alkaline comet single assay has been used to help understand the constitutive and transient changes in DNA structure associated with chromatin packing, (b) the capacity of the TT-comet to differentiate between the presence of SSBs and DSBs (c) and the possible implications of SSBs or DSBs for the assessment of infertility. PMID:25505901

Perfusion-decellularization of human ear grafts enables ECM-based scaffolds for auricular vascularized composite tissue engineering.

PubMed

Duisit, Jérôme; Amiel, Hadrien; Wüthrich, Tsering; Taddeo, Adriano; Dedriche, Adeline; Destoop, Vincent; Pardoen, Thomas; Bouzin, Caroline; Joris, Virginie; Magee, Derek; Vögelin, Esther; Harriman, David; Dessy, Chantal; Orlando, Giuseppe; Behets, Catherine; Rieben, Robert; Gianello, Pierre; Lengelé, Benoît

2018-06-01

Human ear reconstruction is recognized as the emblematic enterprise in tissue engineering. Up to now, it has failed to reach human applications requiring appropriate tissue complexity along with an accessible vascular tree. We hereby propose a new method to process human auricles in order to provide a poorly immunogenic, complex and vascularized ear graft scaffold. 12 human ears with their vascular pedicles were procured. Perfusion-decellularization was applied using a SDS/polar solvent protocol. Cell and antigen removal was examined by histology and DNA was quantified. Preservation of the extracellular matrix (ECM) was assessed by conventional and 3D-histology, proteins and cytokines quantifications. Biocompatibility was assessed by implantation in rats for up to 60 days. Adipose-derived stem cells seeding was conducted on scaffold samples and with human aortic endothelial cells whole graft seeding in a perfusion-bioreactor. Histology confirmed cell and antigen clearance. DNA reduction was 97.3%. ECM structure and composition were preserved. Implanted scaffolds were tolerated in vivo, with acceptable inflammation, remodeling, and anti-donor antibody formation. Seeding experiments demonstrated cell engraftment and viability. Vascularized and complex auricular scaffolds can be obtained from human source to provide a platform for further functional auricular tissue engineered constructs, hence providing an ideal road to the vascularized composite tissue engineering approach. The ear is emblematic in the biofabrication of tissues and organs. Current regenerative medicine strategies, with matrix from donor tissues or 3D-printed, didn't reach any application for reconstruction, because critically missing a vascular tree for perfusion and transplantation. We previously described the production of vascularized and cell-compatible scaffolds, from porcine ear grafts. In this study, we ---- applied findings directly to human auricles harvested from postmortem donors, providing a perfusable matrix that retains the ear's original complexity and hosts new viable cells after seeding. This approach unlocks the ability to achieve an auricular tissue engineering approach, associated with possible clinical translation. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Ectopic bone regeneration by human bone marrow mononucleated cells, undifferentiated and osteogenically differentiated bone marrow mesenchymal stem cells in beta-tricalcium phosphate scaffolds.

PubMed

Ye, Xinhai; Yin, Xiaofan; Yang, Dawei; Tan, Jian; Liu, Guangpeng

2012-07-01

Tissue engineering approaches using the combination of porous ceramics and bone marrow mesenchymal stem cells (BMSCs) represent a promising bone substitute for repairing large bone defects. Nevertheless, optimal conditions for constructing tissue-engineered bone have yet to be determined. It remains unclear if transplantation of predifferentiated BMSCs is superior to undifferentiated BMSCs or freshly isolated bone marrow mononucleated cells (BMNCs) in terms of new bone formation in vivo. The aim of this study was to investigate the effect of in vitro osteogenic differentiation (β-glycerophosphate, dexamethasone, and l-ascorbic acid) of human BMSCs on the capability to form tissue-engineered bone in unloaded conditions after subcutaneous implantation in nude mice. After isolation from human bone marrow aspirates, BMNCs were divided into three parts: one part was seeded onto porous beta-tricalcium phosphate ceramics immediately and transplanted in a heterotopic nude mice model; two parts were expanded in vitro to passage 2 before cell seeding and in vivo transplantation, either under osteogenic conditions or not. Animals were sacrificed for micro-CT and histological evaluation at 4, 8, 12, 16, and 20 weeks postimplantation. The results showed that BMSCs differentiated into osteo-progenitor cells after induction, as evidenced by the altered cell morphology and elevated alkaline phosphatase activity and calcium deposition, but their clonogenicity, proliferating rate, and seeding efficacy were not significantly affected by osteogenic differentiation, compared with undifferentiated cells. Extensive new bone formed in the pores of all the scaffolds seeded with predifferentiated BMSCs at 4 weeks after implantation, and maintained for 20 weeks. On the contrary, scaffolds containing undifferentiated BMSCs revealed limited bone formation only in 1 out of 6 cases at 8 weeks, and maintained for 4 weeks. For scaffolds with BMNCs, woven bone was observed sporadically only in one case at 8 weeks. Overall, this study suggests that ectopic osteogenesis of cell/scaffold composites is more dependent on the in vitro expansion condition, and osteo-differentiated BMSCs hold the highest potential concerning in vivo bone regeneration.

[Experimental study of repairing bone defect with tissue engineered bone seeded with autologous red bone marrow and wrapped by pedicled fascial flap].

PubMed

Yang, Xinming; Shi, Wei; Du, Yakun; Meng, Xianyong; Yin, Yanlin

2009-10-01

To investigate the effect of repairing bone defect with tissue engineered bone seeded with the autologous red bone marrow (ARBM) and wrapped by the pedicled fascial flap and provide experimental foundation for clinical application. Thirty-two New Zealand white rabbits (male and/or female) aged 4-5 months old and weighing 2.0-2.5 kg were used to make the experimental model of bilateral 2 cm defect of the long bone and the periosteum in the radius. The tissue engineered bone was prepared by seeding the ARBM obtained from the rabbits on the osteoinductive absorbing material containing BMP. The left side of the experimental model underwent the implantation of autologous tissue engineered bone serving as the control group (group A). While the right side was designed as the experimental group (group B), one 5 cm x 3 cm fascial flap pedicled on the nameless blood vessel along with its capillary network adjacent to the bone defect was prepared using microsurgical technology, and the autologous tissue engineered bone wrapped by the fascial flap was used to fill the bone defect. At 4, 8, 12, and 16 weeks after operation, X-ray exam, absorbance (A) value test, gross morphology and histology observation, morphology quantitative analysis of bone in the reparative area, vascular image analysis on the boundary area were conducted. X-ray films, gross morphology observation, and histology observation: group B was superior to group A in terms of the growth of blood vessel into the implant, the quantity and the speed of the bone trabecula and the cartilage tissue formation, the development of mature bone structure, the remodeling of shaft structure, the reopen of marrow cavity, and the absorbance and degradation of the implant. A value: there was significant difference between two groups 8, 12, and 16 weeks after operation (P < 0.05), and there were significant differences among those three time points in groups A and B (P < 0.05). For the ratio of neonatal trabecula area to the total reparative area, there were significant differences between two groups 4, 8, 12, and 16 weeks after operation (P < 0.05), and there were significant differences among those four time points in group B (P < 0.05). For the vascular regenerative area in per unit area of the junctional zone, group B was superior to group A 4, 8, 12, and 16 weeks after operation (P < 0.05). Tissue engineered bone, seeded with the ARBM and wrapped by the pedicled fascial flap, has a sound reparative effect on bone defect due to its dual role of constructing vascularization and inducing membrane guided tissue regeneration.

In Vivo Bone Formation Within Engineered Hydroxyapatite Scaffolds in a Sheep Model.

PubMed

Lovati, A B; Lopa, S; Recordati, C; Talò, G; Turrisi, C; Bottagisio, M; Losa, M; Scanziani, E; Moretti, M

2016-08-01

Large bone defects still represent a major burden in orthopedics, requiring bone-graft implantation to promote the bone repair. Along with autografts that currently represent the gold standard for complicated fracture repair, the bone tissue engineering offers a promising alternative strategy combining bone-graft substitutes with osteoprogenitor cells able to support the bone tissue ingrowth within the implant. Hence, the optimization of cell loading and distribution within osteoconductive scaffolds is mandatory to support a successful bone formation within the scaffold pores. With this purpose, we engineered constructs by seeding and culturing autologous, osteodifferentiated bone marrow mesenchymal stem cells within hydroxyapatite (HA)-based grafts by means of a perfusion bioreactor to enhance the in vivo implant-bone osseointegration in an ovine model. Specifically, we compared the engineered constructs in two different anatomical bone sites, tibia, and femur, compared with cell-free or static cell-loaded scaffolds. After 2 and 4 months, the bone formation and the scaffold osseointegration were assessed by micro-CT and histological analyses. The results demonstrated the capability of the acellular HA-based grafts to determine an implant-bone osseointegration similar to that of statically or dynamically cultured grafts. Our study demonstrated that the tibia is characterized by a lower bone repair capability compared to femur, in which the contribution of transplanted cells is not crucial to enhance the bone-implant osseointegration. Indeed, only in tibia, the dynamic cell-loaded implants performed slightly better than the cell-free or static cell-loaded grafts, indicating that this is a valid approach to sustain the bone deposition and osseointegration in disadvantaged anatomical sites.

The Effect of Postmastectomy Radiation Therapy on Breast Implants: Material Analysis on Silicone and Polyurethane Prosthesis.

PubMed

Lo Torto, Federico; Relucenti, Michela; Familiari, Giuseppe; Vaia, Nicola; Casella, Donato; Matassa, Roberto; Miglietta, Selenia; Marinozzi, Franco; Bini, Fabiano; Fratoddi, Ilaria; Sciubba, Fabio; Cassese, Raffaele; Tombolini, Vincenzo; Ribuffo, Diego

2018-05-17

The pathogenic mechanism underlying capsular contracture is still unknown. It is certainly a multifactorial process, resulting from human body reaction, biofilm activation, bacteremic seeding, or silicone exposure. The scope of the present article is to investigate the effect of hypofractionated radiotherapy protocol (2.66 Gy × 16 sessions) both on silicone and polyurethane breast implants. Silicone implants and polyurethane underwent irradiation according to a hypofractionated radiotherapy protocol for the treatment of breast cancer. After irradiation implant shells underwent mechanical, chemical, and microstructural evaluation by means of tensile testing, infrared spectra in attenuated total reflectance mode, nuclear magnetic resonance, and field emission scanning electron microscopy. At superficial analysis, irradiated silicone samples show several visible secondary and tertiary blebs. Polyurethane implants showed an open cell structure, which closely resembles a sponge. Morphological observation of struts from treated polyurethane sample shows a more compact structure, with significantly shorter and thicker struts compared with untreated sample. The infrared spectra in attenuated total reflectance mode spectra of irradiated and control samples were compared either for silicon and polyurethane samples. In the case of silicone-based membranes, treated and control specimens showed similar bands, with little differences in the treated one. Nuclear magnetic resonance spectra on the fraction soluble in CDCl3 support these observations. Tensile tests on silicone samples showed a softer behavior of the treated ones. Tensile tests on Polyurethane samples showed no significant differences. Polyurethane implants seem to be more resistant to radiotherapy damage, whereas silicone prosthesis showed more structural, mechanical, and chemical modifications.

Combination of bone morphogenetic protein-2 plasmid DNA with chemokine CXCL12 creates an additive effect on bone formation onset and volume.

PubMed

Wegman, F; Poldervaart, M T; van der Helm, Y J; Oner, F C; Dhert, W J; Alblas, J

2015-07-27

Bone morphogenetic protein-2 (BMP-2) gene delivery has shown to induce bone formation in vivo in cell-based tissue engineering. In addition, the chemoattractant stromal cell-derived factor-1α (SDF-1α, also known as CXCL12) is known to recruit multipotent stromal cells towards its release site where it enhances vascularisation and possibly contributes to osteogenic differentiation. To investigate potential cooperative behaviour for bone formation, we investigated combined release of BMP-2 and SDF-1α on ectopic bone formation in mice. Multipotent stromal cell-seeded and cell-free constructs with BMP-2 plasmid DNA and /or SDF-1α loaded onto gelatin microparticles, were implanted subcutaneously in mice for a period of 6 weeks. Histological analysis and histomorphometry revealed that the onset of bone formation and the formed bone volume were both enhanced by the combination of BMP-2 and SDF-1α compared to controls in cell-seeded constructs. Samples without seeded multipotent stromal cells failed to induce any bone formation. We conclude that the addition of stromal cell-derived factor-1α to a cell-seeded alginate based bone morphogenetic protein-2 plasmid DNA construct has an additive effect on bone formation and can be considered a promising combination for bone regeneration.

Soy Protein Scaffold Biomaterials for Tissue Engineering and Regenerative Medicine

NASA Astrophysics Data System (ADS)

Chien, Karen B.

Developing functional biomaterials using highly processable materials with tailorable physical and bioactive properties is an ongoing challenge in tissue engineering. Soy protein is an abundant, natural resource with potential use for regenerative medicine applications. Preliminary studies show that soy protein can be physically modified and fabricated into various biocompatible constructs. However, optimized soy protein structures for tissue regeneration (i.e. 3D porous scaffolds) have not yet been designed. Furthermore, little work has established the in vivo biocompatibility of implanted soy protein and the benefit of using soy over other proteins including FDA-approved bovine collagen. In this work, freeze-drying and 3D printing fabrication processes were developed using commercially available soy protein to create porous scaffolds that improve cell growth and infiltration compared to other soy biomaterials previously reported. Characterization of scaffold structure, porosity, and mechanical/degradation properties was performed. In addition, the behavior of human mesenchymal stem cells seeded on various designed soy scaffolds was analyzed. Biological characterization of the cell-seeded scaffolds was performed to assess feasibility for use in liver tissue regeneration. The acute and humoral response of soy scaffolds implanted in an in vivo mouse subcutaneous model was also investigated. All fabricated soy scaffolds were modified using thermal, chemical, and enzymatic crosslinking to change properties and cell growth behavior. 3D printing allowed for control of scaffold pore size and geometry. Scaffold structure, porosity, and degradation rate significantly altered the in vivo response. Freeze-dried soy scaffolds had similar biocompatibility as freeze-dried collagen scaffolds of the same protein content. However, the soy scaffolds degraded at a much faster rate, minimizing immunogenicity. Interestingly, subcutaneously implanted soy scaffolds affected blood glucose and insulin sensitivity levels. Furthermore, soy scaffolds implanted in the intraperitoneal cavity attached to adjacent liver tissue with no abnormalities. In vitro, soy scaffolds supported hMSC viability and transdifferentiation into hepatocyte-like cells. These results support the use of soy scaffolds for liver tissue engineering and for treating metabolic diseases. Based on achievable structural and mechanical properties, as well as systemic effects of ingested and degraded soy proteins, soy protein scaffolds may serve as new multifunctional biomaterials for tissue engineering and regenerative medicine.

In Vitro Maturation and In Vivo Integration and Function of an Engineered Cell-Seeded Disc-like Angle Ply Structure (DAPS) for Total Disc Arthroplasty.

PubMed

Martin, J T; Gullbrand, S E; Kim, D H; Ikuta, K; Pfeifer, C G; Ashinsky, B G; Smith, L J; Elliott, D M; Smith, H E; Mauck, R L

2017-11-17

Total disc replacement with an engineered substitute is a promising avenue for treating advanced intervertebral disc disease. Toward this goal, we developed cell-seeded disc-like angle ply structures (DAPS) and showed through in vitro studies that these constructs mature to match native disc composition, structure, and function with long-term culture. We then evaluated DAPS performance in an in vivo rat model of total disc replacement; over 5 weeks in vivo, DAPS maintained their structure, prevented intervertebral bony fusion, and matched native disc mechanical function at physiologic loads in situ. However, DAPS rapidly lost proteoglycan post-implantation and did not integrate into adjacent vertebrae. To address this, we modified the design to include polymer endplates to interface the DAPS with adjacent vertebrae, and showed that this modification mitigated in vivo proteoglycan loss while maintaining mechanical function and promoting integration. Together, these data demonstrate that cell-seeded engineered discs can replicate many characteristics of the native disc and are a viable option for total disc arthroplasty.

SU-G-IeP4-14: Prostate Brachytherapy Activity Measurement and Source Localization by Using a Dual Photon Emission Computed Tomography System: A Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, C; Lin, H; Chuang, K

2016-06-15

Purpose: To monitor the activity distribution and needle position during and after implantation in operating rooms. Methods: Simulation studies were conducted to assess the feasibility of measurement activity distribution and seed localization using the DuPECT system. The system consists of a LaBr3-based probe and planar detection heads, a collimation system, and a coincidence circuit. The two heads can be manipulated independently. Simplified Yb-169 brachytherapy seeds were used. A water-filled cylindrical phantom with a 40-mm diameter and 40-mm length was used to model a simplified prostate of the Asian man. Two simplified seeds were placed at a radial distance of 10more » mm and tangential distance of 10 mm from the center of the phantom. The probe head was arranged perpendicular to the planar head. Results of various imaging durations were analyzed and the accuracy of the seed localization was assessed by calculating the centroid of the seed. Results: The reconstructed images indicate that the DuPECT can measure the activity distribution and locate the seeds dwelt in different positions intraoperatively. The calculated centroid on average turned out to be accurate within the pixel size of 0.5 mm. The two sources were identified when the duration is longer than 15 s. The sensitivity measured in water was merely 0.07 cps/MBq. Conclusion: Preliminary results show that the measurement of the activity distribution and seed localization are feasible using the DuPECT system intraoperatively. It indicates the DuPECT system has potential to be an approach for dose-distribution-validation. The efficacy of acvtivity distribution measurement and source localization using the DuPECT system will evaluated in more realistic phantom studies (e.g., various attenuation materials and greater number of seeds) in the future investigation.« less

Cobalt chromium alloy with immobilized BMP peptide for enhanced bone growth.

PubMed

Poh, Chye Khoon; Shi, Zhilong; Tan, Xiao Wei; Liang, Zhen Chang; Foo, Xue Mei; Tan, Hark Chuan; Neoh, Koon Gee; Wang, Wilson

2011-09-01

Cobalt chromium (CoCr) alloys are widely used in orthopedic practice, however, lack of integration into the bone for long-term survival often occurs, leading to implant failure. Revision surgery to address such a failure involves increased risks, complications, and costs. Advances to enhancement of bone-implant interactions would improve implant longevity and long-term results. Therefore, we investigated the effects of BMP peptide covalently grafted to CoCr alloy on osteogenesis. The BMP peptide was derived from the knuckle epitope of bone morphogenic protein-2 (BMP-2) and was conjugated via a cysteine amino acid at the N-terminus. X-ray photoelectron spectroscopy and o-phthaldialdehyde were used to verify successful grafting at various stages of surface functionalization. Surface topography was evaluated from the surface profile determined by atomic force microscopy. Osteoblastic cells (MC3T3-E1) were seeded on the substrates, and the effects of BMP peptide on osteogenic differentiation were evaluated by measuring alkaline phosphatase (ALP) activity and calcium mineral deposition. The functionalized surfaces showed a twofold increase in ALP activity after 2 weeks incubation and a fourfold increase in calcium content after 3 weeks incubation compared to the pristine substrate. These findings are potentially useful in the development of improved CoCr implants for use in orthopedic applications. Copyright © 2011 Orthopaedic Research Society.

Effects of cell-attachment and extracellular matrix on bone formation in vivo in collagen-hydroxyapatite scaffolds.

PubMed

Villa, Max M; Wang, Liping; Rowe, David W; Wei, Mei

2014-01-01

Cell-based tissue engineering can be used to replace missing or damaged bone, but the optimal methods for delivering therapeutic cells to a bony defect have not yet been established. Using transgenic reporter cells as a donor source, two different collagen-hydroxyapatite (HA) scaffolds, and a critical-size calvarial defect model, we investigated the effect of a cell-attachment period prior to implantation, with or without an extracellular matrix-based seeding suspension, on cell engraftment and osteogenesis. When quantitatively compared, the in-house scaffold implanted immediately had a higher mean radiopacity than in-house scaffolds incubated overnight. Both scaffold types implanted immediately had significantly higher area fractions of donor cells, while the in-house collagen-HA scaffolds implanted immediately had higher area fractions of the mineralization label compared with groups incubated overnight. When the cell loading was compared in vitro for each delivery method using the in-house scaffold, immediate loading led to higher numbers of delivered cells. Immediate loading may be preferable in order to ensure robust bone formation in vivo. The use of a secondary ECM carrier improved the distribution of donor cells only when a pre-attachment period was applied. These results have improved our understanding of cell delivery to bony defects in the context of in vivo outcomes.

[Post-treatment rehabilitation after autologous chondrocyte implantation: State of the art and recommendations of the Clinical Tissue Regeneration Study Group of the German Society for Accident Surgery and the German Society for Orthopedics and Orthopedic Surgery].

PubMed

Pietschmann, M F; Horng, A; Glaser, C; Albrecht, D; Bruns, J; Scheffler, S; Marlovits, S; Angele, P; Aurich, M; Bosch, U; Fritz, J; Frosch, K H; Kolombe, T; Richter, W; Petersen, J P; Nöth, U; Niemeyer, P; Jagodzinsky, M; Kasten, P; Ruhnau, K; Müller, P E

2014-03-01

Over the course of the past two decades autologous chondrocyte implantation (ACI) has become an important surgical technique for treating large cartilage defects. The original method using a periostal flap has been improved by using cell-seeded scaffolds for implantation, the matrix-based autologous chondrocyte implantation (mb-ACI) procedure. Uniform nationwide guidelines for post-ACI rehabilitation do not exist. A survey was conducted among the members of the clinical tissue regeneration study group concerning the current rehabilitation protocols and the members of the study group published recommendations for postoperative rehabilitation and treatment after ACI based on the results of this survey. There was agreement on fundamentals concerning a location-specific rehabilitation protocol (femoral condyle vs. patellofemoral joint). With regard to weight bearing and range of motion a variety of different protocols exist. Similar to this total agreement on the role of magnetic resonance imaging (MRI) for postsurgical care was found but again a great variety of different protocols exist. This manuscript summarizes the recommendations of the members of the German clinical tissue regeneration study group on postsurgical rehabilitation and MRI assessment after ACI (level IVb/EBM).

Recruitment of host's progenitor cells to sites of human amniotic fluid stem cells implantation.

PubMed

Mirabella, Teodelinda; Poggi, Alessandro; Scaranari, Monica; Mogni, Massimo; Lituania, Mario; Baldo, Chiara; Cancedda, Ranieri; Gentili, Chiara

2011-06-01

The amniotic fluid is a new source of multipotent stem cells with a therapeutic potential for human diseases. Cultured at low cell density, human amniotic fluid stem cells (hAFSCs) were still able to generate colony-forming unit-fibroblast (CFU-F) after 60 doublings, thus confirming their staminal nature. Moreover, after extensive in vitro cell expansion hAFSCs maintained a stable karyotype. The expression of genes, such as SSEA-4, SOX2 and OCT3/4 was confirmed at early and later culture stage. Also, hAFSCs showed bright expression of mesenchymal lineage markers and immunoregulatory properties. hAFSCs, seeded onto hydroxyapatite scaffolds and subcutaneously implanted in nude mice, played a pivotal role in mounting a response resulting in the recruitment of host's progenitor cells forming tissues of mesodermal origin such as fat, muscle, fibrous tissue and immature bone. Implanted hAFSCs migrated from the scaffold to the skin overlying implant site but not to other organs. Given their in vivo: (i) recruitment of host progenitor cells, (ii) homing towards injured sites and (iii) multipotentiality in tissue repair, hAFSCs are a very appealing reserve of stem cells potentially useful for clinical application in regenerative medicine. Copyright © 2011 Elsevier Ltd. All rights reserved.

Source strength verification and quality assurance of preloaded brachytherapy needles using a CMOS flat panel detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Golshan, Maryam, E-mail: maryam.golshan@bccancer.bc.ca; Spadinger, Ingrid; Chng, Nick

2016-06-15

Purpose: Current methods of low dose rate brachytherapy source strength verification for sources preloaded into needles consist of either assaying a small number of seeds from a separate sample belonging to the same lot used to load the needles or performing batch assays of a subset of the preloaded seed trains. Both of these methods are cumbersome and have the limitations inherent to sampling. The purpose of this work was to investigate an alternative approach that uses an image-based, autoradiographic system capable of the rapid and complete assay of all sources without compromising sterility. Methods: The system consists of amore » flat panel image detector, an autoclavable needle holder, and software to analyze the detected signals. The needle holder was designed to maintain a fixed vertical spacing between the needles and the image detector, and to collimate the emissions from each seed. It also provides a sterile barrier between the needles and the imager. The image detector has a sufficiently large image capture area to allow several needles to be analyzed simultaneously.Several tests were performed to assess the accuracy and reproducibility of source strengths obtained using this system. Three different seed models (Oncura 6711 and 9011 {sup 125}I seeds, and IsoAid Advantage {sup 103}Pd seeds) were used in the evaluations. Seeds were loaded into trains with at least 1 cm spacing. Results: Using our system, it was possible to obtain linear calibration curves with coverage factor k = 1 prediction intervals of less than ±2% near the centre of their range for the three source models. The uncertainty budget calculated from a combination of type A and type B estimates of potential sources of error was somewhat larger, yielding (k = 1) combined uncertainties for individual seed readings of 6.2% for {sup 125}I 6711 seeds, 4.7% for {sup 125}I 9011 seeds, and 11.0% for Advantage {sup 103}Pd seeds. Conclusions: This study showed that a flat panel detector dosimetry system is a viable option for source strength verification in preloaded needles, as it is capable of measuring all of the sources intended for implantation. Such a system has the potential to directly and efficiently estimate individual source strengths, the overall mean source strength, and the positions within the seed-spacer train.« less

Phytochemical analysis of the triterpenoids with cytotoxicity and QR inducing properties from the total tea seed saponin of Camellia sinensis.

PubMed

Li, Ning; Ma, Zhong-Jun; Chu, Yang; Wang, Ying; Li, Xian

2013-01-01

The tea seed triterpene saponin (TS) from Camellia sinensis was found to exhibit better antitumor activity in vivo in S180 implanted ICR mice and QR inducing activity for hepa lclc7 cells respectively compared with the total tea seed saponin (TTS), hydrolysate of the TTS and tea seed flavonoid glycosides (TF). By bioassay-guided isolation, the TS fraction was separated and seven major components were purified and identified as theasaponin E1 (1), theasaponin E2 (2), theasaponin C1 (3), assamsaponin C (4), theasaponin H1 (5), theasaponin A9 (6), and theasaponin A8 (7), among which compounds 4 and 5 were isolated from this genus for the first time. The antitumor bioassay of the isolated compounds showed that compounds 1, 2 and 3 exhibited potential activities against the human tumor cell lines K562 and HL60. Furthermore, compound 1 (the major constituent with a mass content of over 1%) showed significant QR inducing activity with an IR value of 4.2 at 4μg/ml. So it can be concluded that tea seed especially the compound 1 (theasaponin E1) could be used as an antitumor agent and a chemoprevention agent of cancer. The preliminary structure-activity relationship in the anti-tumor activity and QR inducing activity of tea saponins was discussed briefly. Copyright © 2012 Elsevier B.V. All rights reserved.

SU-F-T-44: A Comparison of the Pre-Plan, Intra-Operative Plan, and Post-Implant Dosimetry for a Prostate Implant Case Using Prefabricated Linear Polymer-Encapsulated Pd-103

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheu, R; Powers, A; McGee, H

Purpose: To investigate the reproducibility and limitations of Pd-103 prostate brachytherapy using fixed length linear sources (CivaString). Methods: An LDR prostate brachytherapy case which was preplanned on MR images with prefabricated linear polymer-encapsulated Pd-103 sources (CivaString) was studied and compared with ultrasound based intra-operative planning and CT based post-implant dosimetry. We evaluated the following parameters among the three studies: prostate geometry (volume and cross sectional area), needle position and alignment deviations, and dosimetry parameters (D90). Results: The prostate volumes and axial cross sectional areas at center of prostate were measured as 41.8, 39.3 and 36.8 cc, and 14.9, 14.3, andmore » 11.3 respectively on pre-plan MR, inter-op US, and post-implant CT studies. The deviation of prostate volumes and axial cross sectional areas measured on pre-planning MR and intra-operative US were within 5%. 17 out of 19 pre-planned needles were positioned within 5mm (the template grid size). One needle location was adjusted intra-operatively and another needle was removed due to proximity to urethra. The needle pathways were not always parallel to the trans-rectal probe due to the flexibility of CivaString. The angle of deviation was up to 10 degrees. Two pairs of needles were exchanged to better fit the length of prostate at the time of implant. This resulted in a prostate D90 of 153.8 Gy (124%) and 131.4 Gy (106.7%) for intra-op and PID respectively. Conclusion: Preplanning is a necessary part of implants performed with prefabricated linear polymer sources. However, as is often the case, there were real-time deviations from the pre-plan. Intra-op planning provides the ability conform to anatomy at the time of implant. Therefore, we propose to develop a systematic way to order extra strings of different length to provide the flexibility to perform intra-operative planning with fixed length strands.« less

Development of marker-free transgenic Jatropha curcas producing curcin-deficient seeds through endosperm-specific RNAi-mediated gene silencing.

PubMed

Gu, Keyu; Tian, Dongsheng; Mao, Huizhu; Wu, Lifang; Yin, Zhongchao

2015-10-08

Jatropha curcas L. is a potential biofuel plant and its seed oil is suitable for biodiesel production. Despite this promising application, jatropha seeds contain two major toxic components, namely phorbol esters and curcins. These compounds would reduce commercial value of seed cake and raise safety and environment concerns on jatropha plantation and processing. Curcins are Type I ribosome inactivating proteins. Several curcin genes have been identified in the jatropha genome. Among which, the Curcin 1 (C1) gene is identified to be specifically expressed in endosperm, whereas the Curcin 2A (C2A) is mainly expressed in young leaves. A marker-free RNAi construct carrying a β-estradiol-regulated Cre/loxP system and a C1 promoter-driven RNAi cassette for C1 gene was made and used to generate marker-free transgenic RNAi plants to specifically silence the C1 gene in the endosperm of J. curcas. Plants of transgenic line L1, derived from T0-1, carry two copies of marker-free RNAi cassette, whereas plants of L35, derived from T0-35, harbored one copy of marker-free RNAi cassette and three copies of closely linked and yet truncated Hpt genes. The C1 protein content in endosperm of L1 and L35 seeds was greatly reduced or undetectable, while the C2A proteins in young leaves of T0-1 and T0-35 plants were unaffected. In addition, the C1 mRNA transcripts were undetectable in the endosperm of T3 seeds of L1 and L35. The results demonstrated that the expression of the C1 gene was specifically down-regulated or silenced by the double-stranded RNA-mediated RNA interference generated from the RNAi cassette. The C1 promoter-driven RNAi cassette for the C1 gene in transgenic plants was functional and heritable. Both C1 transcripts and C1 proteins were greatly down-regulated or silenced in the endosperm of transgenic J. curcas. The marker-free transgenic plants and curcin-deficient seeds developed in this study provided a solution for the toxicity of curcins in jatropha seeds and addressed the safety concerns of the marker genes in transgenic plants on the environments.

Phage nanofibers induce vascularized osteogenesis in 3D printed bone scaffolds.

PubMed

Wang, Jianglin; Yang, Mingying; Zhu, Ye; Wang, Lin; Tomsia, Antoni P; Mao, Chuanbin

2014-08-06

A virus-activated matrix is developed to overcome the challenge of forming vascularized bone tissue. It is generated by filling a 3D printed bioceramic scaffold with phage nanofibers displaying high-density RGD peptide. After it is seeded with mesenchymal stem cells (MSCs) and implanted into a bone defect, the phage nanofibers induce osteogenesis and angiogenesis by activating endothelialization and osteogenic differentiation of MSCs. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estrogen enhances the bone regeneration potential of periodontal ligament stem cells derived from osteoporotic rats and seeded on nano-hydroxyapatite/collagen/poly(L-lactide).

PubMed

E, Ling-Ling; Xu, Wen-Huan; Feng, Lin; Liu, Yi; Cai, Dong-Qing; Wen, Ning; Zheng, Wen-Jie

2016-06-01

This study investigated the effects of estrogen on the bone regeneration potential of periodontal ligament stem cells (PDLSCs) derived from osteoporotic rats and seeded on a collagen-based composite scaffold [nano-hydroxyapatite/collagen/poly(L-lactide) (nHAC/PLA)]. For this purpose, 48 healthy 3‑month-old Sprague-Dawley female rats were divided into 2 groups as follows: the bilaterally ovariectomized (OVX) rats and sham‑operated rats. The PDLSCs were isolated at 3 months after surgery (by which time postmenopausal osteoporosis had developed). The effects of estrogen on the characteristics of these cells seeded in a culture plate and of the cells seeded on nHAC/PLA were then investigated. The PDLSC + nHAC/PLA constructs were implanted subcutaneously into the backs of severe combined immunodeficient (SCID) mice for 12 weeks in order to examine the role of estrogen in the bone formation ability of PDLSCs derived from osteoporotic rats. The results from methyl thiazolyl tetrazolium (MTT) assay revealed that the proliferation of the cells derived from the rats in the OVX group was significantly higher than that of the cells derived from the rats in the sham-operated group at the stage of logarithmic growth. The staining intensity of alkaline phosphatase (ALP) and the mineralization of the cells derived from the rats in the OVX group was significantly weaker than that of the cells from the rats in the sham-operated group. When the PDLSCs were seeded on nHAC/PLA, ALP activity, osteocalcin (OCN) secretion, mineral formation and the mRNA expression levels of ALP, OCN, estrogen receptor (ER)α and ERβ in the cells derived from the rats in the OVX group were markedly decreased. Treatment with 17β-estradiol (E2) significantly weakened the proliferative ability of the cells derived from the OVX group rats, and enhanced their osteogenic differentiation ability and the mRNA expression levels of ALP, OCN, ERα and ERβ. When the constructs were implanted into the backs of SCID mice for 12 weeks, the results of histological analysis indicated that the constructs derived from the OVX group rats had a few newly formed bones and osteoids; however, a great number of newly formed bones and osteoids were present in the ones from the sham-operated group and the OVX + E2 group rats. Our findings further indicate that estrogen deficiency impairs the osteogenic differentiation potential of PDLSCs, and that ER plays an important role in the bone regeneration ability of PDLSCs. Estrogen enhances the bone regeneration potential of PDLSCs derived from osteoporotic rats and seeded on nHAC/PLA. This study may provide insight into the clinical management of periodontal bone tissue repair in postmenopausal women with the use of estrogen-mediated PDLSCs seeded on nHAC/PLA.

Estrogen enhances the bone regeneration potential of periodontal ligament stem cells derived from osteoporotic rats and seeded on nano-hydroxyapatite/collagen/poly(L-lactide)

PubMed Central

E, LING-LING; XU, WEN-HUAN; FENG, LIN; LIU, YI; CAI, DONG-QING; WEN, NING; ZHENG, WEN-JIE

2016-01-01

This study investigated the effects of estrogen on the bone regeneration potential of periodontal ligament stem cells (PDLSCs) derived from osteoporotic rats and seeded on a collagen-based composite scaffold [nano-hydroxyapatite/collagen/poly(L-lactide) (nHAC/PLA)]. For this purpose, 48 healthy 3-month-old Sprague-Dawley female rats were divided into 2 groups as follows: the bilaterally ovariectomized (OVX) rats and sham-operated rats. The PDLSCs were isolated at 3 months after surgery (by which time postmenopausal osteoporosis had developed). The effects of estrogen on the characteristics of these cells seeded in a culture plate and of the cells seeded on nHAC/PLA were then investigated. The PDLSC + nHAC/PLA constructs were implanted subcutaneously into the backs of severe combined immunodeficient (SCID) mice for 12 weeks in order to examine the role of estrogen in the bone formation ability of PDLSCs derived from osteoporotic rats. The results from methyl thiazolyl tetrazolium (MTT) assay revealed that the proliferation of the cells derived from the rats in the OVX group was significantly higher than that of the cells derived from the rats in the sham-operated group at the stage of logarithmic growth. The staining intensity of alkaline phosphatase (ALP) and the mineralization of the cells derived from the rats in the OVX group was significantly weaker than that of the cells from the rats in the sham-operated group. When the PDLSCs were seeded on nHAC/PLA, ALP activity, osteocalcin (OCN) secretion, mineral formation and the mRNA expression levels of ALP, OCN, estrogen receptor (ER)α and ERβ in the cells derived from the rats in the OVX group were markedly decreased. Treatment with 17β-estradiol (E2) significantly weakened the proliferative ability of the cells derived from the OVX group rats, and enhanced their osteogenic differentiation ability and the mRNA expression levels of ALP, OCN, ERα and ERβ. When the constructs were implanted into the backs of SCID mice for 12 weeks, the results of histological analysis indicated that the constructs derived from the OVX group rats had a few newly formed bones and osteoids; however, a great number of newly formed bones and osteoids were present in the ones from the sham-operated group and the OVX + E2 group rats. Our findings further indicate that estrogen deficiency impairs the osteogenic differentiation potential of PDLSCs, and that ER plays an important role in the bone regeneration ability of PDLSCs. Estrogen enhances the bone regeneration potential of PDLSCs derived from osteoporotic rats and seeded on nHAC/PLA. This study may provide insight into the clinical management of periodontal bone tissue repair in postmenopausal women with the use of estrogen-mediated PDLSCs seeded on nHAC/PLA. PMID:27082697

Development of a 3D cell printed structure as an alternative to autologs cartilage for auricular reconstruction.

PubMed

Park, Ju Young; Choi, Yeong-Jin; Shim, Jin-Hyung; Park, Jeong Hun; Cho, Dong-Woo

2017-07-01

Surgical technique using autologs cartilage is considered as the best treatment for cartilage tissue reconstruction, although the burdens of donor site morbidity and surgical complications still remain. The purpose of this study is to apply three-dimensional (3D) cell printing to fabricate a tissue-engineered graft, and evaluate its effects on cartilage reconstruction. A multihead tissue/organ building system is used to print cell-printed scaffold (CPS), then assessed the effect of the CPS on cartilage regeneration in a rabbit ear. The cell viability and functionality of chondrocytes were significantly higher in CPS than in cell-seeded scaffold (CSS) and cell-seeded hybrid scaffold (CSHS) in vitro. CPS was then implanted into a rabbit ear that had an 8 mm-diameter cartilage defect; at 3 months after implantation the CPS had fostered complete cartilage regeneration whereas CSS and autologs cartilage (AC) fostered only incomplete healing. This result demonstrates that cell printing technology can provide an appropriate environment in which encapsulated chondrocytes can survive and differentiate into cartilage tissue in vivo. Moreover, the effects of CPS on cartilage regeneration were even better than those of AC. Therefore, we confirmed the feasibility of CPS as an alternative to AC for auricular reconstruction. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1016-1028, 2017. © 2016 Wiley Periodicals, Inc.

Osteogenesis and Trophic Factor Secretion are Influenced by the Composition of Hydroxyapatite/Poly(Lactide-Co-Glycolide) Composite Scaffolds

PubMed Central

He, Jiawei; Genetos, Damian C.

2010-01-01

The use of composite biomaterials for bone repair capitalizes on the beneficial aspects of individual materials while tailoring the mechanical properties of the composite. We hypothesized that substrate composition would modulate the osteogenic response and secretion of potent trophic factors by human mesenchymal stem cells (hMSCs). Composite scaffolds were prepared by combining nanosized hydroxyapatite (HA) and microspheres formed of poly(lactic-co-glycolic acid) (PLG) at varying ratios between 0:1 and 5:1. Scaffolds were seeded with hMSCs for culture in osteogenic conditions or subcutaneous implantation into nude rats. Compressive moduli increased with HA content in a near-linear fashion. The osteogenic differentiation of hMSCs increased in a dose-dependent manner as determined by alkaline phosphatase activity and osteopontin secretion after 4 weeks of culture. Further, endogenous secretion of vascular endothelial growth factor was sustained at significantly higher levels over 28 days for hMSCs seeded in 2.5:1 and 5:1 HA:PLG scaffolds. Eight weeks after implantation, scaffolds with higher HA:PLG ratios exhibited greater vascularization and more mineralized tissue. These data demonstrate that the mechanical properties, osteogenic differentiation, as well as the timing and duration of trophic factor secretion by hMSCs can be tailored through controlling the composition of the polymer–bioceramic composite. PMID:19642853

Pulp Cell Tracking by Radionuclide Imaging for Dental Tissue Engineering

PubMed Central

Souron, Jean-Baptiste; Petiet, Anne; Decup, Franck; Tran, Xuan Vinh; Lesieur, Julie; Poliard, Anne; Le Guludec, Dominique; Letourneur, Didier; Chaussain, Catherine; Rouzet, Francois

2014-01-01

Pulp engineering with dental mesenchymal stem cells is a promising therapy for injured teeth. An important point is to determine the fate of implanted cells in the pulp over time and particularly during the early phase following implantation. Indeed, the potential engraftment of the implanted cells in other organs has to be assessed, in particular, to evaluate the risk of inducing ectopic mineralization. In this study, our aim was to follow by nuclear imaging the radiolabeled pulp cells after implantation in the rat emptied pulp chamber. For that purpose, indium-111-oxine (111In-oxine)-labeled rat pulp cells were added to polymerizing type I collagen hydrogel to obtain a pulp equivalent. This scaffold was implanted in the emptied pulp chamber space in the upper first rat molar. Labeled cells were then tracked during 3 weeks by helical single-photon emission computed tomography (SPECT)/computed tomography performed on a dual modality dedicated small animal camera. Negative controls were performed using lysed radiolabeled cells obtained in a hypotonic solution. In vitro data indicated that 111In-oxine labeling did not affect cell viability and proliferation. In vivo experiments allowed a noninvasive longitudinal follow-up of implanted living cells for at least 3 weeks and indicated that SPECT signal intensity was related to implanted cell integrity. Notably, there was no detectable systemic release of implanted cells from the tooth. In addition, histological analysis of the samples showed mitotically active fibroblastic cells as well as neoangiogenesis and nervous fibers in pulp equivalents seeded with entire cells, whereas pulp equivalents prepared from lysed cells were devoid of cell colonization. In conclusion, our study demonstrates that efficient labeling of pulp cells can be achieved and, for the first time, that these cells can be followed up after implantation in the tooth by nuclear imaging. Furthermore, it appears that grafted cells retained the label and are viable to follow the repair process. This technique is expected to be of major interest for monitoring implanted cells in innovative therapies for injured teeth. PMID:23789732

Survival and Functionality of hESC-Derived Retinal Pigment Epithelium Cells Cultured as a Monolayer on Polymer Substrates Transplanted in RCS Rats.

PubMed

Thomas, Biju B; Zhu, Danhong; Zhang, Li; Thomas, Padmaja B; Hu, Yuntao; Nazari, Hossein; Stefanini, Francisco; Falabella, Paulo; Clegg, Dennis O; Hinton, David R; Humayun, Mark S

2016-05-01

To determine the safety, survival, and functionality of human embryonic stem cell-derived RPE (hESC-RPE) cells seeded on a polymeric substrate (rCPCB-RPE1 implant) and implanted into the subretinal (SR) space of Royal College of Surgeons (RCS) rats. Monolayers of hESC-RPE cells cultured on parylene membrane were transplanted into the SR space of 4-week-old RCS rats. Group 1 (n = 46) received vitronectin-coated parylene membrane without cells (rMSPM+VN), group 2 (n = 59) received rCPCB-RPE1 implants, and group 3 (n = 13) served as the control group. Animals that are selected based on optical coherence tomography screening were subjected to visual function assays using optokinetic (OKN) testing and superior colliculus (SC) electrophysiology. At approximately 25 weeks of age (21 weeks after surgery), the eyes were examined histologically for cell survival, phagocytosis, and local toxicity. Eighty-seven percent of the rCPCB-RPE1-implanted animals showed hESC-RPE survivability. Significant numbers of outer nuclear layer cells were rescued in both group 1 (rMSPM+VN) and group 2 (rCPCB-RPE1) animals. A significantly higher ratio of rod photoreceptor cells to cone photoreceptor cells was found in the rCPCB-RPE1-implanted group. Animals with rCPCB-RPE1 implant showed hESC-RPE cells containing rhodopsin-positive particles in immunohistochemistry, suggesting phagocytic function. Superior colliculus mapping data demonstrated that a significantly higher number of SC sites responded to light stimulus at a lower luminance threshold level in the rCPCB-RPE1-implanted group. Optokinetic data suggested both implantation groups showed improved visual acuity. These results demonstrate the safety, survival, and functionality of the hESC-RPE monolayer transplantation in an RPE dysfunction rat model.

Patient Positioning Based on a Radioactive Tracer Implanted in Patients With Localized Prostate Cancer: A Performance and Safety Evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kruijf, Willy J.M. de, E-mail: kruijf.de.w@bvi.nl; Verstraete, Jan; Neustadter, David

2013-02-01

Purpose: To evaluate the performance and safety of a radiation therapy positioning system (RealEye) based on tracking a radioactive marker (Tracer) implanted in patients with localized prostate cancer. Methods and Materials: We performed a single-arm multi-institutional trial in 20 patients. The iridium-192 ({sup 192}Ir)-containing Tracer was implanted in the patient together with 4 standard gold seed fiducials. Patient prostate-related symptoms were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Computed tomography (CT) was performed for treatment planning, during treatment, and after treatment to evaluate the migration stability of the Tracer. At 5 treatment sessions, cone beam CT was performedmore » to test the positioning accuracy of the RealEye. Results: The Tracer was successfully implanted in all patients. No device or procedure-related adverse events occurred. Changes in IPSS scores were limited. The difference between the mean change in Tracer-fiducial distance and the mean change in fiducial-fiducial distance was -0.39 mm (95% confidence interval [CI] upper boundary, -0.22 mm). The adjusted mean difference between Tracer position according to RealEye and the Tracer position on the CBCT for all patients was 1.34 mm (95% CI upper boundary, 1.41 mm). Conclusions: Implantation of the Tracer is feasible and safe. Migration stability of the Tracer is good. Prostate patients can be positioned and monitored accurately by using RealEye.« less

Patient positioning based on a radioactive tracer implanted in patients with localized prostate cancer: a performance and safety evaluation.

PubMed

de Kruijf, Willy J M; Verstraete, Jan; Neustadter, David; Corn, Benjamin W; Hol, Sandra; Venselaar, Jack L M; Davits, Rob J; Wijsman, Bart P; Van den Bergh, Laura; Budiharto, Tom; Oyen, Raymond; Haustermans, Karin; Poortmans, Philip M P

2013-02-01

To evaluate the performance and safety of a radiation therapy positioning system (RealEye) based on tracking a radioactive marker (Tracer) implanted in patients with localized prostate cancer. We performed a single-arm multi-institutional trial in 20 patients. The iridium-192 ((192)Ir)-containing Tracer was implanted in the patient together with 4 standard gold seed fiducials. Patient prostate-related symptoms were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Computed tomography (CT) was performed for treatment planning, during treatment, and after treatment to evaluate the migration stability of the Tracer. At 5 treatment sessions, cone beam CT was performed to test the positioning accuracy of the RealEye. The Tracer was successfully implanted in all patients. No device or procedure-related adverse events occurred. Changes in IPSS scores were limited. The difference between the mean change in Tracer-fiducial distance and the mean change in fiducial-fiducial distance was -0.39 mm (95% confidence interval [CI] upper boundary, -0.22 mm). The adjusted mean difference between Tracer position according to RealEye and the Tracer position on the CBCT for all patients was 1.34 mm (95% CI upper boundary, 1.41 mm). Implantation of the Tracer is feasible and safe. Migration stability of the Tracer is good. Prostate patients can be positioned and monitored accurately by using RealEye. Copyright © 2013 Elsevier Inc. All rights reserved.

Repositioning Titanium: An In Vitro Evaluation of Laser-Generated Microporous, Microrough Titanium Templates As a Potential Bridging Interface for Enhanced Osseointegration and Durability of Implants

PubMed Central

Tang, Daniel; Yang, Liang-Yo; Ou, Keng-Liang; Oreffo, Richard O. C.

2017-01-01

Although titanium alloys remain the preferred biomaterials for the manufacture of biomedical implants today, such devices can fail within 15 years of implantation due to inadequate osseointegration. Furthermore, wear debris toxicity due to alloy metal ion release has been found to cause side-effects including neurotoxicity and chronic inflammation. Titanium, with its known biocompatibility, corrosion resistance, and high elastic modulus, could if harnessed in the form of a superficial scaffold or bridging device, resolve such issues. A novel three-dimensional culture approach was used to investigate the potential osteoinductive and osseointegrative capabilities of a laser-generated microporous, microrough medical grade IV titanium template on human skeletal stem cells (SSCs). Human SSCs seeded on a rough 90-µm pore surface of ethylene oxide-sterilized templates were observed to be strongly adherent, and to display early osteogenic differentiation, despite their inverted culture in basal conditions over 21 days. Limited cellular migration across the template surface highlighted the importance of high surface wettability in maximizing cell adhesion, spreading and cell-biomaterial interaction, while restricted cell ingrowth within the conical-shaped pores underlined the crucial role of pore geometry and size in determining the extent of osseointegration of an implant device. The overall findings indicate that titanium only devices, with appropriate optimizations to porosity and surface wettability, could yet play a major role in improving the long-term efficacy, durability, and safety of future implant technology. PMID:29322044

Pre-implanted Sensory Nerve Could Enhance the Neurotization in Tissue-Engineered Bone Graft.

PubMed

Wu, Yan; Jing, Da; Ouyang, Hongwei; Li, Liang; Zhai, Mingming; Li, Yan; Bi, Long; Guoxian, Pei

2015-08-01

In our previous study, it was found that implanting the sensory nerve tract into the tissue-engineered bone to repair large bone defects can significantly result in better osteogenesis effect than tissue-engineered bone graft (TEBG) alone. To study the behavior of the preimplanted sensory nerve in the TEBG, the TEBG was constructed by seeding bone mesenchymal stem cells into β-tricalcium phosphate scaffold with (treatment group) or without (blank group) implantation of the sensory nerve. The expression of calcitonin gene-related peptide (CGRP), which helps in the healing of bone defect in the treatment group was significantly higher than the blank group at 4, 8, and 12 weeks. The expression of growth-associated protein 43 (GAP43), which might be expressed during nerve healing in the treatment group, was significantly higher than the blank group at 4 and 8 weeks. The nerve tracts of the preimplanted sensory nerve were found in the scaffold by the nerve tracing technique. The implanted sensory nerve tracts grew into the pores of scaffolds much earlier than the vascular. The implanted sensory nerve tracts traced by Dil could be observed at 4 weeks, but at the same time, no vascular was observed. In conclusion, the TEBG could be benefited from the preimplanted sensory nerve through the healing behavior of the sensory nerve. The sensory nerve fibers could grow into the pores of the TEBG rapidly, and increase the expression of CGRP, which is helpful in regulating the bone formation and the blood flow.

Structure Basis for Directional R-loop Formation and Substrate Handover Mechanisms in Type I CRISPR-Cas System.

PubMed

Xiao, Yibei; Luo, Min; Hayes, Robert P; Kim, Jonathan; Ng, Sherwin; Ding, Fang; Liao, Maofu; Ke, Ailong

2017-06-29

Type I CRISPR systems feature a sequential dsDNA target searching and degradation process, by crRNA-displaying Cascade and nuclease-helicase fusion enzyme Cas3, respectively. Here we present two cryo-EM snapshots of the Thermobifida fusca type I-E Cascade: (1) unwinding 11 bp of dsDNA at the seed-sequence region to scout for sequence complementarity, and (2) further unwinding of the entire protospacer to form a full R-loop. These structures provide the much-needed temporal and spatial resolution to resolve key mechanistic steps leading to Cas3 recruitment. In the early steps, PAM recognition causes severe DNA bending, leading to spontaneous DNA unwinding to form a seed-bubble. The full R-loop formation triggers conformational changes in Cascade, licensing Cas3 to bind. The same process also generates a bulge in the non-target DNA strand, enabling its handover to Cas3 for cleavage. The combination of both negative and positive checkpoints ensures stringent yet efficient target degradation in type I CRISPR-Cas systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Decellularized fresh homografts for pulmonary valve replacement: a decade of clinical experience†

PubMed Central

Sarikouch, Samir; Horke, Alexander; Tudorache, Igor; Beerbaum, Philipp; Westhoff-Bleck, Mechthild; Boethig, Dietmar; Repin, Oleg; Maniuc, Liviu; Ciubotaru, Anatol; Haverich, Axel; Cebotari, Serghei

2016-01-01

OBJECTIVES Decellularized homografts have shown auspicious early results when used for pulmonary valve replacement (PVR) in congenital heart disease. The first clinical application in children was performed in 2002, initially using pre-seeding with endogenous progenitor cells. Since 2005, only non-seeded, fresh decellularized allografts have been implanted after spontaneous recellularization was observed by several groups. METHODS A matched comparison of decellularized fresh pulmonary homografts (DPHs) implanted for PVR with cryopreserved pulmonary homografts (CHs) and bovine jugular vein conduits (BJVs) was conducted. Patients’ age at implantation, the type of congenital malformation, number of previous cardiac operations and number of previous PVRs were considered for matching purposes, using an updated contemporary registry of right ventricular outflow tract conduits (2300 included conduits, >12 000 patient-years). RESULTS A total of 131 DPHs were implanted for PVR in the period from January 2005 to September 2015. Of the 131, 38 were implanted within prospective trials on DPH from October 2014 onwards and were therefore not analysed within this study. A total of 93 DPH patients (58 males, 35 females) formed the study cohort and were matched to 93 CH and 93 BJV patients. The mean age at DPH implantation was 15.8 ± 10.21 years (CH 15.9 ± 10.4, BJV 15.6 ± 9.9) and the mean DPH diameter was 23.9 mm (CH 23.3 ± 3.6, BJV 19.9 ± 2.9). There was 100% follow-up for DPH, including 905 examinations with a mean follow-up of 4.59 ± 2.76 years (CH 7.4 ± 5.8, BJV 6.4 ± 3.8), amounting to 427.27 patient-years in total (CH 678.3, BJV 553.0). Tetralogy-of-Fallot was the most frequent malformation (DPH 50.5%, CH 54.8%, BJV 68.8%). At 10 years, the rate of freedom of explantation was 100% for DPH, 84.2% for CH (P = 0.01) and 84.3% for BJV (P= 0.01); the rate of freedom from explantation and peak trans-conduit gradient ≥50 mmHg was 86% for DPH, 64% for CH (n.s.) and 49% for BJV (P < 0.001); the rate of freedom from infective endocarditis (IE) was 100% for DPH, 97.3 ± 1.9% within the matched CH patients (P = 0.2) and 94.3 ± 2.8% for BJV patients (P = 0.06). DPH valve annulus diameters converged towards normal Z-values throughout the observation period, in contrast to other valve prostheses (BJV). CONCLUSIONS Mid-term results of DPH for PVR confirm earlier results of reduced re-operation rates compared with CH and BJV. PMID:27013071

Repair of Segmental Bone Defect Using Totally Vitalized Tissue Engineered Bone Graft by a Combined Perfusion Seeding and Culture System

PubMed Central

Feng, Ya-Fei; Li, Xiang; Hu, Yun-Yu; Wang, Zhen; Ma, Zhen-Sheng; Lei, Wei

2014-01-01

Background The basic strategy to construct tissue engineered bone graft (TEBG) is to combine osteoblastic cells with three dimensional (3D) scaffold. Based on this strategy, we proposed the “Totally Vitalized TEBG” (TV-TEBG) which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect. Methods In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP) scaffold fabricated by Rapid Prototyping (RP) technique. We systemically compared three kinds of TEBG constructed by perfusion seeding and perfusion culture (PSPC) method, static seeding and perfusion culture (SSPC) method, and static seeding and static culture (SSSC) method for their in vitro performance and bone defect healing efficacy with a rabbit model. Results Our study has demonstrated that TEBG constructed by PSPC method exhibited better biological properties with higher daily D-glucose consumption, increased cell proliferation and differentiation, and better cell distribution, indicating the successful construction of TV-TEBG. After implanted into rabbit radius defects for 12 weeks, PSPC group exerted higher X-ray score close to autograft, much greater mechanical property evidenced by the biomechanical testing and significantly higher new bone formation as shown by histological analysis compared with the other two groups, and eventually obtained favorable healing efficacy of the segmental bone defect that was the closest to autograft transplantation. Conclusion This study demonstrated the feasibility of TV-TEBG construction with combination of perfusion seeding, perfusion culture and RP technique which exerted excellent biological properties. The application of TV-TEBG may become a preferred candidate for segmental bone defect repair in orthopedic and maxillofacial fields. PMID:24728277

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roper, J; Bradshaw, B; Godette, K

Purpose: To create a knowledge-based algorithm for prostate LDR brachytherapy treatment planning that standardizes plan quality using seed arrangements tailored to individual physician preferences while being fast enough for real-time planning. Methods: A dataset of 130 prior cases was compiled for a physician with an active prostate seed implant practice. Ten cases were randomly selected to test the algorithm. Contours from the 120 library cases were registered to a common reference frame. Contour variations were characterized on a point by point basis using principle component analysis (PCA). A test case was converted to PCA vectors using the same process andmore » then compared with each library case using a Mahalanobis distance to evaluate similarity. Rank order PCA scores were used to select the best-matched library case. The seed arrangement was extracted from the best-matched case and used as a starting point for planning the test case. Computational time was recorded. Any subsequent modifications were recorded that required input from a treatment planner to achieve an acceptable plan. Results: The computational time required to register contours from a test case and evaluate PCA similarity across the library was approximately 10s. Five of the ten test cases did not require any seed additions, deletions, or moves to obtain an acceptable plan. The remaining five test cases required on average 4.2 seed modifications. The time to complete manual plan modifications was less than 30s in all cases. Conclusion: A knowledge-based treatment planning algorithm was developed for prostate LDR brachytherapy based on principle component analysis. Initial results suggest that this approach can be used to quickly create treatment plans that require few if any modifications by the treatment planner. In general, test case plans have seed arrangements which are very similar to prior cases, and thus are inherently tailored to physician preferences.« less

Signal-on electrochemiluminescence biosensor for microRNA-319a detection based on two-stage isothermal strand-displacement polymerase reaction.

PubMed

Wang, Minghui; Zhou, Yunlei; Yin, Huanshun; Jiang, Wenjing; Wang, Haiyan; Ai, Shiyun

2018-06-01

MicroRNAs play crucial role in regulating gene expression in organism, thus it is very necessary to exploit an efficient method for the sensitive and specific detection of microRNA. Herein, a signal-on electrochemiluminescence biosensor was fabricated for microRNA-319a detection based on two-stage isothermal strand-displacement polymerase reaction (ISDPR). In the presence of target microRNA, amounts of trigger DNA could be generated by the first ISDPR. Then, the trigger DNA and the primer hybridized simultaneously with the hairpin probe to open the stem of the probe, and then the ECL signal will be emitted. In the presence of phi29 DNA polymerase and dNTPs, the trigger DNA could be displaced to initiate a new cycle which was the second ISDPR. Due to the two-stage amplification, this method presented excellent detection sensitivity with a low detection limit of 0.14 fM. Moreover, the applicability of the developed method was demonstrated by detecting the change of microRNA-319a content in the leaves of rice seedlings after the rice seeds were incubated with chemical mutagen of ethyl methanesulfonate. Copyright © 2018 Elsevier B.V. All rights reserved.

PAM-Dependent Target DNA Recognition and Cleavage by C2c1 CRISPR-Cas Endonuclease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Hui; Gao, Pu; Rajashankar, Kanagalaghatta R.

C2c1 is a newly identified guide RNA-mediated type V-B CRISPR-Cas endonuclease that site-specifically targets and cleaves both strands of target DNA. We have determined crystal structures of Alicyclobacillus acidoterrestris C2c1 (AacC2c1) bound to sgRNA as a binary complex and to target DNAs as ternary complexes, thereby capturing catalytically competent conformations of AacC2c1 with both target and non-target DNA strands independently positioned within a single RuvC catalytic pocket. Moreover, C2c1-mediated cleavage results in a staggered seven-nucleotide break of target DNA. crRNA adopts a pre-ordered five-nucleotide A-form seed sequence in the binary complex, with release of an inserted tryptophan, facilitating zippering upmore » of 20-bp guide RNA:target DNA heteroduplex on ternary complex formation. Notably, the PAM-interacting cleft adopts a “locked” conformation on ternary complex formation. Structural comparison of C2c1 ternary complexes with their Cas9 and Cpf1 counterparts highlights the diverse mechanisms adopted by these distinct CRISPR-Cas systems, thereby broadening and enhancing their applicability as genome editing tools.« less

Understanding the core of RNA interference: The dynamic aspects of Argonaute-mediated processes.

PubMed

Zhu, Lizhe; Jiang, Hanlun; Sheong, Fu Kit; Cui, Xuefeng; Wang, Yanli; Gao, Xin; Huang, Xuhui

2017-09-01

At the core of RNA interference, the Argonaute proteins (Ago) load and utilize small guide nucleic acids to silence mRNAs or cleave foreign nucleic acids in a sequence specific manner. In recent years, based on extensive structural studies of Ago and its interaction with the nucleic acids, considerable progress has been made to reveal the dynamic aspects of various Ago-mediated processes. Here we review these novel insights into the guide-strand loading, duplex unwinding, and effects of seed mismatch, with a focus on two representative Agos, the human Ago 2 (hAgo2) and the bacterial Thermus thermophilus Ago (TtAgo). In particular, comprehensive molecular simulation studies revealed that although sharing similar overall structures, the two Agos have vastly different conformational landscapes and guide-strand loading mechanisms because of the distinct rigidity of their L1-PAZ hinge. Given the central role of the PAZ motions in regulating the exposure of the nucleic acid binding channel, these findings exemplify the importance of protein motions in distinguishing the overlapping, yet distinct, mechanisms of Ago-mediated processes in different organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Experimental trials on the feasibility of offshore seed production of the mussel Mytilus edulis in the German Bight: installation, technical requirements and environmental conditions

NASA Astrophysics Data System (ADS)

Buck, Bela Hieronymus

2007-06-01

This study summarizes the activities and findings during a 2 year investigation on the grow-out of blue mussels ( Mytilus edulis) and the technical requirements to withstand harsh weather conditions at an offshore location. The experimental sites were two different test areas, each 5 ha in size, 12-15 m in depth, in the vicinity of the offshore lighthouse “Roter Sand” located 15-17 nautical miles northwest of the city of Bremerhaven (Germany). Two versions of submerged longline systems were deployed: a conventional polypropylene longline in 2002 as well as a steel hawser longline in 2003, both featuring different versions of buoyancy modes. The spat collectors and grow-out ropes were suspended perpendicular from the horizontal longline for several months beginning in March of each respective year. The test sites were visited and sampled on a monthly basis using research vessels. Larval abundances in the surrounding water column reached numbers of up to 1,467 individuals m-3. Post-larval settlement success varied through the entire experimental period, ranging from 29 to 796 individuals of spat per meter of collector. Settled mussels reached a shell length of up to 28 mm 6 months after settlement. Based on the growth rates observed for the seed, it is projected that mussels would reach market size (50 mm) in 12-15 months post settlement, and at the observed densities, each meter of collector rope could yield 10.9 kg of harvestable mussels. The polypropylene line resisted storm conditions with wind waves of up to 6.4 m and current velocities of 1.52 m s-1 and was retrieved in autumn of 2002. In contrast, the steel hawser-based line did not withstand the harsh weather conditions. The steel-based line consisted of six twisted strands that were untwisted by the strong currents and turbulences and consequently the individual strands were torn. Additionally, the line was accidentally cut by a yacht in July 2003. The biological study revealed that the tested location near “Roter Sand” has the potential to become an offshore seed production site as well as being exploitable as a grow-out site for mussel production to market size. In light of the technical results, recommendations for mussel culture strategies using a polypropylene longline system are given.

Metallic artifact mitigation and organ-constrained tissue assignment for Monte Carlo calculations of permanent implant lung brachytherapy.

PubMed

Sutherland, J G H; Miksys, N; Furutani, K M; Thomson, R M

2014-01-01

To investigate methods of generating accurate patient-specific computational phantoms for the Monte Carlo calculation of lung brachytherapy patient dose distributions. Four metallic artifact mitigation methods are applied to six lung brachytherapy patient computed tomography (CT) images: simple threshold replacement (STR) identifies high CT values in the vicinity of the seeds and replaces them with estimated true values; fan beam virtual sinogram replaces artifact-affected values in a virtual sinogram and performs a filtered back-projection to generate a corrected image; 3D median filter replaces voxel values that differ from the median value in a region of interest surrounding the voxel and then applies a second filter to reduce noise; and a combination of fan beam virtual sinogram and STR. Computational phantoms are generated from artifact-corrected and uncorrected images using several tissue assignment schemes: both lung-contour constrained and unconstrained global schemes are considered. Voxel mass densities are assigned based on voxel CT number or using the nominal tissue mass densities. Dose distributions are calculated using the EGSnrc user-code BrachyDose for (125)I, (103)Pd, and (131)Cs seeds and are compared directly as well as through dose volume histograms and dose metrics for target volumes surrounding surgical sutures. Metallic artifact mitigation techniques vary in ability to reduce artifacts while preserving tissue detail. Notably, images corrected with the fan beam virtual sinogram have reduced artifacts but residual artifacts near sources remain requiring additional use of STR; the 3D median filter removes artifacts but simultaneously removes detail in lung and bone. Doses vary considerably between computational phantoms with the largest differences arising from artifact-affected voxels assigned to bone in the vicinity of the seeds. Consequently, when metallic artifact reduction and constrained tissue assignment within lung contours are employed in generated phantoms, this erroneous assignment is reduced, generally resulting in higher doses. Lung-constrained tissue assignment also results in increased doses in regions of interest due to a reduction in the erroneous assignment of adipose to voxels within lung contours. Differences in dose metrics calculated for different computational phantoms are sensitive to radionuclide photon spectra with the largest differences for (103)Pd seeds and smallest but still considerable differences for (131)Cs seeds. Despite producing differences in CT images, dose metrics calculated using the STR, fan beam + STR, and 3D median filter techniques produce similar dose metrics. Results suggest that the accuracy of dose distributions for permanent implant lung brachytherapy is improved by applying lung-constrained tissue assignment schemes to metallic artifact corrected images.

Mechanical and biological evaluations of beta-tricalcium phosphate/silicone rubber composite as a novel soft-tissue implant.

PubMed

Zhang, Yi-ming; Wang, Shao-liang; Lei, Ze-yuan; Fan, Dong-li

2009-09-01

Although silicone rubber (SR) implants are most commonly used and effective for soft-tissue augmentation, they still have been implicated in many adverse reactions. To overcome this problem, a novel composite beta-tricalcium phosphate/silicone rubber (beta-TCP/SR) was prepared by adding beta-TCP into a SR matrix. This study was to evaluate its application potential by investigating the mechanical properties and biocompatibility of beta-TCP/SR. Mechanical properties, including Shore A hardness and tensile strength, were evaluated with 3-mm-thick samples and a universal testing machine. Cytocompatibility tests were conducted in vitro using 0.2-mm-thick beta-TCP/SR samples by seeding fibroblasts onto different samples. Soft-tissue response to beta-TCP/SR and pull-out measurements were investigated 4 weeks and 24 weeks after implantation. The main mechanical properties were all significantly changed after mixing beta-TCP into the SR matrix, except for tearing strength. The cytocompatibility test showed enhanced adhesion and proliferation of fibroblasts onto beta-TCP/SR. Fibrous tissue ingrowth after resorption of beta-TCP was observed by in vivo histologic analysis. The peri-implant capsules in the beta-TCP/SR group were thinner than in the SR group 24 weeks after implantation. In a 24-week test, the maximum force required to pull out the beta-TCP/SR sheet was about six times greater than that needed for SR. Although some mechanical properties were significantly changed, the results of the cytocompatibility test and in vivo animal study still suggest that beta-TCP/SR may be more suitable as a soft-tissue implant than SR and has the potential to be used in plastic surgery.

The effects of diode laser on Staphylococcus aureus biofilm and Escherichia coli lipopolysaccharide adherent to titanium oxide surface of dental implants. An in vitro study.

PubMed

Giannelli, Marco; Landini, Giulia; Materassi, Fabrizio; Chellini, Flaminia; Antonelli, Alberto; Tani, Alessia; Zecchi-Orlandini, Sandra; Rossolini, Gian Maria; Bani, Daniele

2016-11-01

Effective decontamination of biofilm and bacterial toxins from the surface of dental implants is a yet unresolved issue. This in vitro study aims at providing the experimental basis for possible use of diode laser (λ 808 nm) in the treatment of peri-implantitis. Staphylococcus aureus biofilm was grown for 48 h on titanium discs with porous surface corresponding to the bone-implant interface and then irradiated with a diode laser (λ 808 nm) in noncontact mode with airflow cooling for 1 min using a Ø 600-μm fiber. Setting parameters were 2 W (400 J/cm 2 ) for continuous wave mode; 22 μJ, 20 kHz, 7 μs (88 J/cm 2 ) for pulsed wave mode. Bactericidal effect was evaluated using fluorescence microscopy and counting the residual colony-forming units. Biofilm and titanium surface morphology were analyzed by scanning electron microscopy (SEM). In parallel experiments, the titanium discs were coated with Escherichia coli lipopolysaccharide (LPS), laser-irradiated and seeded with RAW 264.7 macrophages to quantify LPS-driven inflammatory cell activation by measuring the enhanced generation of nitric oxide (NO). Diode laser irradiation in both continuous and pulsed modes induced a statistically significant reduction of viable bacteria and nitrite levels. These results indicate that in addition to its bactericidal effect laser irradiation can also inhibit LPS-induced macrophage activation and thus blunt the inflammatory response. The λ 808-nm diode laser emerges as a valuable tool for decontamination/detoxification of the titanium implant surface and may be used in the treatment of peri-implantitis.

Sci—Fri PM: Topics — 02: Evaluation of Dosimetric Variations in Partial Breast Seed Implant (PBSI) due to Patient Arm Position (Up vs. Down)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watt, E; Tom Baker Cancer Centre, Calgary, AB; Long, K

The planning for PBSI is done with the patient's ipsilateral arm raised, however, anatomical changes and variations are unavoidable as the patient resumes her daily activities, potentially resulting in significant deviations in implant geometry from the treatment plan. This study aims to quantify the impact of the ipsilateral arm position on the geometry and dosimetry of the implant at eight weeks, evaluated on post-plans using the MIM Symphony™ software (MIM Software, Cleveland, OH). The average dose metrics for the three patients treated at the TBCC thus far using rigid fusion and contour transfer for the arms up position were 76%more » for the CTV V100, 61% for the PTV V100, and 37% for the PTV V200; and for the arms down position 81% for the CTV V100, 64% for the PTV V100, and 42% for the PTV V200. Qualitative analysis of the post-implant CT for one of the three patients showed poor agreement between the seroma contour transferred from the pre-implant CT and the seroma visible on the post-implant CT. To obtain a clinically accurate plan for that patient, contour modifications were used, yielding improved dose metric averages for the arms-up position for all three patients of 87% for the CTV V100, 68% for the PTV V100, and 39% for the PTV V200. Overall, the data available shows that dosimetric parameters increase with the patient's arm down, both in terms of coverage and in terms of the hot spot, and accrual of more patients may confirm this in a larger population.« less

Mix-and-match nanobiosensor design: Logical and spatial programming of biosensors using self-assembled DNA nanostructures.

PubMed

Liu, Ying; Kumar, Sriram; Taylor, Rebecca E

2018-04-06

The evergrowing need to understand and engineer biological and biochemical mechanisms has led to the emergence of the field of nanobiosensing. Structural DNA nanotechnology, encompassing methods such as DNA origami and single-stranded tiles, involves the base pairing-driven knitting of DNA into discrete one-, two-, and three-dimensional shapes at nanoscale. Such nanostructures enable a versatile design and fabrication of nanobiosensors. These systems benefit from DNA's programmability, inherent biocompatibility, and the ability to incorporate and organize functional materials such as proteins and metallic nanoparticles. In this review, we present a mix-and-match taxonomy and approach to designing nanobiosensors in which the choices of bioanalyte and transduction mechanism are fully independent of each other. We also highlight opportunities for greater complexity and programmability of these systems that are built using structural DNA nanotechnology. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Diagnostic Tools > Biosensing Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology. © 2018 Wiley Periodicals, Inc.

ICTV Virus Taxonomy Profile: Partitiviridae.

PubMed

Vainio, Eeva J; Chiba, Sotaro; Ghabrial, Said A; Maiss, Edgar; Roossinck, Marilyn; Sabanadzovic, Sead; Suzuki, Nobuhiro; Xie, Jiatao; Nibert, Max; Ictv Report Consortium

2018-01-01

The Partitiviridae is a family of small, isometric, non-enveloped viruses with bisegmented double-stranded (ds) RNA genomes of 3-4.8 kbp. The two genome segments are individually encapsidated. The family has five genera, with characteristic hosts for members of each genus: either plants or fungi for genera Alphapartitivirus and Betapartitivirus, fungi for genus Gammapartitivirus, plants for genus Deltapartitivirus and protozoa for genus Cryspovirus. Partitiviruses are transmitted intracellularly via seeds (plants), oocysts (protozoa) or hyphal anastomosis, cell division and sporogenesis (fungi); there are no known natural vectors. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Partitiviridae, which is available at www.ictv.global/report/partitiviridae.

WE-DE-201-04: Cross Validation of Knowledge-Based Treatment Planning for Prostate LDR Brachytherapy Using Principle Component Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roper, J; Ghavidel, B; Godette, K

Purpose: To validate a knowledge-based algorithm for prostate LDR brachytherapy treatment planning. Methods: A dataset of 100 cases was compiled from an active prostate seed implant service. Cases were randomized into 10 subsets. For each subset, the 90 remaining library cases were registered to a common reference frame and then characterized on a point by point basis using principle component analysis (PCA). Each test case was converted to PCA vectors using the same process and compared with each library case using a Mahalanobis distance to evaluate similarity. Rank order PCA scores were used to select the best-matched library case. Themore » seed arrangement was extracted from the best-matched case and used as a starting point for planning the test case. Any subsequent modifications were recorded that required input from a treatment planner to achieve V100>95%, V150<60%, V200<20%. To simulate operating-room planning constraints, seed activity was held constant, and the seed count could not increase. Results: The computational time required to register test-case contours and evaluate PCA similarity across the library was 10s. Preliminary analysis of 2 subsets shows that 9 of 20 test cases did not require any seed modifications to obtain an acceptable plan. Five test cases required fewer than 10 seed modifications or a grid shift. Another 5 test cases required approximately 20 seed modifications. An acceptable plan was not achieved for 1 outlier, which was substantially larger than its best match. Modifications took between 5s and 6min. Conclusion: A knowledge-based treatment planning algorithm for prostate LDR brachytherapy is being cross validated using 100 prior cases. Preliminary results suggest that for this size library, acceptable plans can be achieved without planner input in about half of the cases while varying amounts of planner input are needed in remaining cases. Computational time and planning time are compatible with clinical practice.« less

MRI-alone radiation therapy planning for prostate cancer: Automatic fiducial marker detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghose, Soumya, E-mail: soumya.ghose@case.edu; Mitra, Jhimli; Rivest-Hénault, David

Purpose: The feasibility of radiation therapy treatment planning using substitute computed tomography (sCT) generated from magnetic resonance images (MRIs) has been demonstrated by a number of research groups. One challenge with an MRI-alone workflow is the accurate identification of intraprostatic gold fiducial markers, which are frequently used for prostate localization prior to each dose delivery fraction. This paper investigates a template-matching approach for the detection of these seeds in MRI. Methods: Two different gradient echo T1 and T2* weighted MRI sequences were acquired from fifteen prostate cancer patients and evaluated for seed detection. For training, seed templates from manual contoursmore » were selected in a spectral clustering manifold learning framework. This aids in clustering “similar” gold fiducial markers together. The marker with the minimum distance to a cluster centroid was selected as the representative template of that cluster during training. During testing, Gaussian mixture modeling followed by a Markovian model was used in automatic detection of the probable candidates. The probable candidates were rigidly registered to the templates identified from spectral clustering, and a similarity metric is computed for ranking and detection. Results: A fiducial detection accuracy of 95% was obtained compared to manual observations. Expert radiation therapist observers were able to correctly identify all three implanted seeds on 11 of the 15 scans (the proposed method correctly identified all seeds on 10 of the 15). Conclusions: An novel automatic framework for gold fiducial marker detection in MRI is proposed and evaluated with detection accuracies comparable to manual detection. When radiation therapists are unable to determine the seed location in MRI, they refer back to the planning CT (only available in the existing clinical framework); similarly, an automatic quality control is built into the automatic software to ensure that all gold seeds are either correctly detected or a warning is raised for further manual intervention.« less

MRI-alone radiation therapy planning for prostate cancer: Automatic fiducial marker detection.

PubMed

Ghose, Soumya; Mitra, Jhimli; Rivest-Hénault, David; Fazlollahi, Amir; Stanwell, Peter; Pichler, Peter; Sun, Jidi; Fripp, Jurgen; Greer, Peter B; Dowling, Jason A

2016-05-01

The feasibility of radiation therapy treatment planning using substitute computed tomography (sCT) generated from magnetic resonance images (MRIs) has been demonstrated by a number of research groups. One challenge with an MRI-alone workflow is the accurate identification of intraprostatic gold fiducial markers, which are frequently used for prostate localization prior to each dose delivery fraction. This paper investigates a template-matching approach for the detection of these seeds in MRI. Two different gradient echo T1 and T2* weighted MRI sequences were acquired from fifteen prostate cancer patients and evaluated for seed detection. For training, seed templates from manual contours were selected in a spectral clustering manifold learning framework. This aids in clustering "similar" gold fiducial markers together. The marker with the minimum distance to a cluster centroid was selected as the representative template of that cluster during training. During testing, Gaussian mixture modeling followed by a Markovian model was used in automatic detection of the probable candidates. The probable candidates were rigidly registered to the templates identified from spectral clustering, and a similarity metric is computed for ranking and detection. A fiducial detection accuracy of 95% was obtained compared to manual observations. Expert radiation therapist observers were able to correctly identify all three implanted seeds on 11 of the 15 scans (the proposed method correctly identified all seeds on 10 of the 15). An novel automatic framework for gold fiducial marker detection in MRI is proposed and evaluated with detection accuracies comparable to manual detection. When radiation therapists are unable to determine the seed location in MRI, they refer back to the planning CT (only available in the existing clinical framework); similarly, an automatic quality control is built into the automatic software to ensure that all gold seeds are either correctly detected or a warning is raised for further manual intervention.

Surgical option for the correction of Peyronie's disease: an autologous tissue-engineered endothelialized graft.

PubMed

Imbeault, Annie; Bernard, Geneviève; Ouellet, Gabrielle; Bouhout, Sara; Carrier, Serge; Bolduc, Stéphane

2011-11-01

Surgical treatment is indicated in severe cases of Peyronie's disease. Incision of the plaque with subsequent graft material implantation is the option of choice. Ideal graft tissue is not yet available. To evaluate the use of an autologous tissue-engineered endothelialized graft by the self-assembly method, for tunica albuginea (TA) reconstruction in Peyronie's disease. Two TA models were created. Human fibroblasts were isolated from a skin biopsy and cultured in vitro until formation of fibroblast sheets. After 4 weeks of maturation, human umbilical vein endothelial cells (HUVEC) were seeded on fibroblasts sheets and wrapped around a tubular support to form a cylinder of about 10 layers. After 21 days of tube maturation, HUVEC were seeded into the lumen of the fibroblast tubes for the endothelialized tunica albuginea (ETA). No HUVEC were seeded into the lumen for the TA model. Both constructs were placed under perfusion in a bioreactor for 1 week. Histology, immunohistochemistry, and burst pressure were performed to characterize mature tubular graft. Animal manipulations were also performed to demonstrate the impact of endothelial cells in vivo. Histology showed uniform multilayered fibroblasts. Extracellular matrix, produced entirely by fibroblasts, presented a good staining for collagen 1. Some elastin fibers were also present. For the TA model, anti-human von Willebrand antibody revealed the endothelial cells forming capillary-like structures. TA model reached a burst pressure of 584 mm Hg and ETA model obtained a burst pressure of 719 mm Hg. This tissue-engineered endothelialized tubular graft is structurally similar to normal TA and presents an adequate mechanical resistance. The self-assembly method used and the autologous property of this model could represent an advantage comparatively to other available grafts. Further evaluation including functional testing will be necessary to characterize in vivo implantation and behavior of the graft. © 2011 International Society for Sexual Medicine.

Relative biologic effectiveness in terms of tumor response of {sup 125}I implants compared with {sup 60}Co gamma rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lehnert, Shirley; Reniers, Brigitte; Verhaegen, Frank

2005-09-01

Purpose: To measure the relative biologic effectiveness (RBE) for {sup 125}I seeds compared with external beam radiotherapy using a clinically relevant in vivo system. Methods and Materials: Photon emission from a detailed source model was simulated using the Monte Carlo code MCNP4C, sampling from a {sup 125}I spectrum. The mouse RIF-1 tumor was treated with either temporary implant of an {sup 125}I seed or with {sup 60}Co gamma rays. The tumors were always the same size at the initiation of treatment, and the endpoint was growth inhibition. Results: The dose-response curve for both modalities was close to linear and wasmore » independent of the initial {sup 125}I activity (dose rate) for the range investigated. Calculation of the RBE for tumor response requires assigning a unique value for the tumor dose that is not homogenous but depends on the distance from the {sup 125}I source. Because tumor regrowth will depend on the subpopulation of cells that have the greatest probability of survival (i.e., those at the greatest distance from the {sup 125}I source), one approach is to use the dose to this population. On this basis, the RBE for {sup 125}I compared with {sup 60}Co gamma rays is 1.5. If the {sup 125}I dose is computed as the average dose to the tumor, corrected for the dose that is wasted as overkill in the cell population closest to the center of the {sup 125}I seed, the RBE is 1.4. Conclusion: The result, an RBE of 1.4-1.5 is similar to findings obtained by other methods, supporting the validity of this approach to derive an RBE with validity in a clinical context.« less

Engineering Adipose-like Tissue in vitro and in vivo Utilizing Human Bone Marrow and Adipose-derived Mesenchymal Stem Cells with Silk Fibroin 3D Scaffolds

PubMed Central

Mauney, Joshua R; Nguyen, Trang; Gillen, Kelly; Kirker-Head, Carl; Gimble, Jeffrey M.; Kaplan, David L.

2009-01-01

Biomaterials derived from silk fibrion prepared by aqueous (AB) and organic (HFIP) solvent based processes, along with collagen (COL) and poly-lactic acid (PLA) based scaffolds were studied in vitro and in vivo for their utility in adipose tissue engineering strategies. For in vitro studies, human bone marrow and adipose-derived mesenchymal stem cells (hMSCs and hASCs) were seeded on the various biomaterials and cultured for 21 days in the presence of adipogenic stimulants (AD) or maintained as noninduced controls. Alamar Blue analysis revealed each biomaterial supported initial attachment of hMSCs and hASCs to similar levels for all matrices except COL in which higher levels were observed. hASCs and hMSCs cultured on all biomaterials in the presence of AD showed significant upregulation of adipogenic mRNA transcript levels (LPL, GLUT4, FABP4, PPARγ, adipsin, ACS) to similar extents when compared to noninduced controls. Similarly Oil-Red O analysis of hASC or hMSC-seeded scaffolds displayed substantial amounts of lipid accumulating adipocytes following cultivation with AD. The data revealed AB and HFIP scaffolds supported similar extents of lipid accumulating cells while PLA and COL scaffolds qualitatively displayed lower and higher extents by comparison, respectively. Following a 4 week implantation period in a rat muscle pouch defect model, both AB and HFIP scaffolds supported in vivo adipogenesis either alone or seeded with hASCs or hMSCs as assessed by Oil-Red O analysis, however the presence of exogenous cell sources substantially increased the extent and frequency of adipogenesis observed. In contrast, COL and PLA scaffolds underwent rapid scaffold degradation and were irretrievable following the implantation period. The results suggest that macroporous 3D AB and HFIP silk fibroin scaffolds offer an important platform for cell-based adipose tissue engineering applications, and in particular, provide longer-term structural integrity to promote the maintenance of soft tissue in vivo. PMID:17765303

Brachytherapy dosimetry of 125I and 103Pd sources using an updated cross section library for the MCNP Monte Carlo transport code.

PubMed

Bohm, Tim D; DeLuca, Paul M; DeWerd, Larry A

2003-04-01

Permanent implantation of low energy (20-40 keV) photon emitting radioactive seeds to treat prostate cancer is an important treatment option for patients. In order to produce accurate implant brachytherapy treatment plans, the dosimetry of a single source must be well characterized. Monte Carlo based transport calculations can be used for source characterization, but must have up to date cross section libraries to produce accurate dosimetry results. This work benchmarks the MCNP code and its photon cross section library for low energy photon brachytherapy applications. In particular, we calculate the emitted photon spectrum, air kerma, depth dose in water, and radial dose function for both 125I and 103Pd based seeds and compare to other published results. Our results show that MCNP's cross section library differs from recent data primarily in the photoelectric cross section for low energies and low atomic number materials. In water, differences as large as 10% in the photoelectric cross section and 6% in the total cross section occur at 125I and 103Pd photon energies. This leads to differences in the dose rate constant of 3% and 5%, and differences as large as 18% and 20% in the radial dose function for the 125I and 103Pd based seeds, respectively. Using a partially updated photon library, calculations of the dose rate constant and radial dose function agree with other published results. Further, the use of the updated photon library allows us to verify air kerma and depth dose in water calculations performed using MCNP's perturbation feature to simulate updated cross sections. We conclude that in order to most effectively use MCNP for low energy photon brachytherapy applications, we must update its cross section library. Following this update, the MCNP code system will be a very effective tool for low energy photon brachytherapy dosimetry applications.

Clinical Significance of Accounting for Tissue Heterogeneity in Permanent Breast Seed Implant Brachytherapy Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mashouf, Shahram; Department of Radiation Oncology, Sunnybrook Odette Cancer Centre, Toronto, Ontario; Fleury, Emmanuelle

Purpose: The inhomogeneity correction factor (ICF) method provides heterogeneity correction for the fast calculation TG43 formalism in seed brachytherapy. This study compared ICF-corrected plans to their standard TG43 counterparts, looking at their capacity to assess inadequate coverage and/or risk of any skin toxicities for patients who received permanent breast seed implant (PBSI). Methods and Materials: Two-month postimplant computed tomography scans and plans of 140 PBSI patients were used to calculate dose distributions by using the TG43 and the ICF methods. Multiple dose-volume histogram (DVH) parameters of clinical target volume (CTV) and skin were extracted and compared for both ICF and TG43more » dose distributions. Short-term (desquamation and erythema) and long-term (telangiectasia) skin toxicity data were available on 125 and 110 of the patients, respectively, at the time of the study. The predictive value of each DVH parameter of skin was evaluated using the area under the receiver operating characteristic (ROC) curve for each toxicity endpoint. Results: Dose-volume histogram parameters of CTV, calculated using the ICF method, showed an overall decrease compared to TG43, whereas those of skin showed an increase, confirming previously reported findings of the impact of heterogeneity with low-energy sources. The ICF methodology enabled us to distinguish patients for whom the CTV V{sub 100} and V{sub 90} are up to 19% lower compared to TG43, which could present a risk of recurrence not detected when heterogeneity are not accounted for. The ICF method also led to an increase in the prediction of desquamation, erythema, and telangiectasia for 91% of skin DVH parameters studied. Conclusions: The ICF methodology has the advantage of distinguishing any inadequate dose coverage of CTV due to breast heterogeneity, which can be missed by TG43. Use of ICF correction also led to an increase in prediction accuracy of skin toxicities in most cases.« less

Clinical Significance of Accounting for Tissue Heterogeneity in Permanent Breast Seed Implant Brachytherapy Planning.

PubMed

Mashouf, Shahram; Fleury, Emmanuelle; Lai, Priscilla; Merino, Tomas; Lechtman, Eli; Kiss, Alex; McCann, Claire; Pignol, Jean-Philippe

2016-03-15

The inhomogeneity correction factor (ICF) method provides heterogeneity correction for the fast calculation TG43 formalism in seed brachytherapy. This study compared ICF-corrected plans to their standard TG43 counterparts, looking at their capacity to assess inadequate coverage and/or risk of any skin toxicities for patients who received permanent breast seed implant (PBSI). Two-month postimplant computed tomography scans and plans of 140 PBSI patients were used to calculate dose distributions by using the TG43 and the ICF methods. Multiple dose-volume histogram (DVH) parameters of clinical target volume (CTV) and skin were extracted and compared for both ICF and TG43 dose distributions. Short-term (desquamation and erythema) and long-term (telangiectasia) skin toxicity data were available on 125 and 110 of the patients, respectively, at the time of the study. The predictive value of each DVH parameter of skin was evaluated using the area under the receiver operating characteristic (ROC) curve for each toxicity endpoint. Dose-volume histogram parameters of CTV, calculated using the ICF method, showed an overall decrease compared to TG43, whereas those of skin showed an increase, confirming previously reported findings of the impact of heterogeneity with low-energy sources. The ICF methodology enabled us to distinguish patients for whom the CTV V100 and V90 are up to 19% lower compared to TG43, which could present a risk of recurrence not detected when heterogeneity are not accounted for. The ICF method also led to an increase in the prediction of desquamation, erythema, and telangiectasia for 91% of skin DVH parameters studied. The ICF methodology has the advantage of distinguishing any inadequate dose coverage of CTV due to breast heterogeneity, which can be missed by TG43. Use of ICF correction also led to an increase in prediction accuracy of skin toxicities in most cases. Copyright © 2016 Elsevier Inc. All rights reserved.

ALGEBRA: ALgorithm for the heterogeneous dosimetry based on GEANT4 for BRAchytherapy.

PubMed

Afsharpour, H; Landry, G; D'Amours, M; Enger, S; Reniers, B; Poon, E; Carrier, J-F; Verhaegen, F; Beaulieu, L

2012-06-07

Task group 43 (TG43)-based dosimetry algorithms are efficient for brachytherapy dose calculation in water. However, human tissues have chemical compositions and densities different than water. Moreover, the mutual shielding effect of seeds on each other (interseed attenuation) is neglected in the TG43-based dosimetry platforms. The scientific community has expressed the need for an accurate dosimetry platform in brachytherapy. The purpose of this paper is to present ALGEBRA, a Monte Carlo platform for dosimetry in brachytherapy which is sufficiently fast and accurate for clinical and research purposes. ALGEBRA is based on the GEANT4 Monte Carlo code and is capable of handling the DICOM RT standard to recreate a virtual model of the treated site. Here, the performance of ALGEBRA is presented for the special case of LDR brachytherapy in permanent prostate and breast seed implants. However, the algorithm is also capable of handling other treatments such as HDR brachytherapy.

Effect of pulse sequence parameter selection on signal strength in positive-contrast MRI markers for MRI-based prostate postimplant assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lim, Tze Yee

Purpose: For postimplant dosimetric assessment, computed tomography (CT) is commonly used to identify prostate brachytherapy seeds, at the expense of accurate anatomical contouring. Magnetic resonance imaging (MRI) is superior to CT for anatomical delineation, but identification of the negative-contrast seeds is challenging. Positive-contrast MRI markers were proposed to replace spacers to assist seed localization on MRI images. Visualization of these markers under varying scan parameters was investigated. Methods: To simulate a clinical scenario, a prostate phantom was implanted with 66 markers and 86 seeds, and imaged on a 3.0T MRI scanner using a 3D fast radiofrequency-spoiled gradient recalled echo acquisitionmore » with various combinations of scan parameters. Scan parameters, including flip angle, number of excitations, bandwidth, field-of-view, slice thickness, and encoding steps were systematically varied to study their effects on signal, noise, scan time, image resolution, and artifacts. Results: The effects of pulse sequence parameter selection on the marker signal strength and image noise were characterized. The authors also examined the tradeoff between signal-to-noise ratio, scan time, and image artifacts, such as the wraparound artifact, susceptibility artifact, chemical shift artifact, and partial volume averaging artifact. Given reasonable scan time and managable artifacts, the authors recommended scan parameter combinations that can provide robust visualization of the MRI markers. Conclusions: The recommended MRI pulse sequence protocol allows for consistent visualization of the markers to assist seed localization, potentially enabling MRI-only prostate postimplant dosimetry.« less

Two differentially structured collagen scaffolds for potential urinary bladder augmentation: proof of concept study in a Göttingen minipig model.

PubMed

Leonhäuser, Dorothea; Stollenwerk, Katja; Seifarth, Volker; Zraik, Isabella M; Vogt, Michael; Srinivasan, Pramod K; Tolba, Rene H; Grosse, Joachim O

2017-01-04

The repair of urinary bladder tissue is a necessity for tissue loss due to cancer, trauma, or congenital abnormalities. Use of intestinal tissue is still the gold standard in the urological clinic, which leads to new problems and dysfunctions like mucus production, stone formation, and finally malignancies. Therefore, the use of artificial, biologically derived materials is a promising step towards the augmentation of this specialised tissue. The aim of this study was to investigate potential bladder wall repair by two collagen scaffold prototypes, OptiMaix 2D and 3D, naïve and seeded with autologous vesical cells, as potential bladder wall substitute material in a large animal model. Six Göttingen minipigs underwent cystoplastic surgery for tissue biopsy and cell isolation followed by implantation of unseeded scaffolds. Six weeks after the first operation, scaffolds seeded with the tissue cultured autologous urothelial and detrusor smooth muscle cells were implanted into the bladder together with additional unseeded scaffolds for comparison. Cystography and bladder ultrasound were performed to demonstrate structural integrity and as leakage test of the implantation sites. Eighteen, 22, and 32 weeks after the first operation, two minipigs respectively were sacrificed and the urinary tract was examined via different (immunohistochemical) staining procedures and the usage of two-photon laser scanning microscopy. Both collagen scaffold prototypes in vivo had good ingrowth capacity into the bladder wall including a quick lining with urothelial cells. The ingrowth of detrusor muscle tissue, along with the degradation of the scaffolds, could also be observed throughout the study period. We could show that the investigated collagen scaffolds OptiMaix 2D and 3D are a potential material for bladder wall substitution. The material has good biocompatible properties, shows a good cell growth of autologous cells in vitro, and a good integration into the present bladder tissue in vivo.

Ectopic bone formation by marrow stromal osteoblast transplantation using poly(DL-lactic-co-glycolic acid) foams implanted into the rat mesentery

NASA Technical Reports Server (NTRS)

Ishaug-Riley, S. L.; Crane, G. M.; Gurlek, A.; Miller, M. J.; Yasko, A. W.; Yaszemski, M. J.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

1997-01-01

Porous biodegradable poly(DL-lactic-co-glycolic acid) foams were seeded with rat marrow stromal cells and implanted into the rat mesentery to investigate in vivo bone formation at an ectopic site. Cells were seeded at a density of 6.83 x 10(5) cells/cm2 onto polymer foams having pore sizes ranging from either 150 to 300 to 710 microns and cultured for 7 days in vitro prior to implantation. The polymer/cell constructs were harvested after 1, 7, 28, or 49 days in vivo and processed for histology and gel permeation chromatography. Visual observation of hematoxylin and eosin-stained sections and von Kossa-stained sections revealed the formation of mineralized bonelike tissue in the constructs within 7 days postimplantation. Ingrowth of vascular tissue was also found adjacent to the islands of bone, supplying the necessary metabolic requirements to the newly formed tissue. Mineralization and bone tissue formation were investigated by histomorphometry. The average penetration depth of mineralized tissue in the construct ranged from 190 +/- 50 microns for foams with 500-710-microns pores to 370 +/- 160 microns for foams with 150-300-microns pores after 49 days in vivo. The mineralized bone volume per surface area and total bone volume per surface area had maximal values of 0.28 +/- 0.21 mm (500-710-microns pore size, day 28) and 0.038 +/- 0.024 mm (150-300-microns, day 28), respectively. As much as 11% of the foam volume penetrated by bone tissue was filled with mineralized tissue. No significant trends over time were observed for any of the measured values (penetration depth, bone volume/surface area, or percent mineralized bone volume). These results suggest the feasibility of bone formation by osteoblast transplantation in an orthotopic site where not only bone formation from transplanted cells but also ingrowth from adjacent bone may occur.

X-ray Photoelectron Spectroscopy Analysis of Gold Surfaces after Removal of Thiolated DNA Oligomers by Ultraviolet/Ozone Treatment

PubMed Central

Mirsaleh-Kohan, Nasrin; Bass, Andrew D.; Sanche, Léon

2012-01-01

Well ordered films of molecular DNA can be formed by the attachment of thiolated DNA oligonucleotides to a supporting gold substrate. The gold substrate represents a significant fraction of the total cost of preparing such films and it is thus important to determine whether such substrates can be reused. Here we investigate with X-ray Photoelectron Spectroscopy the suitability of UV/ozonolysis previously employed to remove alkanethiols from gold, for removing 40-mer, single and double stranded synthetic DNA. We find that while UV/O3 can indeed remove thiolated DNA from gold slides, the treatment times required permit the implantation of additional organic contaminants. PMID:20000594

X-ray photoelectron spectroscopy analysis of gold surfaces after removal of thiolated DNA oligomers by ultraviolet/ozone treatment.

PubMed

Mirsaleh-Kohan, Nasrin; Bass, Andrew D; Sanche, Léon

2010-05-04

Well-ordered films of molecular DNA can be formed by the attachment of thiolated DNA oligonucleotides to a supporting gold substrate. The gold substrate represents a significant fraction of the total cost of preparing such films, and it is thus important to determine whether such substrates can be reused. Here, we investigate with X-ray photoelectron spectroscopy the suitability of UV/ozonolysis previously employed to remove alkanethiols from gold, for removing 40-mer, single- and double-stranded synthetic DNA. We find that while UV/O(3) can indeed remove thiolated DNA from gold slides, the treatment times required permit the implantation of additional organic contaminants.

Tension and fatigue behavior of 316LVM 1x7 multi-strand cables used as implantable electrodes.

PubMed

Lewandowski, John J; Varadarajan, Ravikumar; Smith, Brian; Tuma, Chris; Shazly, Mostafa; Vatamanu, Luciano O

2008-07-15

The mechanical behavior of 316LVM 1x7 cables were evaluated in uniaxial tension, and in cyclic strain-controlled fatigue with the use of a Flex tester operated to provide fully reversed bending fatigue. The magnitude of cyclic strains imparted to each cable tested was controlled via the use of different diameter mandrels. Smaller diameter mandrels produced higher values of cyclic strain and lower fatigue life. Multiple samples were tested and analyzed via scanning electron microscopy. The fatigue results were analyzed via a Coffin-Manson-Basquin approach and compared to fatigue data obtained from the literature where testing was conducted on similar materials, but under rotating bending fatigue conditions.

A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice.

PubMed

Laronda, Monica M; Rutz, Alexandra L; Xiao, Shuo; Whelan, Kelly A; Duncan, Francesca E; Roth, Eric W; Woodruff, Teresa K; Shah, Ramille N

2017-05-16

Emerging additive manufacturing techniques enable investigation of the effects of pore geometry on cell behavior and function. Here, we 3D print microporous hydrogel scaffolds to test how varying pore geometry, accomplished by manipulating the advancing angle between printed layers, affects the survival of ovarian follicles. 30° and 60° scaffolds provide corners that surround follicles on multiple sides while 90° scaffolds have an open porosity that limits follicle-scaffold interaction. As the amount of scaffold interaction increases, follicle spreading is limited and survival increases. Follicle-seeded scaffolds become highly vascularized and ovarian function is fully restored when implanted in surgically sterilized mice. Moreover, pups are born through natural mating and thrive through maternal lactation. These findings present an in vivo functional ovarian implant designed with 3D printing, and indicate that scaffold pore architecture is a critical variable in additively manufactured scaffold design for functional tissue engineering.

[In Situ Polymerization and Characterization of Hydroxyapatite/polyurethane Implanted Material].

PubMed

Gu, Muqing; Xiao, Fengjuan; Liang, Ye; Yue, Lin; Li, Song; Li, Lanlan; Feng, Feifei

2015-08-01

In order to improve the interfacial bonding strength of hydroxyapatite/polyurethane implanted material and dispersion of hydroxyapatite in the polyurethane matrix, we in the present study synthesized nano-hydroxyapatite/polyurethane composites by in situ polymerization. We then characterized and analyzed the fracture morphology, thermal stability, glass transition temperature and mechanical properties. We seeded MG63 cells on composites to evaluate the cytocompatibility of the composites. In situ polymerization could improve the interfacial bonding strength, ameliorate dispersion of hydroxyapatite in the properties of the composites. After adding 20 wt% hydroxyapatite into the polyurethane, the thermal stability was improved and the glass transition temperatures were increased. The tensile strength and maximum elongation were 6.83 MPa and 861.17%, respectively. Compared with those of pure polyurethane the tensile strength and maximum elongation increased by 236.45% and 143.30%, respectively. The composites were helpful for cell adhesion and proliferation in cultivation.

Study of Biological Effects of Low Energy Ion Implantation on Tomato and Radish Breeding

NASA Astrophysics Data System (ADS)

Liang, Qiuxia; Huang, Qunce; Cao, Gangqiang; Ying, Fangqing; Liu, Yanbo; Huang, Wen

2008-04-01

Biological effects of 30 keV low energy nitrogen ion implantation on the seeds of five types of tomato and one type of radish were investigated. Results showed that low energy ions have different effects on different vegetables. The whole dose-response curve of the germination ratio did not take on "the shape of saddle", but was a rising and falling waveform with the increase or decrease in ion implantation. In the vegetable of Solanaceae, two outstanding aberrant plants were selected from M1 of Henan No.4 tomato at a dose of 7 × 1017 nitrogen ions/cm2, which had thin-leaves, long-petal and nipple tip fruit stably inherited to M7. Furthermore the analysis of the isozyme showed that the activity of the mutant tomato seedling was distinct in quantity and color. In Raphanus sativus L., the aberrances were obvious in the mutant of radish 791 at a dose of 5 × 1017 nitrogen ions/cm2, and the weight of succulent root and the volume of growth were over twice the control's. At present, many species for breeding have been identified in the field and only stable species have been selected for the experiment of production. It is evident that the low energy ion implantation technology has clear effects on vegetables' genetic improvement.

Biomaterials Transforming growth factor-beta 1 delivery from microporous scaffolds decreases inflammation post-implant and enhances function of transplanted islets

PubMed Central

Liu, JMH; Zhang, J; Zhang, X; Hlavaty, KA; Ricci, CF; Leonard, JN; Shea, LD; Gower, RM

2015-01-01

Biomaterial scaffolds are central to many regenerative strategies as they create a space for infiltration of host tissue and provide a platform to deliver growth factors and progenitor cells. However, biomaterial implantation results in an unavoidable inflammatory response, which can impair tissue regeneration and promote loss or dysfunction of transplanted cells. We investigated localized TGF-β1 delivery to modulate this immunological environment around scaffolds and transplanted cells. TGF-β1 was delivered from layered scaffolds, with protein entrapped within an inner layer and outer layers designed for cell seeding and host tissue integration. Scaffolds were implanted into the epididymal fat pad, a site frequently used for cell transplantation. Expression of cytokines TNF-a, IL-12, and MCP-1 were decreased by at least 40% for scaffolds releasing TGF-β1 relative to control scaffolds. This decrease in inflammatory cytokine production corresponded to a 60% decrease in leukocyte infiltration. Transplantation of islets into diabetic mice on TGF-β1 scaffolds significantly improved the ability of syngeneic islets to control blood glucose levels within the first week of transplant and delayed rejection of allogeneic islets. Together, these studies emphasize the ability of localized TGF-β1 delivery to modulate the immune response to biomaterial implants and enhance cell function in cell-based therapies. PMID:26701143

The effect of coimmobilizing heparin and fibronectin on titanium on hemocompatibility and endothelialization.

PubMed

Li, Guicai; Yang, Ping; Qin, Wei; Maitz, Manfred F; Zhou, Shuo; Huang, Nan

2011-07-01

Currently available cardiovascular implants, such as heart valves and stents, exhibit suboptimal biocompatibility because of the incomplete endothelialization and sequential thrombosis formation especially after a long-term implantation. To improve the blood compatibility and endothelialization simultaneously and ensure the long-term effect of the cardiovascular implants, a technique of combining electrostatic interaction and coimmobilization was developed to form heparin and fibronectin (Hep/Fn) films on aminosilanized titanium (Ti) surfaces. The Hep/Fn coimmobilized films were stable after immersion in PBS for five days, probed by wettability studies and by the release kinetics of heparin and fibronectin. Blood compatibility tests showed that the coimmobilized Hep/Fn films displayed lower hemolysis rate, prolonged blood coagulation time, higher AT III binding density, less platelets activation and aggregation, and less fibrinogen conformational change compared with Ti surface. Endothelial cells (ECs) seeding and fibronectin bioactivity results showed more attached and proliferated ECs and exposed cell-binding sites on the Hep/Fn immobilized samples than that on Ti surfaces. Thus, the Hep/Fn coimmobilized films kept excellent bioactivity even after immersion in PBS for five days. Systemic evaluation suggests that the coimmobilization of Hep/Fn complex improves the blood compatibility and promotes the endothelialization simultaneously. We envisage that this method will provide a potential and effective selection for biomaterials surface modification of cardiovascular implants. Copyright © 2011 Elsevier Ltd. All rights reserved.

Silk fibroin/chitosan scaffold with tunable properties and low inflammatory response assists the differentiation of bone marrow mesenchymal stem cells.

PubMed

Li, Da-Wei; Lei, Xiaohua; He, Feng-Li; He, Jin; Liu, Ya-Li; Ye, Ya-Jing; Deng, Xudong; Duan, Enkui; Yin, Da-Chuan

2017-12-01

The physical and chemical properties of the scaffold are known to play important roles in three-dimensional (3D) cell culture, which always determine the cellular fate or the results of implantation. To control these properties becomes necessary for meeting the requirements of a variety of tissue engineering applications. In this study, a series of silk fibroin/chitosan (SF/CS) scaffolds with tunable properties were prepared using freeze-drying method, and the rat bone marrow-derived mesenchymal stem cells (BM-MSCs) were seeded in these scaffolds to evaluate their availability of use in tissue engineering. The 3D structure, mechanical properties and degradation ability of SF/CS scaffold can be tuned by changing the total concentration of the precursor solution and the blending ratio between SF and CS. BM-MSCs cultured in the SF/CS scaffold exhibited excellent proliferation and multiple morphologies. The induction of osteogenic and adipogenic differentiation of BM-MSCs were successful in this scaffold when cultured in vitro. Subcutaneous implantation of the SF/CS scaffolds did not cause any inflammatory response within four weeks, which revealed good compatibility. Moreover, the implanted scaffold allowed host cells to invade, adhere, grow and form new blood vessels. With these excellent performance, SF/CS scaffold has great potential in preparing implants for tissue engineering applications. Copyright © 2017. Published by Elsevier B.V.

Propionibacterium acnes: from Commensal to Opportunistic Biofilm-Associated Implant Pathogen

PubMed Central

Achermann, Yvonne; Goldstein, Ellie J. C.; Coenye, Tom

2014-01-01

SUMMARY Propionibacterium acnes is known primarily as a skin commensal. However, it can present as an opportunistic pathogen via bacterial seeding to cause invasive infections such as implant-associated infections. These infections have gained more attention due to improved diagnostic procedures, such as sonication of explanted foreign materials and prolonged cultivation time of up to 14 days for periprosthetic biopsy specimens, and improved molecular methods, such as broad-range 16S rRNA gene PCR. Implantassociated infections caused by P. acnes are most often described for shoulder prosthetic joint infections as well as cerebrovascular shunt infections, fibrosis of breast implants, and infections of cardiovascular devices. P. acnes causes disease through a number of virulence factors, such as biofilm formation. P. acnes is highly susceptible to a wide range of antibiotics, including beta-lactams, quinolones, clindamycin, and rifampin, although resistance to clindamycin is increasing. Treatment requires a combination of surgery and a prolonged antibiotic treatment regimen to successfully eliminate the remaining bacteria. Most authors suggest a course of 3 to 6 months of antibiotic treatment, including 2 to 6 weeks of intravenous treatment with a beta-lactam. While recently reported data showed a good efficacy of rifampin against P. acnes biofilms, prospective, randomized, controlled studies are needed to confirm evidence for combination treatment with rifampin, as has been performed for staphylococcal implant-associated infections. PMID:24982315

Anodizing color coded anodized Ti6Al4V medical devices for increasing bone cell functions

PubMed Central

Ross, Alexandra P; Webster, Thomas J

2013-01-01

Current titanium-based implants are often anodized in sulfuric acid (H2SO4) for color coding purposes. However, a crucial parameter in selecting the material for an orthopedic implant is the degree to which it will integrate into the surrounding bone. Loosening at the bone–implant interface can cause catastrophic failure when motion occurs between the implant and the surrounding bone. Recently, a different anodization process using hydrofluoric acid has been shown to increase bone growth on commercially pure titanium and titanium alloys through the creation of nanotubes. The objective of this study was to compare, for the first time, the influence of anodizing a titanium alloy medical device in sulfuric acid for color coding purposes, as is done in the orthopedic implant industry, followed by anodizing the device in hydrofluoric acid to implement nanotubes. Specifically, Ti6Al4V model implant samples were anodized first with sulfuric acid to create color-coding features, and then with hydrofluoric acid to implement surface features to enhance osteoblast functions. The material surfaces were characterized by visual inspection, scanning electron microscopy, contact angle measurements, and energy dispersive spectroscopy. Human osteoblasts were seeded onto the samples for a series of time points and were measured for adhesion and proliferation. After 1 and 2 weeks, the levels of alkaline phosphatase activity and calcium deposition were measured to assess the long-term differentiation of osteoblasts into the calcium depositing cells. The results showed that anodizing in hydrofluoric acid after anodizing in sulfuric acid partially retains color coding and creates unique surface features to increase osteoblast adhesion, proliferation, alkaline phosphatase activity, and calcium deposition. In this manner, this study provides a viable method to anodize an already color coded, anodized titanium alloy to potentially increase bone growth for numerous implant applications. PMID:23319862

The effect of different collagen modifications for titanium and titanium nitrite surfaces on functions of gingival fibroblasts.

PubMed

Ritz, U; Nusselt, T; Sewing, A; Ziebart, T; Kaufmann, K; Baranowski, A; Rommens, P M; Hofmann, Alexander

2017-01-01

Targeted modifications of the bulk implant surfaces using bioactive agents provide a promising tool for improvement of the long-term bony and soft tissue integration of dental implants. In this study, we assessed the cellular responses of primary human gingival fibroblasts (HGF) to different surface modifications of titanium (Ti) and titanium nitride (TiN) alloys with type I collagen or cyclic-RGDfK-peptide in order to define a modification improving long-term implants in dental medicine. Employing Ti and TiN implants, we compared the performance of simple dip coating and anodic immobilization of type I collagen that provided collagen layers of two different thicknesses. HGF were seeded on the different coated implants, and adhesion, proliferation, and gene expression were analyzed. Although there were no strong differences in initial cell adhesion between the groups at 2 and 4 hours, we found that all surface modifications induced higher proliferation rates as compared to the unmodified controls. Consistently, gene expression levels of cell adhesion markers (focal adhesion kinase (FAK), integrin beta1, and vinculin), cell differentiation markers (FGFR1, TGFb-R1), extracellular protein markers (type I collagen, vimentin), and cytoskeletal protein marker aktinin-1 were consistently higher in all surface modification groups at two different time points of investigation as compared to the unmodified controls. Our results indicate that simple dip coating of Ti and TiN with collagen is sufficient to induce in vitro cellular responses that are comparable to those of more reliable coating methods like anodic adsorption, chemical cross-linking, or RGD coating. TiN alloys do not possess any positive or adverse effects on HGF. Our results demonstrate a simple, yet effective, method for collagen coating on titanium implants to improve the long term integration and stability of dental implants.

Anodizing color coded anodized Ti6Al4V medical devices for increasing bone cell functions.

PubMed

Ross, Alexandra P; Webster, Thomas J

2013-01-01

Current titanium-based implants are often anodized in sulfuric acid (H(2)SO(4)) for color coding purposes. However, a crucial parameter in selecting the material for an orthopedic implant is the degree to which it will integrate into the surrounding bone. Loosening at the bone-implant interface can cause catastrophic failure when motion occurs between the implant and the surrounding bone. Recently, a different anodization process using hydrofluoric acid has been shown to increase bone growth on commercially pure titanium and titanium alloys through the creation of nanotubes. The objective of this study was to compare, for the first time, the influence of anodizing a titanium alloy medical device in sulfuric acid for color coding purposes, as is done in the orthopedic implant industry, followed by anodizing the device in hydrofluoric acid to implement nanotubes. Specifically, Ti6Al4V model implant samples were anodized first with sulfuric acid to create color-coding features, and then with hydrofluoric acid to implement surface features to enhance osteoblast functions. The material surfaces were characterized by visual inspection, scanning electron microscopy, contact angle measurements, and energy dispersive spectroscopy. Human osteoblasts were seeded onto the samples for a series of time points and were measured for adhesion and proliferation. After 1 and 2 weeks, the levels of alkaline phosphatase activity and calcium deposition were measured to assess the long-term differentiation of osteoblasts into the calcium depositing cells. The results showed that anodizing in hydrofluoric acid after anodizing in sulfuric acid partially retains color coding and creates unique surface features to increase osteoblast adhesion, proliferation, alkaline phosphatase activity, and calcium deposition. In this manner, this study provides a viable method to anodize an already color coded, anodized titanium alloy to potentially increase bone growth for numerous implant applications.

Effect of zirconium nitride physical vapor deposition coating on preosteoblast cell adhesion and proliferation onto titanium screws.

PubMed

Rizzi, Manuela; Gatti, Giorgio; Migliario, Mario; Marchese, Leonardo; Rocchetti, Vincenzo; Renò, Filippo

2014-11-01

Titanium has long been used to produce dental implants. Problems related to its manufacturing, casting, welding, and ceramic application for dental prostheses still limit its use, which highlights the need for technologic improvements. The aim of this in vitro study was to evaluate the biologic performance of titanium dental implants coated with zirconium nitride in a murine preosteoblast cellular model. The purpose of this study was to evaluate the chemical and morphologic characteristics of titanium implants coated with zirconium nitride by means of physical vapor deposition. Chemical and morphologic characterizations were performed by scanning electron microscopy and energy dispersive x-ray spectroscopy, and the bioactivity of the implants was evaluated by cell-counting experiments. Scanning electron microscopy and energy dispersive x-ray spectroscopy analysis found that physical vapor deposition was effective in covering titanium surfaces with zirconium nitride. Murine MC-3T3 preosteoblasts were seeded onto titanium-coated and zirconium nitride-coated screws to evaluate their adhesion and proliferation. These experiments found a significantly higher number of cells adhering and spreading onto zirconium nitride-coated surfaces (P<.05) after 24 hours; after 7 days, both titanium and zirconium nitride surfaces were completely covered with MC-3T3 cells. Analysis of these data indicates that the proposed zirconium nitride coating of titanium implants could make the surface of the titanium more bioactive than uncoated titanium surfaces. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Biomimetic and synthetic esophageal tissue engineering.

PubMed

Jensen, Todd; Blanchette, Alex; Vadasz, Stephanie; Dave, Apeksha; Canfarotta, Michael; Sayej, Wael N; Finck, Christine

2015-07-01

A tissue-engineered esophagus offers an alternative for the treatment of pediatric patients suffering from severe esophageal malformations, caustic injury, and cancer. Additionally, adult patients suffering from carcinoma or trauma would benefit. Donor rat esophageal tissue was physically and enzymatically digested to isolate epithelial and smooth muscle cells, which were cultured in epithelial cell medium or smooth muscle cell medium and characterized by immunofluorescence. Isolated cells were also seeded onto electrospun synthetic PLGA and PCL/PLGA scaffolds in a physiologic hollow organ bioreactor. After 2 weeks of in vitro culture, tissue-engineered constructs were orthotopically transplanted. Isolated cells were shown to give rise to epithelial, smooth muscle, and glial cell types. After 14 days in culture, scaffolds supported epithelial, smooth muscle and glial cell phenotypes. Transplanted constructs integrated into the host's native tissue and recipients of the engineered tissue demonstrated normal feeding habits. Characterization after 14 days of implantation revealed that all three cellular phenotypes were present in varying degrees in seeded and unseeded scaffolds. We demonstrate that isolated cells from native esophagus can be cultured and seeded onto electrospun scaffolds to create esophageal constructs. These constructs have potential translatable application for tissue engineering of human esophageal tissue. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aortic valve cell seeding into decellularized animal pericardium by perfusion-assisted bioreactor.

PubMed

Amadeo, Francesco; Boschetti, Federica; Polvani, Gianluca; Banfi, Cristina; Pesce, Maurizio; Santoro, Rosaria

2018-04-27

Animal-derived pericardium is the elective tissue employed in manufacturing heart valve prostheses. The preparation of this tissue for biological valve production consists of fixation with aldehydes, which reduces, but not eliminates, the xenoantigens and the donor cellular material. As a consequence, especially in patients below 65-70 years of age, the employment of valve substitutes contaning pericardium is not indicated due to progressive calcification that causes tissue degeneration and recurrence of valve insufficiency. Decellularization with ionic or nonionic detergents has been proposed as an alternative procedure to prepare aldehyde- or xenoantigen-free pericardium for biological valve manufacturing. In the present contribution, we optimized a decellularization procedure that is permissive for seeding and culturing valve competent cells able to colonize and reconstitute a valve-like tissue. A high-efficiency cellularization was achieved by forcing cell penetration inside the pericardium matrix using a perfusion bioreactor. Because the decellularization procedure was found not to alter the collagen composition of the pericardial matrix and cells seeded in the tissue constructs consistently grew and acquired the phenotype of "quiescent" valve interstitial cells, our investigation sets a novel standard in pericardium application for tissue engineering of "living" valve implants. Copyright © 2018 John Wiley & Sons, Ltd.

A radiobiology-based inverse treatment planning method for optimisation of permanent l-125 prostate implants in focal brachytherapy.

PubMed

Haworth, Annette; Mears, Christopher; Betts, John M; Reynolds, Hayley M; Tack, Guido; Leo, Kevin; Williams, Scott; Ebert, Martin A

2016-01-07

Treatment plans for ten patients, initially treated with a conventional approach to low dose-rate brachytherapy (LDR, 145 Gy to entire prostate), were compared with plans for the same patients created with an inverse-optimisation planning process utilising a biologically-based objective. The 'biological optimisation' considered a non-uniform distribution of tumour cell density through the prostate based on known and expected locations of the tumour. Using dose planning-objectives derived from our previous biological-model validation study, the volume of the urethra receiving 125% of the conventional prescription (145 Gy) was reduced from a median value of 64% to less than 8% whilst maintaining high values of TCP. On average, the number of planned seeds was reduced from 85 to less than 75. The robustness of plans to random seed displacements needs to be carefully considered when using contemporary seed placement techniques. We conclude that an inverse planning approach to LDR treatments, based on a biological objective, has the potential to maintain high rates of tumour control whilst minimising dose to healthy tissue. In future, the radiobiological model will be informed using multi-parametric MRI to provide a personalised medicine approach.

A radiobiology-based inverse treatment planning method for optimisation of permanent l-125 prostate implants in focal brachytherapy

NASA Astrophysics Data System (ADS)

Haworth, Annette; Mears, Christopher; Betts, John M.; Reynolds, Hayley M.; Tack, Guido; Leo, Kevin; Williams, Scott; Ebert, Martin A.

2016-01-01

Treatment plans for ten patients, initially treated with a conventional approach to low dose-rate brachytherapy (LDR, 145 Gy to entire prostate), were compared with plans for the same patients created with an inverse-optimisation planning process utilising a biologically-based objective. The ‘biological optimisation’ considered a non-uniform distribution of tumour cell density through the prostate based on known and expected locations of the tumour. Using dose planning-objectives derived from our previous biological-model validation study, the volume of the urethra receiving 125% of the conventional prescription (145 Gy) was reduced from a median value of 64% to less than 8% whilst maintaining high values of TCP. On average, the number of planned seeds was reduced from 85 to less than 75. The robustness of plans to random seed displacements needs to be carefully considered when using contemporary seed placement techniques. We conclude that an inverse planning approach to LDR treatments, based on a biological objective, has the potential to maintain high rates of tumour control whilst minimising dose to healthy tissue. In future, the radiobiological model will be informed using multi-parametric MRI to provide a personalised medicine approach.

3D printed scaffolds of calcium silicate-doped β-TCP synergize with co-cultured endothelial and stromal cells to promote vascularization and bone formation.

PubMed

Deng, Yuan; Jiang, Chuan; Li, Cuidi; Li, Tao; Peng, Mingzheng; Wang, Jinwu; Dai, Kerong

2017-07-17

Synthetic bone scaffolds have potential application in repairing large bone defects, however, inefficient vascularization after implantation remains the major issue of graft failure. Herein, porous β-tricalcium phosphate (β-TCP) scaffolds with calcium silicate (CS) were 3D printed, and pre-seeded with co-cultured human umbilical cord vein endothelial cells (HUVECs) and human bone marrow stromal cells (hBMSCs) to construct tissue engineering scaffolds with accelerated vascularization and better bone formation. Results showed that in vitro β-TCP scaffolds doped with 5% CS (5%CS/β-TCP) were biocompatible, and stimulated angiogenesis and osteogenesis. The results also showed that 5%CS/β-TCP scaffolds not only stimulated co-cultured cells angiogenesis on Matrigel, but also stimulated co-cultured cells to form microcapillary-like structures on scaffolds, and promoted migration of BMSCs by stimulating co-cultured cells to secrete PDGF-BB and CXCL12 into the surrounding environment. Moreover, 5%CS/β-TCP scaffolds enhanced vascularization and osteoinduction in comparison with β-TCP, and synergized with co-cultured cells to further increase early vessel formation, which was accompanied by earlier and better ectopic bone formation when implanted subcutaneously in nude mice. Thus, our findings suggest that porous 5%CS/β-TCP scaffolds seeded with co-cultured cells provide new strategy for accelerating tissue engineering scaffolds vascularization and osteogenesis, and show potential as treatment for large bone defects.

An online x-ray based position validation system for prostate hypofractionated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arumugam, Sankar, E-mail: Sankar.Arumugam@sswahs.nsw.gov.au; Xing, Aitang; Sidhom, Mark

Purpose: Accurate positioning of the target volume during treatment is paramount for stereotactic body radiation therapy (SBRT). In this work, the authors present the development of an in-house software tool to verify target position with an Elekta-Synergy linear accelerator using kV planar images acquired during treatment delivery. Methods: In-house software, SeedTracker, was developed in MATLAB to perform the following three functions: 1. predict intended seed positions in a planar view perpendicular to any gantry angle, simulating a portal imaging device, from the 3D seed co-ordinates derived from the treatment planning system; 2. autosegment seed positions in kV planar images; andmore » 3. report the position shift based on the seed positions in the projection images. The performance of SeedTracker was verified using a CIRS humanoid phantom (CIRS, VA, USA) implanted with three Civco gold seed markers (Civco, IA, USA) in the prostate. The true positive rate of autosegmentation (TPR{sub seg}) and the accuracy of the software in alerting the user when the isocenter position was outside the tolerance (TPR{sub trig}) were studied. Two-dimensional and 3D static position offsets introduced to the humanoid phantom and 3D dynamic offsets introduced to a gel phantom containing gold seeds were used for evaluation of the system. Results: SeedTracker showed a TPR{sub seg} of 100% in the humanoid phantom for projection images acquired at all angles except in the ranges of 80°–100° and 260°–280° where seeds are obscured by anatomy. This resulted in a TPR{sub trig} of 88% over the entire treatment range for considered 3D static offsets introduced to the phantom. For 2D static offsets where the position offsets were only introduced in the anterior–posterior and lateral directions, the TPR{sub trig} of SeedTracker was limited by both seed detectability and positional offset. SeedTracker showed a false positive trigger in the projection angle range between 130°–170° and 310°–350° (a maximum of 24% of treatment time) due to limited information that can be derived from monoscopic images. The system accurately determined the dynamic trajectory of the isocenter position in the superior and inferior direction for the studied dynamic offset scenarios based on the seed position in monoscopic images. Conclusions: The developed software has been shown to accurately autosegment the seed positions in kV planar images except for two 20° arcs where seeds are obscured by anatomical structures. The isocenter trajectories determined by the system, based on the monoscopic images, provide useful information for monitoring the prostate position. The developed system has potential application for monitoring prostate position during treatment delivery in linear accelerator based SBRT.« less

An in vivo model to assess magnesium alloys and their biological effect on human bone marrow stromal cells.

PubMed

Yoshizawa, Sayuri; Chaya, Amy; Verdelis, Kostas; Bilodeau, Elizabeth A; Sfeir, Charles

2015-12-01

Magnesium (Mg) alloys have many unique qualities which make them ideal candidates for bone fixation devices, including biocompatibility and degradation in vivo. Despite a rise in Mg alloy production and research, there remains no standardized system to assess their degradation or biological effect on human stem cells in vivo. In this study, we developed a novel in vivo model to assess Mg alloys for craniofacial and orthopedic applications. Our model consists of a collagen sponge seeded with human bone marrow stromal cells (hBMSCs) around a central Mg alloy rod. These scaffolds were implanted subcutaneously in mice and analyzed after eight weeks. Alloy degradation and biological effect were determined by microcomputed tomography (microCT), histological staining, and immunohistochemistry (IHC). MicroCT showed greater volume loss for pure Mg compared to AZ31 after eight weeks in vivo. Histological analysis showed that hBMSCs were retained around the Mg implants after 8 weeks. Furthermore, immunohistochemistry showed the expression of dentin matrix protein 1 and osteopontin around both pure Mg and AZ31 with implanted hBMSCs. In addition, histological sections showed a thin mineral layer around all degrading alloys at the alloy-tissue interface. In conclusion, our data show that degrading pure Mg and AZ31 implants are cytocompatible and do not inhibit the osteogenic property of hBMSCs in vivo. These results demonstrate that this model can be used to efficiently assess the biological effect of corroding Mg alloys in vivo. Importantly, this model may be modified to accommodate additional cell types and clinical applications. Magnesium (Mg) alloys have been investigated as ideal candidates for bone fixation devices due to high biocompatibility and degradation in vivo, and there is a growing need of establishing an efficient in vivo material screening system. In this study, we assessed degradation rate and biological effect of Mg alloys by transplanting Mg alloy rod with human bone marrow stromal cells seeded on collagen sponge subcutaneously in mice. After 8 weeks, samples were analyzed by microcomputed tomography and histological staining. Our data show that degrading Mg alloys are cytocompatible and do not inhibit the osteogenic property of hBMSCs in vivo. These results demonstrate that this model can be used to efficiently assess the biological effect of corroding Mg alloys in vivo. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

SU-F-T-09: In Phantom Full-Implant Validation of Plastic Scintillation Detectors for in Vivo Dosimetry During Low Dose Rate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Therriault-Proulx, F; Bruno, T; Beddar, S

Purpose: To validate in a water phantom the use of plastic scintillation detectors to measure dose to the urethra and the rectal wall during a clinically realistic low dose rate (LDR) brachytherapy implant. Methods: A template was designed to replicate a clinically realistic LDR brachytherapy prostate implant inside a water phantom. Twenty-two catheters were inserted, including one mimicking the urethra and another the rectal wall. The needles inserted in the remaining 20 catheters were composed of thin-walled nylon tubes in which I-125 radioactive seeds (Air Kerma Strengths of (0.328±0.020)U) were abutted together with plastic spacers to replicate a typical loading.more » A plastic scintillation detector (PSD) with a 5-mm long × 1-mm diameter sensitive element was first placed inside the urethra and 1-second measurements were performed for 60s after each needle implant. Measurements were also performed at multiple positions along the urethra once all the needles were inserted. The procedure was then repeated with the PSD placed at the rectal wall. Results: Individual dose-rates ranging from 0.07µGy/s to 1.5µGy/s were measured after each needle implant. The average absolute relative differences were (6.2±3.6)% and (6.9±6.5)% to the values calculated with the TG-43 formalism, for the urethra and rectal wall respectively. These results are within expectations from the error uncertainty budget once accounting for uncertainties in seeds’ strength and positioning. Interestingly, the PSD allowed for unplanned error detection as the study was performed. Finally, the measured dose after the full implant at different positions along the mimicked organs at risk were in agreement with TG-43 values for all of the positions tested. Conclusion: Plastic scintillation detectors could be used as in vivo detectors for LDR brachytherapy as they would provide accurate dose information after each needle implant as well as along the organs at risk at the end of the implant.« less

Tetrabrachion: a filamentous archaebacterial surface protein assembly of unusual structure and extreme stability.

PubMed

Peters, J; Nitsch, M; Kühlmorgen, B; Golbik, R; Lupas, A; Kellermann, J; Engelhardt, H; Pfander, J P; Müller, S; Goldie, K

1995-01-27

The surface (S-) layer of the hyperthermophilic archaebacterium Staphylothermus marinus was isolated, dissected into separate domains by chemical and proteolytic methods, and analyzed by spectroscopic, electron microscopic and biochemical techniques. The S-layer is formed by a poorly ordered meshwork of branched, filiform morphological subunits resembling dandelion seed-heads. A morphological subunit (christened by us tetrabrachion) consists of a 70 nm long, almost perfectly straight stalk ending in four straight arms of 24 nm length that provide lateral connectivity by end-to-end contacts. At 32 nm from the branching point, tetrabrachion carries two globular particles of 10 nm diameter that have both tryptic and chymotryptic protease activity. Tetrabrachion is built by a tetramer of M(r) 92,000 polypeptides that form a parallel, four-stranded alpha-helical rod and separate at one end into four strands. These strands interact in a 1:1 stoichiometry with polypeptides of M(r) 85,000 to form the arms. The arms are composed entirely of beta-sheets. All S-layer components contain bound carbohydrates (glucose, mannose, and glucosamine) at a ratio of 38 g/100 g protein for the complete tetrabrachion-protease complex. The unique structure of tetrabrachion is reflected in an extreme thermal stability in the presence of strong denaturants (1% (w/v) SDS of 6M guanidine): the arms, which are stabilized by intramolecular disulphide bridges, melt around 115 degrees C under non-reducing conditions, whereas the stalk sustains heating up to about 130 degrees C. Complete denaturation of the stalk domain requires treatment with 70% (v/v) sulfuric acid or with fuming trifluoromethanesulfonic acid. The globular protease can be heated to 90 degrees C in 6M guanidine and to 120 degrees C in 1% SDS and represents one of the most stable proteases characterized to date.

Crystal structure of an essential enzyme in seed starch degradation: barley limit dextrinase in complex with cyclodextrins.

PubMed

Vester-Christensen, Malene Bech; Abou Hachem, Maher; Svensson, Birte; Henriksen, Anette

2010-11-12

Barley limit dextrinase [Hordeum vulgare limit dextrinase (HvLD)] catalyzes the hydrolysis of α-1,6 glucosidic linkages in limit dextrins. This activity plays a role in starch degradation during germination and presumably in starch biosynthesis during grain filling. The crystal structures of HvLD in complex with the competitive inhibitors α-cyclodextrin (CD) and β-CD are solved and refined to 2.5 Å and 2.1 Å, respectively, and are the first structures of a limit dextrinase. HvLD belongs to glycoside hydrolase 13 family and is composed of four domains: an immunoglobulin-like N-terminal eight-stranded β-sandwich domain, a six-stranded β-sandwich domain belonging to the carbohydrate binding module 48 family, a catalytic (β/α)(8)-like barrel domain that lacks α-helix 5, and a C-terminal eight-stranded β-sandwich domain of unknown function. The CDs are bound at the active site occupying carbohydrate binding subsites +1 and +2. A glycerol and three water molecules mimic a glucose residue at subsite -1, thereby identifying residues involved in catalysis. The bulky Met440, a unique residue at its position among α-1,6 acting enzymes, obstructs subsite -4. The steric hindrance observed is proposed to affect substrate specificity and to cause a low activity of HvLD towards amylopectin. An extended loop (Asp513-Asn520) between β5 and β6 of the catalytic domain also seems to influence substrate specificity and to give HvLD a higher affinity for α-CD than pullulanases. The crystal structures additionally provide new insight into cation sites and the concerted action of the battery of hydrolytic enzymes in starch degradation. Copyright © 2010 Elsevier Ltd. All rights reserved.

Purification and Bicelle Crystallization for Structure Determination of the E. coli Outer Membrane Protein TamA.

PubMed

Gruss, Fabian; Hiller, Sebastian; Maier, Timm

2015-01-01

TamA is an Omp85 protein involved in autotransporter assembly in the outer membrane of Escherichia coli. It comprises a C-terminal 16-stranded transmembrane β-barrel as well as three periplasmic POTRA domains, and is a challenging target for structure determination. Here, we present a method for crystal structure determination of TamA, including recombinant expression in E. coli, detergent extraction, chromatographic purification, and bicelle crystallization in combination with seeding. As a result, crystals in space group P21212 are obtained, which diffract to 2.3 Å resolution. This protocol also serves as a template for structure determination of other outer membrane proteins, in particular of the Omp85 family.

A novel imaging approach for prostate cancer is tested in new clinical trial | Center for Cancer Research

Cancer.gov

Prostate cancer patients who have failed standard radiation therapy have the options of surgery, radioactive seed implantation or cryoablation. Deborah Citrin, M.D., of the Radiation Oncology Branch is leading a study of stereotactic body radiation therapy (SBRT) to treat prostate cancer that has recurred locally after standard radiation therapy. The goal of this study is to use a novel imaging approach to guide treatment and to define the best dose of SBRT for patients whose prostate cancer has recurred after standard radiotherapy. Read more...

Tissue engineering of bladder using vascular endothelial growth factor gene-modified endothelial progenitor cells.

PubMed

Chen, Bai-Song; Xie, Hua; Zhang, Sheng-Li; Geng, Hong-Quan; Zhou, Jun-Mei; Pan, Jun; Chen, Fang

2011-12-01

This study assessed the use of vascular endothelial growth factor (VEGF) gene-modified endothelial progenitor cells (EPCs) seeded onto bladder acellular matrix grafts (BAMGs), to enhance the blood supply in tissue-engineered bladders in a porcine model. Autologous porcine peripheral EPCs were isolated, cultured, expanded, characterized, and modified with the VEGF gene using an adenovirus vector. The expression of VEGF was examined using reverse transcriptase polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). VEGF gene modified EPCs were seeded onto BAMG and cultured for 3 days before implantation into pigs for bladder tissue engineering. A partial bladder cystectomy was performed in 12 pigs. The experimental group (6 pigs) received VEGF gene-modified EPC-seeded BAMG. The control group (6 pigs) received BAMG without seeded EPCs. The resulting tissue-engineered bladders were subject to a general and histological analysis. Microvessel density (MVD) was assessed using immunohistochemistry. The ex vivo transfection efficiency of EPCs was greater than 60%-70% when concentrated adenovirus was used. The genetically modified cells expressed both VEGF and green fluorescent protein (GFP). Scanning electron microscopy (SEM) and Masson's trichrome staining of cross sections of the cultured cells seeded to BAMG showed cell attachment and proliferation on the surface of the BAMG. Histological examination revealed bladder regeneration in a time-dependent fashion. Significant increases in MVD were observed in the experimental group, in comparison with the control group. VEGF-modified EPCs significantly enhanced neovascularization, compared with BAMG alone. These results indicate that EPCs, combined with VEGF gene therapy, may be a suitable approach for increasing blood supply in the tissue engineering of bladders. Thus, a useful strategy to achieve a tissue-engineered bladder is indicated.

Transurethral light delivery for prostate photoacoustic imaging

NASA Astrophysics Data System (ADS)

Lediju Bell, Muyinatu A.; Guo, Xiaoyu; Song, Danny Y.; Boctor, Emad M.

2015-03-01

Photoacoustic imaging has broad clinical potential to enhance prostate cancer detection and treatment, yet it is challenged by the lack of minimally invasive, deeply penetrating light delivery methods that provide sufficient visualization of targets (e.g., tumors, contrast agents, brachytherapy seeds). We constructed a side-firing fiber prototype for transurethral photoacoustic imaging of prostates with a dual-array (linear and curvilinear) transrectal ultrasound probe. A method to calculate the surface area and, thereby, estimate the laser fluence at this fiber tip was derived, validated, applied to various design parameters, and used as an input to three-dimensional Monte Carlo simulations. Brachytherapy seeds implanted in phantom, ex vivo, and in vivo canine prostates at radial distances of 5 to 30 mm from the urethra were imaged with the fiber prototype transmitting 1064 nm wavelength light with 2 to 8 mJ pulse energy. Prebeamformed images were displayed in real time at a rate of 3 to 5 frames per second to guide fiber placement and beamformed offline. A conventional delay-and-sum beamformer provided decreasing seed contrast (23 to 9 dB) with increasing urethra-to-target distance, while the short-lag spatial coherence beamformer provided improved and relatively constant seed contrast (28 to 32 dB) regardless of distance, thus improving multitarget visualization in single and combined curvilinear images acquired with the fiber rotating and the probe fixed. The proposed light delivery and beamforming methods promise to improve key prostate cancer detection and treatment strategies.

Decellularized cartilage-derived matrix as substrate for endochondral bone regeneration.

PubMed

Gawlitta, Debby; Benders, Kim E M; Visser, Jetze; van der Sar, Anja S; Kempen, Diederik H R; Theyse, Lars F H; Malda, Jos; Dhert, Wouter J A

2015-02-01

Following an endochondral approach to bone regeneration, multipotent stromal cells (MSCs) can be cultured on a scaffold to create a cartilaginous callus that is subsequently remodeled into bone. An attractive scaffold material for cartilage regeneration that has recently regained attention is decellularized cartilage-derived matrix (CDM). Since this material has shown potential for cartilage regeneration, we hypothesized that CDM could be a potent material for endochondral bone regeneration. In addition, since decellularized matrices are known to harbor bioactive cues for tissue formation, we evaluated the need for seeded MSCs in CDM scaffolds. In this study, ectopic bone formation in rats was evaluated for CDM scaffolds seeded with human MSCs and compared with unseeded controls. The MSC-seeded samples were preconditioned in chondrogenic medium for 37 days. After 8 weeks of subcutaneous implantation, the extent of mineralization was significantly higher in the MSC-seeded constructs versus unseeded controls. The mineralized areas corresponded to bone formation with bone marrow cavities. In addition, rat-specific bone formation was confirmed by collagen type I immunohistochemistry. Finally, fluorochrome incorporation at 3 and 6 weeks revealed that the bone formation had an inwardly directed progression. Taken together, our results show that decellularized CDM is a promising biomaterial for endochondral bone regeneration when combined with MSCs at ectopic locations. Modification of current decellularization protocols may lead to enhanced functionality of CDM scaffolds, potentially offering the prospect of generation of cell-free off-the-shelf bone regenerative substitutes.

Spontaneous Chloroplast Mutants Mostly Occur by Replication Slippage and Show a Biased Pattern in the Plastome of Oenothera[OPEN

PubMed Central

Massouh, Amid; Schubert, Julia; Yaneva-Roder, Liliya; Ulbricht-Jones, Elena S.; Johnson, Marc T.J.; Wright, Stephen I.; Pellizzer, Tommaso; Sobanski, Johanna; Greiner, Stephan

2016-01-01

Spontaneous plastome mutants have been used as a research tool since the beginning of genetics. However, technical restrictions have severely limited their contributions to research in physiology and molecular biology. Here, we used full plastome sequencing to systematically characterize a collection of 51 spontaneous chloroplast mutants in Oenothera (evening primrose). Most mutants carry only a single mutation. Unexpectedly, the vast majority of mutations do not represent single nucleotide polymorphisms but are insertions/deletions originating from DNA replication slippage events. Only very few mutations appear to be caused by imprecise double-strand break repair, nucleotide misincorporation during replication, or incorrect nucleotide excision repair following oxidative damage. U-turn inversions were not detected. Replication slippage is induced at repetitive sequences that can be very small and tend to have high A/T content. Interestingly, the mutations are not distributed randomly in the genome. The underrepresentation of mutations caused by faulty double-strand break repair might explain the high structural conservation of seed plant plastomes throughout evolution. In addition to providing a fully characterized mutant collection for future research on plastid genetics, gene expression, and photosynthesis, our work identified the spectrum of spontaneous mutations in plastids and reveals that this spectrum is very different from that in the nucleus. PMID:27053421

Metallic artifact mitigation and organ-constrained tissue assignment for Monte Carlo calculations of permanent implant lung brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sutherland, J. G. H.; Miksys, N.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca

2014-01-15

Purpose: To investigate methods of generating accurate patient-specific computational phantoms for the Monte Carlo calculation of lung brachytherapy patient dose distributions. Methods: Four metallic artifact mitigation methods are applied to six lung brachytherapy patient computed tomography (CT) images: simple threshold replacement (STR) identifies high CT values in the vicinity of the seeds and replaces them with estimated true values; fan beam virtual sinogram replaces artifact-affected values in a virtual sinogram and performs a filtered back-projection to generate a corrected image; 3D median filter replaces voxel values that differ from the median value in a region of interest surrounding the voxelmore » and then applies a second filter to reduce noise; and a combination of fan beam virtual sinogram and STR. Computational phantoms are generated from artifact-corrected and uncorrected images using several tissue assignment schemes: both lung-contour constrained and unconstrained global schemes are considered. Voxel mass densities are assigned based on voxel CT number or using the nominal tissue mass densities. Dose distributions are calculated using the EGSnrc user-code BrachyDose for{sup 125}I, {sup 103}Pd, and {sup 131}Cs seeds and are compared directly as well as through dose volume histograms and dose metrics for target volumes surrounding surgical sutures. Results: Metallic artifact mitigation techniques vary in ability to reduce artifacts while preserving tissue detail. Notably, images corrected with the fan beam virtual sinogram have reduced artifacts but residual artifacts near sources remain requiring additional use of STR; the 3D median filter removes artifacts but simultaneously removes detail in lung and bone. Doses vary considerably between computational phantoms with the largest differences arising from artifact-affected voxels assigned to bone in the vicinity of the seeds. Consequently, when metallic artifact reduction and constrained tissue assignment within lung contours are employed in generated phantoms, this erroneous assignment is reduced, generally resulting in higher doses. Lung-constrained tissue assignment also results in increased doses in regions of interest due to a reduction in the erroneous assignment of adipose to voxels within lung contours. Differences in dose metrics calculated for different computational phantoms are sensitive to radionuclide photon spectra with the largest differences for{sup 103}Pd seeds and smallest but still considerable differences for {sup 131}Cs seeds. Conclusions: Despite producing differences in CT images, dose metrics calculated using the STR, fan beam + STR, and 3D median filter techniques produce similar dose metrics. Results suggest that the accuracy of dose distributions for permanent implant lung brachytherapy is improved by applying lung-constrained tissue assignment schemes to metallic artifact corrected images.« less

Histological and histomorphometric evaluation of implant with nanometer scale and oxidized surface. in vitro and in vivo study.

PubMed

Corvino, V; Iezzi, G; Trubiani, O; Traini, T; Piattelli, M

2012-01-01

The biological fixation of an implant to bone is influenced by numerous factors, including surface chemistry and surface topography. Various methods have been developed to create rough implant surfaces in order to improve the clinical performance of implants and to guarantee a stable mechanical bone-implant interface. Anodic oxidation is a dental implant surface modification technique that results in oxide layer growth up to a thickness of 1–10 micron. The purpose of this study was to evaluate the performance of the surface through the osteoblasts cells growth and the influence of oxidixed surface on BIC percent, in the human posterior maxilla after 2 months of unloaded healing. In vitro commercially available primary human osteoblasts (NHOst) from both femur and tibia of different donor systems (Lonza Walkersville Inc, Walkersville, MD, USA) were grown in Osteoblast Growth Media (OBM) (Lonza). Osteogenic differentiation was induced for a period of 4 weeks by the OGM medium (OBM basal medium supplemented with 200nM of hydrocortisone-21-hemisuccinate and 7.5 mM of glycerophosphate). The viability of NHOst cells seeded test A and B was measured by the quantitative colorimetric MTT (3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2Htetrazoliumbromide test) (Promega, Milan, Italy). One custom-made 2 x 10-mm site evaluation implant (SEI) with nanometer scale and oxidized surface (test) ( Evo Plan 1 Health s.r.l. - Amaro, UD, Italy), and one SEI with hydroxyapatite sandblasted surface (control) (Osseogrip Plan 1 Health s.r.l. – Amaro, UD, Italy), were placed in the posterior maxilla of 15 patients. Patients received one of each type of SEI placed on controlateral side. The proliferation rate studied by the MTT assay showed that during the incubation time, starting at 24 h, an increased proliferation rate was evident in Test B respect to Test A. After 2 months of unloaded healing BIC percent was significantly higher in oxidized implants. BIC percent mean values for the Osseogrip surface was 36,133 +/-4,888 ER and 53,533 +/- 5,180 ER for the Evo surface(P = 0,028). These results seem to confirm that implant surface topography entails mechanical restrictions to the spread and locomotion of the cells involved in bone healing.

Tissue-engineered cartilaginous constructs for the treatment of caprine cartilage defects, including distribution of laminin and type IV collagen.

PubMed

Jeng, Lily; Hsu, Hu-Ping; Spector, Myron

2013-10-01

The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineered constructs; and (2) the tissue filling cartilage defects in a goat model into which the constructs were implanted, particularly for the presence of the basement membrane molecules, laminin and type IV collagen. Basement membrane molecules are localized to the pericellular matrix in normal adult articular cartilage, but have not been examined in tissue-engineered constructs cultured in vitro or in tissue filling cartilage defects into which the constructs were implanted. Cartilaginous constructs were engineered in vitro using caprine chondrocyte-seeded type II collagen scaffolds. Autologous constructs were implanted into 4-mm-diameter defects created to the tidemark in the trochlear groove in the knee joints of skeletally mature goats. Eight weeks after implantation, the animals were sacrificed. Constructs underwent immunohistochemical and histomorphometric evaluation. Widespread staining for the two basement membrane molecules was observed throughout the extracellular matrix of in vitro and in vivo samples in a distribution unlike that previously reported for cartilage. At sacrifice, 70% of the defect site was filled with reparative tissue, which consisted largely of fibrous tissue and some fibrocartilage, with over 70% of the reparative tissue bonded to the adjacent host tissue. A novel finding of this study was the observation of laminin and type IV collagen in in vitro engineered cartilaginous constructs and in vivo cartilage repair samples from defects into which the constructs were implanted, as well as in normal caprine articular cartilage. Future work is needed to elucidate the role of basement membrane molecules during cartilage repair and regeneration.

Tissue-Engineered Cartilaginous Constructs for the Treatment of Caprine Cartilage Defects, Including Distribution of Laminin and Type IV Collagen

PubMed Central

Jeng, Lily; Hsu, Hu-Ping

2013-01-01

The purpose of this study was the immunohistochemical evaluation of (1) cartilage tissue-engineered constructs; and (2) the tissue filling cartilage defects in a goat model into which the constructs were implanted, particularly for the presence of the basement membrane molecules, laminin and type IV collagen. Basement membrane molecules are localized to the pericellular matrix in normal adult articular cartilage, but have not been examined in tissue-engineered constructs cultured in vitro or in tissue filling cartilage defects into which the constructs were implanted. Cartilaginous constructs were engineered in vitro using caprine chondrocyte-seeded type II collagen scaffolds. Autologous constructs were implanted into 4-mm-diameter defects created to the tidemark in the trochlear groove in the knee joints of skeletally mature goats. Eight weeks after implantation, the animals were sacrificed. Constructs underwent immunohistochemical and histomorphometric evaluation. Widespread staining for the two basement membrane molecules was observed throughout the extracellular matrix of in vitro and in vivo samples in a distribution unlike that previously reported for cartilage. At sacrifice, 70% of the defect site was filled with reparative tissue, which consisted largely of fibrous tissue and some fibrocartilage, with over 70% of the reparative tissue bonded to the adjacent host tissue. A novel finding of this study was the observation of laminin and type IV collagen in in vitro engineered cartilaginous constructs and in vivo cartilage repair samples from defects into which the constructs were implanted, as well as in normal caprine articular cartilage. Future work is needed to elucidate the role of basement membrane molecules during cartilage repair and regeneration. PMID:23672504

Enhanced Magnetization of Cobalt Defect Clusters Embedded in TiO2-δ Films.

PubMed

Cortie, David L; Khaydukov, Yury; Keller, Thomas; Sprouster, David J; Hughes, Jacob S; Sullivan, James P; Wang, Xiaolin L; Le Brun, Anton P; Bertinshaw, Joel; Callori, Sara J; Aughterson, Robert; James, Michael; Evans, Peter J; Triani, Gerry; Klose, Frank

2017-03-15

High magnetizations are desirable for spintronic devices that operate by manipulating electronic states using built-in magnetic fields. However, the magnetic moment in promising dilute magnetic oxide nanocomposites is very low, typically corresponding to only fractions of a Bohr magneton for each dopant atom. In this study, we report a large magnetization formed by ion implantation of Co into amorphous TiO 2-δ films, producing an inhomogeneous magnetic moment, with certain regions producing over 2.5 μ B per Co, depending on the local dopant concentration. Polarized neutron reflectometry was used to depth-profile the magnetization in the Co:TiO 2-δ nanocomposites, thus confirming the pivotal role of the cobalt dopant profile inside the titania layer. X-ray photoemission spectra demonstrate the dominant electronic state of the implanted species is Co 0 , with a minor fraction of Co 2+ . The detected magnetizations have seldom been reported before and lie near the upper limit set by Hund's rules for Co 0 , which is unusual because the transition metal's magnetic moment is usually reduced in a symmetric 3D crystal-field environment. Low-energy positron annihilation lifetime spectroscopy indicates that defect structures within the titania layer are strongly modified by the implanted Co. We propose that a clustering motif is promoted by the affinity of the positively charged implanted species to occupy microvoids native to the amorphous host. This provides a seed for subsequent doping and nucleation of nanoclusters within an unusual local environment.

Tissue-engineered bone constructed in a bioreactor for repairing critical-sized bone defects in sheep.

PubMed

Li, Deqiang; Li, Ming; Liu, Peilai; Zhang, Yuankai; Lu, Jianxi; Li, Jianmin

2014-11-01

Repair of bone defects, particularly critical-sized bone defects, is a considerable challenge in orthopaedics. Tissue-engineered bones provide an effective approach. However, previous studies mainly focused on the repair of bone defects in small animals. For better clinical application, repairing critical-sized bone defects in large animals must be studied. This study investigated the effect of a tissue-engineered bone for repairing critical-sized bone defect in sheep. A tissue-engineered bone was constructed by culturing bone marrow mesenchymal-stem-cell-derived osteoblast cells seeded in a porous β-tricalcium phosphate ceramic (β-TCP) scaffold in a perfusion bioreactor. A critical-sized bone defect in sheep was repaired with the tissue-engineered bone. At the eighth and 16th week after the implantation of the tissue-engineered bone, X-ray examination and histological analysis were performed to evaluate the defect. The bone defect with only the β-TCP scaffold served as the control. X-ray showed that the bone defect was successfully repaired 16 weeks after implantation of the tissue-engineered bone; histological sections showed that a sufficient volume of new bones formed in β-TCP 16 weeks after implantation. Eight and 16 weeks after implantation, the volume of new bones that formed in the tissue-engineered bone group was more than that in the β-TCP scaffold group (P < 0.05). Tissue-engineered bone improved osteogenesis in vivo and enhanced the ability to repair critical-sized bone defects in large animals.

In vivo dosimetry using a linear Mosfet-array dosimeter to determine the urethra dose in 125I permanent prostate implants.

PubMed

Bloemen-van Gurp, Esther J; Murrer, Lars H P; Haanstra, Björk K C; van Gils, Francis C J M; Dekker, Andre L A J; Mijnheer, Ben J; Lambin, Philippe

2009-01-01

In vivo dosimetry during brachytherapy of the prostate with (125)I seeds is challenging because of the high dose gradients and low photon energies involved. We present the results of a study using metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to evaluate the dose in the urethra after a permanent prostate implantation procedure. Phantom measurements were made to validate the measurement technique, determine the measurement accuracy, and define action levels for clinical measurements. Patient measurements were performed with a MOSFET array in the urinary catheter immediately after the implantation procedure. A CT scan was performed, and dose values, calculated by the treatment planning system, were compared to in vivo dose values measured with MOSFET dosimeters. Corrections for temperature dependence of the MOSFET array response and photon attenuation in the catheter on the in vivo dose values are necessary. The overall uncertainty in the measurement procedure, determined in a simulation experiment, is 8.0% (1 SD). In vivo dose values were obtained for 17 patients. In the high-dose region (> 100 Gy), calculated and measured dose values agreed within 1.7% +/- 10.7% (1 SD). In the low-dose region outside the prostate (< 100 Gy), larger deviations occurred. MOSFET detectors are suitable for in vivo dosimetry during (125)I brachytherapy of prostate cancer. An action level of +/- 16% (2 SD) for detection of errors in the implantation procedure is achievable after validation of the detector system and measurement conditions.

Interstitial therapy of perineal and gynecological malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez, A.; Herstein, P.; Portnuff, J.

1983-03-01

Thirty-five patients, 38 to 88 years of age, were treated with 125-Iodine or 192-Iridium interstitial implants at Stanford University Medical Center between July 1974, and December, 1978. There were 25 primary epithelial malignancies, eight extensions from intrapelvic organs and two metastatic tumors (hypernephroma and Hodgkin's disease). The involved sites were: urethra (6 patients); vulva (9 patients); vagina (8 patients); anus (7 patients); cervix (5 patients). Implantation was usually performed to treat evident or microscopic disease in conjunction with external beam pelvic treatment with or without local excision. Computerized implant preplanning was used.125-Iodine seeds were inserted either directly or within absorbablemore » suture Polyglactin 910; 192-Iridium in nylon carriers was placed by suture or transperineal template. Two patients were lost to follow-up leaving 33 patients, 27 of whom are alive and free of local disease from 37 to 76 months. The overall local control rate was 88%, or 29/33 patients. All four local recurrences appeared before 24 months. Minor complications included: 10 patients with transient mucositis, four with superficial ulcers, and one patient with infection at the implanted site. Two major complications occurred: a necrotic rectal ulcer requiring a colostomy and a contracted, painful bladder necessitating a urinary diversion. It is concluded that in selected cases interstitial irradiation provides good local control of perineal and gynecological malignancies with low morbidity in this elderly and quite often fragile group of patients.« less

Hard tissue remodeling using biofabricated coralline biomaterials.

PubMed

Vago, Razi; Plotquin, Daniel; Bunin, Alex; Sinelnikov, Igor; Atar, Dan; Itzhak, David

2002-01-04

Biotechnical and biomedical approaches were combined in an attempt to identify potential uses of biofabricated marine carbonate materials in biomedical applications, particularly as biomatrices for remodeling bone and cartilage tissue. After grafting, it is desirable for bone ingrowth to proceed as quickly as possible because the strength of the implanted region depends on a good mechanical bond forming between the implant and surrounding regions in the body. Ingrowth can take place as a result of growth of tissue and cells into the implanted porous material, or it may be promoted by transplanting cells seeded onto such a material. The rate at which ingrowth occurs is dependent on many factors, including pore size and the interconnectivity of the implanted structure. In vivo graftings into osteochondral defects demonstrated that our biofabricated porous material is highly biocompatible with cartilage and bone tissue. The biofabricated matrix was well incorporated into the biphasic osteochondral area. Resorption was followed by bone and cartilage formation, and after 4 months, the biomaterial had been replaced by new tissue. Ossification was induced and enhanced without introduction of additional factors. We believe that this is the first time that such biofabricated materials have been used for biomedical purposes. In face of the obvious environmental disadvantages of harvesting from limited natural resources, we propose the use of bioengineered coralline and other materials such as those cultured by our group under field and laboratory conditions as a possible biomatrix for hard tissue remodeling.

Research on ribosome-inactivating proteins from angiospermae to gymnospermae and cryptogamia

PubMed Central

Liu, Wang-Yi

2017-01-01

Ribosome-inactivating Proteins (RIPs) are a group of cytotoxin proteins that usually contain a RNA N-glycosidase domain, which irreversibly inactivates ribosome, thus inhibiting protein synthesis. During the past 14 years (1990-2004), the studies conducted in our laboratory had been focusing on the structure and enzymatic mechanism of several PIPs. Herein, we briefly described a summary of the studies conducted mainly in our laboratory on RIPs from angiospermae to gymnospermae and cryptogamia as follows. (1) Cinnamomin is a novel type II RIP isolated from mature seeds of camphor tree. Like ricin, it specifically removes the adenine at A4324 in rat liver 28S rRNA. We systematically studied this low-toxic RIP in term of its enzymatic mechanism, the primary and crystal structure and the nucleotide sequence of its gene, the genetic expression, and its physiological role in the seed cell and the toxicity to human cancer cells and insect larvae. The cleavage of supercoiled double-stranded DNA was its intrinsic property of cinnamomin A-chain, its N- and C-terminal regions were found to be required for deadenylation of rRNA and also necessary for deadenylation of supercoiled double-stranded circular DNA. These results strongly excluded the possibility that cleavage of supercoiled DNA was due to nuclease contamination. (2) Trichosanthin, an abortifacient protein, was purified from the Chinese medicinal herb, Tian-hua-fen, obtained from root tubers of Chinese trichosanthes plant. We proved that trichosanthin was a RNA N-glycosidase, inactivating eukaryotic ribosome by hydrolyzing the N-C glycosidic bond of the adenose at site 4324 in rat 28S rRNA, and inhibited protein synthesis in vitro. (3) A unique Biota orientalis RNase (RNase Bo) was extracted from the mature seeds of the cypress cypress tree (Oriental arborvita), which was gymnospermae plant. It cleaved only a specific phosphodiester bond between C4453 and A4454 of 28S RNA in rat ribosomes, producing a small RNA-fragment (S-fragment), thus inhibiting protein synthesis and belonging to RNase-like RIP, similar to α-sarcin, a special RIP. (4) Lamjapin, the first RIP purified from kelp, the marine cryptogamia algal plant, was shown to be the first single-chained RNA N-glycosidase from marine plant to date. It hydrolyzed rat ribosomal 28S RNA to produce meanly a rather smaller RNA, shorter than the diagnostic R-fragment under the restricted condition. The significance of existence of type I RIP in the lower marine algal plant was briefly discussed. PMID:29312524

Prefabrication of 3D Cartilage Contructs: Towards a Tissue Engineered Auricle – A Model Tested in Rabbits

PubMed Central

von Bomhard, Achim; Veit, Johannes; Bermueller, Christian; Rotter, Nicole; Staudenmaier, Rainer; Storck, Katharina; The, Hoang Nguyen

2013-01-01

The reconstruction of an auricle for congenital deformity or following trauma remains one of the greatest challenges in reconstructive surgery. Tissue-engineered (TE) three-dimensional (3D) cartilage constructs have proven to be a promising option, but problems remain with regard to cell vitality in large cell constructs. The supply of nutrients and oxygen is limited because cultured cartilage is not vascular integrated due to missing perichondrium. The consequence is necrosis and thus a loss of form stability. The micro-surgical implantation of an arteriovenous loop represents a reliable technology for neovascularization, and thus vascular integration, of three-dimensional (3D) cultivated cell constructs. Auricular cartilage biopsies were obtained from 15 rabbits and seeded in 3D scaffolds made from polycaprolactone-based polyurethane in the shape and size of a human auricle. These cartilage cell constructs were implanted subcutaneously into a skin flap (15×8 cm) and neovascularized by means of vascular loops implanted micro-surgically. They were then totally enhanced as 3D tissue and freely re-implanted in-situ through microsurgery. Neovascularization in the prefabricated flap and cultured cartilage construct was analyzed by microangiography. After explantation, the specimens were examined by histological and immunohistochemical methods. Cultivated 3D cartilage cell constructs with implanted vascular pedicle promoted the formation of engineered cartilaginous tissue within the scaffold in vivo. The auricles contained cartilage-specific extracellular matrix (ECM) components, such as GAGs and collagen even in the center oft the constructs. In contrast, in cultivated 3D cartilage cell constructs without vascular pedicle, ECM distribution was only detectable on the surface compared to constructs with vascular pedicle. We demonstrated, that the 3D flaps could be freely transplanted. On a microangiographic level it was evident that all the skin flaps and the implanted cultivated constructs were well neovascularized. The presented method is suggested as a promising alternative towards clinical application of engineered cartilaginous tissue for plastic and reconstructive surgery. PMID:23951215

Prefabrication of 3D cartilage contructs: towards a tissue engineered auricle--a model tested in rabbits.

PubMed

von Bomhard, Achim; Veit, Johannes; Bermueller, Christian; Rotter, Nicole; Staudenmaier, Rainer; Storck, Katharina; The, Hoang Nguyen

2013-01-01

The reconstruction of an auricle for congenital deformity or following trauma remains one of the greatest challenges in reconstructive surgery. Tissue-engineered (TE) three-dimensional (3D) cartilage constructs have proven to be a promising option, but problems remain with regard to cell vitality in large cell constructs. The supply of nutrients and oxygen is limited because cultured cartilage is not vascular integrated due to missing perichondrium. The consequence is necrosis and thus a loss of form stability. The micro-surgical implantation of an arteriovenous loop represents a reliable technology for neovascularization, and thus vascular integration, of three-dimensional (3D) cultivated cell constructs. Auricular cartilage biopsies were obtained from 15 rabbits and seeded in 3D scaffolds made from polycaprolactone-based polyurethane in the shape and size of a human auricle. These cartilage cell constructs were implanted subcutaneously into a skin flap (15 × 8 cm) and neovascularized by means of vascular loops implanted micro-surgically. They were then totally enhanced as 3D tissue and freely re-implanted in-situ through microsurgery. Neovascularization in the prefabricated flap and cultured cartilage construct was analyzed by microangiography. After explantation, the specimens were examined by histological and immunohistochemical methods. Cultivated 3D cartilage cell constructs with implanted vascular pedicle promoted the formation of engineered cartilaginous tissue within the scaffold in vivo. The auricles contained cartilage-specific extracellular matrix (ECM) components, such as GAGs and collagen even in the center oft the constructs. In contrast, in cultivated 3D cartilage cell constructs without vascular pedicle, ECM distribution was only detectable on the surface compared to constructs with vascular pedicle. We demonstrated, that the 3D flaps could be freely transplanted. On a microangiographic level it was evident that all the skin flaps and the implanted cultivated constructs were well neovascularized. The presented method is suggested as a promising alternative towards clinical application of engineered cartilaginous tissue for plastic and reconstructive surgery.

Microfabrication of channel arrays promotes vessel-like network formation in cardiac cell construct and vascularization in vivo.

PubMed

Zieber, Liran; Or, Shira; Ruvinov, Emil; Cohen, Smadar

2014-06-01

Pre-vascularization is important for the reconstruction of dense and metabolically active myocardial tissue and its integration with the host myocardium after implantation. Herein, we demonstrate that the fabrication of micro-channels in alginate scaffold combined with the presentation of adhesion peptides and an angiogenic growth factor promote vessel-like networks in the construct, both in vitro and in vivo. Using a CO2 laser engraving system, 200 µm diameter channels were formed from top to bottom of the 2 mm thick alginate scaffold, with a channel-to-channel distance of 400 µm. Cells were seeded in a sequential manner onto the scaffolds: first, human umbilical vascular endothelial cells (HUVECs) were seeded and cultured for three days, then neonatal rat cardiomyocytes (CMs) and cardiofibroblasts were added at a final cell ratio of 50:35:15, respectively, and the constructs were cultivated for an additional seven days. A vessel-like network was formed within the cell constructs, wherein HUVECs were organized around the channels in a multilayer manner, while the CMs were located in-between the channels and exhibited the characteristic morphological features of a mature cardiac fiber. Acellular scaffolds with the affinity-bound basic fibroblast growth factor were implanted subcutaneously in mice. Increased cell penetration into the channeled scaffold and greater vessel density were found in comparison with the nonchanneled scaffolds. Our results thus point to the importance of micro-channels as a major structural promoter of vascularization in scaffolds, in conjunction with the sequential preculture of ECs and angiogenic factor presentation.

Development of Scaffold-Free Elastic Cartilaginous Constructs with Structural Similarities to Auricular Cartilage

PubMed Central

Giardini-Rosa, Renata; Joazeiro, Paulo P.; Thomas, Kathryn; Collavino, Kristina; Weber, Joanna

2014-01-01

External ear reconstruction with autologous cartilage still remains one of the most difficult problems in the fields of plastic and reconstructive surgery. As the absence of tissue vascularization limits the ability to stimulate new tissue growth, relatively few surgical approaches are currently available (alloplastic implants or sculpted autologous cartilage grafts) to repair or reconstruct the auricle (or pinna) as a result of traumatic loss or congenital absence (e.g., microtia). Alternatively, tissue engineering can offer the potential to grow autogenous cartilage suitable for implantation. While tissue-engineered auricle cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for reconstruction. Similarly, as routine cell expansion can elicit negative effects on chondrocyte function, we have developed an approach to generate large-sized engineered auricle constructs (≥3 cm2) directly from a small population of donor cells (20,000–40,000 cells/construct). Using rabbit donor cells, the developed bioreactor-cultivated constructs adopted structural-like characteristics similar to native auricular cartilage, including the development of distinct cartilaginous and perichondrium-like regions. Both alterations in media composition and seeding density had profound effects on the formation of engineered elastic tissue constructs in terms of cellularity, extracellular matrix accumulation, and tissue structure. Higher seeding densities and media containing sodium bicarbonate produced tissue constructs that were closer to the native tissue in terms of structure and composition. Future studies will be aimed at improving the accumulation of specific tissue constituents and determining the clinical effectiveness of this approach using a reconstructive animal model. PMID:24124666

Development of scaffold-free elastic cartilaginous constructs with structural similarities to auricular cartilage.

PubMed

Giardini-Rosa, Renata; Joazeiro, Paulo P; Thomas, Kathryn; Collavino, Kristina; Weber, Joanna; Waldman, Stephen D

2014-03-01

External ear reconstruction with autologous cartilage still remains one of the most difficult problems in the fields of plastic and reconstructive surgery. As the absence of tissue vascularization limits the ability to stimulate new tissue growth, relatively few surgical approaches are currently available (alloplastic implants or sculpted autologous cartilage grafts) to repair or reconstruct the auricle (or pinna) as a result of traumatic loss or congenital absence (e.g., microtia). Alternatively, tissue engineering can offer the potential to grow autogenous cartilage suitable for implantation. While tissue-engineered auricle cartilage constructs can be created, a substantial number of cells are required to generate sufficient quantities of tissue for reconstruction. Similarly, as routine cell expansion can elicit negative effects on chondrocyte function, we have developed an approach to generate large-sized engineered auricle constructs (≥3 cm(2)) directly from a small population of donor cells (20,000-40,000 cells/construct). Using rabbit donor cells, the developed bioreactor-cultivated constructs adopted structural-like characteristics similar to native auricular cartilage, including the development of distinct cartilaginous and perichondrium-like regions. Both alterations in media composition and seeding density had profound effects on the formation of engineered elastic tissue constructs in terms of cellularity, extracellular matrix accumulation, and tissue structure. Higher seeding densities and media containing sodium bicarbonate produced tissue constructs that were closer to the native tissue in terms of structure and composition. Future studies will be aimed at improving the accumulation of specific tissue constituents and determining the clinical effectiveness of this approach using a reconstructive animal model.

Exploring the in vitro and in vivo compatibility of PLA, PLA/GNP and PLA/CNT-COOH biodegradable nanocomposites: Prospects for tendon and ligament applications.

PubMed

Correia Pinto, Viviana; Costa-Almeida, Raquel; Rodrigues, Ilda; Guardão, Luísa; Soares, Raquel; Miranda Guedes, Rui

2017-08-01

Anterior cruciate ligament (ACL) reconstructive surgeries are the most frequent orthopedic procedures in the knee. Currently, existing strategies fail in completely restoring tissue functionality and have a high failure rate associated, presenting a compelling argument towards the development of novel materials envisioning ACL reinforcement. Tendons and ligaments, in general, have a strong demand in terms of biomechanical features of developed constructs. We have previously developed polylactic acid (PLA)-based biodegradable films reinforced either with graphene nanoplatelets (PLA/GNP) or with carboxyl-functionalized carbon nanotubes (PLA/CNT-COOH). In the present study, we comparatively assessed the biological performance of PLA, PLA/GNP, and PLA/CNT-COOH by seeding human dermal fibroblasts (HFF-1) and studying cell viability and proliferation. In vivo tests were also performed by subcutaneous implantation in 6-week-old C57Bl/6 mice. Results showed that all formulations studied herein did not elicit cytotoxic responses in seeded HFF-1, supporting cell proliferation up to 3 days in culture. Moreover, animal studies indicated no physiological signs of severe inflammatory response after 1 and 2 weeks after implantation. Taken together, our results present a preliminary assessment on the compatibility of PLA reinforced with GNP and CNT-COOH nanofillers, highlighting the potential use of these carbon-based nanofillers for the fabrication of reinforced synthetic polymer-based structures for ACL reinforcement. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2182-2190, 2017. © 2017 Wiley Periodicals, Inc.

Defining the rectal dose constraint for permanent radioactive seed implantation of the prostate.

PubMed

Albert, Michele; Song, Jun S; Schultz, Delray; Cormack, Robert A; Tempany, Clare M; Haker, Steve; Devlin, Phillip M; Beard, Clair; Hurwitz, Mark D; Suh, Wonsuk W; Jolesz, Ferenc; D'Amico, Anthony V

2008-01-01

This study was performed to define the rectal dose constraint that would predict late rectal bleeding requiring argon plasma coagulation (APC) following prostate brachy mono-therapy. Between February 1999 and April 2002, 91 patients with low risk prostate cancer underwent permanent I(125) radioactive seed implantation without the use of supplemental external beam radiation or androgen suppression therapy. Patients received both CT and MRI scans 6 weeks postimplant for evaluation of dosimetry. The CT and MRI scans were fused. Rectal volumes were contoured on the T2 weighted MR images. For those patients requiring APC, the date on which a patient reported rectal bleeding was recorded. A Cox regression analysis was performed to assess whether there was a significant association between the rectal volume (continuous) exceeding 100 Gy time rectal bleeding. Comparisons of estimates of rectal bleeding requiring APC were made using a 2-sided log rank test. There was a significant association (hazard ratio = 5.6 [95% confidence interval: 1.3, 23.8]; P = 0.002) between the rectal volume exceeding 100 Gy and rectal bleeding requiring APC. After a median follow-up of 4.25 (1-6) years, no patient with less than a median value of 8 cc of rectum exceeding 100 Gy required APC, whereas 20% (P = 0.004) were estimated to require APC within 3 years following treatment. Keeping the rectal volume receiving more than 100 Gy below 8 cc will minimize the risk of rectal bleeding requiring APC following I(125) permanent prostate brachy mono-therapy.

Dose Escalation to the Dominant Intraprostatic Lesion Defined by Sextant Biopsy in a Permanent Prostate I-125 Implant: A Prospective Comparative Toxicity Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaudet, Marc; Vigneault, Eric; Aubin, Sylviane

2010-05-01

Purpose: Using real-time intraoperative inverse-planned permanent seed prostate implant (RTIOP/PSI), multiple core biopsy maps, and three-dimensional ultrasound guidance, we planned a boost volume (BV) within the prostate to which hyperdosage was delivered selectively. The aim of this study was to investigate the potential negative effects of such a procedure. Methods and Materials: Patients treated with RTIOP/PSI for localized prostate cancer with topographic biopsy results received an intraprostatic boost (boost group [BG]). They were compared with patients treated with a standard plan (reference group [RG]). Plans were generated using a simulated annealing inverse planning algorithm. Prospectively recorded urinary, rectal, and sexualmore » toxicities and dosimetric parameters were compared between groups. Results: The study included 120 patients treated with boost technique who were compared with 70 patients treated with a standard plan. Boost technique did not significantly change the number of seeds (55.1/RG vs. 53.6/BG). The intraoperative prostate V150 was slightly higher in BG (75.2/RG vs. 77.2/BG, p = 0.039). Urethra V100, urethra D90, and rectal D50 were significantly lower in the BG. No significant differences were seen in acute or late urinary, rectal, or sexual toxicities. Conclusions: Because there were no differences between the groups in acute and late toxicities, we believe that BV can be planned and delivered to the dominant intraprostatic lesion without increasing toxicity. It is too soon to say whether a boost technique will ultimately increase local control.« less

Osteogenic Treatment Initiating a Tissue-Engineered Cartilage Template Hypertrophic Transition.

PubMed

Fu, J Y; Lim, S Y; He, P F; Fan, C J; Wang, D A

2016-10-01

Hypertrophic chondrocytes play a critical role in endochondral bone formation as well as the progress of osteoarthritis (OA). An in vitro cartilage hypertrophy model can be used as a platform to study complex molecular mechanisms involved in these processes and screen new drugs for OA. To develop an in vitro cartilage hypertrophy model, we treated a tissue-engineered cartilage template, living hyaline cartilaginous graft (LhCG), with osteogenic medium for hypertrophic induction. In addition, endothelial progenitor cells (EPCs) were seeded onto LhCG constructs to mimic vascular invasion. The results showed that osteogenic treatment significantly inhibited the synthesis of endostatin in LhCG constructs and enhanced expression of hypertrophic marker-collagen type X (Col X) and osteogenic markers, as well as calcium deposition in vitro. Upon subcutaneous implantation, osteogenic medium-treated LhCG constructs all stained positive for Col X and showed significant calcium deposition and blood vessel invasion. Col X staining and calcium deposition were most obvious in osteogenic medium-treated only group, while there was no difference between EPC-seeded and non-seeded group. These results demonstrated that osteogenic treatment was of the primary factor to induce hypertrophic transition of LhCG constructs and this model may contribute to the establishment of an in vitro cartilage hypertrophy model.

TGF-β1 gene-engineered mesenchymal stem cells induce rat cartilage regeneration using nonviral gene vector.

PubMed

He, Cai-Xia; Zhang, Tian-Yuan; Miao, Pei-Hong; Hu, Zhong-Jie; Han, Min; Tabata, Yasuhiko; Hu, Yu-Lan; Gao, Jian-Qing

2012-01-01

This study evaluated the potential of utilizing transfected pTGFβ-1 gene-engineered rat mesenchymal stem cells (MSCs) using nonviral vector to promote cartilage regeneration. Pullulan-spermine was used as the nonviral gene vector and gelatin sponge was used as the scaffold. MSCs were engineered with TGF-β1 gene with either the three-dimensional (3D) reverse transfection system or the two-dimensional (2D) conventional transfection system. For the 3D reverse transfection system, pullulan-spermine/pTGF-β1 gene complexes were immobilized to the gelatin sponge, followed by the seeding of MSCs. Pullulan-spermine/pTGF-β1 gene complexes were delivered to MSCs cultured in the plate to perform the 2D conventional transfection system, and then MSCs were seeded to the gelatin sponge. Then, TGF-β1 gene-transfected MSC seeded gelatin sponge was implanted to the full-thickness cartilage defect. Compared with the control group, both groups of TGF-β1 gene-engineered MSCs improved cartilage regeneration through optical observation and histology staining. So, with pullulan-spermine as the nonviral vector, TGF-β1-gene engineered MSCs can induce cartilage regeneration in vivo. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

[Repair of swine full-thickness cutaneous deficiency by autogenic BMSCs compounded with collagen membrane].

PubMed

He, Lijuan; Liu, Daqing; Bai, Cixian; Yan, Yingfun; Guan, Lidong; Pei, Xuetao

2009-03-01

To supply references to tissue-engineered skin clinical applications with autogenic BMSCs composited collagen membrane to repair swine full-thickness cutaneous deficiency. Twenty mL bone marrow were obtained respectively from 4 swine, autogenic BMSCs were cultured and passed to the 3rd passage. The fresh bovine tendon treated by means of chemically cross-linked was made 5 cm diameter collagen I (Col I) membrane. The 2 x 10(7)/mL P3 swine autogenic BMSCs labeled DAPI were planted to sterile Col I membrane for 24 hours incubation, then the tissue-engineered skin was constructed. The five full-thickness skin defect of 5 cm diameter was excised to the muscle from forward to backward on the back midline two sides of swine. The tissue-engineered skin were implanted in the experimental group, while Col I membrane was implanted in control group. After 3 and 8 weeks of implantation, the two swine wound surface healing circumstance was observed and further evaluated with histology analysis and TEM. After 3 weeks of implantation, the experimental group were observed with fluorescence microscopy and staining for glycogen. After 3 weeks of implantation, the wound surface of control group were observed nigrescene, scab and putrescence, and after 8 weeks of implantation, also evident putrescence and scar. The wound surface of experiment group was alive after 3 weeks implantation, appearance was leveled off and flexible without evident scar. The wound surface recovered well after 8 weeks of implantation, wound surface healing rate was significantly difference between the two groups (P < 0.01). After 3 weeks of implantation, control group were observed acestoma hyperplasia and no epidermal coverage by histology analysis. The experimental group was showed integrity epidermis and dermis structure. The basal layer was crimson and continuously positive with glycogen staining. After 8 weeks of implantation, the experimental group and control group were emerged normal skin structure. After 3 weeks of implantation in control group, a lot of neutrophilic granulocytes and fibroblasts were noticed, but no epidermal structure was observed under TEM. In the experimental group, a lot of epidermal cells were observed, dermatome connection among epidermal cells and hemidesmosome connection between basilar membrane cells and basal membrane were observed in epidermis. In the dermis experimental group, blood capillary endothelial cells were noticed. Furthermore, considerable collagen fiber deposit was found in the surrounding tissue of fibroblasts. After 3 weeks of implantation, BMSCs labeled with DAPI were located reconstructed epidermal basement membrane and dermis by fluorescence microscopy. Tissue-engineered skin which is composited with autogenic BMSCs as seed cells and collagen membrane were potential prospects in application of repairing swine full-thickness cutaneous deficiency.

Global Analysis of Small RNA Dynamics during Seed Development of Picea glauca and Arabidopsis thaliana Populations Reveals Insights on their Evolutionary Trajectories

PubMed Central

Liu, Yang; El-Kassaby, Yousry A.

2017-01-01

While DNA methylation carries genetic signals and is instrumental in the evolution of organismal complexity, small RNAs (sRNAs), ~18–24 ribonucleotide (nt) sequences, are crucial mediators of methylation as well as gene silencing. However, scant study deals with sRNA evolution via featuring their expression dynamics coupled with species of different evolutionary time. Here we report an atlas of sRNAs and microRNAs (miRNAs, single-stranded sRNAs) produced over time at seed-set of two major spermatophytes represented by populations of Picea glauca and Arabidopsis thaliana with different seed-set duration. We applied diverse profiling methods to examine sRNA and miRNA features, including size distribution, sequence conservation and reproduction-specific regulation, as well as to predict their putative targets. The top 27 most abundant miRNAs were highly overlapped between the two species (e.g., miR166,−319 and−396), but in P. glauca, they were less abundant and significantly less correlated with seed-set phases. The most abundant sRNAs in libraries were deeply conserved miRNAs in the plant kingdom for Arabidopsis but long sRNAs (24-nt) for P. glauca. We also found significant difference in normalized expression between populations for population-specific sRNAs but not for lineage-specific ones. Moreover, lineage-specific sRNAs were enriched in the 21-nt size class. This pattern is consistent in both species and alludes to a specific type of sRNAs (e.g., miRNA, tasiRNA) being selected for. In addition, we deemed 24 and 9 sRNAs in P. glauca and Arabidopsis, respectively, as sRNA candidates targeting known adaptive genes. Temperature had significant influence on selected gene and miRNA expression at seed development in both species. This study increases our integrated understanding of sRNA evolution and its potential link to genomic architecture (e.g., sRNA derivation from genome and sRNA-mediated genomic events) and organismal complexity (e.g., association between different sRNA expression and their functionality). PMID:29046688

The evolution of brachytherapy for prostate cancer.

PubMed

Zaorsky, Nicholas G; Davis, Brian J; Nguyen, Paul L; Showalter, Timothy N; Hoskin, Peter J; Yoshioka, Yasuo; Morton, Gerard C; Horwitz, Eric M

2017-06-30

Brachytherapy (BT), using low-dose-rate (LDR) permanent seed implantation or high-dose-rate (HDR) temporary source implantation, is an acceptable treatment option for select patients with prostate cancer of any risk group. The benefits of HDR-BT over LDR-BT include the ability to use the same source for other cancers, lower operator dependence, and - typically - fewer acute irritative symptoms. By contrast, the benefits of LDR-BT include more favourable scheduling logistics, lower initial capital equipment costs, no need for a shielded room, completion in a single implant, and more robust data from clinical trials. Prospective reports comparing HDR-BT and LDR-BT to each other or to other treatment options (such as external beam radiotherapy (EBRT) or surgery) suggest similar outcomes. The 5-year freedom from biochemical failure rates for patients with low-risk, intermediate-risk, and high-risk disease are >85%, 69-97%, and 63-80%, respectively. Brachytherapy with EBRT (versus brachytherapy alone) is an appropriate approach in select patients with intermediate-risk and high-risk disease. The 10-year rates of overall survival, distant metastasis, and cancer-specific mortality are >85%, <10%, and <5%, respectively. Grade 3-4 toxicities associated with HDR-BT and LDR-BT are rare, at <4% in most series, and quality of life is improved in patients who receive brachytherapy compared with those who undergo surgery.

Total disc replacement using a tissue-engineered intervertebral disc in vivo: new animal model and initial results

PubMed Central

Gebhard, Harry; Bowles, Robby; Dyke, Jonathan; Saleh, Tatianna; Doty, Stephen; Bonassar, Lawrence; Härtl, Roger

2010-01-01

Study type: Basic science Introduction: Chronic back pain due to degenerative disc disease (DDD) is among the most important medical conditions causing morbidity and significant health care costs. Surgical treatment options include disc replacement or fusion surgery, but are associated with significant short- and long-term risks.1 Biological tissue-engineering of human intervertebral discs (IVD) could offer an important alternative.2 Recent in vitro data from our group have shown successful engineering and growth of ovine intervertebral disc composites with circumferentially aligned collagen fibrils in the annulus fibrosus (AF) (Figure 1).3 Figure 1 Tissue-engineered composite disc a Experimental steps to generate composite tissue-engineered IVDs3 b Example of different AF formulations on collagen alignment in the AF. Second harmonic generation and two-photon excited fluorescence images of seeded collagen gels (for AF) of 1 and 2.5 mg/ml over time. At seeding, cells and collagen were homogenously distributed in the gels. Over time, AF cells elongated and collagen aligned parallel to cells. Less contraction and less alignment is noted after 3 days in the 2.5 mg/mL gel. c Imaging-based creation of a virtual disc model that will serve as template for the engineered disc. Total disc dimensions (AF and NP) were retrieved from micro-computer tomography (CT) (left images), and nucleus pulposus (NP) dimensions alone were retrieved from T2-weighted MRI images (right images). Merging of MRI and micro-CT models revealed a composite disc model (middle image)—Software: Microview, GE Healthcare Inc., Princeton, NJ; and slicOmatic v4.3, TomoVision, Montreal, Canada. d Flow chart describing the process for generating multi-lamellar tissue engineered IVDs. IVDs are produced by allowing cell-seeded collagen layers to contract around a cell-seeded alginate core (NP) over time Objective: The next step is to investigate if biological disc implants survive, integrate, and restore function to the spine in vivo. A model will be developed that allows efficient in vivo testing of tissue-engineered discs of various compositions and characteristics. Methods: Athymic rats were anesthetized and a dorsal approach was chosen to perform a microsurgical discectomy in the rat caudal spine (Fig. 2,Fig. 3). Control group I (n = 6) underwent discectomy only, Control group II (n = 6) underwent discectomy, followed by reimplantation of the autologous disc. Two treatment groups (group III, n = 6, 1 month survival; group IV, n = 6, 6 months survival) received a tissue-engineered composite disc implant. The rodents were followed clinically for signs of infection, pain level and wound healing. X-rays and magnetic resonance imaging (MRI) were assessed postoperatively and up to 6 months after surgery (Fig. 6,Fig. 7). A 7 Tesla MRI (Bruker) was implemented for assessment of the operated level as well as the adjacent disc (hydration). T2-weighted sequences were interpreted by a semiquantitative score (0 = no signal, 1 = weak signal, 2 = strong signal and anatomical features of a normal disc). Histology was performed with staining for proteoglycans (Alcian blue) and collagen (Picrosirius red) (Fig. 4,Fig. 5). Figure 2 Disc replacement surgery a Operative situs with native disc that has been disassociated from both adjacent vertebrae b Native disc (left) and tissue-engineered implant (right) c Implant in situ before wound closureAF: Annulus fi brosus, nP: nucleus pulposus, eP: endplate, M: Muscle, T: Tendon, s: skin, art: artery, GP: Growth plate, B: Bone Figure 3 Disc replacement surgery. Anatomy of the rat caudal disc space a Pircrosirius red stained axial cut of native disc space b Saffranin-O stained sagittal cut of native disc space Figure 4 Histologies of three separate motion segments from three different rats. Animal one = native IVD, Animal two = status after discectomy, Animal three = tissue-engineered implant (1 month) a–c H&E (overall tissue staining for light micrsocopy) d–f Alcian blue (proteoglycans) g–i Picrosirius red (collagen I and II) Figure 5 Histology from one motion segment four months after implantation of a bio-engineered disc construct a Picrosirius red staining (collagen) b Polarized light microscopy showing collagen staining and collagen organization in AF region c Increased Safranin-O staining (proteoglycans) in NP region of the disc implant d Higher magnification of figure 5c: Integration between implanted tissue-engineered total disc replacement and vertebral body bone Figure 6 MRI a Disc space height measurements in flash/T1 sequence (top: implant (714.0 micrometer), bottom: native disc (823.5 micrometer) b T2 sequence, red circle surrounding the implant NP Figure 7 7 Tesla MRI imaging of rat tail IVDs showing axial images (preliminary pilot data) a Diffusion tensor imaging (DTI) on two explanted rat tail discs in Formalin b Higher magnification of a, showing directional alignment of collagen fibers (red and green) when compared to the color ball on top which maps fibers' directional alignment (eg, fibers directing from left to right: red, from top to bottom: blue) c Native IVD in vivo (successful imaging of top and bottom of the IVD (red) d Gradient echo sequence (GE) showing differentiation between NP (light grey) and AF (dark margin) e GE of reimplanted tail IVD at the explantation level f T1Rho sequence demonstrating the NP (grey) within the AF (dark margin), containing the yellow marked region of interest for value acquisition (preliminary data are consistent with values reported in the literature). g T2 image of native IVD in vivo for monitoring of hydration (white: NP) Results: The model allowed reproducible and complete discectomies as well as disc implantation in the rat tail spine without any surgical or postoperative complications. Discectomy resulted in immediate collapse of the disc space. Preliminary results indicate that disc space height was maintained after disc implantation in groups II, III and IV over time. MRI revealed high resolution images of normal intervertebral discs in vivo. Eight out of twelve animals (groups III and IV) showed a positive signal in T2-weighted images after 1 month (grade 0 = 4, grade 1 = 4, grade 2 = 4). Positive staining was seen for collagen as well as proteoglycans at the site of disc implantation after 1 month in each of the six animals with engineered implants (group III). Analysis of group IV showed positive T2 signal in five out of six animals and disc-height preservation in all animals after 6 months. Conclusions: This study demonstrates for the first time that tissue-engineered composite IVDs with circumferentially aligned collagen fibrils survive and integrate with surrounding vertebral bodies when placed in the rat spine for up to 6 months. Tissue-engineered composite IVDs restored function to the rat spine as indicated by maintenance of disc height and vertebral alignment. A significant finding was that maintenance of the composite structure in group III was observed, with increased proteoglycan staining in the nucleus pulposus region (Figure 4d–f). Proteoglycan and collagen matrix as well as disc height preservation and positive T2 signals in MRI are promising parameters and indicate functionality of the implants. PMID:23637671

Total disc replacement using a tissue-engineered intervertebral disc in vivo: new animal model and initial results.

PubMed

Gebhard, Harry; Bowles, Robby; Dyke, Jonathan; Saleh, Tatianna; Doty, Stephen; Bonassar, Lawrence; Härtl, Roger

2010-08-01

 Basic science Introduction:  Chronic back pain due to degenerative disc disease (DDD) is among the most important medical conditions causing morbidity and significant health care costs. Surgical treatment options include disc replacement or fusion surgery, but are associated with significant short- and long-term risks.1 Biological tissue-engineering of human intervertebral discs (IVD) could offer an important alternative.2 Recent in vitro data from our group have shown successful engineering and growth of ovine intervertebral disc composites with circumferentially aligned collagen fibrils in the annulus fibrosus (AF) (Figure 1).3 Figure 1 Tissue-engineered composite disc a Experimental steps to generate composite tissue-engineered IVDs3b Example of different AF formulations on collagen alignment in the AF. Second harmonic generation and two-photon excited fluorescence images of seeded collagen gels (for AF) of 1 and 2.5 mg/ml over time. At seeding, cells and collagen were homogenously distributed in the gels. Over time, AF cells elongated and collagen aligned parallel to cells. Less contraction and less alignment is noted after 3 days in the 2.5 mg/mL gel. c Imaging-based creation of a virtual disc model that will serve as template for the engineered disc. Total disc dimensions (AF and NP) were retrieved from micro-computer tomography (CT) (left images), and nucleus pulposus (NP) dimensions alone were retrieved from T2-weighted MRI images (right images). Merging of MRI and micro-CT models revealed a composite disc model (middle image)-Software: Microview, GE Healthcare Inc., Princeton, NJ; and slicOmatic v4.3, TomoVision, Montreal, Canada. d Flow chart describing the process for generating multi-lamellar tissue engineered IVDs. IVDs are produced by allowing cell-seeded collagen layers to contract around a cell-seeded alginate core (NP) over time Objective:  The next step is to investigate if biological disc implants survive, integrate, and restore function to the spine in vivo. A model will be developed that allows efficient in vivo testing of tissue-engineered discs of various compositions and characteristics.  Athymic rats were anesthetized and a dorsal approach was chosen to perform a microsurgical discectomy in the rat caudal spine (Fig. 2,Fig. 3). Control group I (n = 6) underwent discectomy only, Control group II (n = 6) underwent discectomy, followed by reimplantation of the autologous disc. Two treatment groups (group III, n = 6, 1 month survival; group IV, n = 6, 6 months survival) received a tissue-engineered composite disc implant. The rodents were followed clinically for signs of infection, pain level and wound healing. X-rays and magnetic resonance imaging (MRI) were assessed postoperatively and up to 6 months after surgery (Fig. 6,Fig. 7). A 7 Tesla MRI (Bruker) was implemented for assessment of the operated level as well as the adjacent disc (hydration). T2-weighted sequences were interpreted by a semiquantitative score (0 = no signal, 1 = weak signal, 2 = strong signal and anatomical features of a normal disc). Histology was performed with staining for proteoglycans (Alcian blue) and collagen (Picrosirius red) (Fig. 4,Fig. 5). Figure 2 Disc replacement surgery a Operative situs with native disc that has been disassociated from both adjacent vertebrae b Native disc (left) and tissue-engineered implant (right) c Implant in situ before wound closureAF: Annulus fi brosus, nP: nucleus pulposus, eP: endplate, M: Muscle, T: Tendon, s: skin, art: artery, GP: Growth plate, B: BoneFigure 3 Disc replacement surgery. Anatomy of the rat caudal disc space a Pircrosirius red stained axial cut of native disc space b Saffranin-O stained sagittal cut of native disc spaceFigure 4 Histologies of three separate motion segments from three different rats. Animal one = native IVD, Animal two = status after discectomy, Animal three = tissue-engineered implant (1 month) a-c H&E (overall tissue staining for light micrsocopy) d-f Alcian blue (proteoglycans) g-i Picrosirius red (collagen I and II)Figure 5 Histology from one motion segment four months after implantation of a bio-engineered disc construct a Picrosirius red staining (collagen) b Polarized light microscopy showing collagen staining and collagen organization in AF region c Increased Safranin-O staining (proteoglycans) in NP region of the disc implant d Higher magnification of figure 5c: Integration between implanted tissue-engineered total disc replacement and vertebral body boneFigure 6 MRI a Disc space height measurements in flash/T1 sequence (top: implant (714.0 micrometer), bottom: native disc (823.5 micrometer) b T2 sequence, red circle surrounding the implant NPFigure 7 7 Tesla MRI imaging of rat tail IVDs showing axial images (preliminary pilot data) a Diffusion tensor imaging (DTI) on two explanted rat tail discs in Formalin b Higher magnification of a, showing directional alignment of collagen fibers (red and green) when compared to the color ball on top which maps fibers' directional alignment (eg, fibers directing from left to right: red, from top to bottom: blue) c Native IVD in vivo (successful imaging of top and bottom of the IVD (red) d Gradient echo sequence (GE) showing differentiation between NP (light grey) and AF (dark margin) e GE of reimplanted tail IVD at the explantation level f T1Rho sequence demonstrating the NP (grey) within the AF (dark margin), containing the yellow marked region of interest for value acquisition (preliminary data are consistent with values reported in the literature). g T2 image of native IVD in vivo for monitoring of hydration (white: NP) Results:  The model allowed reproducible and complete discectomies as well as disc implantation in the rat tail spine without any surgical or postoperative complications. Discectomy resulted in immediate collapse of the disc space. Preliminary results indicate that disc space height was maintained after disc implantation in groups II, III and IV over time. MRI revealed high resolution images of normal intervertebral discs in vivo. Eight out of twelve animals (groups III and IV) showed a positive signal in T2-weighted images after 1 month (grade 0 = 4, grade 1 = 4, grade 2 = 4). Positive staining was seen for collagen as well as proteoglycans at the site of disc implantation after 1 month in each of the six animals with engineered implants (group III). Analysis of group IV showed positive T2 signal in five out of six animals and disc-height preservation in all animals after 6 months.  This study demonstrates for the first time that tissue-engineered composite IVDs with circumferentially aligned collagen fibrils survive and integrate with surrounding vertebral bodies when placed in the rat spine for up to 6 months. Tissue-engineered composite IVDs restored function to the rat spine as indicated by maintenance of disc height and vertebral alignment. A significant finding was that maintenance of the composite structure in group III was observed, with increased proteoglycan staining in the nucleus pulposus region (Figure 4d-f). Proteoglycan and collagen matrix as well as disc height preservation and positive T2 signals in MRI are promising parameters and indicate functionality of the implants.

Monte Carlo study of a new I‐125 brachytherapy prototype seed with a ceramic radionuclide carrier and radiographic marker

PubMed Central

Paixão, Lucas; Santos, Ana Maria M.; dos Santos, Adriano Márcio; Grynberg, Suely Epsztein

2012-01-01

In prostate cancer treatment, there is an increasing interest in the permanent radioactive seeds implant technique. Currently, in Brazil, the seeds are imported with high prices, which prohibit their use in public hospitals. A ceramic matrix that can be used as a radioisotope carrier and radiographic marker was developed at our institution. The ceramic matrix is distinguished by the characteristic of maintaining the radioactive material uniformly distributed in its surface. In this work, Monte Carlo simulations were performed in order to assess the dose distributions generated by this prototype seed model, with the ceramic matrix encapsulated in titanium, in the same way as the commercial 6711 seed. The obtained data was assessed, as described in the TG‐43U1 report by the American Association of Physicists in Medicine, for two seed models: (1) the most used model 6711 source — for validation and comparison, and (2) for the prototype model with the ceramic matrix. The dosimetric parameters dose rate constant, Λ, radial dose function, gL(r), and anisotropy function, F(r,θ), were derived from simulations by the Monte Carlo method using the MCNP5 code. A Λ 0.992 (±2.33%) cGyh−1U−1 was found for the prototype model. In comparison with the 6711 model, a lower dose fall‐off on transverse axis was found, as well as a lower dose anisotropy for the radius r= 0.25 cm. In general, for all distances, the prototype seed model presents a slightly larger anisotropy between 0° ≤ Θ < 50° and anisotropy similar to the 6711 model for Θ ≥ 50°. The dosimetric characteristics of the prototype model presented in this study suggest that its use is feasible. Because of the model's characteristics, seeds of lower specific activity iodine might be necessary which, on the other hand, would help to reduce costs. However, it has to be emphasized that the proposed source is a prototype, and the required (AAPM prerequisites) experimental study and tolerance manufacturer values are pending for future studies. PACS numbers: 87.53.Jw, 87.55.K PMID:22584172

The impact of various scaffold components on vascularized bone constructs.

PubMed

Eweida, Ahmad; Schulte, Matthias; Frisch, Oliver; Kneser, Ulrich; Harhaus, Leila

2017-06-01

Bone tissue engineering is gaining more interest in the field of craniofacial surgery where continuous efforts are being made to improve the outcomes via modulation of the scaffold components. In an in vitro three dimensional (3D) culture, the effect of bone morphogenic protein 2 (BMP2, 60 μg/ml) and the effect of different cell seeding densities (0.25, 0.5, and 1 × 104) of rat mesenchymal stem cells seeded on nanocrystalline hydroxyapatite in silica gel matrix (Nanobone ® ) on the cell viability and differentiation were studied. Alkaline phosphatase and viability assays were performed at day 7, day 14, and day 21 to assess the differentiation and the relative fraction of viable cells in the 3D cell cultures. In a subsequent in vivo study, we examined the effect of axial vascularization, the scaffold's particle size and the nature of the matrix (collagen type I vs. diluted fibrin) on vascularization and tissue generation in vascularized bone construct in rats. Regarding vascularization, we compared constructs vascularized randomly by extrinsic vascularization from the periphery of the implanted construct with others vascularized axially via an implanted arteriovenous loop (AVL). Regarding the particle size, we compared constructs having a scaffold particle size of 0.2 mm (powder) with other constructs having a particle size of 2 × 0.6 mm (granules). Regarding the matrix we compared constructs having a collagen matrix with others having a fibrin matrix. Various groups were compared regarding the amount of tissue generation, vascularization, and cellular proliferation. The initial seeding density had a temporary and minimal effect on the overall osteogenic differentiation of the cells. On the contrary, adding BMP2 in a concentration of 60 μg/ml over one week led to an overall enhanced osteogenic differentiation despite depressed cell viability. Axial vascularization was mandatory for efficient tissue formation and vascularization of the bone construct. Collagen matrix and a smaller particle size provided more favorable results in terms of vascularization and tissue formation than diluted fibrin and larger Nanobone particles. Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

George Hartley Bryan, Ludwig Boltzmann, and the Stability of Flight

NASA Astrophysics Data System (ADS)

Boyd, T. James M.

2012-03-01

A century ago, George Hartley Bryan (1864-1928) published his classic book, Stability in Aviation. I draw together some strands from events that awakened his interest in the nascent science of aviation, in particular the stability of flight. Prominent among those who influenced him was Ludwig Boltzmann (1844-1906), who held Bryan in high esteem for his contributions to thermodynamics and kinetic theory. I argue that the seeds of Bryan's interest in aviation were sown at the British Association meeting at Oxford in the summer of 1894, at which Boltzmann was guest of honor. A joint discussion between Section A (Mathematical and Physical Science) and Section G (Mechanical Science) was devoted to the problems of flight, during the course of which Boltzmann revealed a hitherto unsuspected enthusiasm for flying.

Arabidopsis ARGONAUTE7 selects miR390 through multiple checkpoints during RISC assembly.

PubMed

Endo, Yayoi; Iwakawa, Hiro-oki; Tomari, Yukihide

2013-07-01

Plant ARGONAUTE7 (AGO7) assembles RNA-induced silencing complex (RISC) specifically with miR390 and regulates the auxin-signalling pathway via production of TAS3 trans-acting siRNAs (tasiRNAs). However, how AGO7 discerns miR390 among other miRNAs remains unclear. Here, we show that the 5' adenosine of miR390 and the central region of miR390/miR390* duplex are critical for the specific interaction with AGO7. Furthermore, despite the existence of mismatches in the seed and central regions of the duplex, cleavage of the miR390* strand is required for maturation of AGO7-RISC. These findings suggest that AGO7 uses multiple checkpoints to select miR390, thereby circumventing promiscuous tasiRNA production.

Casting inorganic structures with DNA molds

PubMed Central

Sun, Wei; Boulais, Etienne; Hakobyan, Yera; Wang, Wei Li; Guan, Amy; Bathe, Mark; Yin, Peng

2014-01-01

We report a general strategy for designing and synthesizing inorganic nanostructures with arbitrarily prescribed three-dimensional shapes. Computationally designed DNA strands self-assemble into a stiff “nano-mold” that contains a user-specified three-dimensional cavity and encloses a nucleating gold “seed”. Under mild conditions, this seed grows into a larger cast structure that fills and thus replicates the cavity. We synthesized a variety of nanoparticles with three nanometer resolution: three distinct silver cuboids with three independently tunable dimensions, silver and gold nanoparticles with diverse cross sections, and composite structures with homo-/heterogeneous components. The designer equilateral silver triangular and spherical nanoparticles exhibited plasmonic properties consistent with electromagnetism-based simulations. Our framework is generalizable to more complex geometries and diverse inorganic materials, offering a range of applications in biosensing, photonics, and nanoelectronics. PMID:25301973

Prostate volume changes during permanent seed brachytherapy: an analysis of intra-operative variations, predictive factors and clinical implication.

PubMed

Chira, Ciprian; Delouya, Guila; Larrivée, Sandra; Carrier, Jean-Francois; Taussky, Daniel

2013-07-09

To determine prostate volume (Pvol) changes at 3 different time points during the course of I¹²⁵ permanent seed brachytherapy (PB). To assess the impact of these changes on acute urinary retention (AUR) and dosimetric outcome. We analyzed 149 hormone-naïve patients. Measurements of the prostate volume were done using three-dimensional transrectal ultrasound (3D-TRUS) in the operating room before insertion of any needle (V1), after the insertion of 2 fixation needles with a harpoon (V2) and upon completion of the implant (V3). The quality of the implant was analyzed with the D90 (minimum dose in Grays received by 90% of the prostate volume) at day 30. Mean baseline prostate volume (V1) was 37.4 ± 9.6 cc. A volume increase of >5% was seen in 51% between V1-V2 (mean = 2.5 cc, p < 0.01), in 42% between V2-V3 (mean = 1.9 cc, p < 0.01) and in 71% between V1-V3 (mean = 4.5 cc, p < 0.01). Pvol changes caused by insertion of the fixation needles were not statistically different than those caused by the implant itself (p = 0.23).In multivariate linear regression analysis, baseline Pvol is predictive of Pvol changes between V2 and V1 and V3 and V1 but not between V3 and V2. The extent of prostate swelling had an influence on D90. An increase of 10% in prostate volume between V1 and V2 results in an increase of D90 at Day 30 by 11.7%. Baseline Pvol (V1) was the only predictor of the duration of urinary retention in both univariate and multivariate (p = 0.04) regression analysis. A large part of intraoperative swelling occurs already after the insertion of the fixation needles. This early prostate swelling predicts for D90 but not for AUR.

SU-F-T-40: Can CBCT Images Be Used for Volume Studies of Prostate Seed Implants for Boost Treatment?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, H; Lee, S; Diwanji, T

Purpose: In our clinic, the planning CT is used for definitive and boost low-dose-rate (LDR) brachytherapy treatments to determine the ultrasound volume in the operating room (OR) at the time of the implant. While the CT overestimation of OR volume is known, a larger estimation discrepancy has been observed for boost treatments. A possible reason is the prostate size reduction during EBRT for boost patients. Since cone-beam CT (CBCT) is often used as routine imaging guidance of EBRT, this prostate volume change may be captured. This study investigates if CBCT taken during EBRT includes the volume change information and thereforemore » beats CT in estimating the prostate OR volumes. Methods: 9 prostate patients treated with EBRT (45Gy in 1.8Gy per fractions to the whole pelvis) and I-125 seed implants (108Gy) were involved in this study. During EBRT, CBCT image guidance was performed on a weekly basis. For each patient, the prostate volumes on the first and the last available CBCT images were manually contoured by a physician. These volumes were then compared to each other and with the contoured volumes from the planning CT and from the ultrasound images in the OR. Results: The first and the last CBCT images did not show significant prostate volume change. Their average +/− standard deviation of prostate volumes were 24.4cc+/−14.6cc and 29.9cc+/−16.1cc, respectively (T-test p=0.68). The ratio of the OR volume to the last CBCT (0.71+/−0.21) was not significantly different from the ratio of OR volumes to the planning CT (0.61+/−0.13) (p=0.25). Conclusion: In this study, CBCT does not show significant prostate volume changes during EBRT. CBCT and CT volumes are quite consistent and no improvement of volume estimation using CBCT is observed. The advantage of CBCT as a replacement of CT for volume study of boost LDR brachytherapy is limited.« less

Nanostructured Ti-Ta thin films synthesized by combinatorial glancing angle sputter deposition

NASA Astrophysics Data System (ADS)

Motemani, Yahya; Khare, Chinmay; Savan, Alan; Hans, Michael; Paulsen, Alexander; Frenzel, Jan; Somsen, Christoph; Mücklich, Frank; Eggeler, Gunther; Ludwig, Alfred

2016-12-01

Ti-Ta alloys are attractive materials for applications in actuators as well as biomedical implants. When fabricated as thin films, these alloys can potentially be employed as microactuators, components for micro-implantable devices and coatings on surgical implants. In this study, Ti100-x Ta x (x = 21, 30) nanocolumnar thin films are fabricated by glancing angle deposition (GLAD) at room temperature using Ti73Ta27 and Ta sputter targets. Crystal structure, morphology and microstructure of the nanostructured thin films are systematically investigated by XRD, SEM and TEM, respectively. Nanocolumns of ˜150-160 nm in width are oriented perpendicular to the substrate for both Ti79Ta21 and Ti70Ta30 compositions. The disordered α″ martensite phase with orthorhombic structure is formed in room temperature as-deposited thin films. The columns are found to be elongated small single crystals which are aligned perpendicular to the (20\\bar{4}) and (204) planes of α″ martensite, indicating that the films’ growth orientation is mainly dominated by these crystallographic planes. Laser pre-patterned substrates are utilized to obtain periodic nanocolumnar arrays. The differences in seed pattern, and inter-seed distances lead to growth of multi-level porous nanostructures. Using a unique sputter deposition geometry consisting of Ti73Ta27 and Ta sputter sources, a nanocolumnar Ti-Ta materials library was fabricated on a static substrate by a co-deposition process (combinatorial-GLAD approach). In this library, a composition spread developed between Ti72.8Ta27.2 and Ti64.4Ta35.6, as confirmed by high-throughput EDX analysis. The morphology over the materials library varies from well-isolated nanocolumns to fan-like nanocolumnar structures. The influence of two sputter sources is investigated by studying the resulting column angle on the materials library. The presented nanostructuring methods including the use of the GLAD technique along with pre-patterning and a combinatorial materials library fabrication strategy offer a promising technological approach for investigating Ti-Ta thin films for a range of applications. The proposed approaches can be similarly implemented for other materials systems which can benefit from the formation of a nanocolumnar morphology.

Alternative to radical surgery for cancer of the prostate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mathes, G.L.; Page, R.C.

1978-08-01

We have used the technique of retropubic implantation of /sup 125/I seeds, as introduced by Whitmore and associates in 1972, in 12 selected patients with prostatic cancer. Morbidity has been minimal, and the tumor has been effectively controlled. This technique delivers more radiation and has fewer side effects than external cobalt irradiation, and it should be offered to the patient as an effective alternative to radical prostatectomy. It is best suited for patients with stage A, stage B, or small stage C lesions who have negative bone scans. Edema of the penis follows the lymphadenectomy but gradually subsides.

Monte Carlo calculated TG-60 dosimetry parameters for the {beta}{sup -} emitter {sup 153}Sm brachytherapy source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadeghi, Mahdi; Taghdiri, Fatemeh; Hamed Hosseini, S.

Purpose: The formalism recommended by Task Group 60 (TG-60) of the American Association of Physicists in Medicine (AAPM) is applicable for {beta} sources. Radioactive biocompatible and biodegradable {sup 153}Sm glass seed without encapsulation is a {beta}{sup -} emitter radionuclide with a short half-life and delivers a high dose rate to the tumor in the millimeter range. This study presents the results of Monte Carlo calculations of the dosimetric parameters for the {sup 153}Sm brachytherapy source. Methods: Version 5 of the (MCNP) Monte Carlo radiation transport code was used to calculate two-dimensional dose distributions around the source. The dosimetric parameters ofmore » AAPM TG-60 recommendations including the reference dose rate, the radial dose function, the anisotropy function, and the one-dimensional anisotropy function were obtained. Results: The dose rate value at the reference point was estimated to be 9.21{+-}0.6 cGy h{sup -1} {mu}Ci{sup -1}. Due to the low energy beta emitted from {sup 153}Sm sources, the dose fall-off profile is sharper than the other beta emitter sources. The calculated dosimetric parameters in this study are compared to several beta and photon emitting seeds. Conclusions: The results show the advantage of the {sup 153}Sm source in comparison with the other sources because of the rapid dose fall-off of beta ray and high dose rate at the short distances of the seed. The results would be helpful in the development of the radioactive implants using {sup 153}Sm seeds for the brachytherapy treatment.« less

A critical role for macrophages in neovessel formation and the development of stenosis in tissue-engineered vascular grafts

PubMed Central

Hibino, Narutoshi; Yi, Tai; Duncan, Daniel R.; Rathore, Animesh; Dean, Ethan; Naito, Yuji; Dardik, Alan; Kyriakides, Themis; Madri, Joseph; Pober, Jordan S.; Shinoka, Toshiharu; Breuer, Christopher K.

2011-01-01

The primary graft-related complication during the first clinical trial evaluating the use of tissue-engineered vascular grafts (TEVGs) was stenosis. We investigated the role of macrophages in the formation of TEVG stenosis in a murine model. We analyzed the natural history of TEVG macrophage infiltration at critical time points and evaluated the role of cell seeding on neovessel formation. To assess the function of infiltrating macrophages, we implanted TEVGs into mice that had been macrophage depleted using clodronate liposomes. To confirm this, we used a CD11b-diphtheria toxin-receptor (DTR) transgenic mouse model. Monocytes infiltrated the scaffold within the first few days and initially transformed into M1 macrophages. As the scaffold degraded, the macrophage infiltrate disappeared. Cell seeding decreased the incidence of stenosis (32% seeded, 64% unseeded, P=0.024) and the degree of macrophage infiltration at 2 wk. Unseeded TEVGs demonstrated conversion from M1 to M2 phenotype, whereas seeded grafts did not. Clodronate and DTR inhibited macrophage infiltration and decreased stenosis but blocked formation of vascular neotissue, evidenced by the absence of endothelial and smooth muscle cells and collagen. These findings suggest that macrophage infiltration is critical for neovessel formation and provides a strategy for predicting, detecting, and inhibiting stenosis in TEVGs.—Hibino, N., Yi, T., Duncan, D. R., Rathore, A., Dean, E., Naito, Y., Dardik, A., Kyriakides, T., Madri, J., Pober, J. S., Shinoka, T., Breuer, C. K. A critical role for macrophages in neovessel formation and the development of stenosis in tissue-engineered vascular grafts. PMID:21865316

The oral cavity is not a primary source for implantable pacemaker or cardioverter defibrillator infections

PubMed Central

2013-01-01

Background To test the hypothesis that the oral cavity is a potential source for implantable pacemaker and cardioverter defibrillators infections, the bacterial diversity on explanted rhythm heart management devices was investigated and compared to the oral microbiome. Methods A metagenomic approach was used to analyze the bacterial diversity on the surfaces of non-infected and infected pacemakers. The DNA from surfaces swaps of 24 non-infected and 23 infected pacemaker were isolated and subjected to bacterial-specific DNA amplification, single strand conformation polymorphism- (SSCP) and sequencing analysis. Species-specific primer sets were used to analyze for any correlation between bacterial diversity on pacemakers and in the oral cavity. Results DNA of bacterial origin was detected in 21 cases on infected pacemakers and assigned to the bacterial phylotypes Staphylococcus epidermidis, Propionibacterium acnes, Staphylococcus aureus, Staphylococcus schleiferi and Stapyhlococcus. In 17 cases bacterial DNA was found on pacemakers with no clinical signs of infections. On the basis of the obtained sequence data, the phylotypes Propionibacterium acnes, Staphylococcus and an uncultured bacterium were identified. Propionibacterium acnes and Staphylococcus epidermidis were the only bacteria detected in pacemeaker (n = 25) and oral samples (n = 11). Conclusions The frequency of the coincidental detection of bacteria on infected devices and in the oral cavity is low and the detected bacteria are highly abundant colonizers of non-oral human niches. The transmission of oral bacteria to the lead or device of implantable pacemaker or cardioverter defibrillators is unlikely relevant for the pathogenesis of pacemaker or cardioverter defibrillators infections. PMID:23575037

RGDfK-Peptide Modified Alginate Scaffold for Cell Transplantation and Cardiac Neovascularization.

PubMed

Sondermeijer, Hugo P; Witkowski, Piotr; Seki, Tetsunori; van der Laarse, Arnoud; Itescu, Silviu; Hardy, Mark A

2018-05-01

Cell implantation for tissue repair is a promising new therapeutic strategy. Although direct injection of cells into tissue is appealing, cell viability and retention are not very good. Cell engraftment and survival following implantation are dependent on a sufficient supply of oxygen and nutrients through functional microcirculation as well as a suitable local microenvironment for implanted cells. In this study, we describe the development of a porous, biocompatible, three-dimensional (3D) alginate scaffold covalently modified with the synthetic cyclic RGDfK (Arg-Gly-Asp-D-Phe-Lys) peptide. Cyclic RGDfK peptide is protease resistant, highly stable in aqueous solutions, and has high affinity for cellular integrins. Cyclic RGDfK-modified alginate scaffolds were generated using a novel silicone sheet sandwich technique in combination with freeze-gelation, resulting in highly porous nonimmunogenic scaffolds that promoted both human and rodent cell survival in vitro, and neoangiogenesis in vivo. Two months following implantation in abdominal rectus muscles in rats, cyclic RGDfK-modified scaffolds were fully populated by host cells, especially microvasculature without an overt immune response or fibrosis, whereas unmodified control scaffolds did not show cell ingrowth. Importantly, modified scaffolds that were seeded with human mesenchymal precursor cells and were patched to the epicardial surface of infarcted myocardium induced myocardial neoangiogenesis and significantly improved cardiac function. In summary, purified cyclic RGDfK peptide-modified 3D alginate scaffolds are biocompatible and nonimmunogenic, enhance cell viability, promote angiogenesis, and may be used as a means to deliver cells to myocardial infarct areas to improve neovascularization and cardiac function.

Silver Coordination Polymers for Prevention of Implant Infection: Thiol Interaction, Impact on Respiratory Chain Enzymes, and Hydroxyl Radical Induction▿ †

PubMed Central

Gordon, Oliver; Vig Slenters, Tünde; Brunetto, Priscilla S.; Villaruz, Amer E.; Sturdevant, Daniel E.; Otto, Michael; Landmann, Regine; Fromm, Katharina M.

2010-01-01

Prosthetic joint replacements are used increasingly to alleviate pain and improve mobility of the progressively older and more obese population. Implant infection occurs in about 5% of patients and entails significant morbidity and high social costs. It is most often caused by staphylococci, which are introduced perioperatively. They are a source of prolonged seeding and difficult to treat due to antibiotic resistance; therefore, infection prevention by prosthesis coating with nonantibiotic-type anti-infective substances is indicated. A renewed interest in topically used silver has fostered development of silver nanoparticles, which, however, present a potential health hazard. Here we present new silver coordination polymer networks with tailored physical and chemical properties as nanostructured coatings on metallic implant substrates. These compounds exhibited strong biofilm sugar-independent bactericidal activity on in vitro-grown biofilms and prevented murine Staphylococcus epidermidis implant infection in vivo with slow release of silver ions and limited transient leukocyte cytotoxicity. Furthermore, we describe the biochemical and molecular mechanisms of silver ion action by gene screening and by targeting cell metabolism of S. epidermidis at different levels. We demonstrate that silver ions inactivate enzymes by binding sulfhydryl (thiol) groups in amino acids and promote the release of iron with subsequent hydroxyl radical formation by an indirect mechanism likely mediated by reactive oxygen species. This is the first report investigating the global metabolic effects of silver in the context of a therapeutic application. We anticipate that the compounds presented here open a new treatment field with a high medical impact. PMID:20660682

Enhanced Magnetization of Cobalt Defect Clusters Embedded in TiO 2-δ Films

DOE PAGES

Cortie, David L.; Khaydukov, Yury; Keller, Thomas; ...

2017-02-23

High magnetizations are desirable for spintronic devices that operate by manipulating electronic states using built-in magnetic fields. However, the magnetic moment in promising dilute magnetic oxide nanocomposites is very low, typically corresponding to only fractions of a Bohr magneton for each dopant atom. In this study, we report a large magnetization formed by ion implantation of Co into amorphous TiO 2-δ films, producing an inhomogeneous magnetic moment, with certain regions producing over 2.5 μ B per Co, depending on the local dopant concentration. Polarized neutron reflectometry was used to depth-profile the magnetization in the Co:TiO 2-δ nanocomposites, thus confirming themore » pivotal role of the cobalt dopant profile inside the titania layer. X-ray photoemission spectra demonstrate the dominant electronic state of the implanted species is Co 0, with a minor fraction of Co 2+. The detected magnetizations have seldom been reported before and lie near the upper limit set by Hund’s rules for Co 0, which is unusual because the transition metal’s magnetic moment is usually reduced in a symmetric 3D crystal-field environment. Low-energy positron annihilation lifetime spectroscopy indicates that defect structures within the titania layer are strongly modified by the implanted Co. We propose that a clustering motif is promoted by the affinity of the positively charged implanted species to occupy microvoids native to the amorphous host. This provides a seed for subsequent doping and nucleation of nanoclusters within an unusual local environment.« less

Functionalization and Characterization of Nanomaterial Gated Field-Effect Transistor-Based Biosensors and the Design of a Multi-Analyte Implantable Biosensing Platform

NASA Astrophysics Data System (ADS)

Croce, Robert A., Jr.

Advances in semiconductor research and complementary-metal-oxide semiconductor fabrication allow for the design and implementation of miniaturized metabolic monitoring systems, as well as advanced biosensor design. The first part of this dissertation will focus on the design and fabrication of nanomaterial (single-walled carbon nanotube and quantum dot) gated field-effect transistors configured as protein sensors. These novel device structures have been functionalized with single-stranded DNA aptamers, and have shown sensor operation towards the protein Thrombin. Such advanced transistor-based sensing schemes present considerable advantages over traditional sensing methodologies in view of its miniaturization, low cost, and facile fabrication, paving the way for the ultimate realization of a multi-analyte lab-on-chip. The second part of this dissertation focuses on the design and fabrication of a needle-implantable glucose sensing platform which is based solely on photovoltaic powering and optical communication. By employing these powering and communication schemes, this design negates the need for bulky on-chip RF-based transmitters and batteries in an effort to attain extreme miniaturization required for needle-implantable/extractable applications. A complete single-sensor system coupled with a miniaturized amperometric glucose sensor has been demonstrated to exhibit reality of this technology. Furthermore, an optical selection scheme of multiple potentiostats for four different analytes (glucose, lactate, O 2 and CO2) as well as the optical transmission of sensor data has been designed for multi-analyte applications. The last part of this dissertation will focus on the development of a computational model for the amperometric glucose sensors employed in the aforementioned implantable platform. This model has been applied to single-layer single-enzyme systems, as well as multi-layer (single enzyme) systems utilizing glucose flux limiting layer-by-layer assembled outer membranes. The concentration of glucose and hydrogen peroxide within the sensor geometry, the transient response and the device response time has been simulated for both systems.

Defining the limits of flowers: the challenge of distinguishing between the evolutionary products of simple versus compound strobili

PubMed Central

Rudall, Paula J.; Bateman, Richard M.

2010-01-01

Recent phylogenetic reconstructions suggest that axially condensed flower-like structures evolved iteratively in seed plants from either simple or compound strobili. The simple-strobilus model of flower evolution, widely applied to the angiosperm flower, interprets the inflorescence as a compound strobilus. The conifer cone and the gnetalean ‘flower’ are commonly interpreted as having evolved from a compound strobilus by extreme condensation and (at least in the case of male conifer cones) elimination of some structures present in the presumed ancestral compound strobilus. These two hypotheses have profoundly different implications for reconstructing the evolution of developmental genetic mechanisms in seed plants. If different flower-like structures evolved independently, there should intuitively be little commonality of patterning genes. However, reproductive units of some early-divergent angiosperms, including the extant genus Trithuria (Hydatellaceae) and the extinct genus Archaefructus (Archaefructaceae), apparently combine features considered typical of flowers and inflorescences. We re-evaluate several disparate strands of comparative data to explore whether flower-like structures could have arisen by co-option of flower-expressed patterning genes into independently evolved condensed inflorescences, or vice versa. We discuss the evolution of the inflorescence in both gymnosperms and angiosperms, emphasising the roles of heterotopy in dictating gender expression and heterochrony in permitting internodal compression. PMID:20047867

Defining the limits of flowers: the challenge of distinguishing between the evolutionary products of simple versus compound strobili.

PubMed

Rudall, Paula J; Bateman, Richard M

2010-02-12

Recent phylogenetic reconstructions suggest that axially condensed flower-like structures evolved iteratively in seed plants from either simple or compound strobili. The simple-strobilus model of flower evolution, widely applied to the angiosperm flower, interprets the inflorescence as a compound strobilus. The conifer cone and the gnetalean 'flower' are commonly interpreted as having evolved from a compound strobilus by extreme condensation and (at least in the case of male conifer cones) elimination of some structures present in the presumed ancestral compound strobilus. These two hypotheses have profoundly different implications for reconstructing the evolution of developmental genetic mechanisms in seed plants. If different flower-like structures evolved independently, there should intuitively be little commonality of patterning genes. However, reproductive units of some early-divergent angiosperms, including the extant genus Trithuria (Hydatellaceae) and the extinct genus Archaefructus (Archaefructaceae), apparently combine features considered typical of flowers and inflorescences. We re-evaluate several disparate strands of comparative data to explore whether flower-like structures could have arisen by co-option of flower-expressed patterning genes into independently evolved condensed inflorescences, or vice versa. We discuss the evolution of the inflorescence in both gymnosperms and angiosperms, emphasising the roles of heterotopy in dictating gender expression and heterochrony in permitting internodal compression.

Spontaneous Chloroplast Mutants Mostly Occur by Replication Slippage and Show a Biased Pattern in the Plastome of Oenothera.

PubMed

Massouh, Amid; Schubert, Julia; Yaneva-Roder, Liliya; Ulbricht-Jones, Elena S; Zupok, Arkadiusz; Johnson, Marc T J; Wright, Stephen I; Pellizzer, Tommaso; Sobanski, Johanna; Bock, Ralph; Greiner, Stephan

2016-04-01

Spontaneous plastome mutants have been used as a research tool since the beginning of genetics. However, technical restrictions have severely limited their contributions to research in physiology and molecular biology. Here, we used full plastome sequencing to systematically characterize a collection of 51 spontaneous chloroplast mutants in Oenothera (evening primrose). Most mutants carry only a single mutation. Unexpectedly, the vast majority of mutations do not represent single nucleotide polymorphisms but are insertions/deletions originating from DNA replication slippage events. Only very few mutations appear to be caused by imprecise double-strand break repair, nucleotide misincorporation during replication, or incorrect nucleotide excision repair following oxidative damage. U-turn inversions were not detected. Replication slippage is induced at repetitive sequences that can be very small and tend to have high A/T content. Interestingly, the mutations are not distributed randomly in the genome. The underrepresentation of mutations caused by faulty double-strand break repair might explain the high structural conservation of seed plant plastomes throughout evolution. In addition to providing a fully characterized mutant collection for future research on plastid genetics, gene expression, and photosynthesis, our work identified the spectrum of spontaneous mutations in plastids and reveals that this spectrum is very different from that in the nucleus. © 2016 American Society of Plant Biologists. All rights reserved.

Atomistic Free Energy Model for Nucleic Acids: Simulations of Single-Stranded DNA and the Entropy Landscape of RNA Stem-Loop Structures.

PubMed

Mak, Chi H

2015-11-25

While single-stranded (ss) segments of DNAs and RNAs are ubiquitous in biology, details about their structures have only recently begun to emerge. To study ssDNA and RNAs, we have developed a new Monte Carlo (MC) simulation using a free energy model for nucleic acids that has the atomisitic accuracy to capture fine molecular details of the sugar-phosphate backbone. Formulated on the basis of a first-principle calculation of the conformational entropy of the nucleic acid chain, this free energy model correctly reproduced both the long and short length-scale structural properties of ssDNA and RNAs in a rigorous comparison against recent data from fluorescence resonance energy transfer, small-angle X-ray scattering, force spectroscopy and fluorescence correlation transport measurements on sequences up to ∼100 nucleotides long. With this new MC algorithm, we conducted a comprehensive investigation of the entropy landscape of small RNA stem-loop structures. From a simulated ensemble of ∼10(6) equilibrium conformations, the entropy for the initiation of different size RNA hairpin loops was computed and compared against thermodynamic measurements. Starting from seeded hairpin loops, constrained MC simulations were then used to estimate the entropic costs associated with propagation of the stem. The numerical results provide new direct molecular insights into thermodynaimc measurement from macroscopic calorimetry and melting experiments.

Enhancing osseointegration of orthopedic implants with titania nanotube surfaces

NASA Astrophysics Data System (ADS)

Baker, Erin A.

Introduction: As joint arthroplasty surgical procedures increase annually, the development of new strategies, including novel materials and surface modifications, to attain solid bone-implant fixation are needed to increase implant terms of service. In this study, we evaluate two morphologies of titania nanotubes in both in vitro and in vivo experiments to quantify osseointegrative potential and material-level biocompatibility. Materials and Methods: Samples were prepared via an electrochemical etching process. Two different titania nanotube (TiNT) morphologies were produced, Aligned and Trabecular. For the in vitro experiment, Sprague Dawley (SD) rat marrow-derived bone marrow cells (BMC) were seeded on samples. Alkaline phosphatase (ALP) activity, osteocalcin (OC) expression, expression of relevant genes as well as cell attachment and morphology were assessed. In the first in vivo experiment, Kirschner wires were implanted unilaterally into SD rat femora with a TiNT-etched or unmodified (Control) implant. General health assessments and weekly body weights were recorded. At a 12-week endpoint, hematologic, systemic metal ion, and histologic analyses were performed. For the second in vivo experiment, Kirschner wires were implanted bilaterally into SD rat femora, with a TiNT-etched implant in one femora and unmodified (Control) implant as an internal control. At 4- and 12-week endpoints, femora were assessed via biomechanics, undecalcified histology, micro-computed tomography (muCT), and backscattered electron imaging (BEI) to characterize de novo bone formation. Results: In vitro experiments demonstrated BMC attachment and differentiation into osteoblasts as well as greater ALP activity, OC expression, total cell counts, and gene expression (of Col1a1, IGF-1, and osteonectin) on TiNT surfaces versus Controls. Cells on TiNT-etched substrates were smaller in diameter and more eccentric than Controls. In the first in vivo experiment, there were significant differences in body weight between groups at Weeks 9 and 11. There were no significant differences in red or white blood cell function between TiNT groups and Control. Aluminum levels in the lungs were significantly greater in the Trabecular TiNT group compared to Control. Histologic analysis showed significantly fewer granulocytes and neutrophils in the distal region of Trabecular TiNT-implanted femora as well as significantly fewer foreign body giant/multinucleated cells and neutrophils in the midshaft region of Aligned TiNT-implanted femora versus Controls. In the second in vivo experiment, at 12 weeks, microCT analysis showed TiNT implants generated greater bone formation than Controls. Histologic analysis demonstrated 1.5 times greater bone-implant contact in TiNT groups than Controls at 12 weeks. TiNT groups exhibited 1.3 to 3.7 times greater strength of fixation than Controls during pull-out testing. Discussion and Conclusions: In vitro data confirmed BMC attachment and differentiation into osteoblasts as well as osteoblastic phenotypic behavior. A clinically-relevant in vivo model of femoral intramedullary fixation, showed increased bone formation and quality in femora implanted with TiNT-etched implants versus Controls. A second in vivo study showed that TiNT surfaces do not generate systemic effects and may beneficially modulate the periprosthetic inflammatory environment.

Tissue engineering penoplasty with biodegradable scaffold Maxpol-T cografted autologous fibroblasts for small penis syndrome.

PubMed

Jin, Zhe; Wu, Yi-Guang; Yuan, Yi-Ming; Peng, Jing; Gong, Yan-Qing; Li, Guang-Yong; Song, Wei-Dong; Cui, Wan-Shou; He, Xue-You; Xin, Zhong-Cheng

2011-01-01

In this study, we investigated the safety and efficacy of a poly acid-co-glycolide biodegradable scaffold (Maxpol-T) coated by autologous fibroblasts (AF) for penile girth enlargement in small penis syndrome (SPS). Eighty patients with SPS were enrolled in a clinical study at 2 medical centers; 69 patients completed the study protocol. Scrotal skin was harvested under local anesthesia, and AFs were cultured and seeded on a Maxpol-T scaffold; the cografted scaffold was implanted under the Buck's fascia of penile shaft via a circumcising incision. Patients were followed up at 1, 3, and 6 months to evaluate penile girth changes. Patient satisfaction was assessed via Visual Analogue Scale and scored on the International Index of Erectile Function-5 (IIEF-5). Mean preoperative penile girth in the flaccid and erect state was 8.18 ± 0.83 cm and 10.26 ± 1.22 cm, respectively. At the 6-month postoperative follow-up, mean penile girth in the flaccid and erect state was increased to 12.19 ± 1.27 cm and 13.18 ± 1.31 cm, respectively (P < .001 for change in both flaccid and erect state). Sixty-five patients (94.2%) reported satisfaction with the procedure. Among them, 4 cases (5.8%) were dissatisfied, 7 cases (10.1%) were satisfied, 26 cases (37.7%) were very satisfied, and 32 cases (46.4%) were extremely satisfied. All men maintained IIEF-5 scores of more than 22. Complications included prolonged subcutaneous edema in 3 patients (4.3%) and pinpoint erosion at the suture area in 3 patients (4.3%). Implantation of autologous fibroblasts seeded on a Maxpol-T collagen scaffold holds promise as a safe and novel technique for penile girth enhancement in patients with SPS.

Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits.

PubMed

Chang, N-J; Lam, C-F; Lin, C-C; Chen, W-L; Li, C-F; Lin, Y-T; Yeh, M-L

2013-10-01

Repairing articular cartilage is clinically challenging. We investigated a simple, effective and clinically feasible cell-based therapeutic approach using a poly(lactide-co-glycolide) (PLGA) scaffold seeded with autologous endothelial progenitor cells (EPC) to repair a full-thickness osteochondral defect in rabbits using a one-step surgery. EPC obtained by purifying a small amount of peripheral blood from rabbits were seeded into a highly porous, biocompatible PLGA scaffold, namely, EPC-PLGA, and implanted into the osteochondral defect in the medial femoral condyle. Twenty two rabbits were randomized into one of three groups: the empty defect group (ED), the PLGA-only group or the EPC-PLGA group. The defect sites were evaluated 4 and 12 weeks after implantation. At the end of testing, only the EPC-PLGA group showed the development of new cartilage tissue with a smooth, transparent and integrated articular surface. Moreover, histological analysis showed obvious differences in cartilage regeneration. At week 4, the EPC-PLGA group showed considerably higher TGF-β2 and TGF-β3 expression, a greater amount of synthesized glycosaminoglycan (GAG) content, and a higher degree of osteochondral angiogenesis in repaired tissues. At week 12, the EPC-PLGA group showed enhanced hyaline cartilage regeneration with a normal columnar chondrocyte arrangement, higher SOX9 expression, and greater GAG and collagen type II (COLII) content. Moreover, the EPC-PLGA group showed organized osteochondral integration, the formation of vessel-rich tubercular bone and significantly higher bone volume per tissue volume and trabecular thickness (Tb.Th). The present EPC-PLGA cell delivery system generates a suitable in situ microenvironment for osteochondral regeneration without the supplement of exogenous growth factors. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Comparison of 3 different postimplant dosimetry methods following permanent {sup 125}I prostate seed brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marcu, Loredana G., E-mail: loredana@marcunet.com; Faculty of Science, University of Oradea; School of Chemistry and Physics, University of Adelaide, South Australia

2013-10-01

Postimplant dosimetry (PID) after Iodine-125 ({sup 125}I) implant of the prostate should offer a reliable qualitative assessment. So far, there is no consensus regarding the optimum PID method, though the latest literature is in favor of magnetic resonance imaging (MRI). This study aims to simultaneously compare 3 PID techniques: (1) MRI-computed tomography (CT) fusion; (2) ultrasound (US)-CT fusion; and (3) manual target delineation on CT. The study comprised 10 patients with prostate cancer. CT/MR scans with urinary catheters in place for PID were done either on day 0 or day 1 postimplantation. The main parameter evaluated and compared among methodsmore » was target D90. The results show that CT-based D90s are lower than US-CT D90s (median difference,−6.85%), whereas MR-CT PID gives higher D90 than US-CT PID (median difference, 4.25%). Manual contouring on CT images tends to overestimate the prostate volume compared with transrectal ultrasound (TRUS) (median difference, 23.33%), whereas on US images the target is overestimated compared with MR-based contouring (median difference, 13.25%). Although there are certain differences among the results given by various PID techniques, the differences are statistically insignificant for this small group of patients. Any dosimetric comparison between 2 PID techniques should also account for the limitations of each technique, to allow for an accurate quantification of data. Given that PID after permanent radioactive seed implant is mandatory for quality assurance, any imaging method–based PID (MR-CT, US-CT, and CT) available in a radiotherapy department can be indicative of the quality of the procedure.« less

Collagen-gelatin-genipin-hydroxyapatite composite scaffolds colonized by human primary osteoblasts are suitable for bone tissue engineering applications: in vitro evidences.

PubMed

Vozzi, G; Corallo, C; Carta, S; Fortina, M; Gattazzo, F; Galletti, M; Giordano, N

2014-05-01

The application of porous hydroxyapatite (HAp)-collagen as a bone tissue engineering scaffold represents a new trend of mimicking the specific bone extracellular matrix (ECM). The use of HAp in reconstructive surgery has shown that it is slowly invaded by host tissue. Therefore, implant compatibility may be augmented by seeding cells before implantation. Human primary osteoblasts were seeded onto innovative collagen-gelatin-genipin (GP)-HAp scaffolds containing respectively 10%, 20%, and 30% HAp. Cellular adhesion, proliferation, alkaline phosphatase (ALP) activity, osteopontin (OPN), and osteocalcin (OC) expressions were evaluated after 3, 7, 15, and 21 days. The three types of scaffolds showed increased cellular proliferation over time in culture (maximum at 21 days) but the highest was recorded in 10% HAp scaffolds. ALP activity was the highest in 10% HAp scaffolds in all the times of evaluation. OC and OPN resulted in higher concentration in 10% HAp scaffolds compared to 20% and 30% HAp (maximum at 21 days). Finally, scanning electron microscopy analysis showed progressive scaffolds adhesion and colonization from the surface to the inside from day 3 to day 21. In vitro attachment, proliferation, and colonization of human primary osteoblasts on collagen-GP-HAp scaffolds with different percentages of HAp (10%, 20%, and 30%) all increased over time in culture, but comparing different percentages of HAp, they seem to increase with decreasing of HAp component. Therefore, the mechanical properties (such as the stiffness due to the HAp%) coupled with a good biomimetic component (collagen) are the parameters to set up in composite scaffolds design for bone tissue engineering. Copyright © 2013 Wiley Periodicals, Inc.

Development of scaffold architectures and heterotypic cell systems for hepatocyte transplantation

NASA Astrophysics Data System (ADS)

Alzebdeh, Dalia Abdelrahim

In vitro assembly of functional liver tissue is needed to enable the transplantation of tissue-engineered livers. In addition, there is an increasing demand for in vitro models that replicate complex events occurring in the liver. However, tissue engineering of sizable implantable liver systems is currently limited by the difficulty of assembling three dimensional hepatocyte cultures of a useful size, while maintaining full cell viability, an issue which is closely related to the high metabolic rate of hepatocytes. In this study, we first compared two designs of highly porous chitosan-heparin scaffolds seeded with hepatocytes in dynamic perfusion bioreactor systems. The aim was to promote cell seeding efficiency by effectively entrapping 100 million hepatocytes at high density. We found that scaffolds with radially tapering pore architecture had highly efficient cell entrapment that maximized donor hepatocyte utilization, compared to alternate pore structures. Hepatocytes showed higher seeding efficiency and metabolic function when seeded as single cell suspensions as opposed to pre-formed, 100microm aggregates. Seeding efficiency was found to increase with flow rate, with single cell and aggregate suspension exhibiting different optimal flow rates. However, metabolic performance results indicated significant shear damage to cells at high efficiency flow rates. To better maintain hepatocyte basement membrane and cell polarity, spheroid co-cultures with mesenchymal stem cells (MSC) were investigated. Hepatocytes and MSCs were seeded in three different architectures in an effort to optimize the spatial arrangement of the two cell types. MSC co-culture greatly enhanced hepatocyte metabolic function in agitated cultures. Interestingly, the effects of diffusion limitations in spheroid culture, coupled with shear damage and subsequent removal of outer hepatocyte layers produced a defined oscillation of urea production rates in certain co-culture arrangements. A mathematical model of urea synthesis in shear-exposed, co-culture spheroids reproduced the metabolic oscillations observed. This result together with culture observations suggests that MSCs can provide both physiological support and some direct shear protection to hepatocytes in perfused or shear-exposed culture environments. Finally, in order to reduce hepatocyte exposure to excessive shear forces in perfused scaffolds, a modular scaffold design based on polyelectrolyte fiber encapsulation was explored. Scaffolds with uniformly distributed, shear protected cells were achieved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huguet, Florence; Department of Radiation Oncology, Hôpitaux Universitaires Paris Est, Hôpital Tenon, University Paris VI, Paris; Yorke, Ellen D.

Purpose: To assess intrafractional positional variations of pancreatic tumors using 4-dimensional computed tomography (4D-CT), their impact on gross tumor volume (GTV) coverage, the reliability of biliary stent, fiducial seeds, and the real-time position management (RPM) external marker as tumor surrogates for setup of respiratory gated treatment, and to build a correlative model of tumor motion. Methods and Materials: We analyzed the respiration-correlated 4D-CT images acquired during simulation of 36 patients with either a biliary stent (n=16) or implanted fiducials (n=20) who were treated with RPM respiratory gated intensity modulated radiation therapy for locally advanced pancreatic cancer. Respiratory displacement relative to end-exhalationmore » was measured for the GTV, the biliary stent, or fiducial seeds, and the RPM marker. The results were compared between the full respiratory cycle and the gating interval. Linear mixed model was used to assess the correlation of GTV motion with the potential surrogate markers. Results: The average ± SD GTV excursions were 0.3 ± 0.2 cm in the left-right direction, 0.6 ± 0.3 cm in the anterior-posterior direction, and 1.3 ± 0.7 cm in the superior-inferior direction. Gating around end-exhalation reduced GTV motion by 46% to 60%. D95% was at least the prescribed 56 Gy in 76% of patients. GTV displacement was associated with the RPM marker, the biliary stent, and the fiducial seeds. The correlation was better with fiducial seeds and with biliary stent. Conclusions: Respiratory gating reduced the margin necessary for radiation therapy for pancreatic tumors. GTV motion was well correlated with biliary stent or fiducial seed displacements, validating their use as surrogates for daily assessment of GTV position during treatment. A patient-specific internal target volume based on 4D-CT is recommended both for gated and not-gated treatment; otherwise, our model can be used to predict the degree of GTV motion.« less

Synthetic scaffold coating with adeno-associated virus encoding BMP2 to promote endogenous bone repair.

PubMed

Dupont, Kenneth M; Boerckel, Joel D; Stevens, Hazel Y; Diab, Tamim; Kolambkar, Yash M; Takahata, Masahiko; Schwarz, Edward M; Guldberg, Robert E

2012-03-01

Biomaterial scaffolds functionalized to stimulate endogenous repair mechanisms via the incorporation of osteogenic cues offer a potential alternative to bone grafting for the treatment of large bone defects. We first quantified the ability of a self-complementary adeno-associated viral vector encoding bone morphogenetic protein 2 (scAAV2.5-BMP2) to enhance human stem cell osteogenic differentiation in vitro. In two-dimensional culture, scAAV2.5-BMP2-transduced human mesenchymal stem cells (hMSCs) displayed significant increases in BMP2 production and alkaline phosphatase activity compared with controls. hMSCs and human amniotic-fluid-derived stem cells (hAFS cells) seeded on scAAV2.5-BMP2-coated three-dimensional porous polymer Poly(ε-caprolactone) (PCL) scaffolds also displayed significant increases in BMP2 production compared with controls during 12 weeks of culture, although only hMSC-seeded scaffolds displayed significantly increased mineral formation. PCL scaffolds coated with scAAV2.5-BMP2 were implanted into critically sized immunocompromised rat femoral defects, both with or without pre-seeding of hMSCs, representing ex vivo and in vivo gene therapy treatments, respectively. After 12 weeks, defects treated with acellular scAAV2.5-BMP2-coated scaffolds displayed increased bony bridging and had significantly higher bone ingrowth and mechanical properties compared with controls, whereas defects treated with scAAV2.5-BMP2 scaffolds pre-seeded with hMSCs failed to display significant differences relative to controls. When pooled, defect treatment with scAAV2.5-BMP2-coated scaffolds, both with or without inclusion of pre-seeded hMSCs, led to significant increases in defect mineral formation at all time points and increased mechanical properties compared with controls. This study thus presents a novel acellular bone-graft-free endogenous repair therapy for orthotopic tissue-engineered bone regeneration.

Maskless nano-implant of 20 keV Ga+ in bulk Si(1 0 0) substrates

NASA Astrophysics Data System (ADS)

Milazzo, R. G.; D'Arrigo, G.; Mio, A. M.; Rimini, E.; Spinella, C.; Peto, L.; Nadzeyka, A.; Bauerdick, S.

2014-12-01

Multidirectional SPEG (Solid Phase Epitaxial Growth) of silicon has been investigated in micro and nanoamorphous structures generated on a crystalline substrate by a nano-sized ion beam, Gaussian shaped and with a standard deviation of about 5 nm. The 20 keV Ga+ ions were implanted at a fluence of 5 × 1014 ions cm-2 in a bulk Si(1 0 0) single crystal. Two structures were used for the implants: circular regions of 100 nm and 1 μm diameters respectively and straight lines 10 nm in width and few microns in length along (1 0 0) or (1 1 0) directions. The lateral spread of ions has been taken into account in the damage estimation. Transmission Electron Microscopy indicates that the structures are made of an amorphous core surrounded by a defective and filamentary shell. The recovery of the damaged outer regions promptly occurs during the early stages of the thermal treatment at 500-600 °C for all the structures. By prolonging annealing time, re-crystallization of the amorphous cores is achieved too by the movement of the underneath crystal-amorphous interface. The re-growth is almost defects free when the contribution of the crystalline seed below the structures is present, defective and twin mediated if it misses as in the thinnest regions of the specimen.

Casting inorganic structures with DNA molds

DOE PAGES

Sun, Wei; Boulais, Etienne; Hakobyan, Yera; ...

2014-10-09

Here we report a general strategy for designing and synthesizing inorganic nanostructures with arbitrarily prescribed three-dimensional shapes. Computationally designed DNA strands self-assemble into a stiff “nano-mold” that contains a user-specified three-dimensional cavity and encloses a nucleating gold “seed”. Under mild conditions, this seed grows into a larger cast structure that fills and thus replicates the cavity. We synthesized a variety of nanoparticles with three nanometer resolution: three distinct silver cuboids with three independently tunable dimensions, silver and gold nanoparticles with diverse cross sections, and composite structures with homo-/heterogeneous components. The designer equilateral silver triangular and spherical nanoparticles exhibited plasmonic propertiesmore » consistent with electromagnetism-based simulations. Our framework is generalizable to more complex geometries and diverse inorganic materials, offering a range of applications in biosensing, photonics, and nanoelectronics.« less

Arabidopsis ARGONAUTE7 selects miR390 through multiple checkpoints during RISC assembly

PubMed Central

Endo, Yayoi; Iwakawa, Hiro-oki; Tomari, Yukihide

2013-01-01

Plant ARGONAUTE7 (AGO7) assembles RNA-induced silencing complex (RISC) specifically with miR390 and regulates the auxin-signalling pathway via production of TAS3 trans-acting siRNAs (tasiRNAs). However, how AGO7 discerns miR390 among other miRNAs remains unclear. Here, we show that the 5′ adenosine of miR390 and the central region of miR390/miR390* duplex are critical for the specific interaction with AGO7. Furthermore, despite the existence of mismatches in the seed and central regions of the duplex, cleavage of the miR390* strand is required for maturation of AGO7–RISC. These findings suggest that AGO7 uses multiple checkpoints to select miR390, thereby circumventing promiscuous tasiRNA production. PMID:23732541

Metallic Nanostructures Based on DNA Nanoshapes

PubMed Central

Shen, Boxuan; Tapio, Kosti; Linko, Veikko; Kostiainen, Mauri A.; Toppari, Jari Jussi

2016-01-01

Metallic nanostructures have inspired extensive research over several decades, particularly within the field of nanoelectronics and increasingly in plasmonics. Due to the limitations of conventional lithography methods, the development of bottom-up fabricated metallic nanostructures has become more and more in demand. The remarkable development of DNA-based nanostructures has provided many successful methods and realizations for these needs, such as chemical DNA metallization via seeding or ionization, as well as DNA-guided lithography and casting of metallic nanoparticles by DNA molds. These methods offer high resolution, versatility and throughput and could enable the fabrication of arbitrarily-shaped structures with a 10-nm feature size, thus bringing novel applications into view. In this review, we cover the evolution of DNA-based metallic nanostructures, starting from the metallized double-stranded DNA for electronics and progress to sophisticated plasmonic structures based on DNA origami objects. PMID:28335274

Graphene oxide scaffold accelerates cellular proliferative response and alveolar bone healing of tooth extraction socket.

PubMed

Nishida, Erika; Miyaji, Hirofumi; Kato, Akihito; Takita, Hiroko; Iwanaga, Toshihiko; Momose, Takehito; Ogawa, Kosuke; Murakami, Shusuke; Sugaya, Tsutomu; Kawanami, Masamitsu

2016-01-01

Graphene oxide (GO) consisting of a carbon monolayer has been widely investigated for tissue engineering platforms because of its unique properties. For this study, we fabricated a GO-applied scaffold and assessed the cellular and tissue behaviors in the scaffold. A preclinical test was conducted to ascertain whether the GO scaffold promoted bone induction in dog tooth extraction sockets. For this study, GO scaffolds were prepared by coating the surface of a collagen sponge scaffold with 0.1 and 1 µg/mL GO dispersion. Scaffolds were characterized using scanning electron microscopy (SEM), physical testing, cell seeding, and rat subcutaneous implant testing. Then a GO scaffold was implanted into a dog tooth extraction socket. Histological observations were made at 2 weeks postsurgery. SEM observations show that GO attached to the surface of collagen scaffold struts. The GO scaffold exhibited an interconnected structure resembling that of control subjects. GO application improved the physical strength, enzyme resistance, and adsorption of calcium and proteins. Cytocompatibility tests showed that GO application significantly increased osteoblastic MC3T3-E1 cell proliferation. In addition, an assessment of rat subcutaneous tissue response revealed that implantation of 1 µg/mL GO scaffold stimulated cellular ingrowth behavior, suggesting that the GO scaffold exhibited good biocompatibility. The tissue ingrowth area and DNA contents of 1 µg/mL GO scaffold were, respectively, approximately 2.5-fold and 1.4-fold greater than those of the control. Particularly, the infiltration of ED2-positive (M2) macrophages and blood vessels were prominent in the GO scaffold. Dog bone-formation tests showed that 1 µg/mL GO scaffold implantation enhanced bone formation. New bone formation following GO scaffold implantation was enhanced fivefold compared to that in control subjects. These results suggest that GO was biocompatible and had high bone-formation capability for the scaffold. The GO scaffold is expected to be beneficial for bone tissue engineering therapy.

45S5-Bioglass®-Based 3D-Scaffolds Seeded with Human Adipose Tissue-Derived Stem Cells Induce In Vivo Vascularization in the CAM Angiogenesis Assay

PubMed Central

Handel, Marina; Hammer, Timo R.; Nooeaid, Patcharakamon; Boccaccini, Aldo R.

2013-01-01

Poor vascularization is the key limitation for long-term acceptance of large three-dimensional (3D) tissue engineering constructs in regenerative medicine. 45S5 Bioglass® was investigated given its potential for applications in bone engineering. Since native Bioglass® shows insufficient angiogenic properties, we used a collagen coating, to seed human adipose tissue-derived stem cells (hASC) confluently onto 3D 45S5 Bioglass®-based scaffolds. To investigate vascularization by semiquantitative analyses, these biofunctionalized scaffolds were then subjected to in vitro human umbilical vein endothelial cells formation assays, and were also investigated in the chorioallantoic membrane (CAM) angiogenesis model, an in vivo angiogenesis assay, which uses the CAM of the hen's egg. In their native, nonbiofunctionalized state, neither Bioglass®-based nor biologically inert fibrous polypropylene control scaffolds showed angiogenic properties. However, significant vascularization was induced by hASC-seeded scaffolds (Bioglass® and polypropylene) in the CAM angiogenesis assay. Biofunctionalized scaffolds also showed enhanced tube lengths, compared to unmodified scaffolds or constructs seeded with fibroblasts. In case of biologically inert hernia meshes, the quantification of vascular endothelial growth factor secretion as the key angiogenic stimulus strongly correlated to the tube lengths and vessel numbers in all models. This correlation proved the CAM angiogenesis assay to be a suitable semiquantitative tool to characterize angiogenic effects of larger 3D implants. In addition, our results suggest that combinations of suitable scaffold materials, such as 45S5 Bioglass®, with hASC could be a promising approach for future tissue engineering applications. PMID:23837884

Lung-Derived Microscaffolds Facilitate Diabetes Reversal after Mouse and Human Intraperitoneal Islet Transplantation.

PubMed

Abualhassan, Nasser; Sapozhnikov, Lena; Pawlick, Rena L; Kahana, Meygal; Pepper, Andrew R; Bruni, Antonio; Gala-Lopez, Boris; Kin, Tatsuya; Mitrani, Eduardo; Shapiro, A M James

2016-01-01

There is a need to develop three-dimensional structures that mimic the natural islet tissue microenvironment. Endocrine micro-pancreata (EMPs) made up of acellular organ-derived micro-scaffolds seeded with human islets have been shown to express high levels of key beta-cell specific genes and secrete quantities of insulin per cell similar to freshly isolated human islets in a glucose-regulated manner for more than three months in vitro. The aim of this study was to investigate the capacity of EMPs to restore euglycemia in vivo after transplantation of mouse or human islets in chemically diabetic mice. We proposed that the organ-derived EMPs would restore the extracellular components of the islet microenvironment, generating favorable conditions for islet function and survival. EMPs seeded with 500 mouse islets were implanted intraperitoneally into streptozotocin-induced diabetic mice and reverted diabetes in 67% of mice compared to 13% of controls (p = 0.018, n = 9 per group). Histological analysis of the explanted grafts 60 days post-transplantation stained positive for insulin and exhibited increased vascular density in a collagen-rich background. EMPs were also seeded with human islets and transplanted into the peritoneal cavity of immune-deficient diabetic mice at 250 islet equivalents (IEQ), 500 IEQ and 1000 IEQ. Escalating islet dose increased rates of normoglycemia (50% of the 500 IEQ group and 75% of the 1000 IEQ group, n = 3 per group). Human c-peptide levels were detected 90 days post-transplantation in a dose-response relationship. Herein, we report reversal of diabetes in mice by intraperitoneal transplantation of human islet seeded on EMPs with a human islet dose as low as 500 IEQ.