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Sample records for allograft cellular bone

  1. Bone graft substitute: allograft and xenograft.

    PubMed

    Shibuya, Naohiro; Jupiter, Daniel C

    2015-01-01

    Rapid bone graft incorporation for structural rigidity is essential. Early range of motion, exercise, and weight-bearing are keys to rehabilitation. Structural and nonstructural bone grafts add length, height, and volume to alter alignment, function, and appearance. Bone graft types include: corticocancellous autograft, allograft, xenograft, and synthetic graft. Autogenic grafts are harvested from the patient, less likely to be rejected, and more likely to be incorporated; however, harvesting adds a procedure and donor site complication is common. Allografts, xenografts, and synthetic grafts eliminate secondary procedures and donor site complications; however, rejection and slower incorporation can occur.

  2. Arthroscopic meniscal allograft transplantation without bone plugs.

    PubMed

    Alentorn-Geli, Eduard; Seijas Vázquez, Roberto; García Balletbó, Montserrat; Álvarez Díaz, Pedro; Steinbacher, Gilbert; Cuscó Segarra, Xavier; Rius Vilarrubia, Marta; Cugat Bertomeu, Ramón

    2011-02-01

    Partial or total meniscectomy are common procedures performed at Orthopedic Surgery departments. Despite providing a great relief of pain, it has been related to early onset knee osteoarthritis. Meniscal allograft transplantation has been proposed as an alternative to meniscectomy. The purposes of this study were to describe an arthroscopic meniscal allograft transplantation without bone plugs technique and to report the preliminary results. All meniscal allograft transplantations performed between 2001 and 2006 were approached for eligibility, and a total of 35 patients (involving 37 menisci) were finally engaged in the study. Patients were excluded if they had ipsilateral knee ligament reconstruction or cartilage repair surgery before meniscal transplantation or other knee surgeries after the meniscal transplantation. Scores on Lysholm, Subjective IKDC Form, and Visual Analogue Scale (VAS) scale for pain were obtained at a mean follow-up of 38.6 months and compared to pre-operative data. Data on chondral lesions were obtained during the arthroscopic procedure and through imaging (radiographs and MRI) studies pre-operatively. Two graft failures out of 59 transplants (3.4%) were found. Daily life accidents were responsible for all graft failures. Significant improvements for Lysholm, Subjective IKDC Form, and VAS for pain scores following the meniscal allograft transplantation were found (P < 0.0001). Controlling for chondral lesion, there was no significant interactions for Lysholm (n.s.), Subjective IKDC Form (n.s.), and VAS for pain scores (n.s.). This study demonstrated that an arthroscopic meniscal allograft transplantation without bone plugs improved knee function and symptoms after a total meniscectomy. Improvements were observed independently of the degree of chondral lesion.

  3. Autograft, allograft and bone substitutes in reconstructive orthopedic surgery.

    PubMed

    Chiarello, Eugenio; Cadossi, Matteo; Tedesco, Giuseppe; Capra, Paola; Calamelli, Carlotta; Shehu, Alba; Giannini, Sandro

    2013-10-01

    Reconstruction of bone defects is a challenge for all orthopedic surgeons worldwide; to overcome this problem there are different options: the use of autografts, allografts and bone substitutes (BSs) to enhance and accelerate bone repair. Autografts have excellent biological properties but are associated with morbidity of the donor site and are restricted in volume. Allografts are available in adequate quantity but concerns still remain about the risk of infections, moreover they do not have osteogenetic properties. Bone substitutes have different indications and are very attractive for orthopedic surgeons. The present paper briefly reviews the advantages and disadvantages of autografts, allografts and BSs for bone reconstruction.

  4. PTH promotes allograft integration in a calvarial bone defect

    PubMed Central

    Sheyn, Dmitriy; Yakubovich, Doron Cohn; Kallai, Ilan; Su, Susan; Da, Xiaoyu; Pelled, Gadi; Tawackoli, Wafa; Cook-Weins, Galen; Schwarz, Edward M.; Gazit, Dan; Gazit, Zulma

    2013-01-01

    Allografts may be useful in craniofacial bone repair, although they often fail to integrate with the host bone. We hypothesized that intermittent administration of parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and differentiation, resulting in allograft osseointegration in cranial membranous bones. Calvarial bone defects were created in transgenic mice, in which luciferase is expressed under the control of the osteocalcin promoter. The mice were given implants of allografts with or without daily PTH treatment. Bioluminescence imaging (BLI) was performed to monitor host osteprogenitor differentiation at the implantation site. Bone formation was evaluated with the aid of fluorescence imaging (FLI) and micro–computed tomography (μCT) as well as histological analyses. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the expression of key osteogenic and angiogenic genes. Osteoprogenitor differentiation, as detected by BLI, in mice treated with an allograft implant and PTH was over 2-fold higher than those in mice treated with an allograft implant without PTH. FLI also demonstrated that the bone mineralization process in PTH-treated allografts was significantly higher than that in untreated allografts. The μCT scans revealed a significant increase in bone formation in Allograft + PTH–treated mice comparing to Allograft + PBS treated mice. The osteogenic genes osteocalcin (Oc/Bglap) and integrin binding sialoprotein (Ibsp) were upregulated in the Allograft + PTH–treated animals. In summary, PTH treatment enhances osteoprogenitor differentiation and augments bone formation around structural allografts. The precise mechanism is not clear, but we show that infiltration pattern of mast cells, associated with the formation of fibrotic tissue, in the defect site is significantly affected by the PTH treatment. PMID:24131143

  5. Porous Allograft Bone Scaffolds: Doping with Strontium

    PubMed Central

    Zhao, Yantao; Guo, Dagang; Hou, Shuxun; Zhong, Hongbin; Yan, Jun; Zhang, Chunli; Zhou, Ying

    2013-01-01

    Strontium (Sr) can promote the process of bone formation. To improve bioactivity, porous allograft bone scaffolds (ABS) were doped with Sr and the mechanical strength and bioactivity of the scaffolds were evaluated. Sr-doped ABS were prepared using the ion exchange method. The density and distribution of Sr in bone scaffolds were investigated by inductively coupled plasma optical emission spectrometry (ICP-OES), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray spectroscopy (EDS). Controlled release of strontium ions was measured and mechanical strength was evaluated by a compressive strength test. The bioactivity of Sr-doped ABS was investigated by a simulated body fluid (SBF) assay, cytotoxicity testing, and an in vivo implantation experiment. The Sr molar concentration [Sr/(Sr+Ca)] in ABS surpassed 5% and Sr was distributed nearly evenly. XPS analyses suggest that Sr combined with oxygen and carbonate radicals. Released Sr ions were detected in the immersion solution at higher concentration than calcium ions until day 30. The compressive strength of the Sr-doped ABS did not change significantly. The bioactivity of Sr-doped material, as measured by the in vitro SBF immersion method, was superior to that of the Sr-free freeze-dried bone and the Sr-doped material did not show cytotoxicity compared with Sr-free culture medium. The rate of bone mineral deposition for Sr-doped ABS was faster than that of the control at 4 weeks (3.28±0.23 µm/day vs. 2.60±0.20 µm/day; p<0.05). Sr can be evenly doped into porous ABS at relevant concentrations to create highly active bone substitutes. PMID:23922703

  6. Porous allograft bone scaffolds: doping with strontium.

    PubMed

    Zhao, Yantao; Guo, Dagang; Hou, Shuxun; Zhong, Hongbin; Yan, Jun; Zhang, Chunli; Zhou, Ying

    2013-01-01

    Strontium (Sr) can promote the process of bone formation. To improve bioactivity, porous allograft bone scaffolds (ABS) were doped with Sr and the mechanical strength and bioactivity of the scaffolds were evaluated. Sr-doped ABS were prepared using the ion exchange method. The density and distribution of Sr in bone scaffolds were investigated by inductively coupled plasma optical emission spectrometry (ICP-OES), X-ray photoelectron spectroscopy (XPS), and energy-dispersive X-ray spectroscopy (EDS). Controlled release of strontium ions was measured and mechanical strength was evaluated by a compressive strength test. The bioactivity of Sr-doped ABS was investigated by a simulated body fluid (SBF) assay, cytotoxicity testing, and an in vivo implantation experiment. The Sr molar concentration [Sr/(Sr+Ca)] in ABS surpassed 5% and Sr was distributed nearly evenly. XPS analyses suggest that Sr combined with oxygen and carbonate radicals. Released Sr ions were detected in the immersion solution at higher concentration than calcium ions until day 30. The compressive strength of the Sr-doped ABS did not change significantly. The bioactivity of Sr-doped material, as measured by the in vitro SBF immersion method, was superior to that of the Sr-free freeze-dried bone and the Sr-doped material did not show cytotoxicity compared with Sr-free culture medium. The rate of bone mineral deposition for Sr-doped ABS was faster than that of the control at 4 weeks (3.28 ± 0.23 µm/day vs. 2.60 ± 0.20 µm/day; p<0.05). Sr can be evenly doped into porous ABS at relevant concentrations to create highly active bone substitutes. PMID:23922703

  7. Three-dimensional virtual bone bank system workflow for structural bone allograft selection: a technical report.

    PubMed

    Ritacco, Lucas Eduardo; Farfalli, German Luis; Milano, Federico Edgardo; Ayerza, Miguel Angel; Muscolo, Domingo Luis; Aponte-Tinao, Luis

    2013-01-01

    Structural bone allograft has been used in bone defect reconstruction during the last fifty years with acceptable results. However, allograft selection methods were based on 2-dimensional templates using X-rays. Thanks to preoperative planning platforms, three-dimensional (3D) CT-derived bone models were used to define size and shape comparison between host and donor. The purpose of this study was to describe the workflow of this virtual technique in order to explain how to choose the best allograft using a virtual bone bank system. We measured all bones in a 3D virtual environment determining the best match. The use of a virtual bone bank system has allowed optimizing the allograft selection in a bone bank, providing more information to the surgeons before surgery. In conclusion, 3D preoperative planning in a virtual environment for allograft selection is an important and helpful tool in order to achieve a good match between host and donor.

  8. Combining bisphosphonates with allograft bone for implant fixation.

    PubMed

    Mathijssen, N M C; Buma, P; Hannink, G

    2014-09-01

    The aim of this review was to discuss the current state of research of combining bisphosphonates with allograft bone for implant fixation. The allograft bone can only be reached by the bisphosphonate once it has been revascularized. However, this can be circumvented by local administration of bisphosphonates. Several animal studies showed that local application of bisphosphonates might protect the graft from resorption. There seems to be an optimum concentration for local application, however, this optimum varies for all different bisphosphonates. It can be concluded that local administration of bisphosphonates might play an important role in improving stability after surgery in which a prosthesis is combined with allograft bone to restore bony defects, however caution should be taken when extrapolating results of animal research to the human clinical situation. More research is needed to study the effect of local bisphophonate use in humans and to study possible side effects.

  9. New bone formation by murine osteoprogenitor cells cultured on corticocancellous allograft bone.

    PubMed

    Nelson, Ehren R; Huang, Zhinong; Ma, Ting; Lindsey, Derek; Jacobs, Christopher; Smith, Robert L; Goodman, Stuart B

    2008-12-01

    The gold standard for bone grafting in orthopedics is autograft, however autograft has a limited supply and is associated with significant morbidity at the harvest site. One alternative, allograft bone, provides an osteoconductive scaffold, is in less limited supply, and it does not require a harvest from the patient. However, allograft lacks both osteogenic cells and osteoinductive proteins that make autograft bone so advantageous. This study provides a model to investigate strategies for augmentation of corticocancellous allograft bone discs with bone marrow-derived osteoprogenitor cells (OPCs) plus exogenous growth factors in vitro. In this model, allograft bone discs were created by cutting 1-mm thick slices from the distal femur and proximal tibia of euthanized mice. The allografts were sterilized and scanned by micro-computed tomography (microCT) to provide the pre-culture graft volume and trabecular characteristics. The discs were then seeded with OPCs harvested from murine bone marrow. The seeded grafts were placed in organ culture until harvest, after which they were re-scanned by microCT and the data compared to the corresponding pre-culture data. In addition, bone morphogenetic protein-7 (BMP-7, also know as osteogenic protein-1 or OP-1), basic fibroblast growth factor (bFGF), and OP-1 combined with bFGF were added on a daily basis to the cultures. After final microCT scanning, all grafts were sectioned and evaluated histologically after hematoxylin and eosin (H&E) staining. microCT scans of cultured allografts with cells at 3, 5, and 9 weeks showed a time-dependent, statistically significant increase in bone volume. The trabecular thickness (Tb.Th.) of grafts, from both groups that were augmented with OP-1, showed a statistically significant increase in trabecular thickness of allografts with OPCs. These data suggest that bone marrow-derived OPCs adhere to, and produce, new bone on corticocancellous allograft in vitro. When exogenous OP-1 is added to

  10. Rinsing of allograft bone does not improve implant fixation

    PubMed Central

    2013-01-01

    Background and purpose Impacted morselized allograft bone is a well-established method for reconstructing bone defects at revision surgery. However, the incorporation of bone graft is not always complete, and a substantial volume of fibrous tissue has been found around grafted implants. We hypothesized that rinsing the bone graft may improve graft incorporation by removing the majority of immunogenic factors present in blood, marrow, and fat. Methods We implanted a cylindrical (10- × 6-mm) porous-coated Ti implant into each proximal tibia of 12 dogs. The implants were surrounded by a 2.5-mm gap into which morselized fresh frozen allograft bone was impacted. The bone graft was either (1) untreated or (2) rinsed in 37°C saline for 3 × 1 min. After 4 weeks, the animals were killed and implant fixation was evaluated by mechanical push-out and histomorphometry. Results The groups (rinsed vs. control) were similar regarding mechanical implant fixation (mean (SD)): shear strength (MPa) 2.7 (1.0) vs. 2.9 (1.2), stiffness (MPa/mm) 15 (6.7) vs. 15 (5.6), and energy absorption (kJ/m2) 0.5 (0.2) vs. 0.6 (0.4), The same was evident for the new bone formation on the implant surface and around the implant: ongrowth (%) 6 vs. 7 and ingrowth (%) 9 vs. 9. Although not statistically significant, a 61% reduction in fibrous tissue ongrowth and 50% reduction in ingrowth were found in the rinsed group. Interpretation Within the limits of this experimental model, we did not detect any benefits of rinsing morselized allograft bone prior to impaction grafting. PMID:23621809

  11. Implant Site Development Using Ti-Mesh and Cellular Allograft in the Esthetic Zone for Restorative-Driven Implant Placement: A Case Report.

    PubMed

    Levine, Robert A; McAllister, Bradley S

    2016-01-01

    This article presents a case report of implant site development in a healthy, nonsmoking 62-year-old man using titanium mesh (Ti-mesh) in conjunction with human cellular allograft for ridge augmentation of a type 4 alveolar ridge defect. The patient presented initially with a severely periodontally abscessed maxillary right central incisor probing to the apex. The tooth was extracted, and after 8 weeks a bone reconstructive procedure was completed using a well-stabilized Ti-mesh and cellular allograft that was covered with a quickly resorbing collagen matrix. After 7 months of undisturbed healing, cone beam computed tomographic evaluation demonstrated a horizontal bone increase of 7 mm and a vertical bone increase of 2.3 mm. This case report demonstrates the benefits of predictable regenerative space maintenance using Ti-mesh in conjunction with a cellular allograft to allow for prosthetically driven implant placement in the esthetic zone. PMID:27100807

  12. Inability of donor total body irradiation to prolong survival of vascularized bone allografts: Experimental study in the rat

    SciTech Connect

    Gonzalez del Pino, J.; Benito, M.; Randolph, M.A.; Weiland, A.J. )

    1990-07-01

    At the present time, the toxic side effects of recipient immunosuppression cannot be justified for human non-vital organ transplantation. Total body irradiation has proven effective in ablating various bone-marrow-derived and endothelial immunocompetent cellular populations, which are responsible for immune rejection against donor tissues. Irradiation at a dose of 10 Gy was given to donor rats six days prior to heterotopic transplantation of vascularized bone allografts to host animals. Another group of recipient rats also received a short-term (sixth to fourteenth day after grafting), low dose of cyclosporine. Total body irradiation was able merely to delay rejection of grafts across a strong histocompatibility barrier for one to two weeks, when compared to nonirradiated allografts. The combination of donor irradiation plus cyclosporine did not delay the immune response, and the rejection score was similar to that observed for control allografts. Consequently, allograft viability was quickly impaired, leading to irreversible bone damage. This study suggest that 10 Gy of donor total body irradiation delivered six days prior to grafting cannot circumvent the immune rejection in a vascularized allograft of bone across a strong histocompatibility barrier.

  13. Molecular profile of osteoprogenitor cells seeded on allograft bone.

    PubMed

    Smith, Kierann E; Huang, Zhinong; Ma, Ting; Irani, Afraaz; Lane Smith, R; Goodman, Stuart B

    2011-10-01

    In order to optimize and modulate bone formation it is essential to understand the expression patterns of key bone-specific growth factors, as osteoprogenitor cells undergo the processes of proliferation, differentiation and maturation. This study reports the sequential expression of bone-related growth and transcription factors when bone marrow-derived osteoprogenitor cells from C57BL mice were cultured on allograft bone discs. Mineralization and osteocalcin protein levels were used to track osteogenic differentiation and maturation. Bone-related growth factors, such as Bmp-2, Bmp-7, Ctnnb-1, Fgf-2, Igf-1, Vegf-a and Tgf-β1, and transcription factors, such as Runx-2 and osteocalcin, were examined by enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). Total density of mineralized bone was significantly increased 7.6 ± 0.7% in allografts cultured with cells, compared with a 0.5 ± 2.0% increase in the controls without cells (p < 0.01). Osteocalcin protein levels peaked at day 4. Protein expression showed peaks of BMP-2 and TGF-β1 on day 2, with VEGF peaking on day 8, and IGF-1 decreasing on day 2. mRNA for Pdgf-a peaked on day 2; Bmp-2 on days 4 and 16; Ctnnb-1 on days 8 and 20; Vegf-a, Fgf-2, Runx-2 and Igf-1 on day 12; Tgf-β1 on day 16; and Pdgf-b on day 20. Osteogenic growth factors correlated with Runx-2 and Ctnnb-1, whereas a predominant vascular growth factor, Vegf-a, did not follow this pattern. Specific bone-related genes and proteins were expressed in a time-dependent manner when osteoprogenitor cells were cultured on cortico-cancellous bone discs in vitro. PMID:21953868

  14. Banking of massive osteoarticular and intercalary bone allografts--12 years' experience.

    PubMed

    Malinin, T I; Martinez, O V; Brown, M D

    1985-01-01

    Preparation and banking of massive osteoarticular allografts and intercalary bone allografts have been performed for the past 12 years. Careful selection of donors as well as extensive laboratory studies of the donor and the allograft have virtually eliminated the danger of transmitting disease from the donor to the recipient. The availability of a variety of allografts in the Tissue Bank allows for the selection, on an anatomic basis, of an allograft best suited for a particular recipient. The authors have supplied several hundred allografts to recipients in many institutions on the premise that excision, preparation, banking, and implantation of bone allografts constitute a clinical service. Thus, the surgeon who excises and prepares the allograft assumes a joint responsibility for the care of the recipient with the surgeon who implants the allograft. This establishes a close working relationship, which encourages frequent consultation between the parties concerned. This relationship is of particular importance in the initial evaluation of the patient and in determining which particular allograft will best serve a given patient. The experience at the authors' institution provides a model for a multiinstitutional facility that may serve as a base for discussion of the methodology involved in the excision, preparation, and storage of bone allografts. The costs associated with the operation of such a facility are not inconsiderable, but the cost of individual osteoarticular and intercalary allografts can be brought down by an increase in the efficiency of operation inherent in the processing of allografts from over 100 donors per year. During the past several years, the cost of excising and preparing intercalary allografts has been $600 per implant, while the cost for osteochondral allografts varied between $900 and $1,200. Such a large multiinstitutional facility offers the advantages of readily available allografts and quality control. However, because of the

  15. Guided bone regeneration using an allograft material: review and case presentations.

    PubMed

    Bhola, Monish; Kinaia, Bassam M; Chahine, Katy

    2008-10-01

    Post extraction sites may have residual ridge deformities with insufficient bone present for future implant placement. This presents a challenge to the clinician attempting to obtain optimum results. To predictably augment these areas and obtain aesthetically pleasing results, bone grafting may be required. Guided bone regeneration with an allograft material is a predictable means by which to solve this challenge. This article describes three case presentations utilizing on allograft material for bone regeneration prior to implant placement.

  16. Revision anterior cruciate ligament reconstruction with bone-patellar tendon-bone allograft and extra-articular iliotibial band tenodesis.

    PubMed

    Mascarenhas, Randy; McConkey, Mark O; Forsythe, Brian; Harner, Christopher D

    2015-04-01

    Revision anterior cruciate ligament (ACL) reconstruction is a technically demanding procedure with outcomes that generally fail to reach those seen with primary ACL reconstruction. With most index procedures using autograft tissue, it is not uncommon for allograft tissue to be required for revision ACL reconstruction. Compared with autografts, allografts take longer to incorporate and lead to more episodes of instability. In this article, we describe ipsilateral iliotibial band tenodesis performed to augment use of bone-patellar tendon-bone allograft in revision ACL reconstruction. This technique adds rotational stability to protect the allograft tissue while it incorporates. PMID:25844596

  17. Revision anterior cruciate ligament reconstruction with bone-patellar tendon-bone allograft and extra-articular iliotibial band tenodesis.

    PubMed

    Mascarenhas, Randy; McConkey, Mark O; Forsythe, Brian; Harner, Christopher D

    2015-04-01

    Revision anterior cruciate ligament (ACL) reconstruction is a technically demanding procedure with outcomes that generally fail to reach those seen with primary ACL reconstruction. With most index procedures using autograft tissue, it is not uncommon for allograft tissue to be required for revision ACL reconstruction. Compared with autografts, allografts take longer to incorporate and lead to more episodes of instability. In this article, we describe ipsilateral iliotibial band tenodesis performed to augment use of bone-patellar tendon-bone allograft in revision ACL reconstruction. This technique adds rotational stability to protect the allograft tissue while it incorporates.

  18. Cross-correlative 3D micro-structural investigation of human bone processed into bone allografts.

    PubMed

    Singh, Atul Kumar; Gajiwala, Astrid Lobo; Rai, Ratan Kumar; Khan, Mohd Parvez; Singh, Chandan; Barbhuyan, Tarun; Vijayalakshmi, S; Chattopadhyay, Naibedya; Sinha, Neeraj; Kumar, Ashutosh; Bellare, Jayesh R

    2016-05-01

    Bone allografts (BA) are a cost-effective and sustainable alternative in orthopedic practice as they provide a permanent solution for preserving skeletal architecture and function. Such BA however, must be processed to be disease free and immunologically safe as well as biologically and clinically useful. Here, we have demonstrated a processing protocol for bone allografts and investigated the micro-structural properties of bone collected from osteoporotic and normal human donor samples. In order to characterize BA at different microscopic levels, a combination of techniques such as Solid State Nuclear Magnetic Resonance (ssNMR), Scanning Electron Microscope (SEM), micro-computed tomography (μCT) and Thermal Gravimetric Analysis (TGA) were used for delineating the ultra-structural property of bone. ssNMR revealed the extent of water, collagen fine structure and crystalline order in the bone. These were greatly perturbed in the bone taken from osteoporotic bone donor. Among the processing methods analyzed, pasteurization at 60 °C and radiation treatment appeared to substantially alter the bone integrity. SEM study showed a reduction in Ca/P ratio and non-uniform distribution of elements in osteoporotic bones. μ-CT and MIMICS (Materialize Interactive Medical Image Control System) demonstrated that pasteurization and radiation treatment affects the BA morphology and cause a shift in the HU unit. However, the combination of all these processes restored all-important parameters that are critical for BA integrity and sustainability. Cross-correlation between the various probes we used quantitatively demonstrated differences in morphological and micro-structural properties between BA taken from normal and osteoporotic human donor. Such details could also be instrumental in designing an appropriate bone scaffold. For the best restoration of bone microstructure and to be used as a biomaterial allograft, a step-wise processing method is recommended that preserves all

  19. Bone marrow-derived T lymphocytes responsible for allograft rejection

    SciTech Connect

    Senjanovic, M.; Marusic, M.

    1984-08-01

    Lethally irradiated mice reconstituted with syngeneic bone marrow cells were grafted with allogeneic skin grafts 6-7 weeks after irradiation and reconstitution. Mice with intact thymuses rejected the grafts whereas the mice thymectomized before irradiation and reconstitution did not. Thymectomized irradiated mice (TIR mice) reconstituted with bone marrow cells from donors immune to the allografts rejected the grafts. Bone marrow cells from immunized donors, pretreated with Thy 1.2 antibody and C', did not confer immunity to TIR recipients. To determine the number of T lymphocytes necessary for the transfer of immunity by bone marrow cells from immunized donors, thymectomized irradiated mice were reconstituted with nonimmune bone marrow cells treated with Thy 1.2 antibody and C' and with various numbers of splenic T lymphocytes from nonimmune and immune donors. Allogeneic skin graft rejection was obtained with 10(6) nonimmune or 10(4) immune T cells. The effect of immune T cells was specific: i.e., immune T cells accelerated only rejection of the relevant skin grafts whereas against a third-party skin grafts acted as normal T lymphocytes.

  20. Sterilization effects on the mechanical properties of human bone-patellar tendon-bone allografts.

    PubMed

    Reid, James; Sikka, Robby; Tsoi, William; Narvy, Steven J; Hedman, Thomas; Lee, Thay Q; Vangsness, C Thomas

    2010-04-01

    Novel allograft processing methods are available from tissue banks to decrease disease transmission. This study evaluated the effects of 3 of these techniques on the initial mechanical properties of bone-patellar tendon-bone (BPTB) allografts: (1) aseptic harvest with low-dose radiation processing, (2) BioCleanse Tissue Processing System, and (3) Clearant Process. Ten-mm BPTB allografts were potted in an MTS 858 machine (MTS Systems Corp, Eden Prairie, Minnesota), cycled, and loaded to failure at a strain rate of 100%/s. Data were critically analyzed for graft dimensions and age and sex of donor. The 10th cycle and last cycle stiffness after 1000 cycles were measured at the toe region and at all points. The 2% yield stress (MPa), Young's modulus (MPa), elongation failure (mm), strain fracture (%), ultimate stress (MPa), and toughness (kJ) were measured. Forty-two tendons were tested (15 control, 11 BioCleanse, and 16 Clearant). No statistically significant differences were detected between the groups at their 10th cycle and last cycle stiffness (P>.05). Yield stress ranged from 19 to 28.8 MPa without a statistically significant difference (P>.05). Young's modulus ranged from 178.3 to 213.8 MPa without a statistically significant difference (P>.05). Similarly, elongation to failure, strain to failure, ultimate stress, and toughness showed no statistically significant differences among the 3 groups (P>.05). These processing techniques did not affect the time zero mechanical properties of the BPTB allograft tendons under these testing conditions. Clinical use of allografts should proceed with caution for selected patients.

  1. Controlled Release of Growth Factors on Allograft Bone in vitro

    PubMed Central

    Ryu, WonHyoung; Ren, Peigen; Fasching, Rainer; Goodman, Stuart B.

    2008-01-01

    Allografts are important alternatives to autografts for treating defects after major bone loss. Bone growth factors have both local autocrine and paracrine effects and regulate the growth, proliferation, and differentiation of osteoprogenitor cells. To study the effects of prolonged, continuous, local delivery of growth factors on bone growth, we developed a new microelectromechanical system (MEMS) drug delivery device. Bone marrow cells from mice were seeded on mouse allograft discs and cultured in osteogenic media with osteogenic protein 1 (OP-1) and/or basic fibroblast growth factor (FGF-2) delivered from MEMS devices for 6 weeks. We monitored bone formation by changes of bone volume using micro-CT scanning and release of osteocalcin using ELISA. The data suggest the MEMS devices delivered constant concentrations of OP-1 and FGF-2 to the media. Bone marrow cells grew on the allografts and increased bone volume. Addition of OP-1 increased bone formation whereas FGF-2 decreased bone formation. Local delivery of growth factors over a prolonged period modulated the differentiation of osteoprogenitor cells on allograft bone. PMID:18509711

  2. Management of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow.

    PubMed

    Datta, N K; Das, K P; Alam, M S; Kaiser, M S

    2014-07-01

    Unicameral bone cyst is a common benign bone tumor and most frequent cause of the pathological fracture in children. We have started a prospective study for that treatment of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnated with autogenous bone marrow in the department of Orthopaedics, Bangabandhu Sheikh Mujib Medical University (BSMMU) during May 1999 to April 2012. Aim of this study was to see Freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow a satisfactory graft material in the treatment of unicameral bone cyst as well as factors such as patients age, sex, cyst size and site of lesion influence on cyst healing. A total 35 patients of unicameral bone cyst were operated. In this study out of 35 patients, male were 22(62.86%) and female were 13(37.14). Male Female ratio 22:13(1.70:1) Age of the patients ranging from 2 years 6 month to 20 years, mean age 12.18 years more common 11 years to 20 years 29(82.86%) patients. Common bones sites involvements are proximal end of Humerus 20(57.14%), proximal end of Femur 7(20 %), proximal end of Tibia 3(8.57%), Calcanium 2(5.71%), proximal end of Ulna 1(2.86%), shaft of Radius 1(2.86%) and Phalanx 1(2.86%). Final clinical outcome of unicameral bone cyst treated by thorough curettage of cavity and tightly filled with freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow in which healed (success rate) 88.57% (31) and recurrence rate is 11.43% (4). P value is <0.001. Follow up period was 6 month to 11 years. From our study it was realized that freeze dried radiation sterilized bone allograft impregnated with autogenous bone marrow is useful graft material for healing of the lesional area as well as restoring structural integrity for the treatment of unicameral bone cyst.

  3. Arthroscopically assisted medial meniscal allograft transplantation using a modified bone plug to facilitate passage: surgical technique.

    PubMed

    Kim, Jin Goo; Lee, Yong Seuk; Lee, Soo Won; Kim, Young Jae; Kong, Doo Hwan; Ko, Min Soo

    2009-07-01

    This article describes a novel medial meniscal allograft transplantation method that permits easy passage of posterior bone plugs and facilitates bone-to-bone healing. With this method, an anterior bone plug with a long cylindrical shape is prepared, and the posterior bone plug is prepared using only a 2-mm deep, flat bone shell containing cancellous material with 6 baseball Ethibond stitches placed around it. The graft is divided into 3 portions, and boundaries of each are marked. Using a posteromedial portal, the posterior bony bed is prepared directly, and the exact anatomic location is visualized. This modified method facilitates graft passage as well as bone-to-bone healing.

  4. Gamma irradiation: effects on biomechanical properties of human bone-patellar tendon-bone allografts.

    PubMed

    Fideler, B M; Vangsness, C T; Lu, B; Orlando, C; Moore, T

    1995-01-01

    Sixty 10-mm bone-patellar tendon-bone allografts from young human donors were placed into four test groups, a control fresh-frozen group and three fresh-frozen irradiated groups. The irradiated groups were exposed to 2.0, 3.0, or 4.0 Mrad of gamma irradiation. The specimens were tested to tensile failure. The initial biomechanical strength of fresh-frozen allografts was reduced up to 15% when compared with fresh-frozen controls after 2.0 Mrad of irradiation. Maximum force, strain energy, modulus, and maximum stress demonstrated a statistically significant reduction after 2.0 Mrad of irradiation (P < 0.01). Stiffness, elongation, and strain were reduced but not with statistical significance. A 10% to 24% and 19% to 46% reduction in all biomechanical properties were found after 3.0 (P < 0.005) and 4.0 (P < 0.0005) Mrad of irradiation, respectively. After irradiation with a 4.0 Mrad dose, the ultimate load was below that of reported values for the human anterior cruciate ligament. It is clinically important to observe and document changes in human ligaments that result from currently used doses of gamma irradiation. The results from this study provide important information regarding the initial biomechanical properties of fresh-frozen human bone-patellar tendon-bone allografts after bacterial sterilization with gamma irradiation. The current accepted dose for sterilization is between 1.5 and 2.5 Mrad. There appeared to be a dose-dependent effect of irradiation on all the biomechanical parameters studied. Four of seven parameters were found to be reduced after 2.0 Mrad of irradiation. Reductions were found in all parameters after 3.0 and 4.0 Mrad of irradiation.

  5. Arthroscopic Meniscal Allograft Transplantation With Soft-Tissue Fixation Through Bone Tunnels

    PubMed Central

    Spalding, Tim; Parkinson, Ben; Smith, Nick A.; Verdonk, Peter

    2015-01-01

    Meniscal allograft transplantation improves clinical outcomes for patients with symptomatic meniscus-deficient knees. We describe an established arthroscopic technique for meniscal allograft transplantation without the need for bone fixation of the meniscal horns. After preparation of the meniscal bed, the meniscus is parachuted into the knee through a silicone cannula and the meniscal horns are fixed with sutures through bone tunnels. The body of the meniscus is then fixed with a combination of all-inside and inside-out sutures. This technique is reliable and reproducible and has clinical outcomes comparable with those of bone plug fixation techniques. PMID:26900554

  6. Biomechanical Evaluation of Posterior Cruciate Ligament Reconstruction With Quadriceps Versus Achilles Tendon Bone Block Allograft

    PubMed Central

    Forsythe, Brian; Haro, Marc S.; Bogunovic, Ljiljana; Collins, Michael J.; Arns, Thomas A.; Trella, Katie J.; Shewman, Elizabeth F.; Verma, Nikhil N.; Bach, Bernard R.

    2016-01-01

    Background: Long-term studies of posterior cruciate ligament (PCL) reconstruction suggest that normal stability is not restored in the majority of patients. The Achilles tendon allograft is frequently utilized, although recently, the quadriceps tendon has been introduced as an alternative option due to its size and high patellar bone density. Purpose/Hypothesis: The purpose of this study was to compare the biomechanical strength of PCL reconstructions using a quadriceps versus an Achilles allograft. The hypothesis was that quadriceps bone block allograft has comparable mechanical properties to those of Achilles bone block allograft. Study Design: Controlled laboratory study. Methods: Twenty-nine fresh-frozen cadaveric knees were assigned to 1 of 3 groups: (1) intact PCL, (2) PCL reconstruction with Achilles tendon allograft, or (3) PCL reconstruction with quadriceps tendon allograft. After reconstruction, all supporting capsular and ligamentous tissues were removed. Posterior tibial translation was measured at neutral and 20° external rotation. Each specimen underwent a preload, 2 cyclic loading protocols of 500 cycles, then load to failure. Results: Construct creep deformation was significantly lower in the intact group compared with both Achilles and quadriceps allograft (P = .008). The intact specimens reached the greatest ultimate load compared with both reconstructions (1974 ± 752 N, P = .0001). The difference in ultimate load for quadriceps versus Achilles allograft was significant (P = .048), with the quadriceps group having greater maximum force during failure testing. No significant differences were noted between quadriceps versus Achilles allograft for differences in crosshead excursion during cyclic testing (peak-valley [P-V] extension stretch), creep deformation, or stiffness. Construct stiffness measured during the failure test was greatest in the intact group (117 ± 9 N/mm, P = .0001) compared with the Achilles (43 ± 11 N/mm) and quadriceps (43

  7. Cyclosporine-impregnated allograft bone sterilized with low-temperature plasma.

    PubMed

    Lu, Haibo; Pei, Guoxian; Zhao, Peiran; Liang, Shuangwu; Jin, Dan; Jiang, Shan

    2010-12-01

    Deep-freezing, freeze-drying and gamma (γ)-irradiation have deleterious effects on bone healing and mechanical properties of allograft bones. We tried preparing bone allografts using cyclosporine plus low-temperature-plasma sterilization. To explore the feasibility of this method of preparation, segmental defects in the right radii of rabbits were repaired with cyclosporine-impregnated allograft bones (CABs) sterilized with low-temperature-plasma (in the study group) and deep-frozen/freeze-dried irradiated allograft bones (D/FIABs) (in the control group). X-ray and quantitative histological analysis, peripheral blood T lymphocyte subset analysis and CD₂₅ molecule immunohistochemistry stain, the four-point bending test and safety evaluations were respectively conducted to compare bone-healing, immunosuppression, mechanical properties and safety between the two groups. X-ray scores were higher in the study group than those in the control (p = 0.032). There were significant differences in new bone areas at most repairs in both groups (p < 0.05). There were no significant differences in the percentages of CD₄(+) T, CD₈(+) T, ratios of CD₄(+) T:CD₈(+) T or serum concentrations of GPT/Cr in both groups (p > 0.05). At 16 weeks postoperatively, the density of CD₂₅ molecules in the control group was higher than that in the study group. The ultimate loading in the study group was significantly higher than that in the control (p = 0.048). Bone marrow stromal cells (BMSCs) grew thickly around and on the surface of a cyclosporine-impregnated allograft. Livers and kidneys in the study and control groups remained histologically normal at 7 days postoperatively. These results indicate that the CAB might be a better material than the D/FIAB in terms of bone healing, preservation of mechanical properties and immunosuppression without severe side-effects. PMID:20665654

  8. Impaction grafting with morsellised allograft and tricalcium phosphate-hydroxyapatite: incorporation within ovine metaphyseal bone defects.

    PubMed

    Pratt, J N J; Griffon, D J; Dunlop, D G; Smith, N; Howie, C R

    2002-08-01

    An ovine model was used to investigate the in vivo properties of impacted tricalcium phosphate-hydroxyapatite (TCP-HA) aggregates, varying in chemical composition (ratio of TCP to HA) and particle size distribution (8 versus 3 particle size ranges). All pellets were impacted to a standard compactive effort. Eight sheep underwent implantation of pellets in 4 metaphyseal defects in both rear limbs. Treatment groups consisted of: (1) allograft (clinical control). (2) 50/50 allograft/80% HA/20% TCP in 8 particle size ranges, (3) 50/50 allograft/80% TCP/20% HA in 8 sizes and (4) 50/50 allograft/80% HA/20% TCP in only 3 sizes of particles. Healing of defects was evaluated at 14 weeks with computed tomography, histology and histomorphometry. The computer tomography (CT) density measured in all defects containing synthetic agents was higher than in defects filled with allograft alone (p<0.01). Defects containing 8 sizes of 80% HA/ 20% TCP granules (group 2) achieved lower histological scores and contained less bone than the clinical control (p<0.05), whereas groups 3 and 4 did not differ from the control. Although all synthetic agents were osteoconductive, our results suggest that increasing the ratio of TCP over HA and limiting the number of particle size ranges to 3 instead of 8 improve the performance of impacted aggregates as graft expanders. Evaluation under loading conditions of morsellised allograft expanded with 80% TCP/20% HA (BoneSave) in 3 particle size ranges is warranted.

  9. Ankle arthrodesis fusion rates for mesenchymal stem cell bone allograft versus proximal tibia autograft.

    PubMed

    Anderson, John J; Boone, Joshua J; Hansen, Myron; Brady, Chad; Gough, Adam; Swayzee, Zflan

    2014-01-01

    Ankle arthrodesis is commonly used in the treatment of ankle arthritis. The present study compared mesenchymal stem cell (MSC) bone allografts and proximal tibia autografts as adjuncts in performing ankle arthrodesis. A total of 109 consecutive ankle fusions performed from 2002 to 2008 were evaluated retrospectively. Of the 109 fusions, 24 were excluded from the present study, leaving 85 patients who had undergone ankle arthrodesis. Of the 85 patients, 41 had received a proximal tibia autograft and 44, an MSC bone allograft. These 2 groups were reviewed and compared retrospectively at least 2 years postoperatively for the overall fusion rate, interval to radiographic fusion, and interval to clinical fusion. A modified and adjusted American College of Foot and Ankle Surgeons ankle scale was used to measure patient satisfaction. The overall fusion rate was 84.1% in the MSC bone allograft group and 95.1% in the proximal tibia autograft group (p = .158). The corresponding mean intervals to radiographic fusion were 13.0 ± 2.5 weeks and 11.3 ± 2.8 weeks (p ≤ .001). The interval to clinical fusion was 13.1 ± 2.1 weeks and 11.0 ± 1.5 weeks (p ≤ .001) in the MSC bone allograft and proximal tibia autograft group, respectively. No statistically significant difference was found in the fusion rates between the MSC bone allograft and proximal tibia autograft groups. Also, no statistically significant difference was found between the preoperative and postoperative scores using a modified and adjusted American College of Foot and Ankle Surgeons ankle scale between the 2 groups (p = .41 and p = .44, respectively). A statistically significant delay to radiographic and clinical fusion was present in the MSC bone allograft group compared with the proximal tibia autograft group; however, no difference was found in patient satisfaction. PMID:25158608

  10. Iliac Crest Bone Graft versus Local Autograft or Allograft for Lumbar Spinal Fusion: A Systematic Review

    PubMed Central

    Tuchman, Alexander; Brodke, Darrel S.; Youssef, Jim A.; Meisel, Hans-Jörg; Dettori, Joseph R.; Park, Jong-Beom; Yoon, S. Tim; Wang, Jeffrey C.

    2016-01-01

    Study Design  Systematic review. Objective  To compare the effectiveness and safety between iliac crest bone graft (ICBG) and local autologous bone and allograft in the lumbar spine. Methods  A systematic search of multiple major medical reference databases identified studies evaluating spinal fusion in patients with degenerative joint disease using ICBG, local autograft, or allograft in the thoracolumbar spine. Results  Six comparative studies met our inclusion criteria. A “low” strength of the overall body of evidence suggested no difference in fusion percentages in the lumbar spine between local autograft and ICBG. We found no difference in fusion percentages based on low evidence comparing allograft with ICBG autograft. There were no differences in pain or functional results comparing local autograft or allograft with ICBG autograft. Donor site pain and hematoma/seroma occurred more frequently in ICBG autograft group for lumbar fusion procedures. There was low evidence around the estimate of patients with donor site pain following ICBG harvesting, ranging from 16.7 to 20%. With respect to revision, low evidence demonstrated no difference between allograft and ICBG autograft. There was no evidence comparing patients receiving allograft with local autograft for fusion, pain, functional, and safety outcomes. Conclusion  In the lumbar spine, ICBG, local autograft, and allograft have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes. However, ICBG is associated with an increased risk for donor site-related complications. Significant limitations exist in the available literature when comparing ICBG, local autograft, and allograft for lumbar fusion, and thus ICBG versus other fusion methods necessitates further investigation. PMID:27556001

  11. The revision acetabulum--allograft and bone substitutes: vestigial organs for bone deficiency.

    PubMed

    Callaghan, J J; Liu, S S; Phruetthiphat, O-A

    2014-11-01

    A common situation presenting to the orthopaedic surgeon today is a worn acetabular liner with substantial acetabular and pelvic osteolysis. The surgeon has many options for dealing with osteolytic defects. These include allograft, calcium based substitutes, demineralised bone matrix, or combinations of these options with or without addition of platelet rich plasma. To date there are no clinical studies to determine the efficacy of using bone-stimulating materials in osteolytic defects at the time of revision surgery and there are surprisingly few studies demonstrating the clinical efficacy of these treatment options. Even when radiographs appear to demonstrate incorporation of graft material CT studies have shown that incorporation is incomplete. The surgeon, in choosing a graft material for a surgical procedure must take into account the efficacy, safety, cost and convenience of that material.

  12. Decalcified allograft in repair of lytic lesions of bone: A study to evolve bone bank in developing countries

    PubMed Central

    Gupta, Anil Kumar; Keshav, Kumar; Kumar, Praganesh

    2016-01-01

    Background: The quest for ideal bone graft substitutes still haunts orthopedic researchers. The impetus for this search of newer bone substitutes is provided by mismatch between the demand and supply of autogenous bone grafts. Bone banking facilities such as deep frozen and freeze-dried allografts are not so widely available in most of the developing countries. To overcome the problem, we have used partially decalcified, ethanol preserved, and domestic refrigerator stored allografts which are economical and needs simple technology for procurement, preparation, and preservation. The aim of the study was to assess the radiological and functional outcome of the partially decalcified allograft (by weak hydrochloric acid) in patients of benign lytic lesions of bone. Through this study, we have also tried to evolve, establish, and disseminate the concept of the bone bank. Materials and Methods: 42 cases of lytic lesions of bone who were treated by decalcified (by weak hydrochloric acid), ethanol preserved, allografts were included in this prospective study. The allograft was obtained from freshly amputated limbs or excised femoral heads during hip arthroplasties under strict aseptic conditions. The causes of lytic lesions were unicameral bone cyst (n = 3), aneurysmal bone cyst (n = 3), giant cell tumor (n = 9), fibrous dysplasia (n = 12), chondromyxoid fibroma, chondroma, nonossifying fibroma (n = 1 each), tubercular osteomyelitis (n = 7), and chronic pyogenic osteomyelitis (n = 5). The cavity of the lesion was thoroughly curetted and compactly filled with matchstick sized allografts. Results: Quantitative assessment based on the criteria of Sethi et al. (1993) was done. There was complete assimilation in 27 cases, partial healing in 12 cases, and failure in 3 cases. Functional assessment was also done according to which there were 29 excellent results, 6 good, and 7 cases of failure (infection, recurrence, and nonunion of pathological fracture). We observed that after

  13. Lower Limb Reconstruction with Tibia Allograft after Resection of Giant Aneurysmal Bone Cyst

    PubMed Central

    2016-01-01

    Aneurysmal bone cysts (ABCs) are benign, expansible, nonneoplastic lesions of the bone, characterized by channels of blood and spaces separated by fibrous septa, which occur in young patients and, occasionally, with aggressive behavior. Giant ABC is an uncommon pathological lesion and can be challenging because of the destructive effect of the cyst on the bones and the pressure on the nearby structures, especially on weight-bearing bones. In this scenario, en bloc resection is the mainstay treatment and often demands complex reconstructions. This paper reports a difficult case of an unusual giant aneurysmal bone cyst, which required extensive resection and a knee fusion like reconstruction with tibia allograft. PMID:27413565

  14. Use of frozen cranial vault bone allografts in the repair of extensive cranial bone defects.

    PubMed

    Vanaclocha, V; Bazan, A; Saiz-Sapena, N; Paloma, V; Idoate, M

    1997-01-01

    In cranioplasty complexity is proportional to the size of the detect, particularly if greater than 50 cm2. If the patient's own bone flap is not available, allogenic frozen bone graft can be used instead. Between June 1990 and June 1995 twenty cranioplasties with allogenic frozen bone grafts were performed. Age of patients ranged between 23 and 63 years (average 38.4 years). Male/female ratio was 2:1.7. Size of craniectomy ranged between 65 and 150 cm2 (average 83.3 cm2). Follow-up ranged between 10 and 58 months (average 41 months). Donors were tested to rule out transmissible diseases, infections, sepsis and/or cancer. Bone grafts were removed under aseptic conditions, microbiological cultures were taken, wrapped in a gauze soaked with Gentamicin sulphate and Bacitracin, sealed in three sterilised vinyl plastic bags, and stored in a deep freezer for a minimum of 30 days (range 36-93 days, average 67 days), at a temperature of -80 degrees C. Grafts were placed in the defect after a step was carved on its borders to facilitate the contact between host and graft. Vancomycin 1 g. IV/12 hours and Ceftriaxone 1 g. IV/12 hours were administered for five days. Grafts were covered by means of scalp flaps. Only one required a musculocutaneous free flap. None was exposed, extruded or had to be removed. Plain skull X-ray studies showed progressive remodelling of the grafts. Partial resorption was observed in two (2/20, 10%) and loss of thickness in another 3/20 (15%), but with no changes in the contour. Biopsies were taken in 3/20 (15%) cases at a second surgical procedure. Areas of osteoclastic resorptive activity mixed with others of osteoblastic bone apposition, showed replacement with new bone. We conclude that cranial vault frozen allografts are a good alternative to autologous bone when the latter is absent or not present in sufficient amount. PMID:9265959

  15. Induction of tolerance to cardiac allografts in lethally irradiated rats reconstituted with syngeneic bone marrow

    SciTech Connect

    Hartnett, L.C.

    1983-01-01

    Generally, organ grafts from one individual animal to another are rejected in one-two weeks. However, if the recipients are given Total Body Irradiation (TBI) just prior to grafting, followed by reconstitution of hemopoietic function with syngeneic (recipient-type) bone marrow cells, then vascularized organ grafts are permanently accepted. Initially after irradiation, it is possible to induce tolerance to many strain combinations in rats. This thesis examines the system of TBI as applied to the induction of tolerance in LEW recipients of WF cardiac allografts. These two rat strains are mismatched across the entire major histocompatibility complex. When the LEW recipient are given 860 rads, a WF cardiac allograft and LEW bone marrow on the same day, 60% of the grafts are accepted. Methods employed to improve the rate of graft acceptance include: treating either donor or recipient with small amounts of methotrexate, or waiting until two days after irradiation to repopulate with bone marrow. It seems from these investigations of some of the early events in the induction of tolerance to allografts following TBI and syngeneic marrow reconstitution that an immature cell population in the bone marrow interacts with a radioresistant cell population in the spleen to produce tolerance to completely MHC-mismatched allografts.

  16. Two-Stage Revision Anterior Cruciate Ligament Reconstruction: Bone Grafting Technique Using an Allograft Bone Matrix.

    PubMed

    Chahla, Jorge; Dean, Chase S; Cram, Tyler R; Civitarese, David; O'Brien, Luke; Moulton, Samuel G; LaPrade, Robert F

    2016-02-01

    Outcomes of primary anterior cruciate ligament (ACL) reconstruction have been reported to be far superior to those of revision reconstruction. However, as the incidence of ACL reconstruction is rapidly increasing, so is the number of failures. The subsequent need for revision ACL reconstruction is estimated to occur in up to 13,000 patients each year in the United States. Revision ACL reconstruction can be performed in one or two stages. A two-stage approach is recommended in cases of improper placement of the original tunnels or in cases of unacceptable tunnel enlargement. The aim of this study was to describe the technique for allograft ACL tunnel bone grafting in patients requiring a two-stage revision ACL reconstruction. PMID:27274452

  17. Two-Stage Revision Anterior Cruciate Ligament Reconstruction: Bone Grafting Technique Using an Allograft Bone Matrix.

    PubMed

    Chahla, Jorge; Dean, Chase S; Cram, Tyler R; Civitarese, David; O'Brien, Luke; Moulton, Samuel G; LaPrade, Robert F

    2016-02-01

    Outcomes of primary anterior cruciate ligament (ACL) reconstruction have been reported to be far superior to those of revision reconstruction. However, as the incidence of ACL reconstruction is rapidly increasing, so is the number of failures. The subsequent need for revision ACL reconstruction is estimated to occur in up to 13,000 patients each year in the United States. Revision ACL reconstruction can be performed in one or two stages. A two-stage approach is recommended in cases of improper placement of the original tunnels or in cases of unacceptable tunnel enlargement. The aim of this study was to describe the technique for allograft ACL tunnel bone grafting in patients requiring a two-stage revision ACL reconstruction.

  18. The modified bone-patellar tendon-bone allograft in single-bundle anterior cruciate ligament reconstruction.

    PubMed

    Kang, Huijun; Wang, Fei

    2011-06-01

    Bone-patellar tendon-bone graft has been an attractive option for single-bundle anterior cruciate ligament reconstruction in clinical practice. However, the graft-tunnel mismatch in the proximal part of the tibial tunnel and the ultimate strength after postoperative ligamentization process have been potential problems for the traditional 10-mm wide graft. We modified the traditional bone-patellar tendon-bone allograft to make it double-layer, as an ideal substitute graft for single-bundle anterior cruciate ligament reconstruction with better graft-tunnel match and higher initial graft strength.

  19. Biocompatibility and chemical reaction kinetics of injectable, settable polyurethane/allograft bone biocomposites.

    PubMed

    Page, Jonathan M; Prieto, Edna M; Dumas, Jerald E; Zienkiewicz, Katarzyna J; Wenke, Joseph C; Brown-Baer, Pamela; Guelcher, Scott A

    2012-12-01

    Injectable and settable bone grafts offer significant advantages over pre-formed implants due to their ability to be administered using minimally invasive techniques and to conform to the shape of the defect. However, injectable biomaterials present biocompatibility challenges due to the potential toxicity and ultimate fate of reactive components that are not incorporated in the final cured product. In this study the effects of stoichiometry and triethylenediamine (TEDA) catalyst concentration on the reactivity, injectability, and biocompatibility of two component lysine-derived polyurethane (PUR) biocomposites were investigated. Rate constants were measured for the reactions of water (a blowing agent resulting in the generation of pores), polyester triol, dipropylene glycol (DPG), and allograft bone particles with the isocyanate-terminated prepolymer using an in situ attenuated total reflection Fourier transform infrared spectroscopy technique. Based on the measured rate constants, a kinetic model predicting the conversion of each component with time was developed. Despite the fact that TEDA is a well-known urethane gelling catalyst, it was found to preferentially catalyze the blowing reaction with water relative to the gelling reactions by a ratio >17:1. Thus the kinetic model predicted that the prepolymer and water proceeded to full conversion, while the conversions of polyester triol and DPG were <70% after 24h, which was consistent with leaching experiments showing that only non-cytotoxic polyester triol and DPG were released from the reactive PUR at early time points. The PUR biocomposite supported cellular infiltration and remodeling in femoral condyle defects in rabbits at 8weeks, and there was no evidence of an adverse inflammatory response induced by unreacted components from the biocomposite or degradation products from the cured polymer. Taken together, these data underscore the utility of the kinetic model in predicting the biocompatibility of reactive

  20. Sterilization of allograft bone: is 25 kGy the gold standard for gamma irradiation?

    PubMed

    Nguyen, Huynh; Morgan, David A F; Forwood, Mark R

    2007-01-01

    For several decades, a dose of 25 kGy of gamma irradiation has been recommended for terminal sterilization of medical products, including bone allografts. Practically, the application of a given gamma dose varies from tissue bank to tissue bank. While many banks use 25 kGy, some have adopted a higher dose, while some choose lower doses, and others do not use irradiation for terminal sterilization. A revolution in quality control in the tissue banking industry has occurred in line with development of quality assurance standards. These have resulted in significant reductions in the risk of contamination by microorganisms of final graft products. In light of these developments, there is sufficient rationale to re-establish a new standard dose, sufficient enough to sterilize allograft bone, while minimizing the adverse effects of gamma radiation on tissue properties. Using valid modifications, several authors have applied ISO standards to establish a radiation dose for bone allografts that is specific to systems employed in bone banking. These standards, and their verification, suggest that the actual dose could be significantly reduced from 25 kGy, while maintaining a valid sterility assurance level (SAL) of 10(-6). The current paper reviews the methods that have been used to develop radiation doses for terminal sterilization of medical products, and the current trend for selection of a specific dose for tissue banks. PMID:16821106

  1. Fibular Allograft and Demineralized Bone Matrix for the Treatment of Slipped Capital Femoral Epiphysis.

    PubMed

    Murray, Travis; Morscher, Melanie A; Krahe, Amy M; Adamczyk, Mark J; Weiner, Dennis S

    2016-05-01

    Previous studies documented the use of fibular allograft in the treatment of slipped capital femoral epiphysis (SCFE) with bone graft epiphysiodesis (BGE). This study describes the results of using a 10-mm diameter premilled fibular allograft packed with demineralized bone matrix placed across the physis in an open surgical approach under image intensification. A review identified 45 cases of BGE using fibular allograft and demineralized bone matrix in 34 patients with a diagnosis of SCFE performed by a single surgeon during an 8-year period. Thirty-four cases (25 patients) had at least 1 year of follow-up and were included in the study. Medical records were reviewed for complications, subsequent surgeries, and time to physeal closure. Of the 34 cases included, there were no cases of acute chondrolysis. Complications included 1 case of bone graft extrusion that required surgical replacement and 1 re-slip requiring surgical stabilization. Five cases of avascular necrosis (AVN) were encountered (1 unstable slip with total head AVN, and 4 stable slips with 3 total head and 1 partial head AVN). In 1 patient, small loose bony fragments were noted on postoperative radiographs that appeared outside of the articular surface of the hip and were asymptomatic. Two patients encountered wound healing issues that resolved with appropriate wound care. In light of the occurrence of AVN in stable cases, BGE with autogenous corticocancellous graft is preferable to BGE with autologous fibular graft for the treatment of SCFE. [Orthopedics. 2016; 39(3):e519-e525.].

  2. Increased Release Time of Antibiotics from Bone Allografts through a Novel Biodegradable Coating

    PubMed Central

    Madácsi, Edit; Kalugyer, Pálma; Vácz, Gabriella; Horváthy, Dénes B.; Szendrői, Miklós; Han, Weiping; Lacza, Zsombor

    2014-01-01

    The use of bone allografts is contraindicated in septic revision surgery due to the high risk of graft reinfection. Antibiotic release from the graft may solve the problem and these combinations can theoretically be used for prevention or even therapy of infection. The present study investigated whether amoxicillin, ciprofloxacin, and vancomycin alone or in combination with chitosan or alginate are suitable for short-term or long-term bone coating. Human bone allografts were prepared from femoral head and lyophilized. Antibiotic coating was achieved by incubating the grafts in antibiotic solution and freeze-drying again. Two biopolymers chitosan and alginate were used for creating sustained-release implantable coatings and the drug release profile was characterized in vitro by spectrophotometry. Using lyophilization with or without chitosan only resulted in short-term release that lasted up to 48 hours. Alginate coating enabled a sustained release that lasted for 8 days with amoxicillin, 28 days with ciprofloxacin coating, and 50 days with vancomycin coating. Using only implantable biodegradable allograft and polymers, a sustained release of antibiotics was achieved with ciprofloxacin and vancomycin for several weeks. Since the calculated daily release of the antibiotic was lower than the recommended IV dose, the calcium alginate coated bone graft can support endoprosthesis revision surgery. PMID:25045678

  3. The long-term fate of fresh and frozen orthotopic bone allografts in genetically defined rats.

    PubMed

    Bos, G D; Goldberg, V M; Gordon, N H; Dollinger, B M; Zika, J M; Powell, A E; Heiple, K G

    1985-01-01

    Fresh and frozen orthotopic iliac crest bone grafts in rats were studied histologically for determination of the long-term effects of histocompatibility matching and the freezing process on orthotopic bone graft incorporation. Grafts exchanged between groups of inbred rats, syngeneic or differing with respect to major or minor histocompatibility loci, were studied histologically at 20, 30, 40, 50, and 150 days after bone transplantation. A numerical histologic scoring system was developed and used by three observers for evaluation of coded hematoxylin and eosin sections. All frozen graft groups had the same fate regardless of histocompatibility relations between donors and recipients, and all grafts were inferior to fresh syngeneic grafts. Both fresh allograft groups received similar scores and initially at 20 and 30 days had scores similar to those of the fresh syngeneic groups. In the later intervals, however, the fresh allografts were inferior to the fresh syngeneic grafts and similar to the frozen groups. This is consistent with an older model describing two distinct phases of osteogenesis. In the long term, frozen syngeneic and fresh and frozen allografts across major and minor histocompatibility barriers were comparable, but all were significantly inferior to fresh syngeneic bone grafts.

  4. Kidney Versus Islet Allograft Survival After Induction of Mixed Chimerism With Combined Donor Bone Marrow Transplantation.

    PubMed

    Oura, Tetsu; Ko, Dicken S C; Boskovic, Svjetlan; O'Neil, John J; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R Neal; Cosimi, A B; Kawai, Tatsuo

    2016-01-01

    We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that included low-dose total body and thymic irradiation, horse Atgam (ATG), six doses of anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine (CyA) (Islet A). In Islet B, anti-CD8 mAb was administered in place of CyA. In Islet C, two recipients were treated with Islet B, but without ATG. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and BM transplantation (Kidney A) following the same conditioning regimen used in Islet A. The majority of kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned islet/BM recipients (Islet A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to CyA toxicity, three recipients were treated with anti-CD8 mAb in place of CyA. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CyA-free regimen that included anti-CD8 mAb. However, unlike the kidney allograft, islet allograft tolerance was not induced with transient chimerism. Induction of more

  5. Stem cells in bone grafting: Trinity allograft with stem cells and collagen/beta-tricalcium phosphate with concentrated bone marrow aspirate.

    PubMed

    Guyton, Gregory P; Miller, Stuart D

    2010-12-01

    The orthopedic foot and ankle surgeon needs bone grafts in the clinical situation of fracture healing and in bone-fusion procedures. This article briefly outlines thought processes and techniques for 2 recent options for the surgeon. The Trinity product is a unique combination of allograft bone and allograft stem cells. The beta-tricalcium phosphate and collagen materials provide an excellent scaffold for bone growth; when combined with concentrated bone marrow aspirate, they also offer osteoconductive and osteoinductive as well as osteogenerative sources for new bone formation.

  6. Cellular requirements for renal allograft rejection in the athymic nude rat

    PubMed Central

    1989-01-01

    This study has examined the ability of adoptively transferred CD4+ and CD8+ T cells to mediate rejection of a fully allogeneic DA renal graft in the PVG nude rat. Transfer, at the time of transplantation, of naive CD4+ T cells caused rapid graft rejection and primed CD4+ cells were several times more potent. In contrast, naive or specifically sensitized CD8+ cells were entirely ineffective at mediating renal allograft rejection. Whereas nonrejecting grafts showed only a mild cellular infiltrate, rejecting grafts in CD4+ reconstituted animals showed a substantial infiltrate and many of the infiltrating cells had a phenotype (MRC OX8+, MRC OX19-), consistent with NK cells. Experiments using a mAb (HIS 41) against an allotypic determinant of the leukocyte common antigen confirmed that the majority (greater than 80%) of the cellular infiltrate in rejecting grafts derived from the host rather than from the CD4+ inoculum. Infiltrating mononuclear cells, obtained from rejecting allografts 7 d after transplantation in CD4+-injected PVG nude hosts, showed high levels of in vitro cytotoxicity against not only kidney donor strain Con A blasts but also third-party allogeneic Con A blasts, as well as against both NK and LAK susceptible targets. When splenocytes from nontransplanted nude PVG rats were tested in vitro they also demonstrated high levels of lytic activity against both NK and LAK susceptible targets as well as allogeneic Con A blasts, which were not susceptible to lysis by spleen cells from euthymic rats. These findings suggest that injected CD4+ cells may cause renal allograft rejection by the recruitment of extrathymically derived, widely alloreactive cells into the kidney in this model of graft rejection. PMID:2659723

  7. Effects of Trypsinization and Mineralization on Intrasynovial Tendon Allograft Healing to Bone

    PubMed Central

    Qu, Jin; van Alphen, Nick A.; Thoreson, Andrew R.; Chen, Qingshan; An, Kai-Nan; Amadio, Peter C.; Schmid, Thomas M.; Zhao, Chunfeng

    2014-01-01

    The purpose of the current study was to develop a novel technology to enhance tendon-to-bone interface healing by trypsinizing and mineralizing (TM) an intrasynovial tendon allograft in a rabbit bone tunnel model. Eight rabbit flexor digitorum profundus (FDP) tendons were used to optimize the trypsinization process. An additional 24 FDP tendons were stratified into control and TM groups; in each group, 4 tendons were used for in vitro evaluation of TM and 8 were transplanted into proximal tibial bone tunnels in rabbits. The samples were evaluated histologically and with mechanical testing at postoperative week 8. Maximum failure strength and linear stiffness were not significantly different between the control and TM tendons. A thin fibrous band of scar tissue formed at the graft-to-bone interface in the control group. However, only the TM group showed obvious new bone formation inside the tendon graft and a visible fibrocartilage layer at the bone tunnel entrance. This study is the first to explore effects of TM on the intrasynovial allograft healing to a bone tunnel. TM showed beneficial effects on chondrogenesis, osteogenesis, and integration of the intrasynovial tendon graft, but mechanical strength was the same as the control tendons in this short-term in vivo study. PMID:25611186

  8. Activity of bone morphogenetic protein-7 after treatment at various temperatures: freezing vs. pasteurization vs. allograft.

    PubMed

    Takata, Munetomo; Sugimoto, Naotoshi; Yamamoto, Norio; Shirai, Toshiharu; Hayashi, Katsuhiro; Nishida, Hideji; Tanzawa, Yoshikazu; Kimura, Hiroaki; Miwa, Shinji; Takeuchi, Akihiko; Tsuchiya, Hiroyuki

    2011-12-01

    Insufficient bone union is the occasional complication of biomechanical reconstruction after malignant bone tumor resection using temperature treated tumor bearing bone; freezing, pasteurization, and autoclaving. Since bone morphogenetic protein (BMP) plays an important role in bone formation, we assessed the amount and activity of BMP preserved after several temperature treatments, including -196 and -73°C for 20 min, 60 and 100°C for 30 min, 60°C for 10h following -80°C for 12h as an allograft model, and 4°C as the control. The material extracted from the human femoral bone was treated, and the amount of BMP-7 was analyzed using an enzyme-linked immunosorbent assay. Then, the activity of recombinant human BMP-7 after the treatment was assessed using a bioassay with NIH3T3 cells and immunoblotting analysis to measure the amount of phospho-Smad, one of the signaling substrates that reflect the intracellular reaction of BMPs. Both experiments revealed that BMP-7 was significantly better preserved in the hypothermia groups. The percentages of the amount of BMP-7 in which the control group was set at 100% were 114%, 108%, 70%, 49%, and 53% in the -196, -73, 60, 100°C, and the allograft-model group, respectively. The percentages of the amount of phospho-Smad were 89%, 87%, 24%, 4.9%, and 14% in the -196, -73, 60, 100°C, and the allograft-model group, respectively. These results suggested that freezing possibly preserves osteoinductive ability than hyperthermia treatment.

  9. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.

    PubMed

    Das, Anusuya; Segar, Claire E; Chu, Yihsuan; Wang, Tiffany W; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C; Cui, Quanjun; Botchwey, Edward A

    2015-09-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects.

  10. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras

    PubMed Central

    Das, Anusuya; Segar, Claire E.; Chu, Yihsuan; Wang, Tiffany W.; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C.; Cui, Quanjun; Botchwey, Edward A.

    2015-01-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. PMID:26125501

  11. Bioactive lipid coating of bone allografts directs engraftment and fate determination of bone marrow-derived cells in rat GFP chimeras.

    PubMed

    Das, Anusuya; Segar, Claire E; Chu, Yihsuan; Wang, Tiffany W; Lin, Yong; Yang, Chunxi; Du, Xeujun; Ogle, Roy C; Cui, Quanjun; Botchwey, Edward A

    2015-09-01

    Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both myeloid and osteogenic cells in remodeling tissue surrounding allografts. FTY720 coatings altered the phenotype of immune cells two weeks post-injury, which was associated with increased vascularization and bone formation surrounding allografts. Consequently, degradable polymer coating strategies that deliver small molecule growth factors such as FTY720 represent a novel therapeutic strategy for harnessing endogenous bone marrow-derived progenitors and enhancing healing in load-bearing bone defects. PMID:26125501

  12. A retrospective study on annual evaluation of radiation processing for frozen bone allografts complying to quality system requirements.

    PubMed

    Ramalingam, Saravana; Mohd, Suhaili; Samsuddin, Sharifah Mazni; Min, N G Wuey; Yusof, Norimah; Mansor, Azura

    2015-12-01

    Bone allografts have been used widely to fill up essential void in orthopaedic surgeries. The benefit of using allografts to replace and reconstruct musculoskeletal injuries, fractures or disease has obtained overwhelming acceptance from orthopaedic surgeons worldwide. However, bacterial infection and disease transmission through bone allograft transplantation have always been a significant issue. Sterilization by radiation is an effective method to eliminate unwanted microorganisms thus assist in preventing life threatening allograft associated infections. Femoral heads procured from living donors and long bones (femur and tibia) procured from cadaveric donors were sterilized at 25 kGy in compliance with international standard ISO 11137. According to quality requirements, all records of bone banking were evaluated annually. This retrospective study was carried out on annual evaluation of radiation records from 1998 until 2012. The minimum doses absorbed by the bones were ranging from 25.3 to 38.2 kGy while the absorbed maximum doses were from 25.4 to 42.3 kGy. All the bones supplied by our UMMC Bone Bank were sterile at the required minimum dose of 25 kGy. Our analysis on dose variation showed that the dose uniformity ratios in 37 irradiated boxes of 31 radiation batches were in the range of 1.003-1.251, which indicated the doses were well distributed. PMID:25687771

  13. UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

    SciTech Connect

    Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A. )

    1990-05-01

    Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms.

  14. Successful liver allografts in mice by combination with allogeneic bone marrow transplantation

    SciTech Connect

    Nakamura, T.; Good, R.A.; Yasumizu, R.; Inoue, S.; Oo, M.M.; Hamashima, Y.; Ikehara, S.

    1986-06-01

    Successful liver allografts were established by combination with allogeneic bone marrow transplantation. When liver tissue of BALB/c (H-2d) or C57BL/6J (H-2b) mice was minced and grafted under the kidney capsules of C3H/HeN (H-2k) mice, it was rejected. However, when C3H/HeN mice were irradiated and reconstituted with T-cell-depleted BALB/c or BALB/c nu/nu bone marrow cells, or with fetal liver cells of BALB/c mice, they accepted both donor (stem-cell)-type (BALB/c) and host (thymus)-type (C3H/HeN) liver tissue. Assays for both mixed-lymphocyte reaction and induction of cytotoxic T lymphocytes revealed that the newly developed T cells were tolerant of both donor (stem-cell)-type and host (thymus)-type major histocompatibility complex determinants. We propose that liver allografts combined with bone marrow transplantation should be considered as a viable therapy for patients with liver disease such as liver cirrhosis and hepatoma.

  15. Benefits of mineralized bone cortical allograft for immediate implant placement in extraction sites: an in vivo study in dogs

    PubMed Central

    2016-01-01

    Purpose The aim of the present study was to evaluate the effectiveness of using a mineralized bone cortical allograft (MBCA), with or without a resorbable collagenous membrane derived from bovine pericardium, on alveolar bone remodeling after immediate implant placement in a dog model. Methods Six mongrel dogs were included. The test and control sites were randomly selected. Four biradicular premolars were extracted from the mandible. In control sites, implants without an allograft or membrane were placed immediately in the fresh extraction sockets. In the test sites, an MBCA was placed to fill the gap between the bone socket wall and implant, with or without a resorbable collagenous membrane. Specimens were collected after 1 and 3 months. The amount of residual particles and new bone quality were evaluated by histomorphometry. Results Few residual graft particles were observed to be closely embedded in the new bone without any contact with the implant surface. The allograft combined with a resorbable collagen membrane limited the resorption of the buccal wall in height and width. The histological quality of the new bone was equivalent to that of the original bone. The MBCA improved the quality of new bone formation, with few residual particles observed at 3 months. Conclusions The preliminary results of this animal study indicate a real benefit in obtaining new bone as well as in enhancing osseointegration due to the high resorbability of cortical allograft particles, in comparison to the results of xenografts or other biomaterials (mineralized or demineralized cancellous allografts) that have been presented in the literature. Furthermore, the use of an MBCA combined with a collagen membrane in extraction and immediate implant placement limited the extent of post-extraction resorption. PMID:27800212

  16. Fresh-frozen human bone allograft in vertical ridge augmentation: clinical and tomographic evaluation of bone formation and resorption.

    PubMed

    Macedo, Luis Guilherme Scavone; Mazzucchelli-Cosmo, Luiz Antonio; Macedo, Nelson Luiz; Monteiro, Adriana Socorro Ferreira; Sendyk, Wilson Roberto

    2012-12-01

    The aim of the current study is to evaluate fresh-frozen human bone allografts (FHBAs) used in vertical ridge augmentation clinically and by computed tomography, and to analyze the resulting bone formation and graft resorption. Sixteen FHBAs were grafted in the maxillae and mandibles of 9 patients. The FHBAs, which were provided by the Musculoskeletal Tissue Bank of Marilia Hospital (Unioss), were frozen at -80°C. After 7 months, dental implants were placed and bone parameters were evaluated. Vertical bone formation was measured by computerized tomography before (T0) and at 7 months (T1) after the surgical procedure. Bone graft resorption was measured clinically from a landmark screw head using a periodontal probe. The results were analyzed by Student's t-test. Significant differences existed in the bone formation values at T0 and T1, with an average change of 4.03 ± 1.69 mm. Bone graft resorption values were 1.0 ± 0.82 mm (20%). Implants were placed with varying insertion torque values (35-45 Ncm), and achieved primary stability. This study demonstrates that FHBAs promote satisfactory vertical bone formation with a low resorption rates, good density, and primary implant stability. PMID:21811779

  17. Histologic Evaluation of Bone Healing Capacity Following Application of Inorganic Bovine Bone and a New Allograft Material in Rabbit Calvaria

    PubMed Central

    Paknejad, Mojgan; Rokn, AmirReza; Rouzmeh, Nina; Heidari, Mohadeseh; Titidej, Azadehzeinab; Kharazifard, Mohammad Javad; Mehrfard, Ali

    2015-01-01

    Objectives: Considering the importance of bone augmentation prior to implant placement in order to obtain adequate bone quality and quantity, many studies have been conducted to evaluate different techniques and materials regarding new bone formation. In this study, we investigated the bone healing capacity of two different materials deproteinized bovine bone mineral (DBBM with the trade name of Bio-Oss) and demineralized freeze-dried bone allograft (DFDBA with the trade name of DynaGraft). Materials and Methods: This randomized blinded prospective study was conducted on twelve New Zealand white rabbits. Three cranial defects with an equal diameter were created on their calvarium. Subsequently, they were distributed into three groups: 1. The control group without any treatment; 2. The Bio-Oss group; 3. The DynaGraft group. After 30 days, the animals were sacrificed for histologic and histomorphometric analysis. Results: Substantial new bone formation was observed in both groups. DynaGraft: 56/1 % ± 15/1 and Bio-Oss: 53/55 % ± 13/5 compared to the control group: 28/6 % ± 11/2. All groups showed slight inflammation and a small amount of residual biomaterial was observed. Conclusion: Considerable new bone formation was demonstrated in both DynaGraft and Bio-Oss groups in comparison with the control group. Both materials are considered biocompatible regarding the negligible foreign body reaction. PMID:26005452

  18. Enhancement by dimethyl myleran of donor type chimerism in murine recipients of bone marrow allografts

    SciTech Connect

    Lapidot, T.; Terenzi, A.; Singer, T.S.; Salomon, O.; Reisner, Y. )

    1989-05-15

    A major problem in using murine models for studies of bone marrow allograft rejection in leukemia patients is the narrow margin in which graft rejection can be analyzed. In mice irradiated with greater than 9 Gy total body irradiation (TBI) rejection is minimal, whereas after administration of 8 Gy TBI, which spares a significant number of clonable T cells, a substantial frequency of host stem cells can also be detected. In current murine models, unlike in humans, bone marrow allograft rejection is generally associated with full autologous hematopoietic reconstitution. In the present study, we investigated the effect of the myeloablative drug dimethyl myleran (DMM) on chimerism status following transplantation of T cell-depleted allogenic bone marrow (using C57BL/6 donors and C3H/HeJ recipients, conditioned with 8 Gy TBI). Donor type chimerism 1 to 2 months post-transplant of 1 to 3 x 10(6) bone marrow cells was markedly enhanced by using DMM one day after TBI and prior to transplantation. Conditioning with cyclophosphamide instead of DMM, in combination with 8 Gy TBI, did not enhance engraftment of donor type cells. Artificial reconstitution of T cells, after conditioning with TBI plus DMM, by adding mature thymocytes, or presensitization with irradiated donor type spleen cells 1 week before TBI and DMM, led to strong graft rejection and consequently to severe anemia. The anti-donor responses in these models were proportional to the number of added T cells and to the number of cells used for presensitization, and they could be neutralized by increasing the bone marrow inoculum.

  19. Remodeling of heat-treated cortical bone allografts for posterior lumbar interbody fusion: serial 10-year follow-up.

    PubMed

    Muramatsu, Koichi; Hachiya, Yudo; Izawa, Hiroyuki; Yamada, Harumoto

    2012-12-01

    We have selected heat-treated bone allografts as the graft material since the Tokai Bone Bank, the first regional bone bank in Japan, was established in 1992. In this study, we examined changes in bone mineral density (BMD), and morphology observed by magnetic resonance imaging (MRI), and histological findings of bone grafts in cases followed up for 7-10 years after bone grafting to grasp the remodeling of heat-treated cortical bone allografts for posterior lumber interbody fusion (PLIF). BMD of bone grafts was reduced by half at 10 years after grafting. MRI revealed that bone grafts were indistinguishable initially in only 22.2% of cases, whereas after a lengthy period of 10 years distinguishable in many cases. Histologically, new bone formation at the graft-host interface was observed earlier, at 1 year after grafting, than that at the periphery of canals in the specimens. The laminated structure of the cortical bone eroded over time, and fragmented bone trabeculae were observed in the specimens at 8 years or longer after grafting, though necrotic bone still remained in some sites.

  20. Sublethal fractionated total-body irradiation and donor bone marrow infusion for induction of allograft tolerance

    SciTech Connect

    Pierce, G.E.; Watts, L.M.; Clancy, J. Jr.

    1985-03-01

    Tolerance to skin allografts across the strong histocompatibility barrier H-2b to H-2d was achieved with sublethal fractionated total-body irradiation, FTBI, delivered to H-2d mice in 3 doses of 250 rads within 24 hr, followed by transfusion of 3 x 10(7) H-2b donor bone marrow (BM) cells. H-2b skin allografts were applied within 48 hr after the initial radiation. 70% of the mice became long-term (greater than 180-day) survivors with fur-bearing grafts. Marked interexperiment variability in survival rates suggested that infection was the major use of death in this model and lower weight gain and survival rates for allogenic BM vs. media-treated controls suggested that graft-versus-host disease (GVHD) was also a factor. The observation, however, that long-term survivors (70% of all mice) gained weight and appeared healthy suggested that the GVHD might be self-limiting. Chimeric analysis revealed that approximately 25% of spleen cells were of donor origin, both at short-term (6 weeks) and long-term (greater than 1 year) intervals after tolerance induction. In spite of hematopoietic chimerism, a low incidence of spontaneous tumors, less than 1%, occurred in the long-term survivors.

  1. Fractionated sublethal total body irradiation and donor bone marrow infusion for induction of specific allograft tolerance

    SciTech Connect

    Pierce, G.E.; Kimler, B.F.; Thomas, J.H.; Watts, L.M.; Kinnaman, M.L.

    1981-03-01

    Fractionated total lymphoid irradiation (FT-lymphoid-I) plus donor bone marrow (BM) can induce tolerance to skin allografts. In the present study, fractionated total body irradiation (FT-body-I) was studied as an alternative to FT-lymphoid-I. FT-body-I produces less pulmonary and gastrointestinal injury than does single exposure total body irradiation, but because of the decreased capacity of lymphoid tissues to recover from the effects of irradiation between fractions, the effect of FT-body-I on lymphoid cells, when delivered within 24 h, is approximately the same as an equivalent single exposure of total body irradiation. Therefore, FT-body-I, like FT-lymphoid-I, has some selectivity for lymphoid tissues and has the advantage that it can be delivered within the time constraints of ex vivo organ preservation.

  2. Prolonging survival in vascularized bone allograft transplantation: developing specific immune unresponsiveness

    SciTech Connect

    Paskert, J.P.; Yaremchuk, M.J.; Randolph, M.A.; Weiland, A.J.

    1987-04-01

    Vascularized bone allografts (VBAs) could be useful adjuncts to the clinical reconstructive surgeon's arsenal. These grafts are known experimentally to be subject to host rejection. One way to control the rejection problem would be to develop specific immune unresponsiveness via host conditioning. Using a proven reliable model in inbred rats for studying heterotopic VBA transplantation, recipient animals were conditioned preoperatively with third-party unrelated blood, donor-specific blood (DSB) alone and with cyclosporine, and ultraviolet irradiated donor-specific blood. The combination of DSB plus cyclosporine delayed rejection of grafts across a strong histocompatibility barrier for three to four weeks. However, rejection was delayed across a weak histocompatibility barrier for five to six weeks using this same host pretreatment. The implications are that specific immunosuppression, although possible, is difficult to achieve in VBA transplantation, and that such techniques will rely on tissue-matching to minimize the genetic disparity between graft and host.

  3. Arthroscopic Treatment for Shoulder Instability with Glenoid Bone Loss Using Distal Tibia Allograft Augmentation - Short Term Results

    PubMed Central

    Wong, Ivan; Amar, Eyal; Coady, Catherine M.; Dilman, Daryl B.; Smith, Ben

    2016-01-01

    Objectives: Background: The results of arthroscopic anterior labral (Bankart) repair have been shown to have high failure rate in patients with significant glenoid bone loss. Several reconstruction procedures using bone graft have been described to overcome the bone loss, including autogenous coracoid transfer to the anterior glenoid (Latarjet procedure) as well as iliac crest autograft and tibial allografts. In recent years, trends toward minimally invasive shoulder surgery along with improvements in technology and technique have led surgeons to expand the application of arthroscopic treatment. Purpose: This study aims to perform a retrospective analysis of prospectively collected data to evaluate the clinical and radiological follow up of patient who underwent anatomic glenoid reconstruction using distal tibia allograft for the treatment of shoulder instability with glenoid bone loss at 1-year post operation time point. Methods: Between December 2011 and January 2015, 55 patients underwent arthroscopic stabilization of the shoulder by means of capsule-labral reattachment to glenoid ream and bony augmentation of glenoid bone loss with distal tibial allograft for recurrent instability of the shoulder. Preoperative and postoperative evaluation included general assessment by the western Ontario shoulder instability index (WOSI) questionnaire, preoperative and postoperative radiographs and CT scans. Results: Fifty-five patients have been evaluated with mean age of 29.73 years at time of the index operation. There were 40 males (mean age of 29.66) and 15 female (mean age of 29.93). Minimum follow up time was 12 months. The following adverse effects were recorded: none suffered from recurrent dislocation, 2 patients suffered from bone resorption but without overt instability, 1 patient had malunion due to screw fracture, none of the patients had nonunion. The mean pre-operative WOSI score was 36.54 and the mean postoperative WOSI score was 61.0. Conclusion: Arthroscopic

  4. [The use of structural proximal tibial allografts coated with human albumin in treating extensive periprosthetic knee-joint bone deficiency and averting late complications. Case report].

    PubMed

    Klára, Tamás; Csönge, Lajos; Janositz, Gábor; Pap, Károly; Lacza, Zsombor

    2015-01-11

    The authors report the history of a 74-year-old patient who underwent surgical treatment for segmental knee-joint periprosthetic bone loss using structural proximal tibial allografts coated with serum albumin. Successful treatment of late complications which occurred in the postoperative period is also described. The authors emphasize that bone replacement with allografts is a physiological process that enables the stable positioning of the implant and the reconstruction of the soft tissues, the replacement of extensive bone loss, and also it is a less expensive operation. It has been already confirmed that treatment of lyophilised allografts with albumin improves the ability of bone marrow-derived mesenchymal stem cells to adhere and proliferate the surface of the allografts, penetrate the pores and reach deeper layers of the graft. Earlier studies have shown osteoblast activity on the surface and interior of the graft.

  5. A biomechanical assessment of superior shoulder translation after reconstruction of anterior glenoid bone defects: The Latarjet procedure versus allograft reconstruction

    PubMed Central

    Degen, Ryan M.; Giles, Joshua W.; Boons, Harm W.; Litchfield, Robert B.; Johnson, James A.; Athwal, George S.

    2013-01-01

    Background: The coracoacromial ligament (CAL) is an important restraint to superior shoulder translation. The effect of CAL release on superior stability following the Latarjet is unknown; therefore, our purpose was to compare the effect of two Latarjet techniques and allograft reconstruction on superior instability. Materials and Methods: Eight cadaveric specimens were tested on a simulator. Superior translation was monitored following an axial force in various glenohumeral rotations (neutral, internal, and external) with and without muscle loading. Three intact CAL states were tested (intact specimen, 30% glenoid bone defect, and allograft reconstruction) and two CAL deficient states (classic Latarjet (classicLAT) and congruent-arc Latarjet (congruentLAT)). Results: In neutral without muscle loading, a significant increase in superior translation occurred with the classicLAT as compared to 30% defect (P = 0.046) and allograft conditions (P = 0.041). With muscle loading, the classicLAT (P = 0.005, 0.002) and the congruentLAT (P = 0.018, 0.021) had significantly greater superior translation compared to intact and allograft, respectively. In internal rotation, only loaded tests produced significant results; specifically, classicLAT increased translation compared to all intact CAL states (P < 0.05). In external rotation, only unloaded tests produced significant results with classicLAT and congruentLAT allowing greater translations than intact (P ≤ 0.028). For all simulations, the allograft was not significantly different than intact (P > 0.05) and no differences (P = 1.0) were found between classicLAT and congruentLAT. Discussion: In most simulations, CAL release with the Latarjet lead to increased superior humeral translation. Conclusion: The choice of technique for glenoid bone loss reconstruction has implications on the magnitude of superior humeral translation. This previously unknown effect requires further study to determine its clinical and kinematic

  6. Effects of gamma irradiation on the initial mechanical and material properties of goat bone-patellar tendon-bone allografts

    SciTech Connect

    Gibbons, M.J.; Butler, D.L.; Grood, E.S.; Bylski-Austrow, D.I.; Levy, M.S.; Noyes, F.R. )

    1991-03-01

    The effects of {sup 60}Co gamma irradiation on the initial mechanical properties of the composite bone-patellar tendon-bone unit (CU) and the tendon midsubstance (TM) were studied. Frozen specimens were exposed to either 2 or 3 Mrad of gamma irradiation. Paired frozen specimens served as intraanimal controls. Treatment effects on the CU were assessed using four mechanical parameters. Effects on the TM were assessed using four material parameters measured using an optical surface-strain analysis system. The maximum force and strain energy to maximum force of the composite unit were significantly reduced 27% and 40%, respectively, after 3 Mrad of irradiation (p less than .05). Mechanical properties of the CU were not significantly altered, however, following 2 Mrad of irradiation. Based on individual paired contrasts between treatment and control, significant differences were also found in the material properties of the tendon midsubstance. The maximum stress, maximum strain, and strain energy density to maximum stress were significantly reduced following 3 Mrad, but not 2 Mrad, of irradiation. The results provide important time zero material property data, which will be useful for later anterior cruciate ligament reconstruction studies using irradiated allograft patellar tendons in the goat model and other animal models as well.

  7. Effects of gamma irradiation on mechanical properties of defatted trabecular bone allografts assessed by speed-of-sound measurement.

    PubMed

    Vastel, L; Masse, C; Crozier, E; Padilla, F; Laugier, P; Mitton, D; Bardonnet, R; Courpied, J-P

    2007-01-01

    New sterilization methods for human bone allografts may lead to alterations in bone mechanical properties, which strongly influence short- and medium-term outcomes. In many sterilization procedures, bone allografts are subjected to gamma irradiation, usually with 25 KGy, after treatment and packaging. We used speed-of-sound (SOS) measurements to evaluate the effects of gamma irradiation on bone. All bone specimens were subjected to the same microbial inactivation procedure. They were then separated into three groups, of which one was treated and not irradiated and two were exposed to 10 and 25 KGy of gamma radiation, respectively. SOS was measured using high- and low-frequency ultrasound beams in each orthogonal direction. SOS and Young modulus were altered significantly in the three groups, compared to native untreated bone. Exposure to 10 or 25 KGy had no noticeable effect on the study variables. The impact of irradiation was small compared to the effects of physical or chemical defatting. Reducing the radiation dose used in everyday practice failed to improve graft mechanical properties in this study.

  8. Development of a cyclosporin-A-induced immune tolerant rat model to test marrow allograft cell type effects on bone repair.

    PubMed

    Espitalier, Florent; Durand, Nicolas; Rémy, Séverine; Corre, Pierre; Sourice, Sophie; Pilet, Paul; Weiss, Pierre; Guicheux, Jérôme; Malard, Olivier

    2015-05-01

    Bone repair is an important concept in tissue engineering, and the ability to repair bone in hypotrophic conditions such as that of irradiated bone, represents a challenge for this field. Previous studies have shown that a combination of bone marrow and (BCP) was effective to repair irradiated bone. However, the origin and role played by each cell type in bone healing still remains unclear. In order to track the grafted cells, the development of an animal model that is immunotolerant to an allograft of bone marrow would be useful. Furthermore, because the immune system interacts with bone turnover, it is of critical importance to demonstrate that immunosuppressive drugs do not interfere with bone repair. After a preliminary study of immunotolerance, cyclosporin-A was chosen to be used in immunosuppressive therapy. Ten rats were included to observe qualitative and quantitative bone repair 8 days and 6 weeks after the creation of bone defects. The defects were filled with an allograft of bone marrow alone or in association with BCP under immunosuppressive treatment (cyclosporin-A). The results showed that there was no significant interaction of cyclosporin-A with osseous regeneration. The use of this new immunotolerant rat model of bone marrow allograft in future studies will provide insight on how the cells within the bone marrow graft contribute to bone healing, especially in irradiated conditions.

  9. Intentional replantation of periodontally hopeless teeth using a combination of enamel matrix derivative and demineralized freeze-dried bone allograft.

    PubMed

    Baltacioglu, Ersa; Tasdemir, Tamer; Yuva, Pinar; Celik, Davut; Sukuroglu, Erkan

    2011-02-01

    This study evaluated the clinical and radiographic results of the intentional replantation of periodontally hopeless teeth with combined enamel matrix derivative and demineralized freeze-dried bone allograft therapy. Eleven patients (five female, six male; age range, 13 to 53 years) with 12 periodontally hopeless teeth resulting from extensive alveolar bone loss and vertical defects extending to the apexes were studied. At the 12-month clinical and radiologic follow-up, significant improvement was observed for all clinical and radiographic parameters except gingival recession (P < .05). These preliminary findings show that intentional replantation combined with regenerative techniques is a successful alternative to tooth extraction.

  10. Reconstruction of compound loss of lateral malleolus and lateral ankle ligaments with double-bundle Achilles tendon-bone allograft.

    PubMed

    Ko, Dukhwan; Jung, Hong-Geun; Kim, Hyeung-June; Cha, Seung-Han; Nam, Kyoung-Mo

    2014-01-01

    Open ankle fracture, including compound loss of the lateral malleolus, lateral ankle ligaments, and overlying skin, is a severe injury and can result in ankle instability and permanent disability. Treatment of this injury is challenging and requires bone grafting and soft tissue reconstruction. In the present report, we describe a unique reconstruction technique for compound loss of the lateral malleolus, lateral ankle ligaments, and the overlying skin using a double-bundle Achilles tendon-bone allograft combined with a reverse sural fasciocutaneous flap. The patient obtained a stable ankle with nearly full range of motion and displayed satisfactory function during the follow-up period.

  11. Socket preservation and sinus augmentation using a medical grade calcium sulfate hemihydrate and mineralized irradiated cancellous bone allograft composite.

    PubMed

    Bagoff, Robert; Mamidwar, Sachin; Chesnoiu-Matei, Ioana; Ricci, John L; Alexander, Harold; Tovar, Nick M

    2013-06-01

    Regeneration and preservation of bone after the extraction of a tooth are necessary for the placement of a dental implant. The goal is to regenerate alveolar bone with minimal postoperative pain. Medical grade calcium sulfate hemihydrate (MGCSH) can be used alone or in combination with other bone grafts; it improves graft handling characteristics and particle containment of particle-based bone grafts. In this case series, a 1:1 ratio mix of MGCSH and mineralized irradiated cancellous bone allograft (MICBA) was mixed with saline and grafted into an extraction socket in an effort to maintain alveolar height and width for future implant placement. MGCSH can be used in combination with other bone grafts and can improve handling characteristics and graft particle containment of particle-based bone grafts. In the cases described, we found that an MGCSH:MICBA graft can potentially be an effective bone graft composite. It has the ability to act as a space maintainer and as an osteoconductive trellis for bone cells, thereby promoting bone regeneration in the extraction socket. MGCSH, a cost-effective option, successfully improved MICBA handling characteristics, prevented soft tissue ingrowth, and assisted in the regeneration of bone.

  12. Cellular therapy in bone-tendon interface regeneration

    PubMed Central

    Rothrauff, Benjamin B; Tuan, Rocky S

    2014-01-01

    The intrasynovial bone-tendon interface is a gradual transition from soft tissue to bone, with two intervening zones of uncalcified and calcified fibrocartilage. Following injury, the native anatomy is not restored, resulting in inferior mechanical properties and an increased risk of re-injury. Recent in vivo studies provide evidence of improved healing when surgical repair of the bone-tendon interface is augmented with cells capable of undergoing chondrogenesis. In particular, cellular therapy in bone-tendon healing can promote fibrocartilage formation and associated improvements in mechanical properties. Despite these promising results in animal models, cellular therapy in human patients remains largely unexplored. This review highlights the development and structure-function relationship of normal bone-tendon insertions. The natural healing response to injury is discussed, with subsequent review of recent research on cellular approaches for improved healing. Finally, opportunities for translating in vivo findings into clinical practice are identified. PMID:24326955

  13. Pre-treatment of allogeneic bone marrow recipients with the CXCR4 antagonist AMD3100 transiently enhances hematopoietic chimerism without promoting donor-specific skin allograft tolerance.

    PubMed

    Li, Zhanzhuo; Xu, Xin; Weiss, Ido D; Jacobson, Orit; Murphy, Philip M

    2015-10-01

    Hematopoietic chimerism established by allogeneic bone marrow transplantation is known to promote donor-specific organ allograft tolerance; however, clinical application is limited by the need for toxic host conditioning and "megadoses" of donor bone marrow cells. A potential solution to this problem has been suggested by the observation that recipient bone marrow mobilization by the CXCR4 antagonist AMD3100 promotes chimerism in congenic bone marrow transplantation experiments in mice. Here we report that a single subcutaneous dose of 10 mg/kg AMD3100 in recipient C57BL/6 mice was able to enhance hematopoietic chimerism when complete MHC-mismatched BALB/c donor bone marrow cells were transplanted 1h after drug dosing. However, levels of chimerism measured 30 days post-transplantation were not sustained when mice were reexamined on day 90 post-transplantation. Moreover, transient chimerism induced by this protocol did not support robust donor-specific skin allograft tolerance. Using the same transient immunosuppression protocol, we confirmed that "megadoses" of donor bone marrow cells could induce durable chimerism associated with donor-specific skin allograft tolerance without AMD3100 pre-treatment. We conclude that in this protocol AMD3100 pretreatment may empty bone marrow niches that become reoccupied by allogeneic donor hematopoietic progenitor cells but not by true long-lived donor hematopoietic stem cells, resulting in short-lived chimerism and failure to support durable donor-specific allograft tolerance.

  14. Bone regeneration: molecular and cellular interactions with calcium phosphate ceramics

    PubMed Central

    Barrère, Florence; van Blitterswijk, Clemens A; de Groot, Klaas

    2006-01-01

    Calcium phosphate bioceramics are widely used in orthopedic and dental applications and porous scaffolds made of them are serious candidates in the field of bone tissue engineering. They have superior properties for the stimulation of bone formation and bone bonding, both related to the specific interactions of their surface with the extracellular fluids and cells, ie, ionic exchanges, superficial molecular rearrangement and cellular activity. PMID:17717972

  15. Allograft anterior cruciate ligament reconstruction in patients younger than 30 years: a matched-pair comparison of bone-patellar tendon-bone and tibialis anterior.

    PubMed

    O'Brien, Daniel F; Kraeutler, Matthew J; Koyonos, Loukas; Flato, Russell R; Ciccotti, Michael G; Cohen, Steven B

    2014-03-01

    We conducted a study to compare patient-reported outcomes and graft-rupture rates of bone-patellar tendon-bone (BPTB) and tibialis anterior (TA) allograft primary anterior cruciate ligament (ACL) reconstruction in patients younger than 30 years. Patients were retrospectively identified as having undergone ACL reconstruction with either a BPTB (n = 20) or a TA (n = 20) allograft. Each patient in the BPTB group was matched to a patient in the TA group based on sex, age at time of surgery, height, weight, and preoperative activity level. The Lysholm Knee Scoring Scale and the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation Form were administered at a minimum of 1 year after surgery. Mean Lysholm scores were 92.9 (BPTB) and 93.0 (TA), and mean IKDC scores were 92.6 (BPTB) and 90.3 (TA). The differences were not statistically significant. Overall graft-rupture rates for the study period were 4.7% (BPTB) and 1.9% (TA) (P = .18). There was no statistically significant difference in patient-rated outcomes and graft-rupture rates between BPTB and TA allografts for ACL reconstruction at a minimum of 1 year after surgery. Future research efforts should focus on mid- and long-term follow-up and objective outcomes.

  16. Computed Tomography and Optical Imaging of Osteogenesis-angiogenesis Coupling to Assess Integration of Cranial Bone Autografts and Allografts.

    PubMed

    Cohn Yakubovich, Doron; Tawackoli, Wafa; Sheyn, Dmitriy; Kallai, Ilan; Da, Xiaoyu; Pelled, Gadi; Gazit, Dan; Gazit, Zulma

    2015-01-01

    A major parameter determining the success of a bone-grafting procedure is vascularization of the area surrounding the graft. We hypothesized that implantation of a bone autograft would induce greater bone regeneration by abundant blood vessel formation. To investigate the effect of the graft on neovascularization at the defect site, we developed a micro-computed tomography (µCT) approach to characterize newly forming blood vessels, which involves systemic perfusion of the animal with a polymerizing contrast agent. This method enables detailed vascular analysis of an organ in its entirety. Additionally, blood perfusion was assessed using fluorescence imaging (FLI) of a blood-borne fluorescent agent. Bone formation was quantified by FLI using a hydroxyapatite-targeted probe and µCT analysis. Stem cell recruitment was monitored by bioluminescence imaging (BLI) of transgenic mice that express luciferase under the control of the osteocalcin promoter. Here we describe and demonstrate preparation of the allograft, calvarial defect surgery, µCT scanning protocols for the neovascularization study and bone formation analysis (including the in vivo perfusion of contrast agent), and the protocol for data analysis. The 3D high-resolution analysis of vasculature demonstrated significantly greater angiogenesis in animals with implanted autografts, especially with respect to arteriole formation. Accordingly, blood perfusion was significantly higher in the autograft group by the 7(th) day after surgery. We observed superior bone mineralization and measured greater bone formation in animals that received autografts. Autograft implantation induced resident stem cell recruitment to the graft-host bone suture, where the cells differentiated into bone-forming cells between the 7(th) and 10(th) postoperative day. This finding means that enhanced bone formation may be attributed to the augmented vascular feeding that characterizes autograft implantation. The methods depicted may serve

  17. Bone defects: molecular and cellular therapeutic targets.

    PubMed

    Desiderio, Vincenzo; Tirino, Virginia; Papaccio, Gianpaolo; Paino, Francesca

    2014-06-01

    Bone defects are one of the most serious pathologies that need tissue regeneration therapies. Studies on mesenchymal stem cells are changing the way we treat bone diseases. MSCs have been used for the treatment of osteogenesis imperfecta, hypophosphatasia, osteonecrosis of the femoral head, osteoporosis, rheumatoid arthritis and osteoarthritis. In this context, it is becoming ever more clear that the future of therapies will be based on the use of stem cells. In this concise review, we highlight the importance of the use of MSCs in bone diseases, focusing on the role of histone deacetylases and Wnt pathways involved in osteogenesis. A better understanding of MSC biology and osteogenesis is needed in order to develop new and targeted therapeutic strategies for the treatment of bone diseases/disorders.

  18. Bone allograft and implant fixation tested under influence of bio-burden reduction, periosteal augmentation and topical antibiotics. Animal experimental studies.

    PubMed

    Barckman, Jeppe

    2014-01-01

    Loosening of an artificial joint prosthesis is a painful and debilitating condition that can be treated only by re-operation. Re-operations accounted for approximately 15% of all hip replacement operations performed in Denmark between the year 1995 and 2010. The process of loosening is often accompanied by destructive inflammation and osteolysis, which leads to insufficient bone stock that often requires extensive bone grafting. Impacted morselized bone graft is a well-established method for improving the amount and quality of bone stock that ensures sufficient stability and anchorage of the revision implants. Among bone graft options, the autologous bone graft is considered the gold standard. It is naturally biocompatible, but its use in revision surgery is curtailed by its limited volume and by considerable donor site morbidity. Allograft bone is readily available and is the most commonly used graft material. However, it has been shown that the incorporation of allograft bone into the host bone is not always complete, and substantial fibrous tissue formation has been described. A reason for this may be that allograft bone is a foreign tissue, which, contrary to autogenic bone, may induce an immunogenic response that leads to increased fibrous tissue formation. Furthermore, the fresh-frozen allograft has minimal osteoinductive and no osteogenic capacity. The studies in this thesis have investigated ways of improving the incorporation of allograft bone by adding osteoinductive cells from the periosteum and reducing the immunogenic load of the allograft bone by rinsing. Furthermore, the impact of antibiotic protection of the bone graft has been evaluated. The same experimental implant model was used in all three studies. This model enables evaluation of early implant fixation and osseointegration of an uncemented implant surrounded by impacted morselized bone graft. Unloaded gap implants were inserted into the metaphysis of the proximal tibia (Study I) and distal

  19. Bone allograft and implant fixation tested under influence of bio-burden reduction, periosteal augmentation and topical antibiotics. Animal experimental studies.

    PubMed

    Barckman, Jeppe

    2014-01-01

    Loosening of an artificial joint prosthesis is a painful and debilitating condition that can be treated only by re-operation. Re-operations accounted for approximately 15% of all hip replacement operations performed in Denmark between the year 1995 and 2010. The process of loosening is often accompanied by destructive inflammation and osteolysis, which leads to insufficient bone stock that often requires extensive bone grafting. Impacted morselized bone graft is a well-established method for improving the amount and quality of bone stock that ensures sufficient stability and anchorage of the revision implants. Among bone graft options, the autologous bone graft is considered the gold standard. It is naturally biocompatible, but its use in revision surgery is curtailed by its limited volume and by considerable donor site morbidity. Allograft bone is readily available and is the most commonly used graft material. However, it has been shown that the incorporation of allograft bone into the host bone is not always complete, and substantial fibrous tissue formation has been described. A reason for this may be that allograft bone is a foreign tissue, which, contrary to autogenic bone, may induce an immunogenic response that leads to increased fibrous tissue formation. Furthermore, the fresh-frozen allograft has minimal osteoinductive and no osteogenic capacity. The studies in this thesis have investigated ways of improving the incorporation of allograft bone by adding osteoinductive cells from the periosteum and reducing the immunogenic load of the allograft bone by rinsing. Furthermore, the impact of antibiotic protection of the bone graft has been evaluated. The same experimental implant model was used in all three studies. This model enables evaluation of early implant fixation and osseointegration of an uncemented implant surrounded by impacted morselized bone graft. Unloaded gap implants were inserted into the metaphysis of the proximal tibia (Study I) and distal

  20. Mouse NK cell–mediated rejection of bone marrow allografts exhibits patterns consistent with Ly49 subset licensing

    PubMed Central

    Sun, Kai; Alvarez, Maite; Ames, Erik; Barao, Isabel; Chen, Mingyi; Longo, Dan L.; Redelman, Doug

    2012-01-01

    Natural killer (NK) cells can mediate the rejection of bone marrow allografts and exist as subsets based on expression of inhibitory/activating receptors that can bind MHC. In vitro data have shown that NK subsets bearing Ly49 receptors for self-MHC class I have intrinsically higher effector function, supporting the hypothesis that NK cells undergo a host MHC-dependent functional education. These subsets also play a role in bone marrow cell (BMC) allograft rejection. Thus far, little in vivo evidence for this preferential licensing across mouse strains with different MHC haplotypes has been shown. We assessed the intrinsic response potential of the different Ly49+ subsets in BMC rejection by using β2-microglobulin deficient (β2m−/−) mice as donors. Using congenic and allogeneic mice as recipients and depleting the different Ly49 subsets, we found that NK subsets bearing Ly49s, which bind “self-MHC” were found to be the dominant subset responsible for β2m−/− BMC rejection. This provides in vivo evidence for host MHC class I–dependent functional education. Interestingly, all H2d strain mice regardless of background were able to resist significantly greater amounts of β2m−/−, but not wild-type BMC than H2b mice, providing evidence that the rheostat hypothesis regarding Ly49 affinities for MHC and NK-cell function impacts BMC rejection capability. PMID:22184406

  1. Supercritical CO2 fluid-foaming of polymers to increase porosity: a method to improve the mechanical and biocompatibility characteristics for use as a potential alternative to allografts in impaction bone grafting?

    PubMed

    Tayton, Edward; Purcell, M; Aarvold, A; Smith, J O; Kalra, S; Briscoe, A; Shakesheff, K; Howdle, S M; Dunlop, D G; Oreffo, R O C

    2012-05-01

    Disease transmission, availability and cost of allografts have resulted in significant efforts to find an alternative for use in impaction bone grafting (IBG). Recent studies identified two polymers with both structural strength and biocompatibility characteristics as potential replacements. The aim of this study was to assess whether increasing the polymer porosity further enhanced the mechanical and cellular compatibility characteristics for use as an osteogenic biomaterial alternative to allografts in IBG. Solid and porous poly(DL-lactide) (P(DL)LA) and poly(DL-lactide-co-glycolide) (P(DL)LGA) scaffolds were produced via melt processing and supercritical CO(2) foaming, and the differences characterized using scanning electron microscopy (SEM). Mechanical testing included milling and impaction, with comparisons made using a shear testing rig as well as a novel agitation test for cohesion. Cellular compatibility tests for cell number, viability, and osteogenic differentiation using WST-1 assays, fluorostaining, and ALP assays were determined following 14 day culture with skeletal stem cells. SEM showed excellent porosity throughout both of the supercritical-foam-produced polymer scaffolds, with pores between 50 and 200 μm. Shear testing showed that the porous polymers exceeded the shear strength of allograft controls (P<0.001). Agitation testing showed greater cohesion between the particles of the porous polymers (P<0.05). Cellular studies showed increased cell number, viability, and osteogenic differentiation on the porous polymers compared to solid block polymers (P<0.05). The use of supercritical CO(2) to generate porous polymeric biodegradable scaffolds significantly improves the cellular compatibility and cohesion observed compared to non-porous counterparts, without substantial loss of mechanical shear strength. These improved characteristics are critical for clinical translation as a potential osteogenic composite for use in IBG.

  2. Cellular and molecular toxicity of lead in bone

    SciTech Connect

    Pounds, J.G. ); Long, G.J.; Rosen, J.F. )

    1991-02-01

    To fully understand the significance of bone as a target tissue of lead toxicity, as well as a reservoir of systemic lead, it is necessary to define the effects of lead on the cellular components of bone. Skeletal development and the regulation of skeletal mass are ultimately determined by the four different types of cells: osteoblasts, lining cells, osteoclasts, and osteocytes. These cells, which line and penetrate the mineralized matrix, are responsible for matrix formation, mineralization, and bone resorption, under the control of both systemic and local factors. Systemic components of regulation include parathyroid hormone, 1,25-dihydroxyvitamin D{sub 3}, and calcitonin; local regulators include numerous cytokines and growth factors. Lead intoxication directly alters many aspects of bone cell function. First, lead may indirectly alter bone cell function through changes in the circulating levels of those hormones, particularly 1,25-dihydroxyvitamin D{sub 3}, which modulate bone cell function. Second, lead may directly alter bone cell function by perturbing the ability of bone cells to respond to hormonal regulation. Third, lead may impair the ability of cells to synthesize or secrete other components of the bone matrix, such as collagen or bone sialoproteins (osteopontin). Finally, lead may directly effect of substitute for calcium in the active sites of the calcium messenger system. The effects of lead on the recruitment and differentiation of bone cells remains to be established. Many of the toxic effects of lead on bone cell function may be produced by perturbation of the calcium and cAMP messenger systems in these cells.

  3. Implication of Ia-positive bone marrow interstitial stem cells in the induction of unresponsiveness to canine renal allografts

    SciTech Connect

    Rapaport, F.T.; Arnold, A.N.; Asari, H.; Sato, K.; Miura, S.; Chanana, A.; Cronkite, E.P.

    1987-02-01

    The removal from stored autologous host bone marrow of a monocytoid cell population by exposure to methylprednisolone is associated with successful introduction of unresponsiveness to renal allografts in irradiated recipients reconstituted with such treated marrow. The eliminated cells are a prominent component of the canine long bone marrow interstitium and share a number of important properties with dendritic cells (DC), including size and shape; poor or nonadherence to plastic or glass surfaces; negative staining for neutral esterase, acid phosphatase, or peroxidase; nonphagocytic; Ia positive, but negative for IgG or IgM; ability to act as accessory cells in augmenting the intensity of allogeneic mixed-lymphocyte reactions. Both cell types are of bone marrow origin and are susceptible to steroids in vitro. The results suggest that the bone marrow interstitial cells identified in the course of this study may be enriched with populations of canine dendritic cell precursors and dendritic cells at various stages of differentiation. The detection of a receptor site for Helix promatia on the surface of such cells may be of usefulness in their further characterization and in the analysis of their precise role in the modulation of allogeneic unresponsiveness.

  4. Early Systemic Cellular Immune Response in Children and Young Adults Receiving Decellularized Fresh Allografts for Pulmonary Valve Replacement

    PubMed Central

    Neumann, Anneke; Breymann, Thomas; Cebotari, Serghei; Boethig, Dietmar; Horke, Alexander; Beerbaum, Philipp; Westhoff-Bleck, Mechthild; Bertram, Harald; Ono, Masamichi; Tudorache, Igor; Haverich, Axel; Beutel, Gernot

    2014-01-01

    Objectives: The longevity of homografts is determined by the activation of the recipients' immune system resulting from allogenic antigen exposition. Fresh decellularized pulmonary homografts (DPH) have shown promising early results in pulmonary valve replacement in children and young adults and could potentially avoid significant activation of the immune system, as more than 99% of the donor DNA is removed during the decellularization process. While the humoral immune response to decellularized allografts has been studied, detailed information on the more significant cellular immune response is currently lacking. Methods and Results: Peripheral blood samples were obtained from patients undergoing pulmonary valve replacement with DPH before, after, and for approximately 3 years after implantation. Absolute counts and percentages of mature T- (CD3+), B- (CD19+), and natural killer- (CD16+/CD56+) cells, as well as T helper- (CD4+) and cytotoxic T-cell- (CD8+) subsets, were determined by fluorescence-activated cell sorting (FACS). Between May 2009 and September 2013, 199 blood samples taken from 47 patients with a mean age at DPH implantation of 16.6±10.8 years were analyzed. The hemodynamic performance of DPH was excellent in all but one patient, and no valve-related deaths or conduit explantations were observed. The short-term follow up revealed a significant postoperative decrease in cell counts of most subtypes with reconstitution after 3 months. Continued assessment did not show any significant deviations in cell counts from their baseline values. Conclusion: The absence of cellular immune response in patients receiving DPH supports the concept that decellularization can provide a basis for autologous regeneration. PMID:24138470

  5. Bone cysts after osteochondral allograft repair of cartilage defects in goats suggest abnormal interaction between subchondral bone and overlying synovial joint tissues.

    PubMed

    Pallante-Kichura, Andrea L; Cory, Esther; Bugbee, William D; Sah, Robert L

    2013-11-01

    The efficacy of osteochondral allografts (OCAs) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12months in vivo. The objectives of this study were to further analyze OCAs and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral bone (ScB) and trabecular bone (TB) structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCAs was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCAs was lower than Non-Op and other OCAs. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCAs did not vary compared to Non-Op, but BS/TV was lower. (2) OCAs contained "basal" cysts, localized to deeper regions, some "subchondral" cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These

  6. [Cellular interplay of bone cells and vascular endothelial cells in bone].

    PubMed

    Hasegawa, Tomoka; Tsuchiya, Erika; Abe, Miki; Amizuka, Norio

    2016-05-01

    During endochondral bone development, the longitudinal vascular invasion into cartilage primordium initially takes place, by which mineralized cartilage matrix would be exposed into bone. Thereafter, osteogenic cells differentiate into mature osteoblasts to deposit new bone onto the exposed mineralized cartilage. New bone formation at the chondro-osseous junction appears to be achieved by the process of modeling, but not by bone remodeling based on cellular coupling between osteoclasts and osteoblasts. Recently, a specific vessel subtype in bone was reported:Vascular endothelial cells close to the chondro-oseous junction showed intense CD31/Endomucin(CD31(hi)Emcn(hi), type H), while the endothelial cells of sinusoidal vessels in diaphysis revealed only weak CD31/Endomucin(CD31(lo)Emcnlo, type L). It is suggested crucial roles of endothelial HIF in controlling bone angiogenesis, type H vessel abundance, endothelial growth factor expression and osteogenesis.

  7. Replacement of the anterior cruciate ligament of the knee with deep frozen bone-tendon-bone allografts.

    PubMed

    Than, P; Bálint, L; Domán, I; Szabó, G

    1999-01-01

    Surgical treatment of the torn anterior cruciate ligament (ACL) and consequent knee instability showed great development over the last decade. Arthroscopic techniques and the use of different allogenic tissues became a routine. Between 1995 and 1998, 31 knees in 30 patients underwent ACL reconstruction of the knee with fresh-frozen allografts at the Department of Orthopedics, Medical University of Pécs, Hungary. The operations were performed with arthroscopic technique. This paper retrospectively assesses the outcomes with an average follow up of 28 months, which showed good results in most of the cases. The authors reviewed the literature emphasizing advantages and disadvantages of the method with special interest to possible complications resulting from the use of allografts: graft rejection, graft re-rupture, transmission of infection and synovitis evoked by immune response.

  8. Replacement of the anterior cruciate ligament of the knee with deep frozen bone-tendon-bone allografts.

    PubMed

    Than, P; Bálint, L; Domán, I; Szabó, G

    1999-01-01

    Surgical treatment of the torn anterior cruciate ligament (ACL) and consequent knee instability showed great development over the last decade. Arthroscopic techniques and the use of different allogenic tissues became a routine. Between 1995 and 1998, 31 knees in 30 patients underwent ACL reconstruction of the knee with fresh-frozen allografts at the Department of Orthopedics, Medical University of Pécs, Hungary. The operations were performed with arthroscopic technique. This paper retrospectively assesses the outcomes with an average follow up of 28 months, which showed good results in most of the cases. The authors reviewed the literature emphasizing advantages and disadvantages of the method with special interest to possible complications resulting from the use of allografts: graft rejection, graft re-rupture, transmission of infection and synovitis evoked by immune response. PMID:10853785

  9. Bone Cysts After Osteochondral Allograft Repair of Cartilage Defects in Goats Suggest Abnormal Interaction Between Subchondral Bone and Overlying Synovial Joint Tissues

    PubMed Central

    Pallante-Kichura, Andrea L.; Cory, Esther; Bugbee, William D.; Sah, Robert L.

    2013-01-01

    The efficacy of osteochondral allografts (OCA) may be affected by osseous support of the articular cartilage, and thus affected by bone healing and remodeling in the OCA and surrounding host. Bone cysts, and their communication pathways, may be present in various locations after OCA insertion and reflect distinct pathogenic mechanisms. Previously, we analyzed the effect of OCA storage (FRESH, 4°C/14d, 4°C/28d, FROZEN) on cartilage quality in fifteen adult goats after 12 months in vivo. The objectives of this study were to further analyze OCA and contralateral non-operated (Non-Op) CONTROLS from the medial femoral condyle to (1) determine the effect of OCA storage on local subchondral (ScB) and trabecular (TB) bone structure, (2) characterize the location and structure of bone cysts and channels, and (3) assess the relationship between cartilage and bone properties. (1) Overall bone structure after OCA was altered compared to Non-Op, with OCA samples displaying bone cysts, ScB channels, and ScB roughening. ScB BV/TV in FROZEN OCA was lower than Non-Op and other OCA. TB BV/TV in FRESH, 4°C/14d, and 4°C/28d OCA did not vary compared to Non-Op, but BS/TV was lower. (2) OCA contained “basal” cysts, localized to deeper regions, some “subchondral” cysts, localized near the bone-cartilage interface, and some ScB channels. TB surrounding basal cysts exhibited higher BV/TV than Non-Op. (3) Basal cysts occurred (a) in isolation, (b) with subchondral cysts and ScB channels, (c) with ScB channels, or (d) with subchondral cysts, ScB channels, and ScB erosion. Deterioration of cartilage gross morphology was strongly associated with abnormal μCT bone structure. Evidence of cartilage-bone communication following OCA repair may favor fluid intrusion as a mechanism for subchondral cyst formation, while bone resorption at the graft-host interface without affecting overall bone and cartilage structure may favor bony contusion mechanism for basal cyst formation. These

  10. Microwave sterilization of femoral head allograft.

    PubMed

    Dunsmuir, Robert A; Gallacher, Grace

    2003-10-01

    The potential shortage of allograft bone has led to the need to investigate other sources of bone for allografts. Some allograft bone donated from primary total hip arthroplasty recipients must be discarded or treated to become usable as a result of bacterial contamination. Femoral head allografts were contaminated with Staphylococcus aureus and Bacillus subtilis. A domestic microwave oven was used. The contaminated bone was exposed to microwave irradiation for different time periods. The samples were then cultured to attempt to grow the two bacterial species. The contaminated bone samples failed to grow any organisms after 2 min of exposure to microwave irradiation. This study shows that sterilization of femoral head allografts contaminated with S. aureus and B. subtilis can be achieved with microwave irradiation in a domestic microwave oven. This method of sterilization of bone allografts is cheap, easily used, and an effective way to process contaminated bone. PMID:14532216

  11. Balancing the rates of new bone formation and polymer degradation enhances healing of weight-bearing allograft/polyurethane composites in rabbit femoral defects.

    PubMed

    Dumas, Jerald E; Prieto, Edna M; Zienkiewicz, Katarzyna J; Guda, Teja; Wenke, Joseph C; Bible, Jesse; Holt, Ginger E; Guelcher, Scott A

    2014-01-01

    There is a compelling clinical need for bone grafts with initial bone-like mechanical properties that actively remodel for repair of weight-bearing bone defects, such as fractures of the tibial plateau and vertebrae. However, there is a paucity of studies investigating remodeling of weight-bearing bone grafts in preclinical models, and consequently there is limited understanding of the mechanisms by which these grafts remodel in vivo. In this study, we investigated the effects of the rates of new bone formation, matrix resorption, and polymer degradation on healing of settable weight-bearing polyurethane/allograft composites in a rabbit femoral condyle defect model. The grafts induced progressive healing in vivo, as evidenced by an increase in new bone formation, as well as a decrease in residual allograft and polymer from 6 to 12 weeks. However, the mismatch between the rates of autocatalytic polymer degradation and zero-order (independent of time) new bone formation resulted in incomplete healing in the interior of the composite. Augmentation of the grafts with recombinant human bone morphogenetic protein-2 not only increased the rate of new bone formation, but also altered the degradation mechanism of the polymer to approximate a zero-order process. The consequent matching of the rates of new bone formation and polymer degradation resulted in more extensive healing at later time points in all regions of the graft. These observations underscore the importance of balancing the rates of new bone formation and degradation to promote healing of settable weight-bearing bone grafts that maintain bone-like strength, while actively remodeling. PMID:23941405

  12. Balancing the Rates of New Bone Formation and Polymer Degradation Enhances Healing of Weight-Bearing Allograft/Polyurethane Composites in Rabbit Femoral Defects

    PubMed Central

    Dumas, Jerald E.; Prieto, Edna M.; Zienkiewicz, Katarzyna J.; Guda, Teja; Wenke, Joseph C.; Bible, Jesse; Holt, Ginger E.

    2014-01-01

    There is a compelling clinical need for bone grafts with initial bone-like mechanical properties that actively remodel for repair of weight-bearing bone defects, such as fractures of the tibial plateau and vertebrae. However, there is a paucity of studies investigating remodeling of weight-bearing bone grafts in preclinical models, and consequently there is limited understanding of the mechanisms by which these grafts remodel in vivo. In this study, we investigated the effects of the rates of new bone formation, matrix resorption, and polymer degradation on healing of settable weight-bearing polyurethane/allograft composites in a rabbit femoral condyle defect model. The grafts induced progressive healing in vivo, as evidenced by an increase in new bone formation, as well as a decrease in residual allograft and polymer from 6 to 12 weeks. However, the mismatch between the rates of autocatalytic polymer degradation and zero-order (independent of time) new bone formation resulted in incomplete healing in the interior of the composite. Augmentation of the grafts with recombinant human bone morphogenetic protein-2 not only increased the rate of new bone formation, but also altered the degradation mechanism of the polymer to approximate a zero-order process. The consequent matching of the rates of new bone formation and polymer degradation resulted in more extensive healing at later time points in all regions of the graft. These observations underscore the importance of balancing the rates of new bone formation and degradation to promote healing of settable weight-bearing bone grafts that maintain bone-like strength, while actively remodeling. PMID:23941405

  13. Effect of electrical current on the healing of mandibular freeze-dried bone allografts in dogs

    SciTech Connect

    Branham, G.B.; Triplett, R.G.; Yeandle, S.; Vieras, F.

    1985-06-01

    Low levels of electrical current have been shown to affect the process of osseous repair. This study experimentally evaluated the effect of electrical stimulation on the healing of freeze-dried mandibular allogeneic bone grafts in dogs. Healing of the grafts was monitored by sequential submento-occlusal radiographs and radionuclide bone imaging at two, four, six, and eight weeks after grafting. Results indicated no significant difference in the osseous repair of stimulated and nonstimulated freeze-dried allogeneic bone grafts.

  14. Effect of platelet-rich plasma on the healing of mandibular defects treated with fresh frozen bone allograft: a radiographic study in dogs.

    PubMed

    Messora, Michel R; Nagata, Maria J H; Fucini, Stephen E; Pola, Natália M; Campos, Natália; de Oliveira, Guillermo C V; Bosco, Alvaro F; Garcia, Valdir G; Furlaneto, Flávia A C

    2014-10-01

    The purpose of this study was to radiographically analyze the effect of autologous platelet rich plasma (PRP) on the healing of fresh frozen bone allograft (FFBA) placed in surgically created resection defects in mandibles of dogs. Bilateral resection defects measuring 1.5 cm × 1 cm were surgically created on the inferior border of the mandible in 10 adult male dogs. The defects were randomly divided into three groups: C, FFBA, and FFBA/PRP. In Group C, the defect was filled by blood clot only. In Group FFBA, the defect was filled with particulate fresh frozen bone allograft. In Group FFBA/PRP, it was filled with particulate fresh frozen bone allograft combined with PRP. At 90 days postoperative, standardized radiographs of the mandibles were obtained and results were quantitatively evaluated. Analysis of digitized radiographs indicated that non-PRP grafts were significantly less dense than the PRP grafts. Group FFBA/PRP also presented a statistically greater mineralized tissue area than Groups C and FFBA. Within the limits of this study, it can be concluded that PRP enhanced the healing of FFBA in resection defects in mandibles of dogs.

  15. Immunomodulatory Effects of Different Cellular Therapies of Bone Marrow Origin on Chimerism Induction and Maintenance Across MHC Barriers in a Face Allotransplantation Model.

    PubMed

    Hivelin, Mikael; Klimczak, Aleksandra; Cwykiel, Joanna; Sonmez, Erhan; Nasir, Serdar; Gatherwright, James; Siemionow, Maria

    2016-08-01

    Many more patients would benefit from vascularized composite allotransplantation if less toxic and safer immunosuppressive protocols will become available. Tolerance induction protocols with donor cells co-transplantation are one of the promising pathways to reduce maintenance immunosupressive regimens. We investigated the role of donor bone marrow cells (BMC), mesenchymal stromal cells (MSC) and in vivo created chimeric cells (CC) used as supportive therapies in a fully MHC-mismatched rat face transplantation model. Twenty-four fully MHC-mismatched hemiface transplantations were performed between ACI (RT1(a)) donors and Lewis (RT1(l)) recipients under combined seven-day immunosuppressive regimen of anti-αβ-T-cell receptor (TCR) monoclonal antibody and cyclosporin A. We studied four experimental groups-group 1: no cellular therapy; group 2: supportive therapy with BMC; group 3: supportive therapy with MSC; group 4: supportive therapy with CC generated in a primary chimera. We evaluated clinical and histological rejection grades, transplanted cells migration, donor-specific chimerism in the peripheral blood and bone marrow compartments, and CD4(+)/CD25(+) T-cell levels. Face allograft rejection was observed at 26.8 ± 0.6 days post-transplant (PT) in the absence of cellular therapy, at 34.5 ± 1.1 days for group 2, 29.3 ± 0.8 days for group 3, and 30.3 ± 1.38 PT for group 4. The longest survival was observed in allografts supported by co-transplantation of BMC. All support in cellular therapies delayed face allograft rejection by chimerism induction and/or immunomodulatory properties of co-transplanted cells. Survival time was comparable between groups, however, further studies, with different cell dosages, delivery routes and delivery times are required. PMID:26708158

  16. Biomechanical comparison between CentraLoc and Intrafix fixation of quadrupled semitendinosus-gracilis allografts in cadaveric tibiae with low bone mineral density.

    PubMed

    Krupp, R; Nyland, J; Smith, C; Nawab, A; Burden, R; Caborn, D N M

    2007-08-01

    Supplementary or back-up tibial tunnel fixation of a quadruple semitendinosus-gracilis (STG) graft is often performed when the knee surgeon questions the integrity of intra-tunnel fixation. Back-up fixation devices such as staples however may contribute to increased knee pain and dysfunction. Both primary extra-tunnel and intra-tunnel fixation devices may provide sufficient quadruple STG graft fixation in a tibial tunnel to preclude the need for back-up fixation. This biomechanical study compared the fixation of quadruple STG allografts in standard drilled tunnels prepared in low apparent bone mineral density (BMD) cadaveric tibiae using either an Intrafix device with primary intra-tunnel fixation in a region of predominantly cancellous trabecular bone, or a CentraLoc device with primary extra-tunnel fixation in a region of predominantly cortical bone. The study hypothesis was that the CentraLoc device would display superior fixation in these low apparent BMD cadaveric tibiae. Matched pair tibiae and quadruple STG allografts were divided into two groups of seven specimens each. Extraction drilled tunnels matched allograft diameter. Constructs were pretensioned on a servo hydraulic device between 10 and 50 N for 10 cycles and isometric pretensioned at 50 N for 1 min prior to undergoing 500 loading cycles (50-250 N) and load to failure testing (20 mm/min). The CentraLoc group displayed superior load at failure (448.4+/-171 N vs. 338.4+/-119 N, P=0.04) and survived more loading cycles (410+/-154 cycles vs. 196+/-230 cycles, P=0.04) than the Intrafix group. Most CentraLoc group specimens (6/7, 85.7%) failed by device pullout with intact quadruple STG allograft strands while all Intrafix group specimens (7/7, 100%) failed by slippage of one or more strands (P=0.005). PMID:17490882

  17. Renal allograft fibrosis: biology and therapeutic targets.

    PubMed

    Boor, P; Floege, J

    2015-04-01

    Renal tubulointerstitial fibrosis is the final common pathway of progressive renal diseases. In allografts, it is assessed with tubular atrophy as interstitial fibrosis/tubular atrophy (IF/TA). IF/TA occurs in about 40% of kidney allografts at 3-6 months after transplantation, increasing to 65% at 2 years. The origin of renal fibrosis in the allograft is complex and includes donor-related factors, in particular in case of expanded criteria donors, ischemia-reperfusion injury, immune-mediated damage, recurrence of underlying diseases, hypertensive damage, nephrotoxicity of immunosuppressants, recurrent graft infections, postrenal obstruction, etc. Based largely on studies in the non-transplant setting, there is a large body of literature on the role of different cell types, be it intrinsic to the kidney or bone marrow derived, in mediating renal fibrosis, and the number of mediator systems contributing to fibrotic changes is growing steadily. Here we review the most important cellular processes and mediators involved in the progress of renal fibrosis, with a focus on the allograft situation, and discuss some of the challenges in translating experimental insights into clinical trials, in particular fibrosis biomarkers or imaging modalities.

  18. Socket Preservation Therapy with Acellular Dermal Matrix and Mineralized Bone Allograft After Tooth Extraction in Humans: A Clinical and Histomorphometric Study.

    PubMed

    Fernandes, Patricia Garani; Muglia, Valdir Antonio; Reino, Danilo Maeda; Maia, Luciana Prado; de Moraes Grisi, Marcio Fernando; de Souza, Sergio Luís; Taba, Mario; Palioto, Daniela Bazan; de Almeida, Adriana G; Novaes, Arthur Belém

    2016-01-01

    The aim of this study was to analyze through clinical and histomorphometric parameters the use of acellular dermal matrix (ADM) with or without mineralized bone allograft (AB) on bone formation in human alveoli after a 6- to 8-month healing period. A total of 19 patients in need of extraction of the maxillary anterior teeth were selected and randomly assigned to the test group (ADM plus AB) or to the control group (ADM only). Clinical and histomorphometric measurements and histologic analysis were recorded 6 to 8 months after ridge preservation procedures. Clinical parameters and amount of mineralized and nonmineralized tissue were measured and analyzed. In the clinical measurements, the test group showed reduced bone loss in the buccopalatal dimension after 6 to 8 months (intragroup analysis P < .01). Histologic findings showed higher percentages of mineralized tissue and lower percentages of nonmineralized tissue in the test group when compared with the control group (P < .05). In this randomized controlled clinical and histomorphometric study in humans, acellular dermal matrix in association with mineralized bone allograft reduced alveolar bone loss in the anterior maxillae both in height and width after a follow-up period of 6 to 8 months. PMID:26901306

  19. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process

    PubMed Central

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix–only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications

  20. Multipotent adult progenitor cells on an allograft scaffold facilitate the bone repair process.

    PubMed

    LoGuidice, Amanda; Houlihan, Alison; Deans, Robert

    2016-01-01

    Multipotent adult progenitor cells are a recently described population of stem cells derived from the bone marrow stroma. Research has demonstrated the potential of multipotent adult progenitor cells for treating ischemic injury and cardiovascular repair; however, understanding of multipotent adult progenitor cells in orthopedic applications remains limited. In this study, we evaluate the osteogenic and angiogenic capacity of multipotent adult progenitor cells, both in vitro and loaded onto demineralized bone matrix in vivo, with comparison to mesenchymal stem cells, as the current standard. When compared to mesenchymal stem cells, multipotent adult progenitor cells exhibited a more robust angiogenic protein release profile in vitro and developed more extensive vasculature within 2 weeks in vivo. The establishment of this vascular network is critical to the ossification process, as it allows nutrient exchange and provides an influx of osteoprogenitor cells to the wound site. In vitro assays confirmed the multipotency of multipotent adult progenitor cells along mesodermal lineages and demonstrated the enhanced expression of alkaline phosphatase and production of calcium-containing mineral deposits by multipotent adult progenitor cells, necessary precursors for osteogenesis. In combination with a demineralized bone matrix scaffold, multipotent adult progenitor cells demonstrated enhanced revascularization and new bone formation in vivo in an orthotopic defect model when compared to mesenchymal stem cells on demineralized bone matrix or demineralized bone matrix-only control groups. The potent combination of angiogenic and osteogenic properties provided by multipotent adult progenitor cells appears to create a synergistic amplification of the bone healing process. Our results indicate that multipotent adult progenitor cells have the potential to better promote tissue regeneration and healing and to be a functional cell source for use in orthopedic applications. PMID

  1. Socket preservation using demineralized freezed dried bone allograft with and without plasma rich in growth factor: A canine study

    PubMed Central

    Mogharehabed, Ahmad; Birang, Reza; Torabinia, Nakisa; Nasiri, Saman; Behfarnia, Parichehr

    2014-01-01

    Background: The accelerating effect of plasma rich in growth factors (PRGFs) in the healing of extraction sockets has been demonstrated by some studies. The aim of the present study was to histologically and histomorphometrically evaluate whether bone formation would increase by the combined use of PRGF and demineralized freeze-dried bone allograft (DFDBA). Materials and Methods: In four female dogs, the distal root of the second, third and fourth lower premolars were extracted bilaterally and the mesial roots were preserved. The extraction sockets were randomly divided into DFDBA + PRGF, DFDBA + saline or control groups. Two dogs were sacrificed after 2 weeks and two dogs were sacrificed after 6 weeks. The extraction sockets were evaluated from both histological and histomorphometrical aspects. The data were analyzed by Mann-Whitney followed by Kruskal-Wallis tests using the Statistical Package for the Social Sciences version 20 (SPSS Inc., Chicago, IL, USA). Significant levels were set at 0.05. Results: The least decrease in socket height was observed in the DFDBA + PRGF group (0.73 ± 0.42 mm). The least decrease in the coronal portion was observed in the DFDBA + PRGF group (1.38 ± 1.35 mm²). The least decrease in the middle surface was observed in the DFDBA group (0.61 ± 0.80 mm²). The least decrease in the apical portion was observed in the DFDBA group (0.34 ± 0.39 mm²). Conclusion: The present study showed better socket preservation subsequent to the application of DFDBA and PRGF combination in comparison with the two other groups. However, the difference was not statistically significant. PMID:25225559

  2. Effect of different sterilization processing methods on the mechanical properties of human cancellous bone allografts.

    PubMed

    Vastel, L; Meunier, A; Siney, H; Sedel, L; Courpied, J-P

    2004-05-01

    Use of new sterilization methods applied to human bone is likely to affect both the mechanical and biological properties of human cancellous grafts. The mechanical properties of the transplanted bone inevitably determine the short- and mid-term results of the orthopedic procedure performed. The aim of this study was to compare, under similar conditions, the mechanical effects of gamma irradiation, lipid extraction, and treatment with 6M urea on trabecular bone samples, through conventional mechanical tests and measurement of the ultrasound wave propagation rate. Deteriorations measured for gamma irradiation and lipid extraction were low: 2.4% and 2.5%, respectively, for ultrasound propagation wave measurements. They were clearly significant for protocol including 6M urea, corresponding to a loss of 30% in values measured in the control sample for the stress to failure, inciting prudence when grafted bone is used for support in orthopedic assembly. High consistency in the results obtained between travel time of the ultrasound wave, easily done, and measurement of stress to failure through conventional tests, favor the use of ultrasound protocol, described as a quality test performed on bone grafts in the tissue bank before distribution and implantation. PMID:14741625

  3. Investigation of effect of variations in bone fraction and red marrow cellularity on bone marrow dosimetry in radio-immunotherapy

    NASA Astrophysics Data System (ADS)

    Wilderman, S. J.; Roberson, P. L.; Bolch, W. E.; Dewaraja, Y. K.

    2013-07-01

    A method is described for computing patient-specific absorbed dose rates to active marrow which accounts for spatial variation in bone volume fraction and marrow cellularity. A module has been added to the 3D Monte Carlo dosimetry program DPM to treat energy deposition in the components of bone spongiosa distinctly. Homogeneous voxels in regions containing bone spongiosa (as defined on CT images) are assumed to be comprised only of bone, active (red) marrow and inactive (yellow) marrow. Cellularities are determined from biopsy, and bone volume fractions are computed from cellularities and CT-derived voxel densities. Electrons are assumed to deposit energy locally in the three constituent components in proportions determined by electron energy absorption fractions which depend on energy, cellularity, and bone volume fraction, and which are either taken from the literature or are derived from Monte Carlo simulations using EGS5. Separate algorithms are used to model primary β particles and secondary electrons generated after photon interactions. Treating energy deposition distinctly in bone spongiosa constituents leads to marrow dosimetry results which differ from homogeneous spongiosa dosimetry by up to 20%. Dose rates in active marrow regions with cellularities of 20, 50, and 80% can vary by up to 20%, and can differ by up to 10% as a function of bone volume fraction. Dose to bone marrow exhibits a strong dependence on marrow cellularity and a potentially significant dependence on bone volume fraction.

  4. A randomized controlled evaluation of alveolar ridge preservation following tooth extraction using deproteinized bovine bone mineral and demineralized freeze-dried bone allograft

    PubMed Central

    Sadeghi, Rokhsareh; Babaei, Maryam; Miremadi, S. Asghar; Abbas, Fatemeh Mashadi

    2016-01-01

    Background: Alveolar ridge preservation could be performed immediately following tooth extraction to limit dimensional changes of alveolar process due to bone resorption. The aim of this study was to compare the clinical and histologic outcomes of socket preservation using two different graft materials; deproteinized bovine bone mineral (DBBM) and demineralized freeze-dried bone allograft (DFDBA) with absorbable collagen membrane. Materials and Methods: Twenty extraction sockets in 20 patients were randomly divided into 2 treatment groups: 10 sockets were augmented with DBBM and collagen membrane whereas 10 sockets were filled with DFDBA and covered by collagen membrane. Primary closure was achieved over extraction sockets by flap advancement. Horizontal and vertical ridge dimensional changes were assessed at baseline and after 4-6 months at the time of implant placement. For histological and histomorphometrical analysis, bone samples were harvested from the augmented sites with trephine during implant surgery. All data were analyzed using SPSS version 18 (α=0.05). Results: Clinical measurements revealed that average horizontal reduction was 2.3 ± 0.64 mm for DFDBA and 2.26 ± 0.51 mm for DBBM. Mean vertical ridge resorption at buccal side was 1.29 ± 0.68 mm for DFDBA and 1.1 ± 0.17 mm for DBBM. Moreover, mean vertical ridge reduction at lingual site was 0.41 ± 0.38 mm and 0.35 ± 0.34 mm for DFDBA and DBBM, respectively. No significant differences were seen between two groups in any of those clinical parameters. Histologic analysis showed statistically significant more new bone deposition for DFDBA compared to DBBM (34.49 ± 3.19 vs. 18.76 ± 3.54) (P < 0.01). Residual graft particles were identified significantly more in DBBM (12.77 ± 1.85) than DFDBA (6.06 ± 1.02). Conclusion: Based on the findings of this study, both materials have positive effect on alveolar ridge preservation after tooth extraction, but there was more new bone formation and less

  5. Properties of the "Orgamax" osteoplastic material made of a demineralized allograft bone

    NASA Astrophysics Data System (ADS)

    Podorognaya, V. T.; Kirilova, I. A.; Sharkeev, Yu. P.; Uvarkin, P. V.; Zhelezny, P. A.; Zheleznaya, A. P.; Akimova, S. E.; Novoselov, V. P.; Tupikova, L. N.

    2016-08-01

    We investigated properties of the "Orgamax" osteoplastic material, which was produced from a demineralized bone, in the treatment of extensive caries, in particular chronic pulpitis of the permanent teeth with unformed roots in children. The "Orgamax" osteoplastic material consists of demineralized bone chips, a collagen additive, and antibiotics. The surface morphology of the "Orgamax" osteoplastic material is macroporous, with the maximum pore size of 250 µm, whereas the surface morphology of the major component of "Orgamax", demineralized bone chips, is microporous, with a pore size of 10-20 µm. Material "Orgamax" is used in the treatment of complicated caries, particularly chronic pulpitis of permanent teeth with unformed roots in children. "Orgamax" filling a formed cavity exhibits antimicrobial properties, eliminates inflammation in the dental pulp, and, due to its osteoconductive and osteoinductive properties, undergoes gradual resorption, stimulates regeneration, and provides replacement of the defect with newly formed tissue. The dental pulp viability is completely restored, which ensures the complete formation of tooth roots with root apex closure in the long-term period.

  6. Molecular examination of bone marrow stromal cells and chondroitinase ABC-assisted acellular nerve allograft for peripheral nerve regeneration

    PubMed Central

    Wang, Ying; Jia, Hua; Li, Wen-Yuan; Guan, Li-Xin; Deng, Lingxiao; Liu, Yan-Cui; Liu, Gui-Bo

    2016-01-01

    The present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC treated ANA then seeded with BMSCs). After 8 weeks, the expression of nerve growth factor, brain-derived neurotrophic factor and vascular endothelial growth factor in the regenerated tissues were detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Axonal regeneration, motor neuron protection and functional recovery were examined by immunohistochemistry, horseradish peroxidase retrograde neural tracing and electrophysiological and tibialis anterior muscle recovery analyses. It was observed that combination therapy enhances the growth response of the donor nerve locally as well as distally, at the level of the spinal cord motoneuron and the target muscle organ. This phenomenon is likely due to the propagation of retrograde and anterograde transport of growth signals sourced from the graft site. Collectively, growth improvement on the donor nerve, target muscle and motoneuron ultimately contribute to efficacious axonal regeneration and functional recovery. Thorough investigation of molecular peripheral nerve injury combinatorial strategies are required for the optimization of efficacious therapy and full functional recovery following ANA. PMID:27698684

  7. Molecular examination of bone marrow stromal cells and chondroitinase ABC-assisted acellular nerve allograft for peripheral nerve regeneration

    PubMed Central

    Wang, Ying; Jia, Hua; Li, Wen-Yuan; Guan, Li-Xin; Deng, Lingxiao; Liu, Yan-Cui; Liu, Gui-Bo

    2016-01-01

    The present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC treated ANA then seeded with BMSCs). After 8 weeks, the expression of nerve growth factor, brain-derived neurotrophic factor and vascular endothelial growth factor in the regenerated tissues were detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Axonal regeneration, motor neuron protection and functional recovery were examined by immunohistochemistry, horseradish peroxidase retrograde neural tracing and electrophysiological and tibialis anterior muscle recovery analyses. It was observed that combination therapy enhances the growth response of the donor nerve locally as well as distally, at the level of the spinal cord motoneuron and the target muscle organ. This phenomenon is likely due to the propagation of retrograde and anterograde transport of growth signals sourced from the graft site. Collectively, growth improvement on the donor nerve, target muscle and motoneuron ultimately contribute to efficacious axonal regeneration and functional recovery. Thorough investigation of molecular peripheral nerve injury combinatorial strategies are required for the optimization of efficacious therapy and full functional recovery following ANA.

  8. Cellular complexity of the bone marrow hematopoietic stem cell niche.

    PubMed

    Calvi, Laura M; Link, Daniel C

    2014-01-01

    The skeleton serves as the principal site for hematopoiesis in adult terrestrial vertebrates. The function of the hematopoietic system is to maintain homeostatic levels of all circulating blood cells, including myeloid cells, lymphoid cells, red blood cells, and platelets. This action requires the daily production of more than 500 billion blood cells. The vast majority of these cells are synthesized in the bone marrow, where they arise from a limited number of hematopoietic stem cells (HSCs) that are multipotent and capable of extensive self-renewal. These attributes of HSCs are best demonstrated by marrow transplantation, where even a single HSC can repopulate the entire hematopoietic system. HSCs are therefore adult stem cells capable of multilineage repopulation, poised between cell fate choices which include quiescence, self-renewal, differentiation, and apoptosis. While HSC fate choices are in part determined by multiple stochastic fluctuations of cell autonomous processes, according to the niche hypothesis, signals from the microenvironment are also likely to determine stem cell fate. While it had long been postulated that signals within the bone marrow could provide regulation of hematopoietic cells, it is only in the past decade that advances in flow cytometry and genetic models have allowed for a deeper understanding of the microenvironmental regulation of HSCs. In this review, we will highlight the cellular regulatory components of the HSC niche.

  9. Improved in vitro biocompatibility of surface-modified hydroxyapatite sponge scaffold with gelatin and BMP-2 in comparison against a commercial bone allograft.

    PubMed

    Carpena, Nathaniel T; Min, Young-Ki; Lee, Byong-Taek

    2015-01-01

    This study aims to demonstrate the morphology and in vitro biocompatibility of neat and surface-modified hydroxyapatite sponge scaffold (SM-HASS) which was fabricated using a sponge replica method, and compared with the commercially available demineralized freeze-dried bone allograft (DFDBA). Surface-modifications were done by coating the surface area of the neat hydroxyapatite sponge scaffold (HASS) with either gelatin alone (HASS/G) or gelatin and BMP-2 growth factor (HASS/G+B). Scanning electron microscope (SEM), Fourier transform infrared (FTIR), porosity, pore size distribution, and compressive strength analyses showed that the addition of gelatin in HASS/G produced a morphologically and structurally similar scaffold to that of the allograft. The addition of BMP-2 improved the biocompatibility of the HASS/G+B in vitro using MC3T3-E1 cells which showed better cell viability, proliferation, and cell adhesion than on the allograft. Therefore, hydroxyapatite scaffold coated with gelatin polymer and gelatin with BMP-2 growth factor showed comparable performance against commercially available DFDBA from cadaver with regards to structure and in vitro biocompatibility.

  10. A comparative evaluation of extraction socket preservation with demineralized freeze-dried bone allograft alone and along with platelet-rich fibrin: A clinical and radiographic study

    PubMed Central

    Thakkar, Dhaval J.; Deshpande, Neeraj C.; Dave, Deepak H.; Narayankar, Suraj D.

    2016-01-01

    Aims: To investigate clinically and radiographically, the bone fill in extraction sockets using demineralized freeze-dried bone allograft alone and along with platelet-rich fibrin (PRF). Materials and Methods: A randomized controlled clinical trial was carried out on 36 nonrestorable single-rooted teeth sites. Sites were randomized into demineralized freeze-dried bone allograft (DFDBA) combined with PRF - test and DFDBA - control groups using a coin toss method. After the placement of graft material, collagen membrane was used to cover it. The clinical parameters recorded were ridge width and ridge height. All the parameters were recorded at baseline and at 90 and 180 days. Statistical Analysis Used: Independent t-test and paired t-test. Results: In both groups, there is significant reduction in loss of ridge width and ridge height from baseline to 90 days (P < 0.001), baseline to 180 days (P < 0.001), and 90–180 days (P < 0.001). However, when both the groups were compared the test group favored in the reduction of ridge width while there was no statistical difference in reduction of ridge height among at different intervals. Conclusions: Although DFDBA is considered as an ideal graft material, PRF can be used as an adjunctive with DFDBA for socket preservation.

  11. A comparative evaluation of extraction socket preservation with demineralized freeze-dried bone allograft alone and along with platelet-rich fibrin: A clinical and radiographic study

    PubMed Central

    Thakkar, Dhaval J.; Deshpande, Neeraj C.; Dave, Deepak H.; Narayankar, Suraj D.

    2016-01-01

    Aims: To investigate clinically and radiographically, the bone fill in extraction sockets using demineralized freeze-dried bone allograft alone and along with platelet-rich fibrin (PRF). Materials and Methods: A randomized controlled clinical trial was carried out on 36 nonrestorable single-rooted teeth sites. Sites were randomized into demineralized freeze-dried bone allograft (DFDBA) combined with PRF - test and DFDBA - control groups using a coin toss method. After the placement of graft material, collagen membrane was used to cover it. The clinical parameters recorded were ridge width and ridge height. All the parameters were recorded at baseline and at 90 and 180 days. Statistical Analysis Used: Independent t-test and paired t-test. Results: In both groups, there is significant reduction in loss of ridge width and ridge height from baseline to 90 days (P < 0.001), baseline to 180 days (P < 0.001), and 90–180 days (P < 0.001). However, when both the groups were compared the test group favored in the reduction of ridge width while there was no statistical difference in reduction of ridge height among at different intervals. Conclusions: Although DFDBA is considered as an ideal graft material, PRF can be used as an adjunctive with DFDBA for socket preservation. PMID:27630503

  12. Reconstruction of massive uncontained acetabular defects using allograft with cage or ring reinforcement: an assessment of the graft's ability to restore bone stock and its impact on the outcome of re-revision.

    PubMed

    Abolghasemian, M; Sadeghi Naini, M; Tangsataporn, S; Lee, P; Backstein, D; Safir, O; Kuzyk, P; Gross, A E

    2014-03-01

    We retrospectively reviewed 44 consecutive patients (50 hips) who underwent acetabular re-revision after a failed previous revision that had been performed using structural or morcellised allograft bone, with a cage or ring for uncontained defects. Of the 50 previous revisions, 41 cages and nine rings were used with allografts for 14 minor-column and 36 major-column defects. We routinely assessed the size of the acetabular bone defect at the time of revision and re-revision surgery. This allowed us to assess whether host bone stock was restored. We also assessed the outcome of re-revision surgery in these circumstances by means of radiological characteristics, rates of failure and modes of failure. We subsequently investigated the factors that may affect the potential for the restoration of bone stock and the durability of the re-revision reconstruction using multivariate analysis. At the time of re-revision, there were ten host acetabula with no significant defects, 14 with contained defects, nine with minor-column, seven with major-column defects and ten with pelvic discontinuity. When bone defects at re-revision were compared with those at the previous revision, there was restoration of bone stock in 31 hips, deterioration of bone stock in nine and remained unchanged in ten. This was a significant improvement (p < 0.001). Morselised allografting at the index revision was not associated with the restoration of bone stock. In 17 hips (34%), re-revision was possible using a simple acetabular component without allograft, augments, rings or cages. There were 47 patients with a mean follow-up of 70 months (6 to 146) available for survival analysis. Within this group, the successful cases had a minimum follow-up of two years after re-revision. There were 22 clinical or radiological failures (46.7%), 18 of which were due to aseptic loosening. The five and ten year Kaplan-Meier survival rate was 75% (95% CI, 60 to 86) and 56% (95% CI, 40 to 70) respectively with aseptic

  13. Alveolar bone loss in osteoporosis: a loaded and cellular affair?

    PubMed

    Jonasson, Grethe; Rythén, Marianne

    2016-01-01

    Maxillary and mandibular bone mirror skeletal bone conditions. Bone remodeling happens at endosteal surfaces where the osteoclasts and osteoblasts are situated. More surfaces means more cells and remodeling. The bone turnover rate in the mandibular alveolar process is probably the fastest in the body; thus, the first signs of osteoporosis may be revealed here. Hormones, osteoporosis, and aging influence the alveolar process and the skeletal bones similarly, but differences in loading between loaded, half-loaded, and unloaded bones are important to consider. Bone mass is redistributed from one location to another where strength is needed. A sparse trabeculation in the mandibular premolar region (large intertrabecular spaces and thin trabeculae) is a reliable sign of osteopenia and a high skeletal fracture risk. Having dense trabeculation (small intertrabecular spaces and well-mineralized trabeculae) is generally advantageous to the individual because of the low fracture risk, but may imply some problems for the clinician.

  14. Alveolar bone loss in osteoporosis: a loaded and cellular affair?

    PubMed Central

    Jonasson, Grethe; Rythén, Marianne

    2016-01-01

    Maxillary and mandibular bone mirror skeletal bone conditions. Bone remodeling happens at endosteal surfaces where the osteoclasts and osteoblasts are situated. More surfaces means more cells and remodeling. The bone turnover rate in the mandibular alveolar process is probably the fastest in the body; thus, the first signs of osteoporosis may be revealed here. Hormones, osteoporosis, and aging influence the alveolar process and the skeletal bones similarly, but differences in loading between loaded, half-loaded, and unloaded bones are important to consider. Bone mass is redistributed from one location to another where strength is needed. A sparse trabeculation in the mandibular premolar region (large intertrabecular spaces and thin trabeculae) is a reliable sign of osteopenia and a high skeletal fracture risk. Having dense trabeculation (small intertrabecular spaces and well-mineralized trabeculae) is generally advantageous to the individual because of the low fracture risk, but may imply some problems for the clinician. PMID:27471408

  15. Biomechanical Evaluation of Different Fixation Methods for Mandibular Anterior Segmental Osteotomy Using Finite Element Analysis, Part Two: Superior Repositioning Surgery With Bone Allograft.

    PubMed

    Kilinç, Yeliz; Erkmen, Erkan; Kurt, Ahmet

    2016-01-01

    In this study, the biomechanical behavior of different fixation methods used to fix the mandibular anterior segment following various amounts of superior repositioning was evaluated by using Finite Element Analysis (FEA). The three-dimensional finite element models representing 3 and 5 mm superior repositioning were generated. The gap in between segments was assumed to be filled by block bone allograft and resignated to be in perfect contact with the mandible and segmented bone. Six different finite element models with 2 distinct mobilization rate including 3 different fixation configurations, double right L (DRL), double left L (DLL), or double I (DI) miniplates with monocortical screws, correspondingly were created. A comparative evaluation has been made under vertical, horizontal and oblique loads. The von Mises and principal maximum stress (Pmax) values were calculated by finite element solver programme. The first part of our ongoing Finite Element Analysis research has been addressed to the mechanical behavior of the same fixation configurations in nongrafted models. In comparison with the findings of the first part of the study, it was concluded that bone graft offers superior mechanical stability without any limitation of mobilization and less stress on the fixative appliances as well as in the bone. PMID:26703029

  16. Biomechanical Evaluation of Different Fixation Methods for Mandibular Anterior Segmental Osteotomy Using Finite Element Analysis, Part Two: Superior Repositioning Surgery With Bone Allograft.

    PubMed

    Kilinç, Yeliz; Erkmen, Erkan; Kurt, Ahmet

    2016-01-01

    In this study, the biomechanical behavior of different fixation methods used to fix the mandibular anterior segment following various amounts of superior repositioning was evaluated by using Finite Element Analysis (FEA). The three-dimensional finite element models representing 3 and 5 mm superior repositioning were generated. The gap in between segments was assumed to be filled by block bone allograft and resignated to be in perfect contact with the mandible and segmented bone. Six different finite element models with 2 distinct mobilization rate including 3 different fixation configurations, double right L (DRL), double left L (DLL), or double I (DI) miniplates with monocortical screws, correspondingly were created. A comparative evaluation has been made under vertical, horizontal and oblique loads. The von Mises and principal maximum stress (Pmax) values were calculated by finite element solver programme. The first part of our ongoing Finite Element Analysis research has been addressed to the mechanical behavior of the same fixation configurations in nongrafted models. In comparison with the findings of the first part of the study, it was concluded that bone graft offers superior mechanical stability without any limitation of mobilization and less stress on the fixative appliances as well as in the bone.

  17. Role of Demineralized Allograft Subchondral Bone in the Treatment of Shoulder Lesions of the Talus: Clinical Results With Two-Year Follow-Up.

    PubMed

    Galli, Melissa M; Protzman, Nicole M; Bleazey, Scott T; Brigido, Stephen A

    2015-01-01

    Cystic osteochondral lesions of the talus present a considerable challenge for foot and ankle surgeons. The purpose of the present study was to evaluate the effect of a medial malleolar osteotomy and implantation of demineralized allograft subchondral bone on pain and function 2 years after surgery. For inclusion, patients demonstrated radiographic evidence of a medial cystic full-thickness osteochondral defect of the talus and previously failed microfracture (N = 12). We hypothesized that improvements in pain and disability would be maintained across time. Compared with the preoperative values, 2 years after surgery, pain and disability had significantly reduced (p < .001). Significant reductions had occurred in postoperative pain from 6 months to 1 year (p = .001) and from 6 months to 2 years (p = .005). Similarly, significant reductions had occurred in postoperative disability from 6 months to 1 year (p = .008) and from 6 months to 2 years (p = .03). The reductions in postoperative pain and disability were maintained from 1 year to 2 years (p ≥ .79). Multiple regression analyses identified depression as a predictor of 2-year postoperative pain (R(2) = 0.36, p = .04). No variables were identified as significant predictors of postoperative disability at 2 years. Other than 1 previously reported peroneal deep venous thrombosis, no additional complications occurred. With successful graft incorporation, no inflammatory response, and no additional complications, the allograft subchondral plug appears to successfully treat osteochondral lesions of the talus and maintain improvements in pain and disability at intermediate follow-up.

  18. Structural and cellular changes during bone growth in healthy children.

    PubMed

    Parfitt, A M; Travers, R; Rauch, F; Glorieux, F H

    2000-10-01

    Normal postnatal bone growth is essential for the health of adults as well as children but has never been studied histologically in human subjects. Accordingly, we analyzed iliac bone histomorphometric data from 58 healthy white subjects, aged 1.5-23 years, 33 females and 25 males, of whom 48 had undergone double tetracycline labeling. The results were compared with similar data from 109 healthy white women, aged 20-76 years, including both young adult reference ranges and regressions on age. There was a significant increase with age in core width, with corresponding increases in both cortical width and cancellous width. In cancellous bone there were increases in bone volume and trabecular thickness, but not trabecular number, wall thickness, interstitial thickness, and inferred erosion depth. Mineral apposition rates declined on the periosteal envelope and on all subdivisions of the endosteal envelope. Because of the concomitant increase in wall thickness, active osteoblast lifespan increased substantially. Bone formation rate was almost eight times higher on the outer than on the inner periosteum, and more than four times higher on the inner than on the outer endocortical surface. On the cancellous surface, bone formation rate and activation frequency declined in accordance with a fifth order polynomial that matched previously published biochemical indices of bone turnover. The analysis suggested the following conclusions: (1) Between 2 and 20 years the ilium grows in width by periosteal apposition (3.8 mm) and endocortical resorption (3.2 mm) on the outer cortex, and net periosteal resorption (0.4 mm) and net endocortical formation (1.0 mm) on the inner cortex. (2) Cortical width increases from 0.52 mm at age 2 years to 1.14 mm by age 20 years. To attain adult values there must be further endocortical apposition of 0.25 mm by age 30 years, at a time when cancellous bone mass is declining. (3) Lateral modeling drift of the outer cortex enlarges the marrow cavity

  19. Osteoblast dysfunctions in bone diseases: from cellular and molecular mechanisms to therapeutic strategies.

    PubMed

    Marie, Pierre J

    2015-04-01

    Several metabolic, genetic and oncogenic bone diseases are characterized by defective or excessive bone formation. These abnormalities are caused by dysfunctions in the commitment, differentiation or survival of cells of the osteoblast lineage. During the recent years, significant advances have been made in our understanding of the cellular and molecular mechanisms underlying the osteoblast dysfunctions in osteoporosis, skeletal dysplasias and primary bone tumors. This led to suggest novel therapeutic approaches to correct these abnormalities such as the modulation of WNT signaling, the pharmacological modulation of proteasome-mediated protein degradation, the induction of osteoprogenitor cell differentiation, the repression of cancer cell proliferation and the manipulation of epigenetic mechanisms. This article reviews our current understanding of the major cellular and molecular mechanisms inducing osteoblastic cell abnormalities in age-related bone loss, genetic skeletal dysplasias and primary bone tumors, and discusses emerging therapeutic strategies to counteract the osteoblast abnormalities in these disorders of bone formation.

  20. The use of osteochondral allograft with bone marrow-derived mesenchymal cells and hinge joint distraction in the treatment of post-collapse stage of osteonecrosis of the femoral head.

    PubMed

    Gagala, J; Tarczynska, M; Gaweda, K; Matuszewski, L

    2014-09-01

    Osteonecrosis of the femoral head is an entity which occurs mainly in young and active patients aged between 20 and 50. The success of hip joint preserving treatments ranges from 15% to 50% depending on the stage and amount of osteonecrotic lesion. Total hip replacement is indicated in late post-collapse hips but it has unsatisfactory survival because of the wear and osteolysis in young and active patients. Osteochondral allografts have been reported in the treatment of large articular lesions with defects in underlying bone in knee, talus and shoulder. By combining osteoconductive properties of osteochondral allograft with osteogenic abilities of bone marrow-derived mesenchymal cells it has a potential to be an alternative to an autologous graft. The adjunct of hinged joint distraction should minimize stresses in subchondral bone to promote creeping substitution and prevent femoral head collapse. Unlike current treatment modalities, it would provide both structural support and allow bony and articular substitution.

  1. A Comparision of Two Types of Decalcified Freeze-Dried Bone Allograft in Treatment of Dehiscence Defects around Implants in Dogs

    PubMed Central

    Abed, Ahmad Moghareh; Pestekan, Rasool Heidari; Yaghini, Jaber; Razavi, Seyed Mohammad; Tavakoli, Mohammad; Amjadi, Mohammad

    2011-01-01

    Background: Decalcified freeze-dried bone allograft (DFDBA) may have the potential to enhance bone formation around dental implants. Our aim in this study was the evaluation and comparison of two types of DFDBA in treatment of dehiscence defects around Euroteknika® implants in dogs. Methods: In this prospective clinical trial animal study, all mandibular premolars of three Iranian dogs were extracted. After 3 months of healing, fifteen SLA type Euroteknika® dental implants (Natea) with 4.1mm diameter and 10mm length were placed in osteotomy sites with dehiscence defects of 5mm length, 4 mm width, and 3mm depth. Guided bone regeneration (GBR) procedures were performed using Cenobone and collagen membrane for six implants, the other six implants received Dembone and collagen membrane and the final three implants received only collagen membrane. All implants were submerged. After 4 months of healing, implants were uncovered and stability (Implant Stability Quotient) of all implants was measured. Then, block biopsies of each implant site were taken and processed for ground sectioning and histomorphometric analysis. The data was analyzed by ANOVA and Pearson tests. P value less than 0.05 was considered to be significant. Results: All implants osseointegrated after 4 months. The mean values of bone to implant contact for histomorphometric measurements of Cenobone, Denobone, and control groups were 77.36 ± 9.96%, 78.91 ± 11.9% and 71.56 ± 5.61% respectively, with no significant differences among the various treatment groups. The correlation of Implant Stability Quotient and histomorphometric techniques was 0.692. Conclusion: In treating of dehiscence defects with GBR technique in this study, adding DFDBA did not significantly enhance the percentages of bone-to-implant contact measurements; and Implant Stability Quotient Resonance Frequency Analysis appeared to be a precise technique. PMID:22013476

  2. Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice

    SciTech Connect

    Colnot, C. . E-mail: colnotc@orthosurg.ucsf.edu; Huang, S.; Helms, J.

    2006-11-24

    The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis.

  3. The use of femoral struts and impacted cancellous bone allograft in patients with severe femoral bone loss who undergo revision total hip replacement: a three- to nine-year follow-up.

    PubMed

    Buttaro, M A; Costantini, J; Comba, F; Piccaluga, F

    2012-02-01

    We determined the midterm survival, incidence of peri-prosthetic fracture and the enhancement of the width of the femur when combining struts and impacted bone allografts in 24 patients (25 hips) with severe femoral bone loss who underwent revision hip surgery. The pre-operative diagnosis was aseptic loosening in 16 hips, second-stage reconstruction in seven, peri-prosthetic fracture in one and stem fracture in one hip. A total of 14 hips presented with an Endoklinik grade 4 defect and 11 hips a grade 3 defect. The mean pre-operative Merle D'Aubigné and Postel score was 5.5 points (1 to 8). The survivorship was 96% (95% confidence interval 72 to 98) at a mean of 54.5 months (36 to 109). The mean functional score was 17.3 points (16 to 18). One patient in which the strut did not completely bypass the femoral defect was further revised using a long cemented stem due to peri-prosthetic fracture at six months post-operatively. The mean subsidence of the stem was 1.6 mm (1 to 3). There was no evidence of osteolysis, resorption or radiolucencies during follow-up in any hip. Femoral width was enhanced by a mean of 41% (19% to 82%). A total of 24 hips had partial or complete bridging of the strut allografts. This combined biological method was associated with a favourable survivorship, a low incidence of peri-prosthetic fracture and enhancement of the width of the femur in revision total hip replacement in patients with severe proximal femoral bone loss.

  4. A mathematical model of cortical bone remodeling at cellular level under mechanical stimulus

    NASA Astrophysics Data System (ADS)

    Qin, Qing-Hua; Wang, Ya-Nan

    2012-12-01

    A bone cell population dynamics model for cortical bone remodeling under mechanical stimulus is developed in this paper. The external experiments extracted from the literature which have not been used in the creation of the model are used to test the validity of the model. Not only can the model compare reasonably well with these experimental results such as the increase percentage of final values of bone mineral content (BMC) and bone fracture energy (BFE) among different loading schemes (which proves the validity of the model), but also predict the realtime development pattern of BMC and BFE, as well as the dynamics of osteoblasts (OBA), osteoclasts (OCA), nitric oxide (NO) and prostaglandin E2 (PGE2) for each loading scheme, which can hardly be monitored through experiment. In conclusion, the model is the first of its kind that is able to provide an insight into the quantitative mechanism of bone remodeling at cellular level by which bone cells are activated by mechanical stimulus in order to start resorption/formation of bone mass. More importantly, this model has laid a solid foundation based on which future work such as systemic control theory analysis of bone remodeling under mechanical stimulus can be investigated. The to-be identified control mechanism will help to develop effective drugs and combined nonpharmacological therapies to combat bone loss pathologies. Also this deeper understanding of how mechanical forces quantitatively interact with skeletal tissue is essential for the generation of bone tissue for tissue replacement purposes in tissue engineering.

  5. Cellular lead toxicity and metabolism in primary and clonal osteoblastic bone cells

    SciTech Connect

    Long, G.J.; Rosen, J.F.; Pounds, J.G. )

    1990-02-01

    A knowledge of bone lead metabolism is critical for understanding the toxicological importance of bone lead, as a toxicant both to bone cells and to soft tissues of the body, as lead is mobilized from large reservoirs in hard tissues. To further understand the processes that mediate metabolism of lead in bone, it is necessary to determine lead metabolism at the cellular level. Experiments were conducted to determine the intracellular steady-state {sup 210}Pb kinetics in cultures of primary and clonal osteoblastic bone cells. Osteoblastic bone cells obtained by sequential collagenase digestion of mouse calvaria or rat osteosarcoma (ROS 17/2.8) cells were labeled with {sup 210}Pb as 5 microM lead acetate for 20 hr, and kinetic parameters were determined by measuring the efflux of {sup 210}Pb from the cells over a {sup 210}-min period. The intracellular metabolism of {sup 210}Pb was characterized by three kinetic pools of {sup 210}Pb in both cell types. Although the values of these parameters differed between the primary osteoblastic cells and ROS cells, the profile of {sup 210}Pb was remarkably similar in both cell types. Both types exhibited one large, slowly exchanging pool (S3), indicative of mitochondrial lead. These data show that primary osteoblastic bone cells and ROS cells exhibit similar steady-state lead kinetics, and intracellular lead distribution. These data also establish a working model of lead kinetics in osteoblastic bone cells and now permit an integrated view of lead kinetics in bone.

  6. Allograft tolerance in pigs after fractionated lymphoid irradiation. I. Skin grafts after partial lateral irradiation and bone marrow cell grafting

    SciTech Connect

    Vaiman, M.; Daburon, F.; Remy, J.; Villiers, P.A.; de Riberolles, C.; Lecompte, Y.; Mahouy, G.; Fradelizi, D.

    1981-05-01

    Experiments with pigs have been performed to establish bone marrow chimerism and skin graft tolerance between SLA genotyped animals. Recipients were conditioned by means of fractionated partial irradiation from lateral cobalt sources (partial lateral irradiation (PLI)). The head, neck, and lungs were protected with lead, the rest of the body being irradiated including the thymus, the majority of lymphoid organs with spleen, and most of the bone marrow sites.

  7. A clinical and radiological evaluation of the relative efficacy of demineralized freeze-dried bone allograft versus anorganic bovine bone xenograft in the treatment of human infrabony periodontal defects: A 6 months follow-up study

    PubMed Central

    Blaggana, Vikram; Gill, Amarjit Singh; Blaggana, Anshu

    2014-01-01

    Background: The ultimate goal of periodontal therapy entails regeneration of the periodontal tissues lost as a consequence of periodontitis. Predictable correction of vertical osseous defects has however posed as a constant therapeutic challenge. The aim of our present study is to evaluate the relative efficacy of demineralized freeze-dried bone allograft (DFDBA) vs anorganic bovine bone xenograft (ABBX) in the treatment of human infrabony periodontal defects. Materials and Methods: 15 patients with 30 bilaterally symmetrical defect sites in either of the arches, in the age group of 25-50 years were selected as part of split-mouth study design. Defect-A (right side) was grafted with DFDBA while Defect-B (left side) was grafted with ABBX. Various clinical and radiographic parameters viz. probing depth(PD), clinical attachment level(CAL) and linear bone fill were recorded preoperatively, 12- & 24-weeks postoperatively. Results: Both defect-A & defect-B sites exhibited a highly significant reduction in probing depth, and gain in clinical attachment level and linear bone fill at 12-weeks & at the end of 24-weeks. Comparative evaluation between the study groups revealed a statistically non-significant reduction in probing depth (P<0.1) and mean gain in linear bone fill (P<0.1). However, there was a statistically significant gain in clinical attachment level (P<0.05) in Defect-A (CD=0.356) as compared to Defect-B (CD=0.346). Conclusions: Within the limits of this study, both the materials viz. ABBX and DFDBA are beneficial for the treatment of periodontal infrabony defects. Both the materials were found to be equally effective in all respects except the gain in attachment level, which was found to be more with DFDBA. Long-term studies are suggested to evaluate further the relative efficacy of the two grafts. PMID:25425822

  8. Evaluation of the Therapeutic Potential of Bone Marrow-Derived Myeloid Suppressor Cell (MDSC) Adoptive Transfer in Mouse Models of Autoimmunity and Allograft Rejection

    PubMed Central

    Bouchet-Delbos, Laurence; Beriou, Gaelle; Merieau, Emmanuel; Hill, Marcelo; Delneste, Yves; Cuturi, Maria Cristina; Louvet, Cedric

    2014-01-01

    Therapeutic use of immunoregulatory cells represents a promising approach for the treatment of uncontrolled immunity. During the last decade, myeloid-derived suppressor cells (MDSC) have emerged as novel key regulatory players in the context of tumor growth, inflammation, transplantation or autoimmunity. Recently, MDSC have been successfully generated in vitro from naive mouse bone marrow cells or healthy human PBMCs using minimal cytokine combinations. In this study, we aimed to evaluate the potential of adoptive transfer of such cells to control auto- and allo-immunity in the mouse. Culture of bone marrow cells with GM-CSF and IL-6 consistently yielded a majority of CD11b+Gr1hi/lo cells exhibiting strong inhibition of CD8+ T cell proliferation in vitro. However, adoptive transfer of these cells failed to alter antigen-specific CD8+ T cell proliferation and cytotoxicity in vivo. Furthermore, MDSC could not prevent the development of autoimmunity in a stringent model of type 1 diabetes. Rather, loading the cells prior to injection with a pancreatic neo-antigen peptide accelerated the development of the disease. Contrastingly, in a model of skin transplantation, repeated injection of MDSC or single injection of LPS-activated MDSC resulted in a significant prolongation of allograft survival. The beneficial effect of MDSC infusions on skin graft survival was paradoxically not explained by a decrease of donor-specific T cell response but associated with a systemic over-activation of T cells and antigen presenting cells, prominently in the spleen. Taken together, our results indicate that in vitro generated MDSC bear therapeutic potential but will require additional in vitro factors or adjunct immunosuppressive treatments to achieve safe and more robust immunomodulation upon adoptive transfer. PMID:24927018

  9. Prolonged bone marrow and skin allograft survival after pretransplant conditioning with cyclophosphamide and total lymphoid irradiation. [Mice

    SciTech Connect

    Kersey, J.H.; Kruger, J.; Song, C.; Kloster, B.

    1980-05-01

    Current studies were designed to provide long-term survival of allogeneic skin and bone marrow in mice preconditioned with various combinations of cyclophosphamide (CY) and/or total lymphoid irradiation (TLI). Long-term skin graft and bone marrow survival was obtained across the major histocompatibility barrier (BALB/c into C57BL/6) using pregrafting conditioning with either fractionated TLI or the combination of CY with a single dose of TLI. CY alone and a single dose of TLI alone were relatively ineffective as regrafting immunosuppressive combinations. Allogeneic bone marrow was required for long-term skin graft survival with either conditioning regimen. Allogeneic marrow transplantation resulted in somewhat more deaths than syngeneic transplantation with both CY + TLI and fractionated TLI.

  10. Transforaminal lumbar interbody fusion rates in patients using a novel titanium implant and demineralized cancellous allograft bone sponge

    PubMed Central

    Girasole, Gerard; Muro, Gerard; Mintz, Abraham; Chertoff, Jason

    2013-01-01

    Background Transforaminal lumbar interbody fusion (TLIF) with grafting and implant options like iliac crest bone graft (ICBG), recombinant bone morphogenetic protein (rhBMP), and polyetheretherketone (PEEK) cages have been reported to achieve extremely high fusion rates. Unfortunately, these options have also been frequently cited in the literature as causing postoperative morbidity and complications at a high cost. Knowing this, we sought to investigate TLIF using an acid-etched, roughened titanium cage that upregulates osteogenesis to see if similar fusion rates to those cited for ICBG, rhBMP, and PEEK cages could be safely achieved with minimal morbidity and complications. Materials and methods A radiographic fusion study of 82 patients who underwent TLIF using an acid-etched, roughened titanium cage with demineralized cancellous bone graft was conducted. Fusion was assessed and graded by an independent radiologist using computed tomography scan with sagittal and coronal reconstructions. Results Fusion rates at 6 months were 41 of 44 (93.2%) and at 12 months were 37 of 38 (97.4%). There were no radiographic device-related complications. Conclusions TLIF with an acid-etched, roughened titanium cage filled with a decalcified bone graft achieved similar fusion rates to historical controls using ICBG, rhBMP, and PEEK. PMID:25580378

  11. Proximal humeral osteoarticular allografts: technique, pearls and pitfalls, outcomes.

    PubMed

    Farfalli, German L; Ayerza, Miguel A; Muscolo, D Luis; Aponte-Tinao, Luis A

    2015-12-01

    Allograft transplantation is a biologic reconstruction option for massive bone defects after resection of bone sarcomas. This type of reconstruction not only restores bone stock but it also allows us to reconstruct the joint anatomically. These factors are a major concern, especially in a young and active population.We are describing indications, surgical techniques, pearls and pitfalls, and outcomes of proximal humeral osteoarticular allografts, done at present time in our institution.We found that allograft fractures and articular complications, as epiphyseal resorption and subchondral fracture, are the main complications observed in proximal humerus osteoarticular allograft reconstructions. Nevertheless, only fractures need a reconstruction revision. Joint complications may adversely affect the limb function, but for this reason, an allograft revision is rarely performed.

  12. Clinical and radiographic evaluation of copolymerized Polylactic/polyglycolic acids as a bone filler in combination with a cellular dermal matrix graft around immediate implants

    PubMed Central

    Soliman, Mahitab M.; Zaki, Azza Abdulrahman; El Gazaerly, Hanaa Mohamed; Shemmrani, Ammar Al; Sorour, Abd El Latif

    2014-01-01

    Objective This study was conducted to evaluate clinically and radiographically the use of a cellular dermal matrix allograft (Alloderm) in combination with PLA/PGA (Fisiograft) around immediate implants. Materials and Methods Fourteen patients were included in this study, three patients received two implants, total of seventeen implants were placed. Periapical radiographs and orthopantomographs were taken. The selected teeth were extracted atraumatically after the reflection of full thickness flaps. One-piece Zimmer implants were placed immediately into the sockets. Weeks from implantation, radiographic evaluation was made at 6 Fisiograft in powder form was placed in the osseous defects around the implants. The implants were immediately restored with provisional crowns free from occlusion. Patients were clinically evaluated at 3, 6, and 14 months after loading which was done after 6 weeks from implantation. Radiographic evaluation was made at 6 and 14 months from implant placement. Results showed that immediate implantation was successful in sixteen out of seventeen implants, clinical parameters regarding plaque index, gingival index, there was a slight decrease through the follow-up periods from 3 to 14 months but it was non-significant, while there was a significant decrease in the probing depth. Radiographically there was a significant increase in the bone density from 6 to 14 months post loading, while the vertical bone defect was significantly decreased. The fisiograft functioned well as space maker and scaffolding material. The Alloderm performed well as a membrane to be used in association with immediate implants and it has a good potentiality for increasing the width of the keratinized gingiva, which is an important feature for implant esthetics. Conclusion the combination technique between the bone graft and the membrane proved to be successful to overcome dehiscence and osseous defects around immediate implants. PMID:25780357

  13. Radiation sterilization of tissue allografts: A review

    PubMed Central

    Singh, Rita; Singh, Durgeshwer; Singh, Antaryami

    2016-01-01

    Tissue substitutes are required in a number of clinical conditions for treatment of injured and diseased tissues. Tissues like bone, skin, amniotic membrane and soft tissues obtained from human donor can be used for repair or reconstruction of the injured part of the body. Allograft tissues from human donor provide an excellent alternative to autografts. However, major concern with the use of allografts is the risk of infectious disease transmission. Therefore, tissue allografts should be sterilized to make them safe for clinical use. Gamma radiation has several advantages and is the most suitable method for sterilization of biological tissues. This review summarizes the use of gamma irradiation technology as an effective method for sterilization of biological tissues and ensuring safety of tissue allografts. PMID:27158422

  14. Cellular and morphological aspects of fibrodysplasia ossificans progressiva. Lessons of formation, repair, and bone bioengineering.

    PubMed

    Martelli, Anderson; Santos, Arnaldo Rodrigues

    2014-01-01

    Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disease that causes bone formation within the muscles, tendons, ligaments and connective tissues. There is no cure for this disorder and only treatment of the symptoms is available. The purpose of this study was to review the literature and describe the clinical, cellular and molecular aspects of FOP. The material used for the study was obtained by reviewing scientific articles published in various literature-indexed databases. In view of its rarity and of the lack of insightful information and the unpredictability of its course, FOP is a challenging disorder for professionals who are confronted by it. However, this rare disease raises a great deal of interest because understanding the mechanism of mature bone formation can encourage research lines related to bone regeneration and the prevention of heterotopic ossification.

  15. [Whole-body MR imaging for evaluation of bone marrow cellularity in aplastic anemia].

    PubMed

    Iizuka, M; Nagai, K; Sugihara, T; Tamada, T; Imai, S; Kojo, T; Kajihara, Y; Fukunaga, M

    2001-08-01

    The aim of this study was to investigate the usefulness of whole-body MRI(WB-MRI) in the evaluation of cellularity in bone marrow and the distribution of fatty marrow in aplastic anemia. WB-MRI was performed on five patients with aplastic anemia who ranged in age from 62 to 70 years of age, and on four controls with malignant lymphoma who ranged in age from 59 to 67 years. Coronal images were obtained using a body coil with an FOV of 48 cm x 48 cm, and with both fast short T1 inversion recovery(STIR) and spin-echo T1-weighted(T1-WI) in three regions: (1) head to thorax, (2) abdomen to pelvis, and (3) lower extremities. The findings on WB-MRI were compared with those of histological studies of bone marrow at the sternum and the posterior iliac crest. The results were as follows: (1) there was a correlation between the cellularity of histological studies of bone marrow and signal intensity on WB-MRI; (2) WB-MRI could detect the activity of bone marrow; and (3) in a comparison of signal intensity in aplastic anemia and control subjects, there were differences of signal intensity in the central marrow. PMID:11577436

  16. Graphene oxide scaffold accelerates cellular proliferative response and alveolar bone healing of tooth extraction socket

    PubMed Central

    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

  17. 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

  18. Induction of donor-type chimerism in murine recipients of bone marrow allografts by different radiation regimens currently used in treatment of leukemia patients

    SciTech Connect

    Salomon, O.; Lapidot, T.; Terenzi, A.; Lubin, I.; Rabi, I.; Reisner, Y. )

    1990-11-01

    Three radiation protocols currently used in treatment of leukemia patients before bone marrow transplantation (BMT) were investigated in a murine model (C57BL/6----C3H/HeJ) for BM allograft rejection. These include (a) a single dose of total body irradiation (8.5 Gy TBI delivered at a dose rate of 0.2 Gy/min), (b) fractionated TBI 12 Gy administered in six fractions, 2 Gy twice a day in 3 days, delivered at a dose rate of 0.1 Gy/min, and (c) hyperfractionated TBI (14.4 Gy administered in 12 fractions, 1.2 Gy three times a day in 3 days, delivered at a dose rate of 0.1 Gy/min). Donor-type chimerism 6 to 8 weeks after BMT and hematologic reconstitution on day 12 after BMT found in these groups were compared with results obtained in mice conditioned with 8 Gy TBI delivered at a dose rate of 0.67 Gy/min, routinely used in this murine model. The results in both parameters showed a marked advantage for the single dose 8.5 Gy TBI over all the other treatments. This advantage was found to be equivalent to three- to fourfold increment in the BM inoculum when compared with hyperfractionated radiation, which afforded the least favorable conditions for development of donor-type chimerism. The fractionated radiation protocol was equivalent in its efficacy to results obtained in mice irradiated by single-dose 8 Gy TBI, both of which afforded a smaller but not significant advantage over the hyperfractionated protocol. This model was also used to test the effect of radiation dose rate on the development of donor-type chimerism. A significant enhancement was found after an increase in dose rate from 0.1 to 0.7 Gy/min. Further enhancement could be achieved when the dose rate was increased to 1.3 Gy/min, but survival at this high dose rate was reduced.

  19. The cellular metabolism of lead and calcium: A kinetic analysis in cultured osteoclastic bone cells

    SciTech Connect

    Rosen, J.F.; Pounds, J.G.

    1986-01-01

    Characterization of lead metabolism in bone is necessary to understand the role of skeletal lead, an endogenous source of this toxic metal, in the expression of adverse effects of lead intoxication in concert with external sources. Moreover, it has been postulated that an early manifestation of lead toxicity common to diverse cell types may be pertubations in intracellular calcium homeostasis. Furthermore, it has been suggested that calciotropic hormones may express their actions on bone cells by modulating the messenger functions of intracellular Ca. Before these postulates can be more fully tested, the homeostasis of intracellular Pb and Ca must be understood more clearly. We have designed experiments to characterize the steady-state kinetic distribution and behavior of /sup 210/Pb and /sup 45/Ca in osteoclastic bone cells and to identify biological structures or functions associated with the kinetic pools. Cultures were labeled with /sup 210/Pb or /sup 45/Ca and the kinetic parameters were obtained by analysis of isotope washout curves. Cellular metabolism was defined by three kinetic pools of intracellular Pb and Ca. The largest and slowest exchanging pool was characterized as a mitochondrial compartment for both metals. These data indicate that Pb and Ca share similar intracellular pathways in osteoclastic bone cells and that both metals are readily exchangeable in this in vitro system. The results of other experiments have revealed that lead, at relatively low medium concentrations, produces a marked increase in all three intracellular Ca compartments. 18 refs., 2 figs.

  20. Cellular and molecular mechanisms for the bone response to mechanical loading

    NASA Technical Reports Server (NTRS)

    Bloomfield, S. A.

    2001-01-01

    To define the cellular and molecular mechanisms for the osteogenic response of bone to increased loading, several key steps must be defined: sensing of the mechanical signal by cells in bone, transduction of the mechanical signal to a biochemical one, and transmission of that biochemical signal to effector cells. Osteocytes are likely to serve as sensors of loading, probably via interstitial fluid flow produced during loading. Evidence is presented for the role of integrins, the cell's actin cytoskeleton, G proteins, and various intracellular signaling pathways in transducing that mechanical signal to a biochemical one. Nitric oxide, prostaglandins, and insulin-like growth factors all play important roles in these pathways. There is growing evidence for modulation of these mechanotransduction steps by endocrine factors, particularly parathyroid hormone and estrogen. The efficiency of this process is also impaired in the aged animal, yet what remains undefined is at what step mechanotransduction is affected.

  1. Septic arthritis following anterior cruciate ligament reconstruction using tendon allografts--Florida and Louisiana, 2000.

    PubMed

    2001-12-01

    In the United States, approximately 50,000 knee surgeries are performed each year for repairing anterior cruciate ligament (ACL) injuries. Tissue allografts frequently are used for ACL reconstruction, and septic arthritis is a rare complication of such procedures. This report describes four patients who acquired postsurgical septic arthritis probably associated with contaminated bone-tendon-bone allografts used for ACL reconstruction. Effective sterilization methods that do not functionally alter musculoskeletal tissue are needed to prevent allograft-related infections.

  2. Septic arthritis following anterior cruciate ligament reconstruction using tendon allografts--Florida and Louisiana, 2000.

    PubMed

    2001-12-01

    In the United States, approximately 50,000 knee surgeries are performed each year for repairing anterior cruciate ligament (ACL) injuries. Tissue allografts frequently are used for ACL reconstruction, and septic arthritis is a rare complication of such procedures. This report describes four patients who acquired postsurgical septic arthritis probably associated with contaminated bone-tendon-bone allografts used for ACL reconstruction. Effective sterilization methods that do not functionally alter musculoskeletal tissue are needed to prevent allograft-related infections. PMID:11770503

  3. The role of the macrophage in cardiac allograft rejection in the rat.

    PubMed

    MacPherson, G G; Christmas, S E

    1984-01-01

    Macrophages (MO) are a well-recognized component of the cellular infiltrate in first-set (acute) allograft rejections. Definition of their actual role in the mediation of rejection depends on showing that they are present in sufficient numbers and at relevant sites in rejecting grafts, that they are capable of mediating damage to graft tissues, and that their absence interfere with rejection. We have used rat heart allografts to investigate these questions. Normal rejection takes 7 days. By this time the MO is the major infiltrating cell and large numbers are present close to myocardial cells. In some cases they appear to push pseudopodia into the cell. Neither they, or other cell types, appear to be interacting with endothelial cells. MO extracted from rejecting allografts are potent secretors of plasminogen activator but show poor glass adherence and phagocytic ability compared to resident peritoneal cells. Graft MO are able to damage beating heart cells in vitro; their activity is not immunologically specific. Peritoneal MO from rats immunised with allogeneic spleen cells and MO grown in vitro from bone marrow in the absence of allostimulators behave similarly. Manipulation of MO behaviour was attempted with rabbit anti-rat MO serum. This did not prolong allograft survival and did not significantly depress blood monocyte levels. 750 rads irradiation prolonged graft survival usually until the death of the animal. Rejection could be restored with small lymphocytes from a normal rat, and the addition of bone-marrow cells had no effect. However, hearts rejected by animals given irradiation and lymphocytes alone contained as many MO as those rejected by normal animals, despite a reduction in blood monocyte levels to less than 5% of normal. We conclude that MO are present in large numbers and at relevant sites in rejecting allografts, and that they show features of activation and have a cytotoxic capability against relevant target cells. However, present approaches

  4. Cellular Mechanisms Underlying Bone-Forming Cell Proliferative Response to Hypergravity

    NASA Technical Reports Server (NTRS)

    Vercoutere, W.; Parra, M.; DaCosta, M.; Wing, A.; Roden, C.; Damsky, C.; Holton, E.; Searby, N.; Globus, R.; Almeida, E.

    2004-01-01

    Life on Earth has evolved under the continuous influence of gravity (1-g). As humans explore and develop space, however, we must learn to adapt to an environment with little or no gravity. Studies indicate that lack of weightbearing for vertebrates occurring with immobilization, paralysis, or in a microgravity environment may cause muscle and bone atrophy through cellular and subcellular level mechanisms. We hypothesize that gravity is needed for the efficient transduction of cell growth and survival signals from the extra-cellular matrix (ECM) (consisting of molecules such as collagen, fibronectin, and laminin) in mechanosensitive tissues. We test for the presence of gravity-sensitive pathways in bone-forming cells (osteoblasts) using hypergravity applied by a cell culture centrifuge. Stimulation of 50 times gravity (50-g) increased proliferation in primary rat osteoblasts for cells grown on collagen Type I and fibronectin, but not on laminin or uncoated surfaces. Survival was also enhanced during hypergravity stimulation by the presence of ECM. Bromodeoxyuridine incorporation in proliferating cells showed an increase in the number of actively dividing cells from about 60% at 1-g to over 90% at 25-g. Reverse transcription-polymerase chain reaction was used to test for all possible integrins. Our combined results indicate that beta1 and/or beta3 integrin subunits may be involved. These data indicate that gravity mechanostimulation of osteoblast proliferation involves specific matrix-integrin signalling pathways which are sensitive to g-level. Further research to define the mechanisms involved will provide direction so that we may better adapt and counteract bone atrophy caused by the lack of weightbearing.

  5. The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation.

    PubMed

    Mulcahy, L E; Curtin, C M; McCoy, R J; O'Brien, F J; Taylor, D; Lee, T C; Duffy, G P

    2015-01-01

    Osteoporosis is one of the most prevalent bone diseases worldwide and is characterised by high levels of bone turnover, a marked loss in bone mass and accumulation of microdamage, which leads to an increased fracture incidence that places a huge burden on global health care systems. Bisphosphonates have been used to treat osteoporosis and have shown great success in conserving bone mass and reducing fracture incidence. In spite of the existing knowledge of the in vivo responses of bone to bisphosphonates, the cellular responses to these drugs have yet to be fully elucidated. In vitro model systems that allow the decoupling of complex highly integrated events, such as bone remodelling, provide a tool whereby these biological processes may be studied in a more simplified context. This study firstly utilised an in vitro model system of bone remodelling and comprising all three major cell types of the bone (osteocytes, osteoclasts and osteoblasts), which was representative of the bone's capacity to sense microdamage and subsequently initiate a basic multicellular unit response. Secondly, this system was used to study the effect of two commonly utilised aminobisphosphonate treatments for osteoporosis, alendronate and zoledronate. We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis. Furthermore, bisphosphonates increased the osteogenic potential following microinjury. Thus, we have shown for the first time that bisphosphonates act at all three stages of bone remodelling, from microinjury to osteoclastogenesis and ultimately osteogenesis.

  6. The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation.

    PubMed

    Mulcahy, L E; Curtin, C M; McCoy, R J; O'Brien, F J; Taylor, D; Lee, T C; Duffy, G P

    2015-01-01

    Osteoporosis is one of the most prevalent bone diseases worldwide and is characterised by high levels of bone turnover, a marked loss in bone mass and accumulation of microdamage, which leads to an increased fracture incidence that places a huge burden on global health care systems. Bisphosphonates have been used to treat osteoporosis and have shown great success in conserving bone mass and reducing fracture incidence. In spite of the existing knowledge of the in vivo responses of bone to bisphosphonates, the cellular responses to these drugs have yet to be fully elucidated. In vitro model systems that allow the decoupling of complex highly integrated events, such as bone remodelling, provide a tool whereby these biological processes may be studied in a more simplified context. This study firstly utilised an in vitro model system of bone remodelling and comprising all three major cell types of the bone (osteocytes, osteoclasts and osteoblasts), which was representative of the bone's capacity to sense microdamage and subsequently initiate a basic multicellular unit response. Secondly, this system was used to study the effect of two commonly utilised aminobisphosphonate treatments for osteoporosis, alendronate and zoledronate. We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis. Furthermore, bisphosphonates increased the osteogenic potential following microinjury. Thus, we have shown for the first time that bisphosphonates act at all three stages of bone remodelling, from microinjury to osteoclastogenesis and ultimately osteogenesis. PMID:26614482

  7. Histomorphometric and 3D Cone-Beam Computerized Tomographic Evaluation of Socket Preservation in Molar Extraction Sites Using Human Particulate Mineralized Cancellous Allograft Bone With a Porcine Collagen Xenograft Barrier: A Case Series.

    PubMed

    Wallace, Stephen

    2015-06-01

    The purpose of this study was to evaluate the results of socket preservation after extraction using human particulate mineralized cancellous allograft bone (MCAB) and type I porcine collagen membranes (PCM) as a guided bone regeneration barrier. Fourteen patients, 12 women and 2 men, were selected who had a diagnosis of one or more unsalvageable teeth with a treatment plan to replace them with implant-supported single crown restorations. Extractions were preformed atraumatically by sectioning teeth for removal to avoid damaging the socket walls and by immediately placing MCAB graft to fill the sockets. The sockets were occluded with a new PCM. The membranes were cut to overlap the facial and lingual (or palatal) socket rim by at least 5 mm (or more if necessary) to cover bony wall fenestration or dehiscence defects. Implants were then placed 16 weeks after the extractions and augmentation. The results were evaluated clinically, histomorphometrically, and with cone-beam computerized tomographic scanning. The formation of new bone in the treated sites averaged 11.2%, with a range of 1.8% to 43%, in bone biopsies trephined from the center of the grafted socket sites. Density, calculated with proprietary software and measured in Hounsfield units (HUs), was 543 HU with a range of 420 to 822 HU. The resulting new bone regeneration varied widely, but the barrier membranes showed potential for promoting significant bone regeneration. A larger sample of treated cases is needed. Wall defects did not appear to influence the histologic results, but the number of sites was too small to determine their significance.

  8. Targeting the Molecular and Cellular Interactions of the Bone Marrow Niche in Immunologic Disease

    PubMed Central

    Brozowski, Jaime M.; Billard, Matthew J.

    2014-01-01

    Recent investigations have expanded our knowledge of the regulatory bone marrow (BM) niche, which is critical in maintaining and directing hematopoietic stem cell (HSC) self-renewal and differentiation. Osteoblasts, mesenchymal stem cells (MSCs), and CXCL12-abundant reticular (CAR) cells are niche components in close association with HSCs and have been more clearly defined in immune cell function and homeostasis. Importantly, cellular inhabitants of the BM niche signal through G protein-coupled surface receptors (GPCRs) for various appropriate immune functions. In this article, recent literature on BM niche inhabitants (HSCs, osteoblasts, MSCs, CAR cells) and their GPCR mechanistic interactions are reviewed for better understanding of the BM cells involved in immune development, immunologic disease, and current immune reconstitution therapies. PMID:24408534

  9. Surfactant tuning of hydrophilicity of porous degradable copolymer scaffolds promotes cellular proliferation and enhances bone formation.

    PubMed

    Yassin, Mohammed A; Leknes, Knut N; Sun, Yang; Lie, Stein A; Finne-Wistrand, Anna; Mustafa, Kamal

    2016-08-01

    Poly(l-lactide-co-ɛ-caprolactone) (poly(LLA-co-CL)) has been blended with Tween 80 to tune the material properties and optimize cell-material interactions. Accordingly, the aims of this study were fourfold: to evaluate the effect of low concentrations of Tween 80 on the surface microstructure of 3D poly(LLA-co-CL) porous scaffolds: to determine the effect of different concentrations of Tween 80 on proliferation of bone marrow stromal cells (BMSCs) in vitro under dynamic cell culture at 7 and 21 days; to assess the influence of Tween 80 on the degradation rate of poly(LLA-co-CL) at 7 and 21 days; and in a subcutaneous rat model, to evaluate the effect on bone formation of porous scaffolds modified with 3% Tween 80 at 2 and 8 weeks. Blending 3% (w/w) Tween 80 with poly(LLA-co-CL) improves the surface wettability (p < 0.001). Poly(LLA-co-CL)/3% Tween 80 shows significantly increased cellular proliferation at days 7 and 21 (p < 0.001). Moreover, the presence of Tween 80 facilitates the degradation of poly(LLA-co-CL). Two weeks post-implantation, the poly(LLA-co-CL)/3% Tween 80 scaffolds exhibit significant mRNA expression of Runx2 (p = 0.004). After 8 weeks, poly(LLA-co-CL)/3% Tween 80 scaffolds show significantly increased de novo bone formation, demonstrated by μ-CT (p = 0.0133) and confirmed histologically. It can be concluded that blending 3% (w/w) Tween 80 with poly (LLA-co-CL) improves the hydrophilicity and osteogenic potential of the scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2049-2059, 2016.

  10. Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

    PubMed Central

    Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

    2011-01-01

    Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

  11. Tantalum trabecular metal - addition of human skeletal cells to enhance bone implant interface strength and clinical application.

    PubMed

    Smith, J O; Sengers, B G; Aarvold, A; Tayton, E R; Dunlop, D G; Oreffo, R O C

    2014-04-01

    The osteo-regenerative properties of allograft have recently been enhanced by addition of autogenous human bone marrow stromal cells (HBMSCs). Limitations in the use of allograft have prompted the investigation of tantalum trabecular metal (TTM) as a potential alternative. TTM is already in widespread orthopaedic use, although in applications where there is poor initial stability, or when TTM is used in conjunction with bone grafting, initial implant loading may need to be limited. The aim of this study was to evaluate the osteo-regenerative potential of TTM with HBMSCs, in direct comparison to human allograft and autograft. HBMSCs were cultured on blocks of TTM, allograft or autograft in basal and osteogenic media. Molecular profiling, confocal and scanning electron microscopy (SEM) and biochemical assays were used to characterize cell adherence, proliferation and phenotype. Mechanical testing was used to define the tensile characteristics of the constructs. HBMSCs displayed adherence and proliferation throughout TTM, evidenced by immunocytochemistry and SEM, with significant cellular ingrowth and matrix production through TTM. In contrast to cells cultured with allograft, cell proliferation assays showed significantly higher activity with TTM (p < 0.001), although molecular profiling confirmed no significant difference in expression of osteogenic genes. In contrast to acellular constructs, mechanical testing of cell-TTM constructs showed enhanced tensile characteristics, which compared favourably to cell-allograft constructs. These studies demonstrated the ability of TTM to support HBMSC growth and osteogenic differentiation comparable to allograft. Thus, TTM represents an alternative to allograft for osteo-regenerative strategies, extending its clinical applications as a substitute for allograft.

  12. Self-setting collagen-calcium phosphate bone cement: mechanical and cellular properties.

    PubMed

    Moreau, Jennifer L; Weir, Michael D; Xu, Hockin H K

    2009-11-01

    Calcium phosphate cement (CPC) can conform to complex bone cavities and set in-situ to form bioresorbable hydroxyapatite. The aim of this study was to develop a CPC-collagen composite with improved fracture resistance, and to investigate the effects of collagen on mechanical and cellular properties. A type-I bovine-collagen was incorporated into CPC. MC3T3-E1 osteoblasts were cultured. At CPC powder/liquid mass ratio of 3, the work-of-fracture (mean +/- sd; n = 6) was increased from (22 +/- 4) J/m(2) at 0% collagen, to (381 +/- 119) J/m(2) at 5% collagen (p < or = 0.05). At 2.5-5% of collagen, the flexural strength at powder/liquid ratios of 3 and 3.5 was 8-10 MPa. They matched the previously reported 2-11 MPa of sintered porous hydroxyapatite implants. SEM revealed that the collagen fibers were covered with nano-apatite crystals and bonded to the CPC matrix. Higher collagen content increased the osteoblast cell attachment (p < or = 0.05). The number of live cells per specimen area was (382 +/- 99) cells/mm(2) on CPC containing 5% collagen, higher than (173 +/- 42) cells/mm(2) at 0% collagen (p < or = 0.05). The cytoplasmic extensions of the cells anchored to the nano-apatite crystals of the CPC matrix. In summary, collagen was incorporated into in situ-setting, nano-apatitic CPC, achieving a 10-fold increase in work-of-fracture (toughness) and two-fold increase in osteoblast cell attachment. This moldable/injectable, mechanically strong, nano-apatite-collagen composite may enhance bone regeneration in moderate stress-bearing applications.

  13. Clinical and Histological Comparison of Extraction Socket Healing Following the Use of Autologous Platelet-Rich Fibrin Matrix (PRFM) to Ridge Preservation Procedures Employing Demineralized Freeze Dried Bone Allograft Material and Membrane

    PubMed Central

    Simon, B.I; Zatcoff, A.L; Kong, J.J.W; O’Connell, S.M

    2009-01-01

    Background: The healing potential of platelet growth factors has generated interest in using Platelet-Rich Plasma (PRP) in ridge preservation procedures. A canine study was performed to determine if extraction sites treated with platelet-rich fibrin matrix (PRFM) exhibit enhanced healing compared to sites treated with non-viable materials. Methods: Four dog’s extraction sockets were treated individually with PRFM, PRFM and membrane, Demineralized Freeze-Dried Bone Allograft (DFDBA) and membrane, PRFM and DFDBA, and untreated control. Treatment sequencing permitted clinical and histologic evaluation of healing at 10 days, 2, 3, 6 and 12 weeks. Results: Healing was more rapid in the PRFM and PRFM and membrane sites. By 3 weeks those sockets had osseous fill. Sites containing DFDBA had little new bone at 6 weeks. By 12 weeks those sockets had osseous fill but DFDBA particles were still noted in coronal areas. Conclusions: PRFM alone may be the best graft for ridge preservation procedures. Advantages: faster healing, and elimination of disadvantages involved in using barrier membranes. PMID:19543550

  14. 1. Morphological Implication on Cellular Response to Mechanical Stress in Bone.

    PubMed

    Amizuka, Norio

    2016-08-01

    In bone, there are 3 distinct cell types: an osteoblast, a bone forming cell; an osteocyte embedded in bone matrix as a consequence of being differentiated from an osteoblast; and an osteoclast, a multinucleated giant cell responsible for bone resorption. Bone is always remodeled by replacing old bone with new bone (bone remodeling), by which bone can maintain its stiffness and flexibility. However, in an osteoporotic state, the disrupted balance between bone resorption and formation results in not only markedly reduced bone mass, but also in disorganized geometry of trabecules, which can often give rise to a bone fracture. Osteocytes located in their lacunae insert their fine cytoplasmic processes into narrow passageways referred to as osteocytic canaliculi. Neighboring osteocytes connect to each other by means of a gap junction in their cytoplasmic processes. Therefore, osteocytes and their lacunae/canaliculi appear to form functional syncytium called osteocytic lacunar canalicular system (OLCS). The geometrical distribution of OLCS is poorly arranged in immature bone, while it appears well-arranged distribution in mature bone (cortical bone), in which molecular transports and sensing mechanical stress seems to be efficient, and therefore, may be able to respond to mechanical stress. In this seminar, I will introduce our recent findings on the morphology and function of OLCS which may respond to mechanical stress. PMID:27441762

  15. Anterior cruciate ligament allograft transplantation for intraarticular ligamentous reconstruction.

    PubMed

    Goertzen, M; Dellmann, A; Gruber, J; Clahsen, H; Bürrig, K F

    1992-01-01

    A multiplicity of surgical operations have been developed in an attempt to achieve satisfactory function after anterior cruciate ligament (ACL) repair. None of these procedures have been able to reproduce the fiber organization anatomy of attachment site, vascularity, or function of the ACL. Twenty-nine foxhounds received a deep-frozen bone-ACL-bone allograft and a ligament augmentation device (LAD). Biomechanical, microvascular, and histological changes were evaluated 3, 6, and 12 months following implantation. The maximum loads of the allograft/LADs were 34.3% (387.2 N) after 3 months, 49.3% (556.6 N) after 6 months, and 61.1% (698.8 N) after a year. The maximum load was 69.1% (780 N). In general, after 6 months the allografts showed normal collagen orientation. The allografts demonstrated no evidence of infection or immune reaction. No bone ingrowth into the LAD was observed. Polarized light microscopy and periodic acid-schiff staining showed that the new bone-ligament substance interface had intact fiber orientation at the area of the ligament insertion. Microvascular examination using the Spalteholtz technique revealed revascularization and the importance of an infrapatellar fat pad for the nourishment of ACL allografts.

  16. Anterior cruciate ligament allograft transplantation for intraarticular ligamentous reconstruction.

    PubMed

    Goertzen, M; Dellmann, A; Gruber, J; Clahsen, H; Bürrig, K F

    1992-01-01

    A multiplicity of surgical operations have been developed in an attempt to achieve satisfactory function after anterior cruciate ligament (ACL) repair. None of these procedures have been able to reproduce the fiber organization anatomy of attachment site, vascularity, or function of the ACL. Twenty-nine foxhounds received a deep-frozen bone-ACL-bone allograft and a ligament augmentation device (LAD). Biomechanical, microvascular, and histological changes were evaluated 3, 6, and 12 months following implantation. The maximum loads of the allograft/LADs were 34.3% (387.2 N) after 3 months, 49.3% (556.6 N) after 6 months, and 61.1% (698.8 N) after a year. The maximum load was 69.1% (780 N). In general, after 6 months the allografts showed normal collagen orientation. The allografts demonstrated no evidence of infection or immune reaction. No bone ingrowth into the LAD was observed. Polarized light microscopy and periodic acid-schiff staining showed that the new bone-ligament substance interface had intact fiber orientation at the area of the ligament insertion. Microvascular examination using the Spalteholtz technique revealed revascularization and the importance of an infrapatellar fat pad for the nourishment of ACL allografts. PMID:1389780

  17. Cellular composition of the bone marrow in the chicken. II. Effect of age and the influence of the bursa of Fabricius on the size of cellular compartments

    SciTech Connect

    Glick, B.; Rosse, C.

    1981-01-01

    The blood and bone marrow of New Hampshire chicks were analyzed quantitatively from the time of hatch to 8 weeks of age. Hormonal bursectomy was performed by treating embryonating eggs on the 11th day of incubation with testosterone propionate (TP) which resulted in severe hypogammaglobulinemia and complete atrophy of the bursa of Fabricius. TP-treated birds exhibited some lymphocytopenia, reduced splenic weight, and lack of plasma cells in their bone marrow. The number of cells per milligram bone marrow was comparable in normal and TP-treated birds, falling in the range reported for laboratory rodents. The chick medullary hemopoiesis is characterized by the predominance of erythroblasts throughout early development; granulocytes and lymphocytes represent much smaller cellular compartments than in rodents. In the chick granulocytes tend to decrease after hatch, whereas in rodents they tend to increase. The normal chick shows a temporary increase in marrow lymphocytes after hatch, similar to that observed in some young rodents, but on a much smaller scale. Hormonal bursectomy did not prevent the development of a lymphocyte population in the bone marrow. These cells were fewer in TP-treated birds at hatch and at 4 weeks than in normal birds, but at 8 weeks of age normal and bursectomized chicks had comparable numbers of lymphocytes in their marrow. Although some lymphocytes in avain bone marrow may depend on the bursa of Fabricius for their development, a substantial proportion of bone marrow lymphocytes in the chick are bursa independent. The cell surface phenotype and site of origin of these cells remains to be investigated. 40 references, 1 figure, 3 tables.

  18. Enhancement of bone marrow allografts from nude mice into mismatched recipients by T cells void of graft-versus-host activity

    SciTech Connect

    Lapidot, T.; Lubin, I.; Terenzi, A.; Faktorowich, Y.; Erlich, P.; Reisner, Y. )

    1990-06-01

    Transplantation of 8 x 10(6) C57BL/6-Nu+/Nu+ (nude) bone marrow cells into C3H/HeJ recipients after conditioning with 8 Gy of total body irradiation has resulted in a markedly higher rate of graft rejection or graft failure compared to that found in recipients of normal C57BL/6 or C57BL/6-Bg+/Bg+ (beige) T-cell-depleted bone marrow. Mixing experiments using different numbers of nude bone marrow cells with or without mature thymocytes (unagglutinated by peanut agglutinin) revealed that engraftment of allogeneic T-cell-depleted bone marrow is T-cell dependent. To ensure engraftment, a large inoculum of nude bone marrow must be supplemented with a trace number of donor T cells, whereas a small bone marrow dose from nude donors requires a much larger number of T cells for engraftment. Marked enhancement of donor type chimerism was also found when F1 thymocytes were added to nude bone marrow cells, indicating that the enhancement of bone marrow engraftment by T cells is not only mediated by alloreactivity against residual host cells but may rather be generated by growth factors, the release of which may require specific interactions between T cells and stem cells or between T cells and bone marrow stroma cells.

  19. CELLULAR MECHANISMS OF BONE REGENERATION: ROLE OF WNT-1 IN BONE-MUSCLE INTERACTION DURING PHYSICAL ACTIVITY39.

    PubMed

    Colaianni, G; Cuscito, C; Mongelli, T; Pignataro, P; Tamma, R; Oranger, A; Colucci, S; Grano, M

    2015-01-01

    Wnt1 is one of the several glycoproteins activating Wnt signaling, critical for normal skeletal development and bone homeostasis. Wnt1 was previously believed to solely regulate central nervous system development, in particular in midbrain and cerebellum. However, remarkable findings have recently shown that several patients affected by severe form of Osteogenesis Imperfecta (OI) display a Wnt1 mutation thereby revealing a possible role of Wnt1 in bone metabolism. Here, we show that recombinant Wnt1 (r-Wnt1) strongly increases differentiation of bone marrow stromal cells into mature osteoblasts, as demonstrated by the enhanced number of cells positively stained for alkaline phosphatase, one of the osteoblastic marker genes, whose mRNA levels are also significantly up-regulated. Furthermore, other osteogenic master genes such as Collagen I and Osteopontin are also enhanced when bone marrow precursors were differentiated toward osteoblastic phenotype in the presence of r-Wnt1. Intriguingly, by in vivo and in vitro findings, we report that in the bone marrow of mice subjected to physical activity there is a high endogenous Wnt1 synthesis compared to mice kept in resting conditions. Moreover, conditioned medium collected from ex vivo myoblasts, harvested from exercised mice, up-regulates Wnt1 expression in osteoblast cell cultures obtained from control mice. Overall our findings support the role of Wnt1 in regulating bone metabolism and suggest that this molecule could be one of the mediators through which physical activity may exert beneficial effect on bone. PMID:26652489

  20. Kidney allograft survival in dogs treated with total lymphoid irradiation

    SciTech Connect

    Howard, R.J.; Sutherland, D.E.R.; Lum, C.T.; Lewis, W.I.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1981-02-01

    Total lymphoid irradiation (TLI) is immunosuppressive and, in rodents, can induce a state where transplantation of allogenic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950 to 3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned for a mean +- (SE) of 4.7 +- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15 to 76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemaglutinin and in mixed lymphocyte culture was suppressed for at least one month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients.

  1. Autograft Versus Nonirradiated Allograft Tissue for Anterior Cruciate Ligament Reconstruction

    PubMed Central

    Mariscalco, Michael W.; Magnussen, Robert A.; Mehta, Divyesh; Hewett, Timothy E.; Flanigan, David C.; Kaeding, Christopher C.

    2014-01-01

    Background An autograft has traditionally been the gold standard for anterior cruciate ligament reconstruction (ACLR), but the use of allograft tissue has increased in recent years. While numerous studies have demonstrated that irradiated allografts are associated with increased failure rates, some report excellent results after ACLR with nonirradiated allografts. The purpose of this systematic review was to determine whether the use of nonirradiated allograft tissue is associated with poorer outcomes when compared with autografts. Hypothesis Patients undergoing ACLR with autografts versus nonirradiated allografts will demonstrate no significant differences in graft failure risk, laxity on postoperative physical examination, or differences in patient-oriented outcome scores. Study Design Systematic review. Methods A systematic review was performed to identify prospective or retrospective comparative studies (evidence level 1, 2, or 3) of autografts versus nonirradiated allografts for ACLR. Outcome data included graft failure based on clinical findings and instrumented laxity, postoperative laxity on physical examination, and patient-reported outcome scores. Studies were excluded if they did not specify whether the allograft had been irradiated. Quality assessment and data extraction were performed by 2 examiners. Results Nine studies comparing autografts and nonirradiated allografts were included. Six of the 9 studies compared bone– patellar tendon–bone (BPTB) autografts with BPTB allografts. Two studies compared hamstring tendon autografts to hamstring tendon allografts, and 1 study compared hamstring tendon autografts to tibialis anterior allografts. The mean patient age in 7 of 9 studies ranged from 24.5 to 32 years, with 1 study including only patients older than 40 years and another not reporting patient age. The mean follow-up duration was 24 to 94 months. Six of 9 studies reported clinical graft failure rates, 8 of 9 reported postoperative instrumented

  2. Biodegradable foam coating of cortical allografts.

    PubMed

    Bondre, S; Lewandrowski, K U; Hasirci, V; Cattaneo, M V; Gresser, J D; Wise, D L; Tomford, W W; Trantolo, D J

    2000-06-01

    Clinical outcomes of bone allograft procedures may be improved by modifying the surface of the graft with an osteoconductive biopolymeric coating. In this comparative in vitro study, we evaluated the dimensional stability, mechanical strength, hydrophilicity, and water uptake of biodegradable foams of poly(propylene fumarate) (PPF) and poly(d,l-lactic-co glycolic acid) (PLGA) when applied as surface coatings to cortical bone. Cortical bone samples were divided into four groups: Type I, untreated bone; Type II, laser-perforated bone; Type III, partially demineralized bone; and Type IV, laser-perforated and partially demineralized bone. Results show that PPF wets easily, achieving 12.5% wt/wt in 30 min. Compressive tests on the PPF foam material showed that the compressive strength was 6.8 MPa prior to in vitro incubation but then gradually reduced to 1.9 MPa at 8 weeks. Push-out and pulloff strength tests showed that initially both PPF and PLGA foam coatings had comparable adherence strengths to the cortical bone samples (100-150 N). When additional geometrical surface alteration by perforation and demineralization of the bony substrate was employed, in vitro adherence of the PPF foam coating was further increased to 120 N, demonstrating a statistically significant improvement of push-out strength throughout the entire 8-week observation period (p<0.0002 for all four data points). The pore geometry of PPF-foam coatings changed little over the 2-month evaluation period. In comparison, PLGA foam coating around the cortical bone samples rapidly lost structure with a decrease of 67% in strength seen after 1-week in vitro incubation. These new types of bone allografts may be particularly useful where the use of other replacement materials is not feasible or practical.

  3. A supra-cellular model for coupling of bone resorption to formation during remodeling: lessons from two bone resorption inhibitors affecting bone formation differently.

    PubMed

    Jensen, Pia Rosgaard; Andersen, Thomas Levin; Pennypacker, Brenda L; Duong, Le T; Engelholm, Lars H; Delaissé, Jean-Marie

    2014-01-10

    The bone matrix is maintained functional through the combined action of bone resorbing osteoclasts and bone forming osteoblasts, in so-called bone remodeling units. The coupling of these two activities is critical for securing bone replenishment and involves osteogenic factors released by the osteoclasts. However, the osteoclasts are separated from the mature bone forming osteoblasts in time and space. Therefore the target cell of these osteoclastic factors has remained unknown. Recent explorations of the physical microenvironment of osteoclasts revealed a cell layer lining the bone marrow and forming a canopy over the whole remodeling surface, spanning from the osteoclasts to the bone forming osteoblasts. Several observations show that these canopy cells are a source of osteoblast progenitors, and we hypothesized therefore that they are the likely cells targeted by the osteogenic factors of the osteoclasts. Here we provide evidence supporting this hypothesis, by comparing the osteoclast-canopy interface in response to two types of bone resorption inhibitors in rabbit lumbar vertebrae. The bisphosphonate alendronate, an inhibitor leading to low bone formation levels, reduces the extent of canopy coverage above osteoclasts. This effect is in accordance with its toxic action on periosteoclastic cells. In contrast, odanacatib, an inhibitor preserving bone formation, increases the extent of the osteoclast-canopy interface. Interestingly, these distinct effects correlate with how fast bone formation follows resorption during these respective treatments. Furthermore, canopy cells exhibit uPARAP/Endo180, a receptor able to bind the collagen made available by osteoclasts, and reported to mediate osteoblast recruitment. Overall these observations support a mechanism where the recruitment of bone forming osteoblasts from the canopy is induced by osteoclastic factors, thereby favoring initiation of bone formation. They lead to a model where the osteoclast-canopy interface is

  4. Healing properties of allograft from alendronate-treated animal in lumbar spine interbody cage fusion.

    PubMed

    Xue, Qingyun; Li, Haisheng; Zou, Xuenong; Bünger, Mathias; Egund, Niels; Lind, Martin; Christensen, Finn Bjarke; Bünger, Cody

    2005-04-01

    This study investigated the healing potential of allograft from bisphosphonate-treated animals in anterior lumbar spine interbody fusion. Three levels of anterior lumbar interbody fusion with Brantigan cages were performed in two groups of five landrace pigs. Empty Brantigan cages or cages filled with either autograft or allograft were located randomly at different levels. The allograft materials for the treatment group were taken from the pigs that had been fed with alendronate, 10 mg daily for 3 months. The histological fusion rate was 2/5 in alendronate-treated allograft and 3/5 in non-treated allograft. The mean bone volume was 39% and 37.2% in alendronate-treated or non-treated allograft (NS), respectively. No statistical difference was found between the same grafted cage comparing two groups. The histological fusion rate was 7/10 in all autograft cage levels and 5/10 in combined allograft cage levels. No fusion was found at all in empty cage levels. With the numbers available, no statistically significant difference was found in histological fusion between autograft and allograft applications. There was a significant difference of mean bone volume between autograft (49.2%) and empty cage (27.5%) (P<0.01). In conclusion, this study did not demonstrate different healing properties of alendronate-treated and non-treated allograft for anterior lumbar interbody fusion in pigs. PMID:15248057

  5. Micro-organisms isolated from cadaveric samples of allograft musculoskeletal tissue.

    PubMed

    Varettas, Kerry

    2013-12-01

    Allograft musculoskeletal tissue is commonly used in orthopaedic surgical procedures. Cadaveric donors of musculoskeletal tissue supply multiple allografts such as tendons, ligaments and bone. The microbiology laboratory of the South Eastern Area Laboratory Services (SEALS, Australia) has cultured cadaveric allograft musculoskeletal tissue samples for bacterial and fungal isolates since 2006. This study will retrospectively review the micro-organisms isolated over a 6-year period, 2006-2011. Swab and tissue samples were received for bioburden testing and were inoculated onto agar and/or broth culture media. Growth was obtained from 25.1 % of cadaveric allograft musculoskeletal tissue samples received. The predominant organisms isolated were coagulase-negative staphylococci and coliforms, with the heaviest bioburden recovered from the hemipelvis. The rate of bacterial and fungal isolates from cadaveric allograft musculoskeletal tissue samples is higher than that from living donors. The type of organism isolated may influence the suitability of the allograft for transplant.

  6. Results of 32 Allograft-prosthesis Composite Reconstructions of the Proximal Femur

    PubMed Central

    Larousserie, Frédérique; Thévenin, Fabrice; Piperno-Neumann, Sophie; Anract, Philippe

    2009-01-01

    The use of allograft-prosthesis composites for reconstruction after bone tumor resection at the proximal femur has generated considerable interest since the mid1980s on the basis that their use would improve function and survival, and restore bone stock. Although functional improvement has been documented, it is unknown whether these composites survive long periods and whether they restore bone stock. We therefore determined long-term allograft-prosthesis composite survival, identified major complications that led to revision, and determined whether allograft bone stock could be spared at the time of revision. We also compared the radiographic appearance of allografts sterilized by gamma radiation and fresh-frozen allografts. We retrospectively reviewed 32 patients with bone malignancy in the proximal femur who underwent reconstruction with a cemented allograft-prosthesis composite. The allograft-prosthesis composite was a primary reconstruction for 23 patients and a revision procedure for nine. The minimum followup was 2 months (median, 68 months; range, 2–232 months). The cumulative incidence of revision for any reason was 14% at 5 years (95% confidence interval, 1%–28%) and 19% at 10 years (95% confidence interval, 3%–34%). Nine patients (28%) had revision of the reconstruction during followup; four of these patients had revision surgery for infection. Allografts sterilized by gamma radiation showed worse resorption than fresh-frozen allografts. Based on reported results, allograft-composite prostheses do not appear to improve survival compared with megaprostheses. Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence. PMID:19851817

  7. CT Lesion Model-Based Structural Allografts: Custom Fabrication and Clinical Experience

    PubMed Central

    Brune, Jan Claas; Hesselbarth, Uwe; Seifert, Philipp; Nowack, Dimitri; von Versen, Rüdiger; Smith, Mark David; Seifert, Dirk

    2012-01-01

    Summary Background Patients requiring knee and hip revision arthroplasty often present with difficult anatomical situations that limit options for surgery. Customised mega-implants may be one of few remaining treatment options. However, extensive damage to residual bone stock may also be present, and in such cases even customised prosthetics may be difficult to implant. Small quantities of lost bone can be replaced with standard allografts or autologous bone. Larger defects may require structural macro-allografts, sometimes in combination with implants (allograft-prosthesis composites). Methods Herein, we describe a process for manufacturing lesion-specific large structural allografts according to a 3D, full-scale, lithographically generated defect model. These macro-allografts deliver the volume and the mechanical stability necessary for certain complex revisions. They are patient-and implant-matched, negate some requirements for additional implants and biomaterials and save time in the operating theatre by eliminating the requirement for intra-operative sizing and shaping of standard allografts. Conclusion While a robust data set from long-term follow-up of patients receiving customised macro-allografts is not yet available, initial clinical experience and results suggest that lesion-matched macro-allografts can be an important component of revision joint surgery. PMID:23800856

  8. Fresh-frozen Complete Extensor Mechanism Allograft versus Autograft Reconstruction in Rabbits

    PubMed Central

    Chen, Guanyin; Zhang, Hongtao; Ma, Qiong; Zhao, Jian; Zhang, Yinglong; Fan, Qingyu; Ma, Baoan

    2016-01-01

    Different clinical results have been reported in the repair of extensor mechanism disruption using fresh-frozen complete extensor mechanism (CEM) allograft, creating a need for a better understanding of fresh-frozen CME allograft reconstruction. Here, we perform histological and biomechanical analyses of fresh-frozen CEM allograft or autograft reconstruction in an in vivo rabbit model. Our histological results show complete incorporation of the quadriceps tendon into the host tissues, patellar survival and total integration of the allograft tibia, with relatively fewer osteocytes, into the host tibia. Vascularity and cellularity are reduced and delayed in the allograft but exhibit similar distributions to those in the autograft. The infrapatellar fat pad provides the main blood supply, and the lowest cellularity is observed in the patellar tendon close to the tibia in both the allograft and autograft. The biomechanical properties of the junction of quadriceps tendon and host tissues and those of the allograft patellar tendon are completely and considerably restored, respectively. Therefore, fresh-frozen CEM allograft reconstruction is viable, but the distal patellar tendon and the tibial block may be the weak links of the reconstruction. These findings provide new insight into the use of allograft in repairing disruption of the extensor mechanism. PMID:26911538

  9. Infusion-rate independent cellular adriamycin concentrations and cytotoxicity to human bone marrow clonogenic cells (CFU-GM).

    PubMed Central

    Raijmakers, R.; Speth, P.; de Witte, T.; Linssen, P.; Wessels, J.; Haanen, C.

    1987-01-01

    The effect of adriamycin (ADM) infusion-rate on cellular ADM concentrations and on clonogenicity of human haematopoietic cells was studied in vivo and in vitro. In patients an ADM dose of 30 mg m-2 was administered as a bolus injection, or as a 4 h or a 24 h infusion. In vitro the effect of ADM on clonogenic cell growth was determined after exposure during 5 min, 2 h and 24 h of human bone marrow cells to increasing ADM concentrations. ADM showed rapid intracellular accumulation, to levels 100-fold the plasma concentration in vivo or the incubation medium concentration in the in vitro experiments. After a bolus injection or 5 min exposure only approximately 10% of the cellular peak ADM was retained after elimination of the drug from the plasma or the incubation medium. Ninety percent of the ADM was apparently 'loosely' bound. After 4 h and 24 h constant-rate infusions and also after 2 h and 24 h incubations in vitro, the cells accumulated ADM gradually, and the subsequent washing-out of the cellular ADM was substantially less, most of the ADM being 'tightly' bound. Despite these different patterns of uptake and retention after in vivo short- and long-lasting infusion of the same total dose, the 'tightly-bound' cellular ADM concentrations were the same. Moreover, comparable cellular ADM concentrations, retained after efflux of the 'loosely-bound' cellular ADM fraction were equally cytotoxic to normal human clonogenic cells. Short-lasting cellular peak ADM concentrations which occur after a bolus injection or after short exposure to high ADM concentrations are not essential for the cytotoxic effect, in contrast to the retained, 'tightly-bound' cellular ADM levels. PMID:3663464

  10. The influence of polymer scaffolds on cellular behaviour of bone marrow derived human mesenchymal stem cells.

    PubMed

    Wang, Weiwei; Ma, Nan; Kratz, Karl; Xu, Xun; Li, Zhengdong; Roch, Toralf; Bieback, Karen; Jung, Friedrich; Lendlein, Andreas

    2012-01-01

    Mesenchymal stem cells (MSCs) are multipotent stem cells that can differentiate into a variety of cell types. Therefore, they are widely explored in regenerative medicine. The interaction of MSCs with biomaterials is of great importance for cell proliferation, differentiation and function, and can be strongly influenced by numerous factors, such as the chemical nature and the mechanical properties of the material surface. In this study, we investigated the interaction of bone marrow derived human MSCs with different amorphous and transparent polymers namely polystyrene (PS), polycarbonate (PC), poly(ether imide) (PEI), polyetherurethane (PEU) and poly(styrene-co-acrylonitrile) (PSAN). To ensure that the MSCs were solely in contact to the testing material we applied polymeric inserts, which were prepared from the aforementioned polymers via injection molding. The explored inserts exhibited a similar wettability with advancing contact angles ranging from 84 ± 7° (PEU) to 99 ± 5° (PS) and a surface roughness of Rq ≤ 0.86 μm. The micromechanical properties determined by AFM indentation varied from 6 ± 1 GPa (PEU) to 24 ± 5 GPa (PSAN). Cells presented different adhesion rates on the polymer surfaces 24 hours after seeding (45 ± 7% (PS), 63 ± 1% (PC), 75 ± 4% (PEI), 69 ± 2% (PEU) and 61 ± 5% (PSAN)). The cells could proliferate on the polymer surfaces, and the fold change of cell number after 16 days of culture reached to 1.93 ± 0.07 (PS), 3.38 ± 0.11 (PC), 3.65 ± 0.04 (PEI), 2.24 ± 0.15 (PEU) and 3.36 ± 0.09 (PSAN). Differences in cell apoptosis could be observed during the culture. After 7 days, the apoptosis of cells on PC, PEI and PSAN decreased to a level comparable to that on standard tissue culture plate (TCP). All of the tested polymers exhibited low cytotoxicity and allowed high cell viability. Compared to cells on TCP, cells on PC and PEI showed similar morphology, distribution as well as F-actin cytoskeleton organization, whereas cells on

  11. Adult bone marrow: which stem cells for cellular therapy protocols in neurodegenerative disorders?

    PubMed

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Rogister, Bernard

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy.

  12. Cellular behavior as a dynamic field for exploring bone bioengineering: a closer look at cell-biomaterial interface.

    PubMed

    Gemini-Piperni, Sara; Takamori, Esther Rieko; Sartoretto, Suelen Cristina; Paiva, Katiúcia B S; Granjeiro, José Mauro; de Oliveira, Rodrigo Cardoso; Zambuzzi, Willian Fernando

    2014-11-01

    Bone is a highly dynamic and specialized tissue, capable of regenerating itself spontaneously when afflicted by minor injuries. Nevertheless, when major lesions occur, it becomes necessary to use biomaterials, which are not only able to endure the cellular proliferation and migration, but also to substitute the original tissue or integrate itself to it. With the life expectancy growth, regenerative medicine has been gaining constant attention in the reconstructive field of dentistry and orthopedy. Focusing on broadening the therapeutic possibilities for the regeneration of injured organs, the development of biomaterials allied with the applicability of gene therapy and bone bioengineering has been receiving vast attention over the recent years. The progress of cellular and molecular biology techniques gave way to new-guided therapy possibilities. Supported by multidisciplinary activities, tissue engineering combines the interaction of physicists, chemists, biologists, engineers, biotechnologist, dentists and physicians with common goals: the search for materials that could promote and lead cell activity. A well-oriented combining of scaffolds, promoting factors, cells, together with gene therapy advances may open new avenues to bone healing in the near future. In this review, our target was to write a report bringing overall concepts on tissue bioengineering, with a special attention to decisive biological parameters for the development of biomaterials, as well as to discuss known intracellular signal transduction as a new manner to be explored within this field, aiming to predict in vitro the quality of the host cell/material and thus contributing with the development of regenerative medicine. PMID:24976174

  13. Comparison of cellular responses of mesenchymal stem cells derived from bone marrow and synovium on combined silk scaffolds.

    PubMed

    Liu, Haifeng; Wei, Xing; Ding, Xili; Li, Xiaoming; Zhou, Gang; Li, Ping; Fan, Yubo

    2015-01-01

    As a brand new member in mesenchymal stem cells (MSCs) families, synovium-derived mesenchymal stem cells (SMSCs) have been increasingly regarded as a promising therapeutic cell species for musculoskeletal regeneration. However, there are few reports mentioning ligamentogenesis of SMSCs and especially null for their engineering use towards ligament regeneration. The aim of this study was to investigate and compare the cellular responses of MSCs derived from bone marrow and synovium on combined silk scaffolds that can be used to determine the cell source most appropriate for tissue-engineered ligament. Rabbit SMSCs and bone marrow-derived mesenchymal stem cells (BMSCs) were isolated and cultured in vitro for two weeks after seeding on the combined silk scaffolds. Samples were studied and compared for their cellular morphology, proliferation, collagen production, gene, and protein expression of ligament-related extracellular matrix (ECM) markers. In addition, the two cell types were transfected with green fluorescent protein to evaluate their fate after implantation in an intraarticular environment of the knee joint. After 14 days of culturing, SMSCs showed a significant increase in proliferation as compared with BMSCs. The transcript and protein expression levels of ligament-related ECM markers in SMSCs were significantly higher than those in BMSCs. Moreover, 6 weeks postoperatively, more viable cells were presented in SMSC-loaded constructs than in BMSC-loaded constructs. Therefore, based on the cellular response in vitro and in vivo, SMSCs may represent a more suitable cell source than BMSCs for further study and development of tissue-engineered ligament.

  14. A comparative evaluation of freeze-dried bone allograft with and without bioabsorbable guided tissue regeneration membrane Healiguide® in the treatment of Grade II furcation defects: A clinical study

    PubMed Central

    Jain, Deept; Deepa, Dhruvakumar

    2015-01-01

    Background: Furcation defects represent one of the most demanding therapeutic challenges for periodontal therapy. Various treatment modalities have been tried with different success rates. The present study was undertaken to evaluate the efficacy of freeze-dried bone allograft (FDBA) with and without bioabsorbable guided tissue regeneration (GTR) membrane Healiguide® in the treatment of Grade II furcation defects. Materials and Methods: Ten patients with bilateral Grade II furcation defects were selected for the study. After phase I therapy, subjects were divided into two arms and treated in a split-mouth design. Ten defects were treated with FDBA alone in the control arm. Ten defects were treated with FDBA in conjunction with bioabsorbable GTR membrane Healiguide® in test arm. Clinical parameters like plaque index, gingival index, vertical probing depth, horizontal probing depth, and relative attachment level (RAL) were assessed at baseline, 3 months, and 6 months postoperatively. Results: At 6 months, clinical improvement was seen in both the arms with mean pocket depth reduction of 1.2 ± 1.032 mm and 1.7 ± 0.948 mm and mean horizontal probing depth reduction being 2.1 ± 1.969 mm and 1.6 ± 1.264 mm in control and test arm, respectively. Both surgical procedures resulted in a statistically significant reduction in vertical and horizontal probing depths. Conclusion: Both the arms demonstrated a significant improvement in the probing depth, horizontal furcation depth, and RAL at 6 months postsurgery in the treatment of Grade II furcation defects. However, on the intergroup comparison, there was no statistically significant difference in the results achieved between two arms. PMID:26941515

  15. Biodegradable, Phosphate-containing, Dual-Gelling Macromers for Cellular Delivery in Bone Tissue Engineering

    PubMed Central

    Watson, Brendan M.; Vo, Tiffany N.; Tatara, Alexander M.; Shah, Sarita R.; Scott, David W.; Engel, Paul S.; Mikos, Antonios G.

    2015-01-01

    Injectable, biodegradable, dual-gelling macromer solutions were used to encapsulate mesenchymal stem cells (MSCs) within stable hydrogels when elevated to physiologic temperature. Pendant phosphate groups were incorporated in the N-isopropyl acrylamide-based macromers to improve biointegration and facilitate hydrogel degradation. The MSCs were shown to survive the encapsulation process, and live cells were detected within the hydrogels for up to 28 days in vitro. Cell-laden hydrogels were shown to undergo significant mineralization in osteogenic medium. Cell-laden and acellular hydrogels were implanted into a critical-size rat cranial defect for 4 and 12 weeks. Both cell-laden and acellular hydrogels were shown to degrade in vivo and help to facilitate bone growth into the defect. Improved bone bridging of the defect was seen with the incorporation of cells, as well as with higher phosphate content of the macromer. Furthermore, direct bone-to-hydrogel contact was observed in the majority of implants, which is not commonly seen in this model. The ability of these macromers to deliver stem cells while forming in situ and subsequently degrade while facilitating bone ingrowth into the defect makes this class of macromers a promising material for craniofacial bone tissue engineering. PMID:26232878

  16. Evaluation of platelet-rich plasma alone or in combination with demineralized freeze dried bone allograft in treatment of periodontal infrabony defects: A comparative clinical trial

    PubMed Central

    Agarwal, Prerna; Chatterjee, Anirban; Gokhale, Shankar; Singh, Himanshu Pratap; Kandwal, Abhishek

    2016-01-01

    Aims: The use of platelet-rich plasma (PRP) alone in periodontal defects has been controversial and inconclusive. Hence, the present study was designed with the aim to assess the clinical and radiographic effectiveness of PRP alone in infrabony defects. Materials and Methods: Thirty infrabony defects were treated with either autologous PRP with open flap debridement (OFD) or autologous PRP + demineralized freeze dried bone graft (DFDBA) with OFD or OFD alone. Clinical parameters recorded were gingival index, plaque index, probing depth (PD), clinical attachment level (CAL), and gingival recession (REC). Radiographic parameters included defect depth reduction, defect resolution, and crestal bone level. All the parameters were recorded at baseline and 12 months postoperatively. Results: Mean PD reduction and CAL gain were greater in PRP + DFDBA (4.88 ± 1.12 mm and 4.26 ± 1.85 mm) and PRP (4.86 ± 2.12 mm and 4.10 ± 1.47 mm) groups than the control group (2.69 ± 1.37 mm and 1.27 ± 0.89 mm). Conclusions: Within the limits of the study, all the three groups showed significant improvement in clinical parameters from baseline to postoperative 12 months. The amount of defect depth reduction and defect resolution treated with PRP alone group were significantly < PRP + DFDBA. The results pertaining to these parameters were significantly better than the control group. PMID:27041837

  17. Determination of mechanical properties of impacted human morsellized cancellous allografts for revision joint arthroplasty.

    PubMed

    Tanabe, Y; Wakui, T; Kobayashi, A; Ohashi, H; Kadoya, Y; Yamano, Y

    1999-12-01

    This paper deals with the characterization of mechanical properties of impacted morsellized cancellous allograft (IMCA) produced by dynamic compaction of allograft femoral heads ground by commercially available bone mills, i.e. rotating rasp and reciprocating type bone mills. Various ranges and profiles of particle size in the graft aggregates were obtained using these bone mills, and the effect of number of compaction as well as the distribution of particle sizes on the mechanical properties of IMCA under quasistatic compression and shear loading conditions was discussed. The morsellized cancellous allograft prepared by the reciprocating type bone mill showed a broad distribution of particle sizes, and gave IMCA superior mechanical properties to the graft with a more uniform size distribution, or prepared by the rotating rasp type bone mills. The increase of number of compaction also improved the mechanical properties of IMCA in compression.

  18. Siliceous mesostructured cellular foams/poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) composite biomaterials for bone regeneration

    PubMed Central

    Yang, Shengbing; Xu, Shuogui; Zhou, Panyu; Wang, Jing; Tan, Honglue; Liu, Yang; Tang, TingTing; Liu, ChangSheng

    2014-01-01

    Osteoinductive and biodegradable composite biomaterials for bone regeneration were prepared by combining poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) with siliceous mesostructured cellular foams (SMC), using the porogen leaching method. Surface hydrophilicity, morphology, and recombinant human bone morphogenetic protein 2 adsorption/release behavior of the SMC/PHBHHx scaffolds were analyzed. Results of scanning electron microscopy indicated that the SMC was uniformly dispersed in the PHBHHx scaffolds, and SMC modification scaffolds have an interconnected porous architecture with pore sizes ranging from 200 to 400 μm. The measurements of the water contact angles suggested that the incorporation of SMC into PHBHHx improves the hydrophilicity of the composite. In vitro studies with simulated body fluid show great improvements to bioactivity and biodegradability versus pure PHBHHx scaffolds. Cell adhesion and cell proliferation on the scaffolds was also evaluated, and the new tools provide a better environment for human mesenchymal stem cell attachment, spreading, proliferation, and osteogenic differentiation on PHBHHx scaffolds. Moreover, micro-computed tomography and histological evaluation confirmed that the SMC/PHBHHx scaffolds improved the efficiency of new bone regeneration with excellent biocompatibility and biodegradability and faster and more effective osteogenesis in vivo. PMID:25364243

  19. Siliceous mesostructured cellular foams/poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) composite biomaterials for bone regeneration.

    PubMed

    Yang, Shengbing; Xu, Shuogui; Zhou, Panyu; Wang, Jing; Tan, Honglue; Liu, Yang; Tang, TingTing; Liu, ChangSheng

    2014-01-01

    Osteoinductive and biodegradable composite biomaterials for bone regeneration were prepared by combining poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) with siliceous mesostructured cellular foams (SMC), using the porogen leaching method. Surface hydrophilicity, morphology, and recombinant human bone morphogenetic protein 2 adsorption/release behavior of the SMC/PHBHHx scaffolds were analyzed. Results of scanning electron microscopy indicated that the SMC was uniformly dispersed in the PHBHHx scaffolds, and SMC modification scaffolds have an interconnected porous architecture with pore sizes ranging from 200 to 400 μm. The measurements of the water contact angles suggested that the incorporation of SMC into PHBHHx improves the hydrophilicity of the composite. In vitro studies with simulated body fluid show great improvements to bioactivity and biodegradability versus pure PHBHHx scaffolds. Cell adhesion and cell proliferation on the scaffolds was also evaluated, and the new tools provide a better environment for human mesenchymal stem cell attachment, spreading, proliferation, and osteogenic differentiation on PHBHHx scaffolds. Moreover, micro-computed tomography and histological evaluation confirmed that the SMC/PHBHHx scaffolds improved the efficiency of new bone regeneration with excellent biocompatibility and biodegradability and faster and more effective osteogenesis in vivo. PMID:25364243

  20. Positive culture in allograft ACL-reconstruction: what to do?

    PubMed

    Díaz-de-Rada, P; Barriga, A; Barroso, J L; García-Barrecheguren, E; Alfonso, M; Valentí, J R

    2003-07-01

    The transmission of disease or infection from the donor to the recipient is always a risk with the use of allografts. We carried out a research study on the behavioural pattern of implanted allografts, which were initially stored in perfect conditions (all cultures being negative) but later presented positive cultures at the implantation stage. Because there is no information available on how to deal with this type of situation, our aim was to set guidelines on the course of action which would be required in such a case. We conducted a retrospective study of 181 patients who underwent an ACL reconstruction using BPTB allografts. All previous bone and blood cultures and tests for hepatitis B and C, syphilis and HIV were negative. An allograft sample was taken for culture in the operating theatre just before its implantation. The results of the cultures were obtained 3-5 days after the operation. We had 24 allografts with positive culture (13.25%) after the implantation with no clinical infection in any of these patients. Positive cultures could be caused by undetected contamination while harvesting, storing or during manipulation before implantation. The lack of clinical signs of infection during the follow-up of our patients may indicate that no specific treatment-other than an antibiotic protocol-would be required when facing a case of positive culture of a graft piece after its implantation.

  1. Positive culture in allograft ACL-reconstruction: what to do?

    PubMed

    Díaz-de-Rada, P; Barriga, A; Barroso, J L; García-Barrecheguren, E; Alfonso, M; Valentí, J R

    2003-07-01

    The transmission of disease or infection from the donor to the recipient is always a risk with the use of allografts. We carried out a research study on the behavioural pattern of implanted allografts, which were initially stored in perfect conditions (all cultures being negative) but later presented positive cultures at the implantation stage. Because there is no information available on how to deal with this type of situation, our aim was to set guidelines on the course of action which would be required in such a case. We conducted a retrospective study of 181 patients who underwent an ACL reconstruction using BPTB allografts. All previous bone and blood cultures and tests for hepatitis B and C, syphilis and HIV were negative. An allograft sample was taken for culture in the operating theatre just before its implantation. The results of the cultures were obtained 3-5 days after the operation. We had 24 allografts with positive culture (13.25%) after the implantation with no clinical infection in any of these patients. Positive cultures could be caused by undetected contamination while harvesting, storing or during manipulation before implantation. The lack of clinical signs of infection during the follow-up of our patients may indicate that no specific treatment-other than an antibiotic protocol-would be required when facing a case of positive culture of a graft piece after its implantation. PMID:12827226

  2. The effect of mesenchymal stem cell sheets on structural allograft healing of critical-sized femoral defects in mice

    PubMed Central

    Long, Teng; Zhu, Zhenan; Awad, Hani A.; Schwarz, Edward M.; Hilton, Matthew J.; Dong, Yufeng

    2014-01-01

    Structural bone allografts are widely used in the clinic to treat critical sized bone defects, despite lacking the osteoinductive characteristics of live autografts. To address this, we generated revitalized structural allografts wrapped with mesenchymal stem/progenitor cell (MSC) sheets, which were produced by expanding primary syngenic bone marrow derived cells on temperature-responsive plates, as a tissue engineered periosteum. In vitro assays demonstrated maintenance of the MSC phenotype in the sheets, suggesting that short-term culturing of MSC sheets is not detrimental. To test their efficacy in vivo, allografts wrapped with MSC sheets were transplanted into 4-mm murine femoral defects and compared to allografts with direct seeding of MSCs and allografts without cells. Evaluations consisted of x-ray plain radiography, 3D microCT, histology, and biomechanical testing at 4- and 6-weeks post-surgery. Our findings demonstrate that MSC sheets induce prolonged cartilage formation at the graft-host junction and enhanced bone callus formation, as well as graft-host osteointegration. Moreover, a large periosteal callus was observed spanning the allografts with MSC sheets, which partially mimics live autograft healing. Finally, biomechanical testing showed a significant increase in the structural and functional properties of MSC sheet grafted femurs. Taken together, MSC sheets exhibit enhanced osteogenicity during critical sized bone defect repair, demonstrating the feasibility of this tissue engineering solution for massive allograft healing. PMID:24393269

  3. The effect of mesenchymal stem cell sheets on structural allograft healing of critical sized femoral defects in mice.

    PubMed

    Long, Teng; Zhu, Zhenan; Awad, Hani A; Schwarz, Edward M; Hilton, Matthew J; Dong, Yufeng

    2014-03-01

    Structural bone allografts are widely used in the clinic to treat critical sized bone defects, despite lacking the osteoinductive characteristics of live autografts. To address this, we generated revitalized structural allografts wrapped with mesenchymal stem/progenitor cell (MSC) sheets, which were produced by expanding primary syngenic bone marrow derived cells on temperature-responsive plates, as a tissue-engineered periosteum. In vitro assays demonstrated maintenance of the MSC phenotype in the sheets, suggesting that short-term culturing of MSC sheets is not detrimental. To test their efficacy in vivo, allografts wrapped with MSC sheets were transplanted into 4-mm murine femoral defects and compared to allografts with direct seeding of MSCs and allografts without cells. Evaluations consisted of X-ray plain radiography, 3D microCT, histology, and biomechanical testing at 4- and 6-weeks post-surgery. Our findings demonstrate that MSC sheets induce prolonged cartilage formation at the graft-host junction and enhanced bone callus formation, as well as graft-host osteointegration. Moreover, a large periosteal callus was observed spanning the allografts with MSC sheets, which partially mimics live autograft healing. Finally, biomechanical testing showed a significant increase in the structural and functional properties of MSC sheet grafted femurs. Taken together, MSC sheets exhibit enhanced osteogenicity during critical sized bone defect repair, demonstrating the feasibility of this tissue engineering solution for massive allograft healing.

  4. Effects of freezing on bone histological morphology.

    PubMed

    Andrade, Miguel Gustavo Setúbal; Sá, Camila Neves; Marchionni, Antônio Márcio Teixeira; dos Santos Calmon de Bittencourt, Thereza Cristina Bório; Sadigursky, Moysés

    2008-12-01

    Allograft bone has been widely used for reconstruction of different portions of the skeleton. The fragment of bone harvested must be kept under low temperatures. The cryopreservation also contributes to decrease the antigenic potential of the tissue. Although this technique is considered safe, there is little information about the morphological modifications that the medullary and cortical portions of bone suffer after freezing. Hence, the aim of this study was to investigate the morphology of bone tissue after freezing under different temperatures and periods. Twelve rabbits were used to analyze the effects of two temperatures, -20 degrees C and -70 degrees C, during four periods of time: 30, 60, 90, 120 days. Tissues were analyzed by HE, picro-sirius stains and also by Feulgen's reaction, through qualitative and morphometric ways, considering the area occupied by cells and nuclei, medullary and cortical portions, as well as by collagen expression at cortical. The differences among the treatments were analyzed by Tukey s test, at 5% significance level. Bone freezing increased cellular and nuclear areas at cancellous bone and diminished nuclear area at the cortical bone. Cortical bone collagen suffered denaturation proportionally to temperature decrease and to freezing duration. These alterations compromised the morphology of tissues after 90 or 120 days of freezing at the temperature of -70 degrees C. Cells necrosed during freezing, contributing to reduce bone antigenicity.

  5. Regenerative Effects of Three Types of Allografts on Rabbit Calvarium: An Animal Study

    PubMed Central

    Rokn, Amir Reza; Shakeri, Abbas Seyed; Etemad-Moghadam, Shahroo; Alaeddini, Mojgan; Shamshiri, Ahmad Reza; Manasheof, Rebecca; Barikani, Hamidreza

    2015-01-01

    Objectives: The aim of this study was to histologically compare the regenerative properties of two allografts manufactured by two Iranian companies. Materials and Methods: In this study, four 8-mm defects were produced in the calvaria of 12 rabbits. In three defects, three types of allografts namely ITB, CenoBone and Grafton were placed and one defect served as control. Samples were prepared and histomorphometric evaluations were carried out after healing periods of four weeks (interval 1) and eight weeks (interval 2). Qualitative and quantities variables were compared and analyzed with SPSS software. Results: Mild inflammation was observed in 45% and 12.5% of the samples in the first and second intervals, respectively. Foreign body reaction was observed in only 5% of the samples. The quality of regenerated bone was immature, mixed and lamellar in 54.5%, 15.9% and 4.5% of the samples, respectively. The rate of allograft resorption was the highest and lowest in the CenoBone and Grafton samples, respectively. The mean amount of regenerated bone was higher in areas containing Grafton; however, the differences were not statistically significant. Conclusion: Despite the differences in the numerical values of bone regeneration, there were no statistically significant differences in bone generation among the material groups, and allografts manufactured in Iran can be suitable alternatives to Grafton with the same good properties. Further studies are necessary to clarify the efficacy of these allografts. PMID:27507993

  6. Evaluation of early cellular influences of bone morphogenetic proteins 12 and 2 on equine superficial digital flexor tenocytes and bone marrow–derived mesenchymal stem cells in vitro

    PubMed Central

    Murray, Shannon J.; Santangelo, Kelly S.; Bertone, Alicia L.

    2014-01-01

    Objective To evaluate early cellular influences of bone morphogenetic protein (BMP)12 and BMP2 on equine superficial digital flexor tenocytes (SDFTNs) and equine bone marrow–derived mesenchymal stem cells (BMDMSCs). Animals 9 adult clinically normal horses. Procedures BMDMSCs and SDFTNs were cultured in monolayer, either untreated or transduced with adenovirus encoding green fluorescent protein, adenovirus encoding BMP12, or adenovirus encoding BMP2. Cytomorphologic, cytochemical, immunocytochemical, and reverse transcriptase–quantitative PCR (RT-qPCR) analyses were performed on days 3 and 6. Genetic profiling for effects of BMP12 was evaluated by use of an equine gene expression microarray on day 6. Results BMDMSCs and SDFTNs had high BMP12 gene expression and remained viable and healthy for at least 6 days. Type l collagen immunocytochemical staining for SDFTNs and tenocyte-like morphology for SDFTNs and BMDMSCs were greatest in BMP12 cells. Cartilage oligomeric matrix protein, as determined via RT-qPCR assay, and chondroitin sulfate, as determined via gene expression microarray analysis, were upregulated relative to control groups in SDFTN-BMP12 cells. The BMDMSCs and SDFTNs became mineralized with BMP2, but not BMP12. Superficial digital flexor tenocytes responded to BMP12 with upregulation of genes relevant to tendon healing and without mineralization as seen with BMP2. Conclusions and Clinical Relevance Targeted equine SDFTNs may respond to BMP12 with improved tenocyte morphology and without mineralization, as seen with BMP2. Bone marrow–derived mesenchymal stem cells may be able to serve as a cell delivery method for BMP12. PMID:20043789

  7. A cellular perspective to bioceramic scaffolds for bone tissue engineering: the state of the art.

    PubMed

    Guda, T; Appleford, M; Oh, S; Ong, J L

    2008-01-01

    A vast number of manufacturing techniques have been employed in the last five years to manufacture three dimensional (3D) calcium phosphate (CaP) scaffolds, with the intention to replicate the architecture of native bone as well as to repair and restore bone function. Design features such as architectural control and sintering temperature and their impact on scaffold performance is presented in this review. In vitro cell responses to bioceramic scaffolds and their in vivo performances have been enhanced. Current frontiers of active research on HA scaffolds have included the relationship between fluid flow and mechanotransduction as well as cell signaling pathways that induce endothelial cell recruitment and angiogenesis. Additionally, current research has focused on a better understanding of cell signaling and its environmental cues. The availability of non-invasive and non-destructive quantitative imaging modalities has also become critical in aiding the characterization of scaffolds and predicting scaffold performance. It is thus anticipated that further knowledge gained from this research will allow the overall advancement of scaffolds that can be clinically used to restore large bone defects.

  8. Zirconia toughened alumina ceramic foams for potential bone graft applications: fabrication, bioactivation, and cellular responses.

    PubMed

    He, X; Zhang, Y Z; Mansell, J P; Su, B

    2008-07-01

    Zirconia toughened alumina (ZTA) has been regarded as the next generation orthopedic graft material due to its excellent mechanical properties and biocompatibility. Porous ZTA ceramics with good interconnectivity can potentially be used as bone grafts for load-bearing applications. In this work, three-dimensional (3D) interconnected porous ZTA ceramics were fabricated using a direct foaming method with egg white protein as binder and foaming agent. The results showed that the porous ZTA ceramics possessed a bimodal pore size distribution. Their mechanical properties were comparable to those of cancellous bone. Due to the bio-inertness of alumina and zirconia ceramics, surface bioactivation of the ZTA foams was carried out in order to improve their bioactivity. A simple NaOH soaking method was employed to change the surface chemistry of ZTA through hydroxylation. Treated samples were tested by conducting osteoblast-like cell culture in vitro. Improvement on cells response was observed and the strength of porous ZTA has not been deteriorated after the NaOH treatment. The porous 'bioactivated' ZTA ceramics produced here could be potentially used as non-degradable bone grafts for load-bearing applications. PMID:18305904

  9. Inhibition of the immune response to experimental fresh osteoarticular allografts

    SciTech Connect

    Rodrigo, J.J.; Schnaser, A.M.; Reynolds, H.M. Jr.; Biggart, J.M. 3d.; Leathers, M.W.; Chism, S.E.; Thorson, E.; Grotz, T.; Yang, Q.M. )

    1989-06-01

    The immune response to osteoarticular allografts is capable of destroying the cartilage--a tissue that has antigens on its cells identical to those on the bone and marrow cells. Osteoarticular allografts of the distal femur were performed in rats using various methods to attempt to temporarily inhibit the antibody response. The temporary systemic immunosuppressant regimens investigated were cyclophosphamide, azathioprine and prednisolone, cyclosporine A, and total lymphoid irradiation. The most successful appeared to be cyclosporine A, but significant side effects were observed. To specifically inhibit the immune response in the allograft antigens without systemically inhibiting the entire immune system, passive enhancement and preadministration of donor blood were tried. Neither was as effective as coating the donor bone with biodegradable cements, a method previously found to be successful. Cyclosporine A was investigated in dogs in a preliminary study of medial compartmental knee allografts and was found to be successful in inhibiting the antibody response and in producing a more successful graft; however, some significant side effects were similarly observed.

  10. Characterization of Cellular and Molecular Heterogeneity of Bone Marrow Stromal Cells

    PubMed Central

    Elsafadi, Mona; Manikandan, Muthurangan; Atteya, Muhammad; Hashmi, Jamil Amjad; Iqbal, Zafar; Aldahmash, Abdullah; Alfayez, Musaad

    2016-01-01

    Human bone marrow-derived stromal stem cells (hBMSC) exhibit multiple functions, including differentiation into skeletal cells (progenitor function), hematopoiesis support, and immune regulation (nonprogenitor function). We have previously demonstrated the presence of morphological and functional heterogeneity of hBMSC cultures. In the present study, we characterized in detail two hTERT-BMSC clonal cell populations termed here CL1 and CL2 that represent an opposing phenotype with respect to morphology, markers expression: alkaline phosphatase (ALP) and CD146, and ex vivo differentiation potential. CL1 differentiated readily to osteoblasts, adipocytes, and chondrocytes as shown by expression of lineage specific genes and proteins. Whole genome transcriptome profiling of CL1 versus CL2 revealed enrichment in CL1 of bone-, mineralization-, and skeletal muscle-related genes, for example, ALP, POSTN, IGFBP5 BMP4, and CXCL12. On the other hand, CL2 transcriptome was enriched in immune modulatory genes, for example, CD14, CD99, NOTCH3, CXCL6, CFB, and CFI. Furthermore, gene expression microarray analysis of osteoblast differentiated CL1 versus CL2 showed significant upregulation in CL1 of bone development and osteoblast differentiation genes which included several homeobox genes: TBX15, HOXA2 and HOXA10, and IGF1, FGFR3, BMP6, MCAM, ITGA10, IGFBP5, and ALP. siRNA-based downregulation of the ALP gene in CL1 impaired osteoblastic and adipocytic differentiation. Our studies demonstrate the existence of molecular and functional heterogeneity in cultured hBMSC. ALP can be employed to identify osteoblastic and adipocytic progenitor cells in the heterogeneous hBMSC cultures.

  11. Characterization of Cellular and Molecular Heterogeneity of Bone Marrow Stromal Cells.

    PubMed

    Elsafadi, Mona; Manikandan, Muthurangan; Atteya, Muhammad; Hashmi, Jamil Amjad; Iqbal, Zafar; Aldahmash, Abdullah; Alfayez, Musaad; Kassem, Moustapha; Mahmood, Amer

    2016-01-01

    Human bone marrow-derived stromal stem cells (hBMSC) exhibit multiple functions, including differentiation into skeletal cells (progenitor function), hematopoiesis support, and immune regulation (nonprogenitor function). We have previously demonstrated the presence of morphological and functional heterogeneity of hBMSC cultures. In the present study, we characterized in detail two hTERT-BMSC clonal cell populations termed here CL1 and CL2 that represent an opposing phenotype with respect to morphology, markers expression: alkaline phosphatase (ALP) and CD146, and ex vivo differentiation potential. CL1 differentiated readily to osteoblasts, adipocytes, and chondrocytes as shown by expression of lineage specific genes and proteins. Whole genome transcriptome profiling of CL1 versus CL2 revealed enrichment in CL1 of bone-, mineralization-, and skeletal muscle-related genes, for example, ALP, POSTN, IGFBP5 BMP4, and CXCL12. On the other hand, CL2 transcriptome was enriched in immune modulatory genes, for example, CD14, CD99, NOTCH3, CXCL6, CFB, and CFI. Furthermore, gene expression microarray analysis of osteoblast differentiated CL1 versus CL2 showed significant upregulation in CL1 of bone development and osteoblast differentiation genes which included several homeobox genes: TBX15, HOXA2 and HOXA10, and IGF1, FGFR3, BMP6, MCAM, ITGA10, IGFBP5, and ALP. siRNA-based downregulation of the ALP gene in CL1 impaired osteoblastic and adipocytic differentiation. Our studies demonstrate the existence of molecular and functional heterogeneity in cultured hBMSC. ALP can be employed to identify osteoblastic and adipocytic progenitor cells in the heterogeneous hBMSC cultures. PMID:27610142

  12. Characterization of Cellular and Molecular Heterogeneity of Bone Marrow Stromal Cells

    PubMed Central

    Elsafadi, Mona; Manikandan, Muthurangan; Atteya, Muhammad; Hashmi, Jamil Amjad; Iqbal, Zafar; Aldahmash, Abdullah; Alfayez, Musaad

    2016-01-01

    Human bone marrow-derived stromal stem cells (hBMSC) exhibit multiple functions, including differentiation into skeletal cells (progenitor function), hematopoiesis support, and immune regulation (nonprogenitor function). We have previously demonstrated the presence of morphological and functional heterogeneity of hBMSC cultures. In the present study, we characterized in detail two hTERT-BMSC clonal cell populations termed here CL1 and CL2 that represent an opposing phenotype with respect to morphology, markers expression: alkaline phosphatase (ALP) and CD146, and ex vivo differentiation potential. CL1 differentiated readily to osteoblasts, adipocytes, and chondrocytes as shown by expression of lineage specific genes and proteins. Whole genome transcriptome profiling of CL1 versus CL2 revealed enrichment in CL1 of bone-, mineralization-, and skeletal muscle-related genes, for example, ALP, POSTN, IGFBP5 BMP4, and CXCL12. On the other hand, CL2 transcriptome was enriched in immune modulatory genes, for example, CD14, CD99, NOTCH3, CXCL6, CFB, and CFI. Furthermore, gene expression microarray analysis of osteoblast differentiated CL1 versus CL2 showed significant upregulation in CL1 of bone development and osteoblast differentiation genes which included several homeobox genes: TBX15, HOXA2 and HOXA10, and IGF1, FGFR3, BMP6, MCAM, ITGA10, IGFBP5, and ALP. siRNA-based downregulation of the ALP gene in CL1 impaired osteoblastic and adipocytic differentiation. Our studies demonstrate the existence of molecular and functional heterogeneity in cultured hBMSC. ALP can be employed to identify osteoblastic and adipocytic progenitor cells in the heterogeneous hBMSC cultures. PMID:27610142

  13. The efficacy of mineralized allograft cortical and cancellous chips in maxillary sinus augmentations.

    PubMed

    Nevins, Myron; Parma-Benfenati, Stefano; Janke, Ulrich W; Kleyer, Aimé; Rasperini, Giulio; Tinti, Carlo; Schupbach, Peter; Kim, David M

    2014-01-01

    A mixture of mineralized allograft cortical and cancellous chips was used to augment the maxillary sinuses of 10 patients. Eleven sinus augmentation procedures were performed, and 19 bone cores were obtained at reentry after 6 to 7 months. Computed tomography at 6 months postaugmentation demonstrated bone formation in all sites. Light microscopic and histomorphometric evaluation confirmed bone formation at the treatment site that would receive osseointegrated implants to replace the missing maxillary posterior teeth. These encouraging results support the use of a mixture of mineralized allograft cortical and cancellous chips for sinus augmentation.

  14. Imaging characteristics of bone graft materials.

    PubMed

    Beaman, Francesca D; Bancroft, Laura W; Peterson, Jeffrey J; Kransdorf, Mark J; Menke, David M; DeOrio, James K

    2006-01-01

    Bone graft materials are widely used in reconstructive orthopedic procedures to promote new bone formation and bone healing, provide a substrate and scaffolding for development of bone structure, and function as a means for direct antibiotic delivery. Bone graft materials include autografts, allografts, and synthetic substitutes. An autograft (from the patient's own bone) supplies both bone volume and osteogenic cells capable of new bone formation. The imaging appearance of an autograft depends on its type, composition, and age. Autografts often appear as osseous fragments at radiography. At computed tomography (CT), autografts appear similar to the adjacent cortical bone. At magnetic resonance (MR) imaging, however, autografts have a variable appearance as a consequence of the viable marrow inside them, a feature not present in other graft materials. An allograft (from cadaveric bone) has an appearance similar to that of cortical bone on radiographs and CT images. An allograft in the form of bone chips or morsels does not show those features on radiographs and CT images, but instead appears as a conglomerate with medium to high opacity and attenuation within the bone defect. In the immediate postoperative period, allografts appear hypointense on both T1- and T2-weighted MR images. Hematopoietic tissue replaces the normal fatty marrow in the later phases of graft incorporation. Synthetic bone substitutes are much more variable in imaging appearance. As the use of bone allografts and synthetic substitutes increases, familiarity with postoperative imaging features is essential for differentiation between grafts and residual or recurrent disease.

  15. Numerical simulation on the adaptation of forms in trabecular bone to mechanical disuse and basic multi-cellular unit activation threshold at menopause

    NASA Astrophysics Data System (ADS)

    Gong, He; Fan, Yubo; Zhang, Ming

    2008-04-01

    The objective of this paper is to identify the effects of mechanical disuse and basic multi-cellular unit (BMU) activation threshold on the form of trabecular bone during menopause. A bone adaptation model with mechanical- biological factors at BMU level was integrated with finite element analysis to simulate the changes of trabecular bone structure during menopause. Mechanical disuse and changes in the BMU activation threshold were applied to the model for the period from 4 years before to 4 years after menopause. The changes in bone volume fraction, trabecular thickness and fractal dimension of the trabecular structures were used to quantify the changes of trabecular bone in three different cases associated with mechanical disuse and BMU activation threshold. It was found that the changes in the simulated bone volume fraction were highly correlated and consistent with clinical data, and that the trabecular thickness reduced significantly during menopause and was highly linearly correlated with the bone volume fraction, and that the change trend of fractal dimension of the simulated trabecular structure was in correspondence with clinical observations. The numerical simulation in this paper may help to better understand the relationship between the bone morphology and the mechanical, as well as biological environment; and can provide a quantitative computational model and methodology for the numerical simulation of the bone structural morphological changes caused by the mechanical environment, and/or the biological environment.

  16. Suppression of serum iron-binding capacity and bone marrow cellularity in pigs fed aflatoxin

    SciTech Connect

    Harvey, R.B.; Clark, D.E.; Huff, W.E.; Kubena, L.F.; Corrier, D.E.; Phillips, I.D.

    1988-04-01

    Flavus-parasiticus species of the genus Aspergillus are recognized as the primary producers of aflatoxins B/sub 1/, B/sup 2/, G/sup 1/, and G/sup 2/, hereafter referred to as aflatoxin (AF). The effects of feeding AF-contaminated diets to growing and finishing pigs have been described with changes in clinical performance, serum biochemistry, histology, and hematology attributed to aflatoxicosis. However, most of these studies evaluated AF-induced changes for a single AF dosage at a given point in time. The present study was designed to characterize how various AF dosages influence bone marrow histology, hematology, prothrombin and activated thromboplastin times, serum amino acids, and serum iron binding capacity during aflatoxicosis in growing pigs.

  17. Suppression of serum iron-binding capacity and bone marrow cellularity in pigs fed aflatoxin

    SciTech Connect

    Harvey, R.B.; Clark, D.E.; Huff, W.E.; Kubena, L.F.; Corrier, D.E. ); Phillips, T.D. )

    1988-05-01

    Flavus-parasiticus species of the genus Aspergillus are recognized as the primary producers of aflatoxins B{sub 1}, B{sub 2}, G{sub 1}, and G{sub 2}, hereafter referred to as aflatoxin (AF). The effects of feeding AF-contaminated diets to growing and finishing pigs have been described with changes in clinical performance, serum biochemistry, histology, and hematology attributed to aflatoxicosis. However, most of these studies evaluated AF-induced changes for a single AF dosage at a given point in time. The present study was designed to characterize how various AF dosages influence bone marrow histology, hematology, prothrombin and activated thromboplastin times, serum amino acids, and serum iron binding capacity during aflatoxicosis in growing pigs.

  18. Cellular reactions of osteoblast-like cells to a novel nanocomposite membrane for guided bone regeneration

    NASA Astrophysics Data System (ADS)

    Meng, Yao; Liu, Man; Wang, Shao-An; Mo, An-Chun; Huang, Cui; Zuo, Yi; Li, Ji-Dong

    2008-11-01

    This study investigated the bioactivity and biocompatibility of hydroxyapatite nanoparticles (n-HA)/Polyamide-66 (PA66) nanocomposite membrane and expanded-polytetrafluoroethylene (e-PTFE) membrane (as control) to MG63 osteoblast-like cells. The attachment and proliferation of the cells on the porous surface of nHA/PA66 membrane and the surface of e-PTFE membrane were evaluated by scanning electron microscope (SEM) observation and the MTT assay. The bioactivity of the cells on the surface of the two membranes was evaluated by testing cell viability and alkaline phosphatase (ALP) activities. The results suggested that the bioresponse of MG63 osteoblast-like cells on the porous surface of nHA/PA66 membrane was better than the bioresponse on the opposite surface of e-PTFE membrane. Because of a better cell attachment manner, there is a potential utilization of the guided bone regeneration (GBR) membrane to substitute nHA/PA66 membrane for e-PTFE membrane.

  19. Bone

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.; Hoffmann, Ralf-Thorsten

    The typical clinical signs in bone tumours are pain, destruction and destabilization, immobilization, neurologic deficits, and finally functional impairment. Primary malignant bone tumours are a rare entity, accounting for about 0.2% of all malignancies. Also benign primary bone tumours are in total rare and mostly asymptomatic. The most common symptomatic benign bone tumour is osteoid osteoma with an incidence of 1:2000.

  20. Anterior cruciate ligament reconstruction with BPTB autograft, irradiated versus non-irradiated allograft: a prospective randomized clinical study.

    PubMed

    Sun, Kang; Tian, Shaoqi; Zhang, Jihua; Xia, Changsuo; Zhang, Cailong; Yu, Tengbo

    2009-05-01

    The effect of using gamma irradiation to sterilize bone-patellar tendon-bone (BPTB) allograft on the clinical outcomes of anterior cruciate ligament (ACL) reconstruction with irradiated allograft remains controversial. Our study was aimed to analyze the clinical outcomes of arthroscopic ACL reconstruction with irradiated BPTB allograft compared with non-irradiated allograft and autograft. All BPTB allografts were obtained from a single tissue bank and the irradiated allografts were sterilized with 2.5 Mrad of irradiation prior to distribution. A total of 102 patients undergoing arthroscopic ACL reconstruction were prospectively randomized consecutively into three groups. The same surgical technique was used in all operations done by the same senior surgeon. Before surgery and at the average of 31 months follow-up (range 24-47 months) patients were evaluated by the same observer according to objective and subjective clinical evaluations. Of these patients, 99 (autograft 33, non-irradiated allograft 34, irradiated allograft 32) were available for full evaluation. When compared the irradiated allograft group to non-irradiated allograft group or autograft group at 31 months follow-up by the Lachman test, ADT, pivot shift test and KT-2000 arthrometer testing, statistically significant differences were found. Most importantly, 87.8% of patients in the Auto group, 85.3% in the Non-Ir-Auto group and just only 31.3% in the Ir-Allo group had a side-to-side difference of less than 3 mm according to KT-2000. The failure rate of the ACL reconstruction with irradiated allograft (34.4%) was higher than that with autograft (6.1%) and non-irradiated allograft (8.8%). The anterior and rotational stability decreased significantly in the irradiated allograft group. According to the overall IKDC, functional, subjective evaluations and activity level testing, no statistically significant differences were found between the three groups. However, there was a trend that the functional and

  1. Donation FAQs (Bone and Tissue Allografts)

    MedlinePlus

    ... donor family services. Most organ, tissue and eye banks that are members of MTF send tissue to ... according to exact surgical specifications. Small, local tissue banks could not provide this level of quality in ...

  2. The Central Nervous System (CNS)-independent Anti-bone-resorptive Activity of Muscle Contraction and the Underlying Molecular and Cellular Signatures*

    PubMed Central

    Qin, Weiping; Sun, Li; Cao, Jay; Peng, Yuanzhen; Collier, Lauren; Wu, Yong; Creasey, Graham; Li, Jianhua; Qin, Yiwen; Jarvis, Jonathan; Bauman, William A.; Zaidi, Mone; Cardozo, Christopher

    2013-01-01

    Muscle and bone work as a functional unit. Cellular and molecular mechanisms underlying effects of muscle activity on bone mass are largely unknown. Spinal cord injury (SCI) causes muscle paralysis and extensive sublesional bone loss and disrupts neural connections between the central nervous system (CNS) and bone. Muscle contraction elicited by electrical stimulation (ES) of nerves partially protects against SCI-related bone loss. Thus, application of ES after SCI provides an opportunity to study the effects of muscle activity on bone and roles of the CNS in this interaction, as well as the underlying mechanisms. Using a rat model of SCI, the effects on bone of ES-induced muscle contraction were characterized. The SCI-mediated increase in serum C-terminal telopeptide of type I collagen (CTX) was completely reversed by ES. In ex vivo bone marrow cell cultures, SCI increased the number of osteoclasts and their expression of mRNA for several osteoclast differentiation markers, whereas ES significantly reduced these changes; SCI decreased osteoblast numbers, but increased expression in these cells of receptor activator of NF-κB ligand (RANKL) mRNA, whereas ES increased expression of osteoprotegerin (OPG) and the OPG/RANKL ratio. A microarray analysis revealed that ES partially reversed SCI-induced alterations in expression of genes involved in signaling through Wnt, FSH, parathyroid hormone (PTH), oxytocin, and calcineurin/nuclear factor of activated T-cells (NFAT) pathways. ES mitigated SCI-mediated increases in mRNA levels for the Wnt inhibitors DKK1, sFRP2, and sclerostin in ex vivo cultured osteoblasts. Our results demonstrate an anti-bone-resorptive activity of muscle contraction by ES that develops rapidly and is independent of the CNS. The pathways involved, particularly Wnt signaling, suggest future strategies to minimize bone loss after immobilization. PMID:23530032

  3. Immune response to nonspecific and altered tissue antigens in soft tissue allografts.

    PubMed

    Pinkowski, J L; Rodrigo, J J; Sharkey, N A; Vasseur, P B

    1996-05-01

    Soft tissue allografts have many uses in orthopaedic surgery, including knee ligament reconstruction, hand tendon surgery, shoulder instability, and rotator cuff reconstruction. The predictable biologic incorporation of soft tissue allografts without rejection or fear of disease transmission continues to be a goal of basic science researchers. A review of the current knowledge if the immune system response to donor specific, nonspecific, and altered tissue antigens in soft tissue or tendon allografts is presented. An in vitro study was done in an attempt to decrease immunogenicity of a frozen bone-ligament graft by adding irrigation with Betadine scrub solution and hydrogen peroxide to the conventional storage process of freezing. Although the irrigation with cytotoxic agents would undoubtedly further decrease immunogenicity, it also decreased stiffness and maximum load by 15%. Whether this decreased strength and stiffness would compromise the incorporation and long term success of soft tissue allografts would need to be studied by in vitro experiments.

  4. Double-chamber rotating bioreactor for dynamic perfusion cell seeding of large-segment tracheal allografts: comparison to conventional static methods.

    PubMed

    Haykal, Siba; Salna, Michael; Zhou, Yingzhe; Marcus, Paula; Fatehi, Mostafa; Frost, Geoff; Machuca, Tiago; Hofer, Stefan O P; Waddell, Thomas K

    2014-08-01

    Tracheal transplantation with a long-segment recellularized tracheal allograft has previously been performed without the need for immunosuppressive therapy. Recipients' mesenchymal stromal cells (MSC) and tracheal epithelial cells (TEC) were harvested, cultured, expanded, and seeded on a donor trachea within a bioreactor. Prior techniques used for cellular seeding have involved only static-seeding methods. Here, we describe a novel bioreactor for recellularization of long-segment tracheae. Tracheae were recellularized with epithelial cells on the luminal surface and bone marrow-derived MSC on the external surface. We used dynamic perfusion seeding for both cell types and demonstrate an increase in both cellular counts and homogeneity scores compared with traditional methods. Despite these improvements, orthotopic transplantation of these scaffolds revealed no labeled cells at postoperative day 3 and lack of re-epithelialization within the first 2 weeks. The animals in this study had postoperative respiratory distress and tracheal collapse that was incompatible with life. PMID:24392662

  5. Renal Allograft Torsion: US and CT Imaging Findings of a Rare Posttransplant Complication.

    PubMed

    Dewan, Rohit; Dasyam, Anil K; Tan, Henke; Furlan, Alessandro

    2016-01-01

    Vascular torsion is a rare renal transplant complication which requires prompt diagnosis and surgery to salvage allograft function. We report here a case of renal allograft torsion with interesting imaging findings on unenhanced CT and color Doppler ultrasound. A 60-year-old woman with a history of pancreas and kidney transplant presented to the emergency room with nausea, vomiting, abdominal pain, and minimal urine output. Unenhanced CT of the abdomen demonstrated an enlarged and malrotated renal allograft with moderate hydronephrosis. Color Doppler ultrasound demonstrated lack of vascularity within the allograft. The patient was taken urgently to the operating room where the renal allograft was found twisted 360 degrees around the vascular pedicle. After the allograft was detorsed, the color of the kidney returned and the Doppler signals for arterial flow improved. Intraoperative biopsy showed no evidence of infarct or acute cellular rejection. The detorsed kidney was surgically fixed in position in its upper and lower poles. Follow-up ultrasound 1 day later demonstrated normal blood flow to the renal allograft and the serum level of creatinine returned to normal.

  6. Preparation, characterization, in vitro bioactivity, and cellular responses to a polyetheretherketone bioactive composite containing nanocalcium silicate for bone repair.

    PubMed

    Ma, Rui; Tang, Songchao; Tan, Honglue; Qian, Jun; Lin, Wentao; Wang, Yugang; Liu, Changsheng; Wei, Jie; Tang, Tingting

    2014-08-13

    In this study, a nanocalcium silicate (n-CS)/polyetheretherketone (PEEK) bioactive composite was prepared using a process of compounding and injection-molding. The mechanical properties, hydrophilicity, and in vitro bioactivity of the composite, as well as the cellular responses of MC3T3-E1 cells (attachment, proliferation, spreading, and differentiation) to the composite, were investigated. The results showed that the mechanical properties and hydrophilicity of the composites were significantly improved by the addition of n-CS to PEEK. In addition, an apatite-layer formed on the composite surface after immersion in simulated body fluid (SBF) for 7 days. In cell culture tests, the results revealed that the n-CS/PEEK composite significantly promoted cell attachment, proliferation, and spreading compared with PEEK or ultrahigh molecular weight polyethylene (UHMWPE). Moreover, cells grown on the composite exhibited higher alkaline phosphatase (ALP) activity, more calcium nodule-formation, and higher expression levels of osteogenic differentiation-related genes than cells grown on PEEK or UHMWPE. These results indicated that the incorporation of n-CS to PEEK could greatly improve the bioactivity and biocompatibility of the composite. Thus, the n-CS/PEEK composite may be a promising bone repair material for use in orthopedic clinics.

  7. Preparation, characterization, in vitro bioactivity, and cellular responses to a polyetheretherketone bioactive composite containing nanocalcium silicate for bone repair.

    PubMed

    Ma, Rui; Tang, Songchao; Tan, Honglue; Qian, Jun; Lin, Wentao; Wang, Yugang; Liu, Changsheng; Wei, Jie; Tang, Tingting

    2014-08-13

    In this study, a nanocalcium silicate (n-CS)/polyetheretherketone (PEEK) bioactive composite was prepared using a process of compounding and injection-molding. The mechanical properties, hydrophilicity, and in vitro bioactivity of the composite, as well as the cellular responses of MC3T3-E1 cells (attachment, proliferation, spreading, and differentiation) to the composite, were investigated. The results showed that the mechanical properties and hydrophilicity of the composites were significantly improved by the addition of n-CS to PEEK. In addition, an apatite-layer formed on the composite surface after immersion in simulated body fluid (SBF) for 7 days. In cell culture tests, the results revealed that the n-CS/PEEK composite significantly promoted cell attachment, proliferation, and spreading compared with PEEK or ultrahigh molecular weight polyethylene (UHMWPE). Moreover, cells grown on the composite exhibited higher alkaline phosphatase (ALP) activity, more calcium nodule-formation, and higher expression levels of osteogenic differentiation-related genes than cells grown on PEEK or UHMWPE. These results indicated that the incorporation of n-CS to PEEK could greatly improve the bioactivity and biocompatibility of the composite. Thus, the n-CS/PEEK composite may be a promising bone repair material for use in orthopedic clinics. PMID:25013988

  8. Microparticulate Cortical Allograft: An Alternative to Autograft in the Treatment of Osseous Defects

    PubMed Central

    Temple, H. Thomas; Malinin, Theodore I

    2008-01-01

    Benign bone tumors are commonly diagnosed and treated. Following tumor removal, the defect in the bone can be filled with auto- or allografts, (degradable) bone substitutes or non-degradable polymethylmethacrylate. The ideal substitute for this purpose should provide immediate structural support and readily incorporate into bone over a short period of time. Experimentally, microparticulate allograft has been shown to incorporate quickly in metaphyseal and metadiaphyseal cortico-cancellous defects in primates [1]. Using a combination of small allogeneic cortical graft particles (< 250 µm), bone defects were filled following intralesional excision in 97 consecutive patients with benign and low grade malignant tumors and tumor-like conditions of bone. The clinical results and rate of radiographic incorporation and osseous consolidation were recorded and analyzed. These patients underwent 104 procedures in which osseous defects were packed with microparticulate allograft. The follow-up was from 23 to 49 months. There were 94 (90.3%) closed defects and 10 (9.7%) open defects. The average size of the grafted defect was 42.8 cm3 (0.48 - 315.0 cm3). Internal fixation was used in 11 of the 104 procedures (10.6 %). Radiographically, incorporation was observed in 91% of patients and consolidation in 60%. There were eleven failures (10.6 %), eight (72 %) due to tumor recurrence. Seven of eight patients with tumor recurrence underwent a second resection and grafting procedure that resulted in allograft incorporation and defect healing. There were two deep infections requiring debridement with retention of the graft; both resolved with satisfactory healing. Both incorporation and consolidation were observed in over 90% of patients with a low rate of complications. The use of small-particle cortical allograft proved to be an effective alternative to autogenous bone graft in patients with metaphyseal and metadiaphyseal surgical bone defects. PMID:19478936

  9. Healing of fractures with freeze-dried cortical bone plates. Comparison with compression plating.

    PubMed

    Malinin, T; Latta, L L; Wagner, J L; Brown, M D

    1984-11-01

    The healing of fractures of the radius with internal fixation by stainless-steel compression plates was compared with fractures fixed with freeze-dried bone-plate allografts. Fractures fixed with metallic plates gained slightly less than half the biomechanical strength of the contralateral control bone and healed without noticeable external callus formation. Bone-plated fractures regained three-fourths of the biomechanical strength of controls and healed by forming an external callus. Bone-plate allografts were eventually incorporated in the host bone. Allograft plates were vascularized and remodeled into cancellous bone in the process of incorporation in the host bones.

  10. Interplay between immune responses to HLA and non-HLA self-antigens in allograft rejection.

    PubMed

    Angaswamy, Nataraju; Tiriveedhi, Venkataswarup; Sarma, Nayan J; Subramanian, Vijay; Klein, Christina; Wellen, Jason; Shenoy, Surendra; Chapman, William C; Mohanakumar, T

    2013-11-01

    Recent studies strongly suggest an increasing role for immune responses against self-antigens (Ags) which are not encoded by the major histocompatibility complex in the immunopathogenesis of allograft rejection. Although, improved surgical techniques coupled with improved methods to detect and avoid sensitization against donor human leukocyte antigen (HLA) have improved the immediate and short term function of transplanted organs. However, acute and chronic rejection still remains a vexing problem for the long term function of the transplanted organ. Immediately following organ transplantation, several factors both immune and non immune mechanisms lead to the development of local inflammatory milieu which sets the stage for allograft rejection. Traditionally, development of antibodies (Abs) against mismatched donor HLA have been implicated in the development of Ab mediated rejection. However, recent studies from our laboratory and others have demonstrated that development of humoral and cellular immune responses against non-HLA self-Ags may contribute in the pathogenesis of allograft rejection. There are reports demonstrating that immune responses to self-Ags especially Abs to the self-Ags as well as cellular immune responses especially through IL17 has significant pro-fibrotic properties leading to chronic allograft failure. This review summarizes recent studies demonstrating the role for immune responses to self-Ags in allograft immunity leading to rejection as well as present recent evidence suggesting there is interplay between allo- and autoimmunity leading to allograft dysfunction.

  11. Comparison of immune response to nerve allograft segments in fetal and adult rabbits: a histological study.

    PubMed

    Ağaoğlu, G; Kayikçioğlu, A; Sargon, M; Erk, Y; Mavili, E

    2000-04-01

    Fetuses, as opposed to adults, are immature immunologically and it has been proved that they can tolerate allograft materials much better than adults. In this study the rejection phenomenon of nerve allografts was compared histologically in fetuses and adults. The study was performed in 60 New Zealand rabbits (30 pregnant and 30 nonpregnant), and allograft nerve segments were obtained from Chinchilla rabbits. The animals were divided into fetal and adult groups. Each group was studied at various time periods. Nerve allografts were placed under the panniculus carnosus in the interscapular region of the fetuses and adults. In both fetal and adult groups, the nerve allograft segments were assessed histologically after 1, 7, and 30 days. The criteria used during the evaluation were the degenerative findings in the myelinated axons (large, medium, and small axons), changes in Schwann's cells, and the quantity of infiltrating cells. The changes were graded microscopically from 0 (no change) to 3 (severe destruction and cellular infiltration). Cellular infiltration was more extensive in the adult groups than in the fetal groups. Earlier fetal groups showed minimal infiltration, but the response became more extensive in the later fetal groups. This is probably related to the removal of the fetuses from their intrauterine environment. When comparing fetal and adult groups, the results were significant (p < 0.05). The fetuses tolerated the nerve allograft segments better than the adults. This may be related to the immature immune system of the fetuses.

  12. Filgrastim-Stimulated Bone Marrow Compared with Filgrastim-Mobilized Peripheral Blood in Myeloablative Sibling Allografting for Patients with Hematologic Malignancies: A Randomized Canadian Blood and Marrow Transplant Group Study.

    PubMed

    Couban, Stephen; Aljurf, Mahmoud; Lachance, Sylvie; Walker, Irwin; Toze, Cynthia; Rubinger, Morel; Lipton, Jeffrey H; Lee, Stephanie J; Szer, Richard; Doocey, R; Lewis, Ian D; Huebsch, Lothar; Howson-Jan, Kang; Lalancette, Michel; Almohareb, Fahad; Chaudhri, Nadeem; Ivison, Sabine; Broady, Raewyn; Levings, Megan; Fairclough, Diane; Devins, Gerald; Szwajcer, David; Foley, Ronan; Smith, Clayton; Panzarella, Tony; Kerr, Holly; Kariminia, Amina; Schultz, Kirk R

    2016-08-01

    In adult hematopoietic cell transplantation (HCT), filgrastim-mobilized peripheral blood (G-PB) has largely replaced unstimulated marrow for allografting. Although the use of G-PB results in faster hematopoietic recovery, it is also associated with more chronic graft-versus-host disease (cGVHD). A potential alternative allograft is filgrastim-stimulated marrow (G-BM), which we hypothesized may be associated with prompt hematopoietic recovery but with less cGVHD. We conducted a phase 3, open-label, multicenter randomized trial of 230 adults with hematologic malignancies receiving allografts from siblings after myeloablative conditioning to compare G-PB with G-BM. The primary endpoint was time to treatment failure, defined as a composite of extensive cGVHD, relapse/disease progression, and death. With a median follow-up of 36 months (range, 9.6 to 48), comparing G-BM with G-PB, there was no difference between the 2 arms with respect to the primary outcome of this study (hazard ratio [HR], .91; 95% confidence interval [CI], .68 to 1.22; P = .52). However, the cumulative incidence of overall cGVHD was lower with G-BM (HR, .66; 95% CI, .46 to .95; P = .007) and there was no difference in the risk of relapse or progression (P = .35). The median times to neutrophil recovery (P = .0004) and platelet recovery (P = .012) were 3 days shorter for recipients allocated to G-PB compared with those allocated to G-BM, but there were no differences in secondary engraftment-related outcomes, such as time to first hospital discharge (P = .17). In addition, there were no graft failures in either arm. This trial demonstrates that, compared with G-PB, the use of G-BM allografts leads to a significantly lower rate of overall cGVHD without a loss of the graft-versus-tumor effect and comparable overall survival. Our findings suggest that further study of this type of allograft is warranted.

  13. [Bone transplant].

    PubMed

    San Julián, M; Valentí, A

    2006-01-01

    We describe the methodology of the Bone and Soft Tissue Bank, from extraction and storage until use. Since the year 1986, with the creation of the Bone Bank in the University Clinic of Navarra, more than 3,000 grafts have been used for very different types of surgery. Bone grafts can be classified into cortical and spongy; the former are principally used in surgery to save tumour patients, in large post-traumatic reconstructions and in replacement surgery where there are massive bone defects and a structural support is required. The spongy grafts are the most used due to their numerous indications; they are especially useful in filling cavities that require a significant quantity of graft when the autograft is insufficient, or as a complement. They are also of special help in treating fractures when there is bone loss and in the treatment of delays in consolidation and pseudoarthrosis in little vascularized and atrophic zones. They are also used in prosthetic surgery against the presence of cavity type defects. Allografts of soft tissues are specially recognised in multiple ligament injuries that require reconstructions. Nowadays, the most utilised are those employed in surgery of the anterior cruciate ligament although they can be used for filling any ligament or tendon defect. The principal difficulties of the cortical allografts are in the consolidation of the ends with the bone itself and in tumour surgery, given that these are patients immunodepressed by the treatment, the incidence of infection is increased with respect to spongy grafts and soft tissues, which is irrelevant. In short, the increasingly widespread use of allografts is an essential therapeutic weapon in orthopaedic surgery and traumatology. It must be used by expert hands.

  14. [Bone transplant].

    PubMed

    San Julián, M; Valentí, A

    2006-01-01

    We describe the methodology of the Bone and Soft Tissue Bank, from extraction and storage until use. Since the year 1986, with the creation of the Bone Bank in the University Clinic of Navarra, more than 3,000 grafts have been used for very different types of surgery. Bone grafts can be classified into cortical and spongy; the former are principally used in surgery to save tumour patients, in large post-traumatic reconstructions and in replacement surgery where there are massive bone defects and a structural support is required. The spongy grafts are the most used due to their numerous indications; they are especially useful in filling cavities that require a significant quantity of graft when the autograft is insufficient, or as a complement. They are also of special help in treating fractures when there is bone loss and in the treatment of delays in consolidation and pseudoarthrosis in little vascularized and atrophic zones. They are also used in prosthetic surgery against the presence of cavity type defects. Allografts of soft tissues are specially recognised in multiple ligament injuries that require reconstructions. Nowadays, the most utilised are those employed in surgery of the anterior cruciate ligament although they can be used for filling any ligament or tendon defect. The principal difficulties of the cortical allografts are in the consolidation of the ends with the bone itself and in tumour surgery, given that these are patients immunodepressed by the treatment, the incidence of infection is increased with respect to spongy grafts and soft tissues, which is irrelevant. In short, the increasingly widespread use of allografts is an essential therapeutic weapon in orthopaedic surgery and traumatology. It must be used by expert hands. PMID:16998521

  15. Urine Metabolite Profiles Predictive of Human Kidney Allograft Status.

    PubMed

    Suhre, Karsten; Schwartz, Joseph E; Sharma, Vijay K; Chen, Qiuying; Lee, John R; Muthukumar, Thangamani; Dadhania, Darshana M; Ding, Ruchuang; Ikle, David N; Bridges, Nancy D; Williams, Nikki M; Kastenmüller, Gabi; Karoly, Edward D; Mohney, Robert P; Abecassis, Michael; Friedewald, John; Knechtle, Stuart J; Becker, Yolanda T; Samstein, Benjamin; Shaked, Abraham; Gross, Steven S; Suthanthiran, Manikkam

    2016-02-01

    Noninvasive diagnosis and prognostication of acute cellular rejection in the kidney allograft may help realize the full benefits of kidney transplantation. To investigate whether urine metabolites predict kidney allograft status, we determined levels of 749 metabolites in 1516 urine samples from 241 kidney graft recipients enrolled in the prospective multicenter Clinical Trials in Organ Transplantation-04 study. A metabolite signature of the ratio of 3-sialyllactose to xanthosine in biopsy specimen-matched urine supernatants best discriminated acute cellular rejection biopsy specimens from specimens without rejection. For clinical application, we developed a high-throughput mass spectrometry-based assay that enabled absolute and rapid quantification of the 3-sialyllactose-to-xanthosine ratio in urine samples. A composite signature of ratios of 3-sialyllactose to xanthosine and quinolinate to X-16397 and our previously reported urinary cell mRNA signature of 18S ribosomal RNA, CD3ε mRNA, and interferon-inducible protein-10 mRNA outperformed the metabolite signatures and the mRNA signature. The area under the receiver operating characteristics curve for the composite metabolite-mRNA signature was 0.93, and the signature was diagnostic of acute cellular rejection with a specificity of 84% and a sensitivity of 90%. The composite signature, developed using solely biopsy specimen-matched urine samples, predicted future acute cellular rejection when applied to pristine samples taken days to weeks before biopsy. We conclude that metabolite profiling of urine offers a noninvasive means of diagnosing and prognosticating acute cellular rejection in the human kidney allograft, and that the combined metabolite and mRNA signature is diagnostic and prognostic of acute cellular rejection with very high accuracy.

  16. Freeze-dried microarterial allografts

    SciTech Connect

    Raman, J.; Hargrave, J.C.

    1990-02-01

    Rehydrated freeze-dried microarterial allografts were implanted to bridge arterial defects using New Zealand White rabbits as the experimental model. Segments of artery from the rabbit ear and thigh were harvested and preserved for a minimum of 2 weeks after freeze-drying. These allografts, approximately 1 mm in diameter and ranging from 1.5 to 2.5 cm in length, were rehydrated and then implanted in low-pressure and high-pressure arterial systems. Poor patency was noted in low-pressure systems in both allografts and autografts, tested in 12 rabbits. In the high-pressure arterial systems, allografts that were freeze-dried and reconstituted failed in a group of 10 rabbits with an 8-week patency rate of 30 percent. Gamma irradiation in an effort to reduce infection and antigenicity of grafts after freeze-drying was associated with a patency rate of 10 percent at 8 weeks in this system in another group of 10 rabbits. Postoperative cyclosporin A therapy was associated with a patency rate of 22.2 percent in the high-pressure arterial system in a 9-rabbit group. Control autografts in this system in a group of 10 rabbits showed a 100 percent patency at 8 weeks. Microarterial grafts depend on perfusion pressure of the vascular bed for long-term patency. Rehydrated freeze-dried microarterial allografts do not seem to function well in lengths of 1 to 2.5 cm when implanted in a high-pressure arterial system. Freeze-dried arterial allografts are probably not antigenic.

  17. Comparison of Clinical Outcome of Autograft and Allograft Reconstruction for Anterior Cruciate Ligament Tears

    PubMed Central

    Jia, Yu-Hua; Sun, Peng-Fei

    2015-01-01

    Background: Hamstring (HS) autograft and bone-patellar tendon-bone allograft are the most common choice for reconstruction of anterior cruciate ligament (ACL). There was a little report about the clinical outcome and difference of arthroscopic ACL reconstruction using allograft and autograft. This study aimed to compare the clinical outcome of autograft and allograft reconstruction for ACL tears. Methods: A total of 106 patients who underwent surgery because of ACL tear were included in this study. The patients were randomly divided into two groups, including 53 patients in each group. The patients in group I underwent standard ACL reconstruction with HS tendon autografts, while others in group II underwent reconstruction with bone-patellar tendon-bone allograft. All the patients were followed up and analyzed; the mean follow-up was 81 months (range: 28–86 months). Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC), Lysholm scores, physical instability tests, and patient satisfaction questionnaires. The complication rates of both groups were compared. Tibial and femoral tunnel widening were assessed using lateral and anteroposterior radiographs. Results: At the end of follow-up, no significant differences were found between the groups in terms of IKDC, Lysholm scores, physical instability tests, patient satisfaction questionnaires, and incidences of arthrofibrosis. Tibial and femoral tunnel widening was less in the HS tendon autografts. This difference was more significant on the tibial side. Conclusions: In the repair of ACL tears, allograft reconstruction is as effective as the autograft reconstruction, but the allograft can lead to more tunnel widening evidently in the tibial tunnel, particularly. PMID:26612290

  18. Emphysema in the renal allograft

    SciTech Connect

    Potter, J.L.; Sullivan, B.M.; Fluornoy, J.G.; Gerza, C.

    1985-04-01

    Two diabetic patients in whom emphysematous pyelonephritis developed after renal transplantation are described. Clinical recognition of this unusual and serious infection is masked by the effects of immunosuppression. Abdominal radiographic, ultrasound, and computed tomography findings are discussed. The clinical presentation includes urinary tract infection, sepsis, and acute tubular malfunction of the allograft in insulin-dependent diabetics.

  19. Experimental rat models of chronic allograft nephropathy: a review

    PubMed Central

    Shrestha, Badri; Haylor, John

    2014-01-01

    Chronic allograft nephropathy (CAN) is the leading cause of late allograft loss after renal transplantation (RT), which continues to remain an unresolved problem. A rat model of CAN was first described in 1969 by White et al. Although the rat model of RT can be technically challenging, it is attractive because the pathogenesis of CAN is similar to that following human RT and the pathological features of CAN develop within months as compared with years in human RT. The rat model of RT is considered as a useful investigational tool in the field of experimental transplantation research. We have reviewed the literature on studies of rat RT reporting the donor and recipient strain combinations that have investigated resultant survival and histological outcomes. Several different combinations of inbred and outbred rat combinations have been reported to investigate the multiple aspects of transplantation, including acute rejection, cellular and humoral rejection mechanisms and their treatments, CAN, and potential targets for its prevention. PMID:25092995

  20. An audit of consent for allograft use in elective orthopaedic surgery.

    PubMed

    Mullan, C J; Pagoti, R; Davison, H; McAlinden, M G

    2016-04-01

    Introduction Patients receiving musculoskeletal allografts may be at risk of postoperative infection. The General Medical Council guidelines on consent highlight the importance of providing patients with the information they want or need on any proposed investigation or treatment, including any potential adverse outcomes. With the increased cost of defending medicolegal claims, it is paramount that adequate, clear informed patient consent be documented. Methods We retrospectively examined the patterns of informed consent for allograft bone use during elective orthopaedic procedures in a large unit with an onsite bone bank. The initial audit included patients operated over the course of 1 year. Following a feedback session, a re-audit was performed to identify improvements in practice. Results The case mix of both studies was very similar. Revision hip arthroplasty surgery constituted the major subgroup requiring allograft (48%), followed by foot and ankle surgery (16.3%) and revision knee arthroplasty surgery (11.4%) .On the initial audit, 17/45 cases (38%) had either adequate preoperative documentation of the outpatient discussion or an appropriately completed consent form on the planned use of allograft. On the re-audit, 44/78 cases (56%) had adequate pre-operative documentation. There was little correlation between how frequently a surgeon used allograft and the adequacy of consent (Correlation coefficient -0.12). Conclusions Although the risk of disease transmission with allograft may be variable, informed consent for allograft should be a routine part of preoperative discussions in elective orthopaedic surgery. Regular audit and feedback sessions may further improve consent documentation, alongside the targeting of high volume/low compliance surgeons.

  1. Bone graft and mesenchimal stem cells: clinical observations and histological analysis

    PubMed Central

    Bertolai, Roberto; Catelani, Carlo; Aversa, Alessandro; Rossi, Alessandro; Giannini, Domenico; Bani, Daniele

    2015-01-01

    Summary Autologous bone, for its osteoconductive, osteoinductive and osteogenetic properties, has been considered to be the gold standard for maxillary sinus augmentation procedures. Autograft procedures bring also some disadvantages: sometimes the limited amount of available intraoral bone makes necessary to obtain bone from an extraoral site, and this carries an associated morbidity. To overcome this problem we started using homologous freeze-dried bone in maxillary sinus augmentation procedures. This bone is industrially processed with γ-irradiation to eliminate its disease transmission potential and it’s considered safe, but this treatment also eliminates the osteoinductive and osteogenetic properties, making it just an inert scaffold for regeneration. Mesenchymal stem cells are successfully used in and orthopedic surgery for their amplification potential of healing mechanisms. We assumed that mesenchymal stem cells can restore the osteogenetic and osteoinductive properties in homologous bone grafts. The aim of this study was an histological evaluation of bone regeneration in maxillary sinus elevation using: 1) mesenchymal stem cells engineered freeze-dried bone allografts; 2) freeze-dried bone allografts. Twenty patients (10M, 10F) with a mean age of 55.2 years affected by severe maxillary atrophy were treated with bilateral maxillary sinus floor elevation. For each patient were randomly assigned a “test” side and a “control” side, different from each other exclusively in the composition of the graft material. The “control” sides were composed by corticocancellous freeze-dried bone chips and the “test” sides were composed by corticocancellous freeze-dried bone chips engineered in a bone marrow mesenchymal stem cells concentrate. After three months bone biopsies were performed on the grafts and histological specimens were made in order to evaluate the healed bone from an histological point of view. Histologically all the specimens showed

  2. Multipotent Mesenchymal Stromal Stem Cell Expansion by Plating Whole Bone Marrow at a Low Cellular Density: A More Advantageous Method for Clinical Use

    PubMed Central

    Mareschi, Katia; Rustichelli, Deborah; Calabrese, Roberto; Gunetti, Monica; Sanavio, Fiorella; Castiglia, Sara; Risso, Alessandra; Ferrero, Ivana; Tarella, Corrado; Fagioli, Franca

    2012-01-01

    Mesenchymal stem cells (MSCs) are a promising source for cell therapy due to their pluripotency and immunomodulant proprieties. As the identification of “optimal” conditions is important to identify a standard procedure for clinical use. Percoll, Ficoll and whole bone marrow directly plated were tested from the same sample as separation methods. The cells were seeded at the following densities: 100 000, 10 000, 1000, 100, 10 cells/cm2. After reaching confluence, the cells were detached, pooled and re-plated at 1000, 500, 100, and 10 cells/cm2. Statistical analyses were performed. Cumulative Population Doublings (PD) did not show significant differences for the separation methods and seeding densities but only for the plating density. Some small quantity samples plated in T25 flasks at plating densities of 10 and 100 cells/cm2 did not produce any expansion. However, directly plated whole bone marrow resulted in a more advantageous method in terms of CFU-F number, cellular growth and minimal manipulation. No differences were observed in terms of gross morphology, differentiation potential or immunophenotype. These data suggest that plating whole bone marrow at a low cellular density may represent a good procedure for MSC expansion for clinical use. PMID:23715383

  3. Multipotent mesenchymal stromal stem cell expansion by plating whole bone marrow at a low cellular density: a more advantageous method for clinical use.

    PubMed

    Mareschi, Katia; Rustichelli, Deborah; Calabrese, Roberto; Gunetti, Monica; Sanavio, Fiorella; Castiglia, Sara; Risso, Alessandra; Ferrero, Ivana; Tarella, Corrado; Fagioli, Franca

    2012-01-01

    Mesenchymal stem cells (MSCs) are a promising source for cell therapy due to their pluripotency and immunomodulant proprieties. As the identification of "optimal" conditions is important to identify a standard procedure for clinical use. Percoll, Ficoll and whole bone marrow directly plated were tested from the same sample as separation methods. The cells were seeded at the following densities: 100 000, 10 000, 1000, 100, 10 cells/cm(2). After reaching confluence, the cells were detached, pooled and re-plated at 1000, 500, 100, and 10 cells/cm(2). Statistical analyses were performed. Cumulative Population Doublings (PD) did not show significant differences for the separation methods and seeding densities but only for the plating density. Some small quantity samples plated in T25 flasks at plating densities of 10 and 100 cells/cm(2) did not produce any expansion. However, directly plated whole bone marrow resulted in a more advantageous method in terms of CFU-F number, cellular growth and minimal manipulation. No differences were observed in terms of gross morphology, differentiation potential or immunophenotype. These data suggest that plating whole bone marrow at a low cellular density may represent a good procedure for MSC expansion for clinical use.

  4. Increased Risk of Revision after ACL Reconstruction with Soft Tissue Allograft Compared to Autograft

    PubMed Central

    Maletis, Gregory; Chen, Jason; Inacio, Maria Carolina Secorun; Love, Rebecca; Funahashi, Tadashi Ted

    2016-01-01

    Objectives: The use of allograft tissue for anterior cruciate ligament reconstruction (ACLR) remains controversial. Numerous meta-analysis and systematic reviews of small clinical studies have not found differences between autograft and allograft outcomes but large registry studies have shown an increased risk of revision with allografts. The purpose of this study was to compare the risk of aseptic revision between bone-patellar tendon-bone (BPTB) autografts, hamstring tendon autografts and soft tissue allografts. Methods: A retrospective cohort study of prospectively collected data was conducted using an US ACLR Registry. A cohort of primary unilateral ACLR cases reconstructed with BPTB autografts, hamstring autografts and soft tissue allografts (from any site) was identified. Aseptic revision was the end point of the study. Type of graft and allograft processing methods (non-processed, <1.8Mrads with and without chemical processing (Allowash or AlloTrue methods), >1.8 Mrads irradiation with and without chemical processing, and chemical processing alone (BioCleanse)) were the exposures of interest evaluated. Time from surgery was evaluated as an effect modifier. All analyses were adjusted for age, gender, and race. Kaplan-Meier curves and Cox proportional hazard models were employed. Hazard ratios (HR), 95% confidence intervals (CI) are provided. Results: The cohort had 14015 cases, 8924 (63.7%) were male, 6397 (45.6%) were White, 4557 (32.5%) cases used BPTB autograft, 3751 (26.8%) cases used soft tissue allograft and 5707 (40.7%) cases used hamstring autograft. The median age was 34.6 years-old (IQR 24.1-43.2) for allograft cases and 24.3 years-old (IQR 17.7-33.8) for hamstring autograft cases, and 22.0 years-old (IQR 17.6-30.0) for BPTB autograft cases. Compared to hamstring tendon autografts, an increased risk of revision was found in allografts processed with >1.8Mrads without chemical processing after 2.5 years (HR: 3.88 95%CI 1.48-10.12), and >1.8Mrads with

  5. Anterior cruciate ligament reconstruction with allograft tendons.

    PubMed

    Strickland, Sabrina M; MacGillivray, John D; Warren, Russell F

    2003-01-01

    Allograft tissue allows reconstruction of the ACL without the donor site morbidity that can be caused by autograft harvesting. Patients who must kneel as a part of their occupation or chosen sport are particularly good candidates for allograft reconstruction. Patients over 45 years of age and those requiring revision ACL surgery can also benefit from the use and availability of allograft tendons. In some cases, patients or surgeons may opt for allograft tendons to maximize the result or morbidity ratio. Despite advances in cadaver screening and graft preparation, there remain risks of disease transmission and joint infection after allograft implantation. Detailed explanation and informed consent is vitally important in cases in which allograft tissue is used.

  6. Anterior cruciate ligament reconstruction with allograft tendons.

    PubMed

    Strickland, Sabrina M; MacGillivray, John D; Warren, Russell F

    2003-01-01

    Allograft tissue allows reconstruction of the ACL without the donor site morbidity that can be caused by autograft harvesting. Patients who must kneel as a part of their occupation or chosen sport are particularly good candidates for allograft reconstruction. Patients over 45 years of age and those requiring revision ACL surgery can also benefit from the use and availability of allograft tendons. In some cases, patients or surgeons may opt for allograft tendons to maximize the result or morbidity ratio. Despite advances in cadaver screening and graft preparation, there remain risks of disease transmission and joint infection after allograft implantation. Detailed explanation and informed consent is vitally important in cases in which allograft tissue is used. PMID:12735200

  7. Osteoarticular Allograft Reconstruction for an Angiosarcoma of the Distal Radius.

    PubMed

    Mavrogenis, Andreas F; Galanopoulos, John; Vottis, Christos; Megaloikonomos, Panayiotis D; Palmerini, Emanuela; Kokkalis, Zinon T

    2016-01-01

    Angiosarcoma of bone is a rare high-grade malignant vascular tumor accounting for <1% of malignant bone tumors. Tumor location in the distal radius is very rare. Complete surgical resection with limb salvage surgery or amputation is essential for the outcome of the patient. However, the literature is vague regarding the best surgical approach for resection of the distal radius and the optimal reconstruction option after a bone tumor resection. Several reconstruction techniques have been described, varying from arthrodesis to arthroplasties. In this article, we present a report of a patient with angiosarcoma of the distal radius treated with complete resection and reconstruction with a distal radius osteoarticular allograft. We discuss the advantages and the limitations of this surgical technique for the distal radius. PMID:27649764

  8. Autophagy in allografts rejection: A new direction?

    PubMed

    Sun, Hukui; Cheng, Dayan; Ma, Yuanyuan; Wang, Huaiquan; Liang, Ting; Hou, Guihua

    2016-03-18

    Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection is still a major risk for graft survival. Modulating the dosage of immunosuppressive drugs is not a good choice for all patients, new rejection mechanisms discovery are crucial to limit the inflammatory process and preserve the function of the transplant. Autophagy, a fundamental cellular process, can be detected in all subsets of lymphocytes and freshly isolated naive T lymphocytes. It is required for the homeostasis and function of T lymphocytes, which lead to cell survival or cell death depending on the context. T cell receptor (TCR) stimulation and costimulator signals induce strong autophagy, and autophagy deficient T cells leads to rampant apoptosis upon TCR stimulation. Autophagy has been proved to be activated during ischemia-reperfusion (I/R) injury and associated with grafts dysfunction. Furthermore, Autophagy has also emerged as a key mechanism in orchestrating innate and adaptive immune response to self-antigens, which relates with negative selection and Foxp3(+) Treg induction. Although, the role of autophagy in allograft rejection is unknown, current data suggest that autophagy indeed sweeps across both in the graft organs and recipients lymphocytes after transplantation. This review presents the rationale for the hypothesis that targeting the autophagy pathway could be beneficial in promoting graft survival after transplantation. PMID:26876576

  9. Autophagy in allografts rejection: A new direction?

    PubMed

    Sun, Hukui; Cheng, Dayan; Ma, Yuanyuan; Wang, Huaiquan; Liang, Ting; Hou, Guihua

    2016-03-18

    Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection is still a major risk for graft survival. Modulating the dosage of immunosuppressive drugs is not a good choice for all patients, new rejection mechanisms discovery are crucial to limit the inflammatory process and preserve the function of the transplant. Autophagy, a fundamental cellular process, can be detected in all subsets of lymphocytes and freshly isolated naive T lymphocytes. It is required for the homeostasis and function of T lymphocytes, which lead to cell survival or cell death depending on the context. T cell receptor (TCR) stimulation and costimulator signals induce strong autophagy, and autophagy deficient T cells leads to rampant apoptosis upon TCR stimulation. Autophagy has been proved to be activated during ischemia-reperfusion (I/R) injury and associated with grafts dysfunction. Furthermore, Autophagy has also emerged as a key mechanism in orchestrating innate and adaptive immune response to self-antigens, which relates with negative selection and Foxp3(+) Treg induction. Although, the role of autophagy in allograft rejection is unknown, current data suggest that autophagy indeed sweeps across both in the graft organs and recipients lymphocytes after transplantation. This review presents the rationale for the hypothesis that targeting the autophagy pathway could be beneficial in promoting graft survival after transplantation.

  10. Mucormycosis (zygomycosis) of renal allograft.

    PubMed

    Gupta, Krishan L; Joshi, Kusum; Kohli, Harbir S; Jha, Vivekanand; Sakhuja, Vinay

    2012-12-01

    Fungal infection is relatively common among renal transplant recipients from developing countries. Mucormycosis, also known as zygomycosis, is one of the most serious fungal infections in these patients. The most common of presentation is rhino-cerebral. Isolated involvement of a renal allograft is very rare. A thorough search of literature and our medical records yielded a total of 24 cases with mucormycosis of the transplanted kidney. There was an association with cytomegalovirus (CMV) infection and anti-rejection treatment in these patients and most of these transplants were performed in the developing countries from unrelated donors. The outcome was very poor with an early mortality in 13 (54.5%) patients. Renal allograft mucormycosis is a relatively rare and potentially fatal complication following renal transplantation. Early diagnosis, graft nephrectomy and appropriate antifungal therapy may result in an improved prognosis for these patients.

  11. ENDOTHELIAL CELLS IN ALLOGRAFT REJECTION

    PubMed Central

    Al-Lamki, Rafia S.; Bradley, John R.; Pober, Jordan S.

    2008-01-01

    In organ transplantation, blood borne cells and macromolecules (e.g. antibodies) of the host immune system are brought into direct contact with the endothelial cell (EC) lining of graft vessels. In this location, graft ECs play several roles in allograft rejection, including the initiation of rejection responses by presentation of alloantigen to circulating T cells; the development of inflammation and thrombosis; and as targets of injury and agents of repair. PMID:19034000

  12. Bone Allografts: What Is the Risk of Disease Transmission with Bone Allografts?

    MedlinePlus

    ... Sample Device Evaluation Form Instructions for Using the Sample Screening Form Glossary Research & Publications Oral Health In America: Summary of the Surgeon General's Report Journal Articles Oral Health Data Tools Water Fluoridation Reporting System Water Fluoridation Reporting System Data ...

  13. Composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation model of bone marrow transplantation.

    PubMed

    Bozkurt, Mehmet; Klimczak, Aleksandra; Nasir, Serdar; Zor, Fatih; Krokowicz, Lukasz; Siemionow, Maria

    2013-01-01

    Cellular and vascularized bone marrow cells have been used to induce donor-specific chimerism in various models of composite tissue allotransplantation. Although thymus transplantation has been reported in the literature, the effect of thymus transplantation on chimerism levels in vascularized bone containing composite tissue allotransplantation has not been reported. In this study, a new method for composite vascularized sternal bone marrow transplant model is descried that can be applied to augment chimerism after transplantation. A total of seven composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin transplantations were performed in two groups. The first group (n = 5) was designed as an allotransplantation group and the second group (n = 2) was designed as an isotransplantation group. Composite osseomusculocutaneous sternum, ribs, thymus, and pectoralis muscles allografts were harvested on the common carotid artery and external jugular vein and a heterotopic transplantation was performed to the inguinal region of the recipient rat. Cyclosporine A monotherapy was administered in order to prevent acute and chronic allograft rejection. Animals sacrificed when any sign of rejection occurred. The longest survival was 156 day post-transplant. Assessment of bone marrow cells within sternum bone component and flow cytometry analysis of donor-specific chimerism in the peripheral blood of recipients were evaluated. Our results showed that this composite allograft carried 7.5 × 10(6) of viable hematopoietic cells within the sternum component. At day 7 post-transplant chimerism was developed in T-cell population and mean level was assessed at 2.65% for RT1(n) /CD4 and at 1.0% for RT1(n) /CD8. In this study, a new osseomusculocutaneous sternum, ribs, thymus, pectoralis muscle, and skin allotransplantation model is reported which can be used to augment hematopoietic activity for chimerism induction after transplantation.

  14. Arthroscopic Anatomic Humeral Head Reconstruction With Osteochondral Allograft Transplantation for Large Hill-Sachs Lesions

    PubMed Central

    Snir, Nimrod; Wolfson, Theodore S.; Hamula, Mathew J.; Gyftopoulos, Soterios; Meislin, Robert J.

    2013-01-01

    Anatomic reconstruction of the humeral head with osteochondral allograft has been reported as a solution for large Hill-Sachs lesions with or without glenoid bone loss. However, to date, varying techniques have been used. This technical note describes an arthroscopic reconstruction technique using fresh-frozen, side- and size-matched osteochondral humeral head allograft. Allograft plugs are press fit into the defect without internal fixation and seated flush with the surrounding articular surface. This technique restores the native articular contour of the humeral head without compromising shoulder range of motion. Potential benefits of this all-arthroscopic approach include minimal trauma to the soft tissue and articular surface without the need for hardware or staged reoperation. PMID:24266001

  15. Characterization, corrosion behavior, cellular response and in vivo bone tissue compatibility of titanium-niobium alloy with low Young's modulus.

    PubMed

    Bai, Yanjie; Deng, Yi; Zheng, Yunfei; Li, Yongliang; Zhang, Ranran; Lv, Yalin; Zhao, Qiang; Wei, Shicheng

    2016-02-01

    β-Type titanium alloys with a low elastic modulus are a potential strategy to enhance bone remodeling and to mitigate the concern over the risks of osteanabrosis and bone resorption caused by stress shielding, when used to substitute irreversibly impaired hard tissue. Hence, in this study, a Ti-45Nb alloy with low Young's modulus and high strength was developed, and microstructure, mechanical properties, corrosion behaviors, cytocompatibility and in vivo osteo-compatibility of the alloy were systematically investigated for the first time. The results of mechanical tests showed that Young's modulus of the Ti-Nb alloy was reduced to about 64.3GPa (close to human cortical bone) accompanied with higher tensile strength and hardness compared with those of pure Ti. Importantly, the Ti-Nb alloy exhibited superior corrosion resistance to Ti in different solutions including SBF, MAS and FAAS (MAS containing NaF) media. In addition, the Ti-Nb alloy produced no deleterious effect to L929 and MG-63 cells, and cells performed excellent cell attachment onto Ti-Nb surface, indicating a good in vitro cytocompatibility. In vivo evaluations indicated that Ti-Nb had comparable bone tissue compatibility to Ti determined from micro-CT and histological evaluations. The Ti-Nb alloy with an elasticity close to human bone, thus, could be suitable for orthopedic/dental applications.

  16. Characterization, corrosion behavior, cellular response and in vivo bone tissue compatibility of titanium-niobium alloy with low Young's modulus.

    PubMed

    Bai, Yanjie; Deng, Yi; Zheng, Yunfei; Li, Yongliang; Zhang, Ranran; Lv, Yalin; Zhao, Qiang; Wei, Shicheng

    2016-02-01

    β-Type titanium alloys with a low elastic modulus are a potential strategy to enhance bone remodeling and to mitigate the concern over the risks of osteanabrosis and bone resorption caused by stress shielding, when used to substitute irreversibly impaired hard tissue. Hence, in this study, a Ti-45Nb alloy with low Young's modulus and high strength was developed, and microstructure, mechanical properties, corrosion behaviors, cytocompatibility and in vivo osteo-compatibility of the alloy were systematically investigated for the first time. The results of mechanical tests showed that Young's modulus of the Ti-Nb alloy was reduced to about 64.3GPa (close to human cortical bone) accompanied with higher tensile strength and hardness compared with those of pure Ti. Importantly, the Ti-Nb alloy exhibited superior corrosion resistance to Ti in different solutions including SBF, MAS and FAAS (MAS containing NaF) media. In addition, the Ti-Nb alloy produced no deleterious effect to L929 and MG-63 cells, and cells performed excellent cell attachment onto Ti-Nb surface, indicating a good in vitro cytocompatibility. In vivo evaluations indicated that Ti-Nb had comparable bone tissue compatibility to Ti determined from micro-CT and histological evaluations. The Ti-Nb alloy with an elasticity close to human bone, thus, could be suitable for orthopedic/dental applications. PMID:26652409

  17. mTOR masters monocytic myeloid-derived suppressor cells in mice with allografts or tumors

    PubMed Central

    Wu, Tingting; Zhao, Yang; Wang, Hao; Li, yang; Shao, Lijuan; Wang, Ruoyu; Lu, Jun; Yang, Zhongzhou; Wang, Junjie; Zhao, Yong

    2016-01-01

    CD11b+ Gr1+ myeloid-derived suppressor cells (MDSCs) play critical roles in controlling the processes of tumors, infections, autoimmunity and graft rejection. Immunosuppressive drug rapamycin (RPM), targeting on the key cellular metabolism molecule mTOR, is currently used in clinics to treat patients with allo-grafts, autoimmune diseases and tumors. However, the effect of RPM on MDSCs has not been studied. RPM significantly decreases the cell number and the immunosuppressive ability on T cells of CD11b+ Ly6Chigh monocytic MDSCs (M-MDSCs) in both allo-grafts-transplanted and tumor-bearing mice respectively. Mice with a myeloid-specific deletion of mTOR have poor M-MDSCs after grafting with allo-skin tissue or a tumor. Grafting of allo-skin or tumors significantly activates glycolysis pathways in myeloid precursor cells in bone marrow, which is inhibited by RPM or mTOR deletion. 2-deoxyglucose (2-DG), an inhibitor of the glycolytic pathway, inhibits M-MDSC differentiation from precursors, while enhancing glycolysis by metformin significantly rescues the RPM-caused deficiency of M-MDSCs. Therefore, we offer evidence supporting that mTOR is an intrinsic factor essential for the differentiation and immunosuppressive function of M-MDSCs and that these metabolism-relevant medicines may impact MDSCs-mediated immunosuppression or immune tolerance induction, which is of considerable clinical importance in treating graft rejection, autoimmune diseases and cancers. PMID:26833095

  18. Functional regulatory T cells produced by inhibiting cyclic nucleotide phosphodiesterase type 3 prevent allograft rejection

    PubMed Central

    Feng, Gang; Nadig, Satish N.; Bäckdahl, Liselotte; Beck, Stephan; Francis, Ross S.; Schiopu, Alexandru; Whatcott, Andrew; Wood, Kathryn J.; Bushell, Andrew

    2012-01-01

    Regulatory T cells (Tregs) manipulated ex vivo have potential as cellular therapeutics in autoimmunity and transplantation. Although it is possible to expand naturally occurring Tregs, an attractive alternative possibility, particularly suited to solid organ and bone marrow transplantation, is the stimulation of total T cell populations with defined allogeneic antigen presenting cells under conditions that lead to the generation or expansion of donor-reactive, adaptive Tregs. Here we demonstrate that stimulation of mouse CD4+ T cells by immature allogeneic dendritic cells (DCs) combined with pharmacological inhibition of phosphodiesterase 3 (PDEi) results in a functional enrichment of Foxp3+ T cells. Without further manipulation or selection, the resultant population delayed skin allograft rejection mediated by polyclonal CD4+ effectors or donor-reactive CD8+ TCR transgenic T cells and inhibited both effector cell proliferation and T cell priming for IFN-γ production. Notably, PDE inhibition also enhanced the enrichment of human Foxp3+ CD4+ T cells driven by allogeneic APC. These cells inhibited T cell proliferation in a standard in vitro mixed lymphocyte assay and importantly, attenuated the development of vasculopathy mediated by autologous PBMC in a functionally relevant humanized mouse transplant model. These data establish a method for the ex vivo generation of graft-reactive, functional mouse and human Tregs that uses a clinically approved agent, making pharmacological PDE inhibition a potential strategy for Treg-based therapies PMID:21593400

  19. Allografts in Soft Tissue Reconstructive Procedures

    PubMed Central

    Giedraitis, Andrius; Arnoczky, Steven P.; Bedi, Asheesh

    2014-01-01

    Context Allografts offer several important advantages over autografts in musculoskeletal reconstructive procedures, such as anterior cruciate ligament reconstruction. Despite growing widespread use of allograft tissue, serious concerns regarding safety and functionality remain. We discuss the latest knowledge of the potential benefits and risks of allograft use and offer a critical review of allograft tissue regulation, management, and sterilization to enable the surgeon to better inform athletes considering reconstructive surgery options. Evidence Acquisition A review of sources published in the past 10 years is the primary basis of this research. Study Design: Observational analysis (cohort study). Level of Evidence: Level 3. Results Comparable outcome data for autografts and allografts do not support universal standards for anterior cruciate ligament reconstruction, and physician recommendation and bias appear to significantly influence patient preference and satisfaction. Sterilization by gamma and electron-beam irradiation diminishes the biomechanical integrity of allograft tissue, but radioprotective agents such as collagen cross-linking and free radical scavengers appear to have potential in mitigating the deleterious effects of irradiation and preserving tissue strength and stability. Conclusion Allografts offer greater graft availability and reduced morbidity in orthopaedic reconstructive procedures, but greater expansion of their use by surgeons is challenged by the need to maintain tissue sterility and biomechanical functionality. Advances in the radioprotection of irradiated tissue may lessen concerns regarding allograft safety and structural stability. PMID:24790696

  20. Demand for human allograft tissue in Canada.

    PubMed

    Lakey, Jonathan R T; Mirbolooki, Mohammadreza; Rogers, Christina; Mohr, Jim

    2007-01-01

    There is relatively little known about the demand for allograft tissues in Canada. The Canadian Council for Donation and Transplantation (CCDT) is a national advisory body that undertook a comprehensive "market survey" to estimate surgical demand for human allograft tissues in Canada. The report "Demand for Human Allograft Tissue in Canada" reflects survey results sent to 5 prominent User Groups. User Groups were identified as orthopaedic surgeons; neurosurgeons; corneal transplant surgeons; plastic surgeons, specifically those at Canadian Burn Units; and cardiac surgeons (adult and paediatric surgery). The demand for allograft grafts was determined and then extrapolated across the total User Group and then increases in allograft tissue use over the next 1-2 years across User Groups were predicted. The overall response rate for the survey was 21.4%. It varied from a low of 19.6% for the orthopaedic survey to a high of 40.5% for the corneal survey. The estimated current demand for allograft tissue in Canada ranges from a low of 34,442 grafts per year to a high of 62,098 grafts per year. The predicted increase in use of allograft tissue over the next 1-2 year period would suggest that annual demand could rise to somewhere in the range of 42,589-72,210 grafts. The highest rated preferences (98% and 94%) were for accredited and Canadian tissue banks, respectively. This study represents a key step in addressing the paucity of information concerning the demand for allograft tissue in Canada.

  1. Allograft Replacement for Absent Native Tissue

    PubMed Central

    Chaudhury, Salma; Wanivenhaus, Florian; Fox, Alice J.; Warren, Russell F.; Doyle, Maureen; Rodeo, Scott A.

    2013-01-01

    Context: Structural instability due to poor soft tissue quality often requires augmentation. Allografts are important biological substitutes that are used for the symptomatic patient in the reconstruction of deficient ligaments, tendons, menisci, and osteochondral defects. Interest in the clinical application of allografts has arisen from the demand to obtain stable anatomy with restoration of function and protection against additional injury, particularly for high-demand patients who participate in sports. Traditionally, allografts were employed to reinforce weakened tissue. However, they can also be employed to substitute deficient or functionally absent tissue, particularly in the sports medicine setting. Objective: This article presents a series of 6 cases that utilized allografts to restore functionally deficient anatomic architecture, rather than just simply augmenting the degenerated or damaged native tissue. Detailed discussions are presented of the use of allografts as a successful treatment strategy to replace functionally weakened tissue, often after failed primary repairs. PMID:24427387

  2. Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient

    NASA Technical Reports Server (NTRS)

    Sun, E.; Gao, Y.; Chen, J.; Roberts, A. I.; Wang, X.; Chen, Z.; Shi, Y.

    2004-01-01

    Cell death through apoptosis plays a critical role in regulating cellular homeostasis. Whether the disposal of apoptotic cells through phagocytosis can actively induce immune tolerance in vivo, however, remains controversial. Here, we report in a rat model that without using immunosuppressants, transfusion of apoptotic splenocytes from the donor strain prior to transplant dramatically prolonged survival of heart allografts. Histological analysis verified that rejection signs were significantly ameliorated. Splenocytes from rats transfused with donor apoptotic cells showed a dramatically decreased response to donor lymphocyte stimulation. Most importantly, blockade of phagocytosis in vivo, either with gadolinium chloride to disrupt phagocyte function or with annexin V to block binding of exposed phosphotidylserine to its receptor on phagocytes, abolished the beneficial effect of transfused apoptotic cells on heart allograft survival. Our results demonstrate that donor apoptotic cells promote specific allograft acceptance and that phagocytosis of apoptotic cells in vivo plays a crucial role in maintaining immune tolerance.

  3. Recipient treatment to overcome the allograft reaction, with special reference to nature's own solution.

    PubMed

    Billingham, R E; Head, J R

    1986-01-01

    The 6th decade of this century was particularly important for transplantation immunology. The universality of allograft rejection by normal hosts had won general acceptance and, experimentally, several means of abrogating host reactivity to allografts were discovered. These included sub-lethal whole body irradiation, administration of certain corticosteroid hormones and inoculation of very young animals with living cellular inocula from the future graft donor--i.e., classic, neonatal tolerance. The latter was particularly important since it indicated the feasibility of a specific, permanent solution to the clinical allograft problem. Radiation and drug-induced tolerance in adult subjects came along and chemical immunosuppressants, which led to successful clinical use of azathioprine. The important rediscovery of ALS pointed towards the development and clinical application of monoclonal antibodies many years later. With the development of immunogenetics and transplantation biology came recognition that the conceptus is a highly successful allograft, raising the question of how it is able to withstand rejection by its immunocompetent mother for the duration of pregnancy. Hopefully, knowledge of the principle(s) involved when they are finally elucidated will be applicable to clinical allograft recipients. Although functional hypoantigenicity of the syncytial trophoblast probably plays a major role in protecting the allogeneic conceptus, a strong case now exists that local, cell-based, immunosuppressive and immunoprotective activity within the placenta and decidua, mediated by suppressor and other cells, is important.

  4. Effect of systemic injection of heterogenous and homogenous opioids on peripheral cellular immune response in rats with bone cancer pain: A comparative study

    PubMed Central

    Du, Jun-Ying; Liang, Yi; Fang, Jun-Fan; Jiang, Yong-Liang; Shao, Xiao-Mei; He, Xiao-Fen; Fang, Jian-Qiao

    2016-01-01

    Exogenous and endogenous opioids have been shown to modulate the immune system. Morphine-induced immunosuppression has been investigated extensively. However, the immune-regulating function of endogenous opioid peptides is unclear. The present study aimed to evaluate the difference in effects on cellular immune function between recombinant rat β-endorphin (β-EP; 50 µg/kg) and plant source morphine (10 mg/kg) via intraperitoneal injection treatment in a rat model of bone cancer pain. Walker 256 cells were injected into a tibial cavity injection to establish the bone cancer pain model. The paw withdrawal thresholds and body weights were measured prior to surgery, at 6 days after surgery, and following 1, 3,6 and 8 treatments. The spleen cells were harvested for detection of T cell proliferation, natural killer (NK) cell cytotoxicity, and the relative quantities of T cell subtypes (CD3+, CD4+ and CD8+ cells). Plasma levels of interleukin-2 (IL-2) were also determined. It was found that single or multiple treatments with β-EP (a homogenous opioid peptide) and morphine (a heterogenous opioid) had good analgesic effects on bone cancer pain, while the analgesia provided by morphine was stronger than that of β-EP. Treatment with β-EP 3, 6 and 8 times increased the body weight gain in the rat model of bone cancer pain, while morphine treatment had on effect on it. With regard to immunomodulatory functions, β-EP treatment increased T cell proliferation and NK cell cytotoxicity, and increased the relative quantities of T cell subtypes, but no effect on T cell secretion. However, morphine treatment decreased T cell proliferation and the levels of T cell subtypes. These data indicate that opioids from different sources have different effects on cellular immune function in vivo. A small dose of homogenous opioid peptide exhibited positive effects (analgesia and immune enhancement) on cancer pain. These results provide experimental evidence supporting the exploitation of

  5. Radiation sterilization of skin allograft

    NASA Astrophysics Data System (ADS)

    Kairiyama, E.; Horak, C.; Spinosa, M.; Pachado, J.; Schwint, O.

    2009-07-01

    In the treatment of burns or accidental loss of skin, cadaveric skin allografts provide an alternative to temporarily cover a wounded area. The skin bank facility is indispensable for burn care. The first human skin bank was established in Argentina in 1989; later, 3 more banks were established. A careful donor selection is carried out according to the national regulation in order to prevent transmissible diseases. As cadaveric human skin is naturally highly contaminated, a final sterilization is necessary to reach a sterility assurance level (SAL) of 10 -6. The sterilization dose for 106 batches of processed human skin was determined on the basis of the Code of Practice for the Radiation Sterilization of Tissue Allografts: Requirements for Validation and Routine Control (2004) and ISO 11137-2 (2006). They ranged from 17.6 to 33.4 kGy for bioburdens of >10-162.700 CFU/100 cm 2. The presence of Gram negative bacteria was checked for each produced batch. From the analysis of the experimental results, it was observed that the bioburden range was very wide and consequently the estimated sterilization doses too. If this is the case, the determination of a tissue-specific dose per production batch is necessary to achieve a specified requirement of SAL. Otherwise if the dose of 25 kGy is preselected, a standardized method for substantiation of this dose should be done to confirm the radiation sterilization process.

  6. Future of allografts in sports medicine.

    PubMed

    Harner, Christopher D; Lo, Marvin Y

    2009-04-01

    Allografts play a prominent role in sports medicine, and their usage has increased dramatically over the past few decades, but the role of allograft in the future of sports medicine largely depends on several factors: (1) the ability of the tissue banking industry to convince both surgeons and the general population that tissue procurement is safe and nearly disease-free, (2) the ability to sterilize tissue with minimal compromise to tissue integrity, (3) successful clinical outcomes with allograft, and (4) the advent of artificial scaffolds and ligaments that function as well. PMID:19306738

  7. Allograft safety in anterior cruciate ligament reconstruction.

    PubMed

    Cohen, Steven B; Sekiya, Jon K

    2007-10-01

    Allograft tissue seems to provide an excellent option for reconstruction of the ACL in the primary and revision setting. Although in general the risks of using allograft tissue in ACL reconstruction are low, the consequences of complications associated with disease or infection transmission or of recurrent instability secondary to graft failure are large. Surgeons should provide patients with the information available regarding allograft risks and should have thorough knowledge of the source and preparation of the grafts by their tissue bank before implantation for ACL reconstruction.

  8. Allograft safety in anterior cruciate ligament reconstruction.

    PubMed

    Cohen, Steven B; Sekiya, Jon K

    2007-10-01

    Allograft tissue seems to provide an excellent option for reconstruction of the ACL in the primary and revision setting. Although in general the risks of using allograft tissue in ACL reconstruction are low, the consequences of complications associated with disease or infection transmission or of recurrent instability secondary to graft failure are large. Surgeons should provide patients with the information available regarding allograft risks and should have thorough knowledge of the source and preparation of the grafts by their tissue bank before implantation for ACL reconstruction. PMID:17920955

  9. Novel treatment of a failed quadriceps tendon repair in a diabetic patient using a patella-quadriceps tendon allograft.

    PubMed

    Druskin, Sasha C; Rodeo, Scott A

    2013-07-01

    Recurrent quadriceps tendon rupture is a debilitating condition that may be challenging to treat, especially in the presence of systemic disease such as diabetes mellitus (Bedi et al., J Shoulder Elbow Surg 19:978-988, 2010; Chbnou and Frenette, Am J Physiol Regul Integr Comp Physiol 5:R952-R957, 2004; Chen et al., J Shoulder Elbow Surg 5:416-421, 2003). Many surgical treatment protocols have been proposed (Azar, in Canale and Beatty, eds., Campbell's Operative Orthopedics, Mosby/Elsevier, Philadelphia, PA, 2008; Ilan et al., J Am Acad Orthop Surg 3:192-200, 2003; Rodeo and Izawa, in Garrett et al., eds., Principles and Practice of Orthopedic Sports Medicine, Lippincott Williams & Wilkins, Philadelphia, PA, 2000). We report the case of a diabetic male with multiple treatment failures. He ultimately sustained a good outcome following treatment with a novel surgical technique that utilized a patella quadriceps tendon allograft. Tendon allograft-to-native bone healing had previously failed in this patient, so we used a bone-tendon construct allograft to provide an allograft bone-to-native bone healing site. Now, 13 months postoperative, the patient has increased strength, minimal pain, 20 ° of extensor lag and 130 ° of flexion.

  10. Molecular and cellular mechanisms of bone morphogenetic proteins and activins in the skin: potential benefits for wound healing.

    PubMed

    Moura, J; da Silva, L; Cruz, M T; Carvalho, E

    2013-09-01

    Bone morphogenetic proteins (BMPs) and activins are phylogenetically conserved proteins, belonging to the transforming growth factor-β superfamily, that signal through the phosphorylation of receptor-regulated Smad proteins, activating different cell responses. They are involved in various steps of skin morphogenesis and wound repair, as can be evidenced by the fact that their expression is increased in skin injuries. BMPs play not only a role in bone regeneration but are also involved in cartilage, tendon-like tissue and epithelial regeneration, maintain vascular integrity, capillary sprouting, proliferation/migration of endothelial cells and angiogenesis, promote neuron and dendrite formation, alter neuropeptide levels and are involved in immune response modulation, at least in animal models. On the other hand, activins are involved in wound repair through the regulation of skin and immune cell migration and differentiation, re-epithelialization and granulation tissue formation, and also promote the expression of collagens by fibroblasts and modulate scar formation. This review aims at enunciating the effects of BMPs and activins in the skin, namely in skin development, as well as in crucial phases of skin wound healing, such as inflammation, angiogenesis and repair, and will focus on the effects of these proteins on skin cells and their signaling pathways, exploring the potential therapeutic approach of the application of BMP-2, BMP-6 and activin A in chronic wounds, particularly diabetic foot ulcerations.

  11. Cellular Origins of Regenerating Nodules and Malignancy in the FAH Model of Liver Injury after Bone Marrow Cell Transplantation

    PubMed Central

    Wang, Pei-Rong; Li, Yi

    2016-01-01

    In previous reports, we and other groups have shown that proliferating hepatocytes are formed by the fusion of donor hematopoietic cells with host hepatocytes in the Fah−/− model. Thus, it would be interesting to determine whether cell fusion occurs during malignancy. However, it is difficult to demonstrate such processes using this model. Therefore, we established a new strain to study the processes of regenerating nodules and malignancy and their origins. The FAH−/− mouse model was crossed with the ROSAnZ strain and their offspring was genotyped for FAH−/− and ROSAnZ mutations to create a new strain (Fah−/−-ROSAnZ). Using this strain as recipients, we performed bone marrow transplantation experiments. As a result, we could not demonstrate the presence of any epithelial cells except hepatocytes that were of donor origin in regenerating tissue, and no evidence of cell fusion was found in tumors. The hepatic malignancy was of host origin in these mice. There was higher expression of extracellular matrix proteins and more inflammatory cells in liver tumor nodules than in regenerating normal liver nodules. Hepatocytes generated by fusion with bone marrow cells did not form malignant tumors. Extracellular matrix and inflammatory cells had significantly accumulated in liver tumors. PMID:26962307

  12. Biomechanical analysis of patellar tendon allografts as a function of donor age.

    PubMed

    Flahiff, C M; Brooks, A T; Hollis, J M; Vander Schilden, J L; Nicholas, R W

    1995-01-01

    We evaluated the biomechanical properties of patellar tendon allografts from donors aged 18 to 55 years. Bone-patellar tendon-bone complexes were harvested from acceptable donors and processed. Fat and soft tissue were removed, and the tendons were sectioned lengthwise leaving the central third. Area measurements were taken, and mechanical testing was performed. Specimens were pulled to failure at a rate of 10% of the initial length per second. The force at failure, tensile stress, modulus of elasticity, and percent elongation were determined for each specimen. There was no significant correlation (P > 0.05) between age and any of the mechanical properties. Load at failure ranged from 2110 to 4650 N, with a mean of 3424 N. Regression analysis showed slightly decreasing tensile stress with increasing age, but the correlation was not significant. It appears that patellar tendon allografts from donors up to age 55 have similar mechanical properties.

  13. Molecular Characterization of Prospectively Isolated Multipotent Mesenchymal Progenitors Provides New Insight into the Cellular Identity of Mesenchymal Stem Cells in Mouse Bone Marrow

    PubMed Central

    Badaloni, Aurora; Chiara, Francesca; Stjernberg, Jenny; Polisetti, Naresh; Nihlberg, Kristian; Consalez, G. Giacomo; Sigvardsson, Mikael

    2013-01-01

    Despite great progress in the identification of mesenchymal stem cells (MSCs) from bone marrow (BM), our knowledge of their in vivo cellular identity remains limited. We report here that cells expressing the transcription factor Ebf2 in adult BM display characteristics of MSCs. The Ebf2+ cells are highly clonal and physiologically quiescent. In vivo lineage-tracing experiments, single cell clone transplantations, and in vitro differentiation assays revealed their self-renewal and multilineage differentiation capacity. Gene expression analysis of the freshly sorted Ebf2+ cells demonstrated the expression of genes previously reported to be associated with MSCs and the coexpression of multiple lineage-associated genes at the single-cell level. Thus, Ebf2 expression is not restricted to committed osteoblast progenitor cells but rather marks a multipotent mesenchymal progenitor cell population in adult mouse BM. These cells do not appear to completely overlap the previously reported MSC populations. These findings provide new insights into the in vivo cellular identity and molecular properties of BM mesenchymal stem and progenitor cells. PMID:23184664

  14. Cellular function and adhesion mechanisms of human bone marrow mesenchymal stem cells on multi-walled carbon nanotubes.

    PubMed

    Kroustalli, Anthoula A; Kourkouli, Souzana N; Deligianni, Despina D

    2013-12-01

    Multiwalled carbon nanotubes (MWCNTs) are considered to be excellent reinforcements for biorelated applications, but, before being incorporated into biomedical devices, their biocompatibility need to be investigated thoroughly. We investigated the ability of films of pristine MWCNTs to influence human mesenchymal stem cells' proliferation, morphology, and differentiation into osteoblasts. Moreover, the selective integrin subunit expression and the adhesion mechanism to the substrate were evaluated on the basis of adherent cell number and adhesion strength, following the treatment of cells with blocking antibodies to a series of integrin subunits. Results indicated that MWCNTs accelerated cell differentiation to a higher extent than tissue culture plastic, even in the absence of additional biochemical inducing agents. The pre-treatment with anti-integrin antibodies decreased number of adherent cells and adhesion strength at 4-60%, depending on integrin subunit. These findings suggest that pristine MWCNTs represent a suitable reinforcement for bone tissue engineering scaffolds.

  15. Is there significant variation in the material properties of four different allografts implanted for ACL reconstruction.

    PubMed

    Penn, David; Willet, Thomas L; Glazebrook, Mark; Snow, Martyn; Stanish, William D

    2009-03-01

    The aims of our study were to: (1) determine if there are differences in the material properties of tendon obtained from implanted tibialis anterior, achilles, bone-patella- bone and tibialis posterior allografts; (2) determine the variability in material properties between the implanted specimens. A total of 60 specimens were collected from fresh frozen allografts implanted at ACL reconstruction. Specimens collected included 15 tibialis anterior, 15 tibialis posterior, 15 achilles and 15 bone-patella-bone tendons. Each specimen was mounted in a custom made cryogrip. The mounted specimens were loaded onto a MTS Testline servo-hydraulic testing machine in a uni-axial tensile test configuration. Specimens were subjected to a strain rate of 5% per second until the ultimate tensile stress (UTS), failure strain and high strain modulus was calculated for each specimen after being normalized for specimen dimensions. Individual material properties were tested using one way analysis of variance (ANOVA) and post hoc Tukey's B test with a P value of <0.05 considered significant. Homogeneity of variance was assessed using the Levene's test. As a result, no significant difference was found between all four grafts with regards to UTS, failure strain or high strain linear modulus. The UTS was plotted against the modulus demonstrating a linear relationship which is typical of soft tissues. Significant variability in the results were observed. In conclusion, there was no significant statistical difference between the material properties of the four tendon allografts tested. But significant variability in results was observed within groups and between groups, which may provide one explanation for the range of results in allograft ACL reconstruction reported in the literature.

  16. Is there significant variation in the material properties of four different allografts implanted for ACL reconstruction.

    PubMed

    Penn, David; Willet, Thomas L; Glazebrook, Mark; Snow, Martyn; Stanish, William D

    2009-03-01

    The aims of our study were to: (1) determine if there are differences in the material properties of tendon obtained from implanted tibialis anterior, achilles, bone-patella- bone and tibialis posterior allografts; (2) determine the variability in material properties between the implanted specimens. A total of 60 specimens were collected from fresh frozen allografts implanted at ACL reconstruction. Specimens collected included 15 tibialis anterior, 15 tibialis posterior, 15 achilles and 15 bone-patella-bone tendons. Each specimen was mounted in a custom made cryogrip. The mounted specimens were loaded onto a MTS Testline servo-hydraulic testing machine in a uni-axial tensile test configuration. Specimens were subjected to a strain rate of 5% per second until the ultimate tensile stress (UTS), failure strain and high strain modulus was calculated for each specimen after being normalized for specimen dimensions. Individual material properties were tested using one way analysis of variance (ANOVA) and post hoc Tukey's B test with a P value of <0.05 considered significant. Homogeneity of variance was assessed using the Levene's test. As a result, no significant difference was found between all four grafts with regards to UTS, failure strain or high strain linear modulus. The UTS was plotted against the modulus demonstrating a linear relationship which is typical of soft tissues. Significant variability in the results were observed. In conclusion, there was no significant statistical difference between the material properties of the four tendon allografts tested. But significant variability in results was observed within groups and between groups, which may provide one explanation for the range of results in allograft ACL reconstruction reported in the literature. PMID:19039574

  17. Computational Biology: Modeling Chronic Renal Allograft Injury.

    PubMed

    Stegall, Mark D; Borrows, Richard

    2015-01-01

    New approaches are needed to develop more effective interventions to prevent long-term rejection of organ allografts. Computational biology provides a powerful tool to assess the large amount of complex data that is generated in longitudinal studies in this area. This manuscript outlines how our two groups are using mathematical modeling to analyze predictors of graft loss using both clinical and experimental data and how we plan to expand this approach to investigate specific mechanisms of chronic renal allograft injury.

  18. Treatment of lymphocele in renal allograft recipients.

    PubMed

    Greenberg, B M; Perloff, L J; Grossman, R A; Naji, A; Barker, C F

    1985-04-01

    Retroperitoneal lymphoceles developed in 12 renal allograft recipients during the last nine years. The interval between transplantation and the development of symptoms averaged seven months. The specific syndrome suggesting the presence of a lymphocele included lower abdominal swelling, weight gain, and, occasionally, fever without an obvious source of infection. Although these symptoms mimicked allograft rejection, diagnosis was easily made by ultrasound and intravenous pyelogram. Surgical marsupialization of the lymphocele with drainage into the peritoneal cavity proved to be an effective treatment.

  19. Prolonged renal allograft survival by donor interleukin-6 deficiency: association with decreased alloantibodies and increased intragraft T regulatory cells.

    PubMed

    Wang, Hao; Guan, Qiunong; Lan, Zhu; Li, Shuyuan; Ge, Wei; Chen, Huifang; Nguan, Christopher Y C; Du, Caigan

    2012-01-15

    Both humoral and cellular immune responses are involved in renal allograft rejection. Interleukin (IL)-6 is a regulatory cytokine for both B and Foxp3 (forkhead box P3)-expressing regulatory T (Treg) cells. This study was designed to investigate the impact of donor IL-6 production on renal allograft survival. Donor kidneys from IL-6 knockout (KO) vs. wild-type (WT) C57BL/6 mice (H-2(b)) were orthotopically transplanted to nephrotomized BALB/c mice (H-2(d)). Alloantibodies and Treg cells were examined by fluorescence-activated cell sorting analysis. Graft survival was determined by the time to graft failure. Here, we showed that a deficiency in IL-6 expression in donor kidneys significantly prolonged renal allograft survival compared with WT controls. IL-6 protein was upregulated in renal tubules and endothelium of renal allografts following rejection, which correlated with an increase in serum IL-6 compared with that in those receiving KO grafts or naive controls. The absence of graft-producing IL-6 or lower levels of serum IL-6 in the recipients receiving IL-6 KO allografts was associated with decreased circulating anti-graft alloantibodies and increased the percentage of intragraft CD4(+)CD25(+)Foxp3(+) Treg cells compared with those with WT allografts. In conclusion, the lack of graft-producing IL-6 significantly prolongs renal allograft survival, which is associated with reduced alloantibody production and/or increased intragraft Treg cell population, implying that targeting donor IL-6 may effectively prevent both humoral and cellular rejection of kidney transplants.

  20. Transplantation of cryopreserved canine venous allografts.

    PubMed

    Bank, H L; Schmehl, M K; Warner, R; Pratt, M F; Albernaz, M S; Metcalf, J S; Darcy, M

    1991-01-01

    Local vascular reconstructions frequently require the use of vein grafts to bridge arterial or venous defects. Most previous studies on the use of cryopreserved veins have used relatively large caliber vessels. There have been few studies on the effectiveness of cryopreserved micro- or small-venous allografts. Here, we tested two types of cryopreserved venous allografts: (1) 1.5- to 1.9-mm diameter microvenous grafts (MVG); and (2) 4- to 5-mm diameter small venous grafts (SVG). Cryopreserved MVG allografts were placed into saphenous arteries of six experimental dogs and SVG cryopreserved allografts were placed into femoral arteries of six experimental dogs for 3 to 6 weeks. Two fresh MVG autografts were also transplanted into experimental dogs as controls and autografts were transferred to the contralateral side in SVG dogs as controls. None of the six cryopreserved MVG grafts retained patency but three/six cryopreserved SVG allografts were patent at harvest. Histological examination of grfts revealed control autografts were undergoing arterialization with an intact intima. Experimental cryopreserved allografts showed extensive medial fibrosis, significant lymphocytic infiltrates, and sporadic areas of intact intima for both patent and nonpatent grafts.

  1. Invasive Streptococcus pyogenes after allograft implantation--Colorado, 2003.

    PubMed

    2003-12-01

    Allograft tissues are used for various orthopedic procedures (e.g., ligament reconstruction, meniscal transplantation, and spinal surgery). In 2002, approximately one million allografts were distributed for transplantation (American Association of Tissue Banks [AATB], unpublished data, 2002). Recent reports of allograft-associated infections have prompted evaluation of the processing and quality-control methods employed by tissue processors. This report describes a case of invasive disease with Streptococcus pyogenes (i.e., group A streptococcus [GAS]), after reconstructive knee surgery using contaminated allograft tissue and provides recommendations to reduce the risk for allograft-associated infections. Although allograft infections are rare, they highlight the need for improved tissue evaluation and processing standards.

  2. The effectiveness of bone banking in Central Serbia: audit of the first seven years.

    PubMed

    Stepanovic, Zeljko Lj; Ristic, Branko M

    2014-12-01

    We analyzed the incidence and predisposing factors for overall discard rate after retrieval of 295 femoral head allografts. The aim of the present study was to evaluate the quality system of institutional bone banking and to ensure that we can provide high standard allografts with low infection rate. Audit of bone banking was conducted on 295 donors and 180 recipients. Of the 295 donated femoral heads 77 were discarded, giving an overall discard rate of 26.1 %. At retrieval, 37 allografts were positive, giving an overall contamination rate of 12.54 %. The organism most commonly identified was Staphylococcus species. Seven (2.37 %) of the 295 allografts failed the blood screening tests. Twelve allografts (4.06 %) were discarded because of suspected damage of the packaging or disuse during surgery. Due to donor death or inability to perform serology retests, 21 (7.11 %) allografts were discarded. In the postoperative survey an infection rate of 2.22 % was found. After 7 years of bone banking, our results show that overall discard rate and allograft related infection rate are in accordance with the international standards. The leading cause of allograft discarding was bacterial contamination influenced by the surgical team. We suggest stringent aseptic allograft handling during harvesting and thawing within highly concentrated antibiotic solution to reduce a possibility of its contamination.

  3. Assessing bone banking activities at University of Malaya medical centre.

    PubMed

    Mohd, Suhaili; Samsuddin, Sharifah Mazni; Ramalingam, Saravana; Min, Ng Wuey; Yusof, Norimah; Zaman, T Kamarul; Mansor, Azura

    2015-12-01

    The main advantage of establishing in-house bone banks is its ability to readily provide allograft bones for local surgeries. Bone procurement activities of our university bone bank during the 10 years of operation were reviewed. Socio-demographic data of donors, types of bone procured, cases of rejected bones and types of allograft bones transplanted are presented. From 179 potential donors, 73 % were accepted with 213 procured bones. Femoral head was the common bone transplanted (45 %), as it was also the most common procured (82 %). Bones were rejected mainly due to non-technical reasons (83 %) rather than positive results of microbiological (13 %) and serological (4 %) tests. Comprehensive data could not be obtained for further analysis due to difficulties in retrieving information. Therefore, quality assurance system was improved to establish more systematic documentations, as the basis of good banking practice with process control hence allowing traceability. PMID:25656787

  4. Assessing bone banking activities at University of Malaya medical centre.

    PubMed

    Mohd, Suhaili; Samsuddin, Sharifah Mazni; Ramalingam, Saravana; Min, Ng Wuey; Yusof, Norimah; Zaman, T Kamarul; Mansor, Azura

    2015-12-01

    The main advantage of establishing in-house bone banks is its ability to readily provide allograft bones for local surgeries. Bone procurement activities of our university bone bank during the 10 years of operation were reviewed. Socio-demographic data of donors, types of bone procured, cases of rejected bones and types of allograft bones transplanted are presented. From 179 potential donors, 73 % were accepted with 213 procured bones. Femoral head was the common bone transplanted (45 %), as it was also the most common procured (82 %). Bones were rejected mainly due to non-technical reasons (83 %) rather than positive results of microbiological (13 %) and serological (4 %) tests. Comprehensive data could not be obtained for further analysis due to difficulties in retrieving information. Therefore, quality assurance system was improved to establish more systematic documentations, as the basis of good banking practice with process control hence allowing traceability.

  5. Induced regulatory T cells in allograft tolerance via transient mixed chimerism

    PubMed Central

    Hotta, Kiyohiko; Aoyama, Akihiro; Oura, Tetsu; Yamada, Yohei; Tonsho, Makoto; Huh, Kyu Ha; Kawai, Kento; Schoenfeld, David; Allan, James S.; Madsen, Joren C.; Benichou, Gilles; Smith, Rex-Neal; Colvin, Robert B.; Sachs, David H.; Cosimi, A. Benedict

    2016-01-01

    Successful induction of allograft tolerance has been achieved in nonhuman primates (NHPs) and humans via induction of transient hematopoietic chimerism. Since allograft tolerance was achieved in these recipients without durable chimerism, peripheral mechanisms are postulated to play a major role. Here, we report our studies of T cell immunity in NHP recipients that achieved long-term tolerance versus those that rejected the allograft (AR). All kidney, heart, and lung transplant recipients underwent simultaneous or delayed donor bone marrow transplantation (DBMT) following conditioning with a nonmyeloablative regimen. After DBMT, mixed lymphocyte culture with CFSE consistently revealed donor-specific loss of CD8+ T cell responses in tolerant (TOL) recipients, while marked CD4+ T cell proliferation in response to donor antigens was found to persist. Interestingly, a significant proportion of the proliferated CD4+ cells were FOXP3+ in TOL recipients, but not in AR or naive NHPs. In TOL recipients, CD4+FOXP3+ cell proliferation against donor antigens was greater than that observed against third-party antigens. Finally, the expanded Tregs appeared to be induced Tregs (iTregs) that were converted from non-Tregs. These data provide support for the hypothesis that specific induction of iTregs by donor antigens is key to long-term allograft tolerance induced by transient mixed chimerism. PMID:27446989

  6. Heart and kidney transplantation using total lymphoid irradiation and donor bone marrow in mongrel dogs

    SciTech Connect

    Kahn, D.R.; Dufek, J.H.; Hong, R.; Caldwell, W.L.; Thomas, F.J.; Kolenda, D.R.; Swanson, D.K.; Struble, R.A.

    1980-07-01

    Heart and kidney allografts showed markedly prolonged survival in unrelated mongrel dogs following total lymphoid irradiation (TLI) and donor bone marrow without any other immunosuppression. In every animal the heart survived longer than the kidney. Placing the kidney allograft in the abdomen with the bone marrow given intraperitoneally doubled kidney survival over placement in the neck, but heart survival was equally prolonged in the abdomen or neck. Splenectomy before TLI or after TLI, but just before transplantation, almost completely eliminated the prolonged survival of both heart and kidney allografts. Thus there is suggestive evidence that TLI plus bone marrow from the donor may be valuable for transplantation in man, particularly heart transplantation.

  7. Comparative cellular and molecular analyses of pooled bone marrow multipotent mesenchymal stromal cells during continuous passaging and after successive cryopreservation.

    PubMed

    Mamidi, Murali Krishna; Nathan, Kavitha Ganesan; Singh, Gurbind; Thrichelvam, Saratha Thevi; Mohd Yusof, Nurul Ain Nasim; Fakharuzi, Noor Atiqah; Zakaria, Zubaidah; Bhonde, Ramesh; Das, Anjan Kumar; Majumdar, Anish Sen

    2012-10-01

    The clinical application of human bone marrow derived multipotent mesenchymal stromal cells (MSC) requires expansion, cryopreservation, and transportation from the laboratory to the site of cell implantation. The cryopreservation and thawing process of MSCs may have important effects on the viability, growth characteristics and functionality of these cells both in vitro and in vivo. More importantly, MSCs after two rounds of cryopreservation have not been as well characterized as fresh MSCs from the transplantation perspective. The objective of this study was to determine if the effect of successive cryopreservation of pooled MSCs during the exponential growth phase could impair their morphology, phenotype, gene expression, and differentiation capabilities. MSCs cryopreserved at passage 3 (cell bank) were thawed and expanded up to passage 4 and cryopreserved for the second time. These cells (passive) were then thawed and cultured up to passage 6, and, at each passage MSCs were characterized. As control, pooled passage 3 cells (active) after one round of cryopreservation were taken all the way to passage 6 without cryopreservation. We determined the growth rate of MSCs for both culture conditions in terms of population doubling number (PDN) and population doubling time (PDT). Gene expression profiles for pluripotency markers and tissue specific markers corresponding to neuroectoderm, mesoderm and endoderm lineages were also analyzed for active and passive cultures of MSC. The results show that in both culture conditions, MSCs exhibited similar growth properties, phenotypes and gene expression patterns as well as similar differentiation potential to osteo-, chondro-, and adipo-lineages in vitro. To conclude, it appears that successive or multiple rounds of cryopreservation of MSCs did not alter the fundamental characteristics of these cells and may be used for clinical therapy. PMID:22615164

  8. Reconstruction of complex osteochondral lesions of the talus with cylindrical sponge allograft and particulate juvenile cartilage graft: provisional results with a short-term follow-up.

    PubMed

    Bleazey, Scott; Brigido, Stephen A

    2012-10-01

    Osteochondral lesions of the talus can be a challenging injury to treat for even the most experienced foot and ankle surgeon. Although the advances in imaging have made the diagnosis of chondral lesions more accurate, surgeons are still struggling to find ways to reliably treat advanced lesions with subchondral bone damage. This article looks at the use of allograft bone and particulate juvenile cartilage in patients with advanced subchondral bone damage and osteochondral lesions of the talus.

  9. Glomerular thrombi in renal allografts associated with cyclosporin treatment.

    PubMed Central

    Neild, G H; Reuben, R; Hartley, R B; Cameron, J S

    1985-01-01

    We have found glomerular capillary thrombi or afferent arteriolar thrombosis in eight renal biopsy specimens from seven renal allograft recipients. All patients were receiving cyclosporin and prednisolone. Biopsies were performed either routinely one and four weeks after transplantation or during periods of renal dysfunction. None of the patients whose biopsy material contained glomerular thrombi was considered, in retrospect, to have been undergoing rejection at the time of biopsy. Thrombi consisted of finely granular material partially obstructing glomerular capillaries. By light microscopy the staining characteristics of the thrombi were compatible with platelet-fibrin aggregates, and this was confirmed by immunoperoxidase examination. Such thrombi have not previously been seen in biopsy material from patients treated with prednisolone and azathioprine, except rarely associated with acute vascular injection. In none of these patients was there haematological evidence of the haemolytic uraemic syndrome as has been reported in bone marrow recipients treated with cyclosporin. Images PMID:3882763

  10. Preliminary Results of Bioactive Amniotic Suspension with Allograft for Achieving One and Two-Level Lumbar Interbody Fusion

    PubMed Central

    Kerr, Eubulus J.; Utter, Philip A.; Cavanaugh, David A.; Frank, Kelly A.; Moody, Devan; McManus, Brian; Stone, Marcus B.

    2016-01-01

    Background Bone graft material for lumbar fusion was historically autologous bone graft (ABG). In recent years alternatives such as allograft, demineralized bone matrix (DBM), ceramics, and bone morphogenetic protein (BMP) have gained favor, although the complications of these are not fully understood. Bioactive amniotic suspension (BAS) with allograft is a new class of material derived from human amniotic tissue. Methods Eligible patients receiving a one or two level lumbar interbody fusion with Nucel, a BAS with allograft, were contacted and scheduled for a mininmim 12 month follow-up visit. Patients were evaluated for fusion using CT's and plain radiographs. Clincal outcomes, including ODI, VAS back and leg were collected, as well as comorbidities including BMI, smoking status, diabetes and previous lumbar surgery. Results One-level patients (N=38) were 71.1% female with mean age of 58.4 ± 12.7 and mean BMI of 30.6 ± 6.08. Two-level patients (N=34) were 58.8% female with mean age of 49.3 ±10.9 and mean BMI of 30.1 ± 5.82. Kinematic fusion was achieved in 97.4% of one-level patients and 100% of two-level patients. Baseline comorbidities were present in 89.5% of one-level patients and 88.2% of two-level patients. No adverse events related to BAS were reported in this study. Conclusion Fusion status is evaluated with many different biologics and varying methods in the literature. BAS with allograft in this study demonstrated high fusion rates with no complications within a largely comorbid population. Although a small population, BAS with allograft results were encouraging for one and two-level lumbar interbody fusion in this study. Further prospective studies should be conducted to investigate safety and efficacy in a larger population. PMID:27162714

  11. Age and Bone Marrow Cellularity are Associated with Response to Eltrombopag in Japanese Adult Immune Thrombocytopenia Patients: A Retrospective Single-Center Study.

    PubMed

    Uto, Yui; Fujiwara, Shun; Arai, Nana; Kawaguchi, Yukiko; Kabasawa, Nobuyuki; Tsukamoto, Hiroyuki; Ariizumi, Hirotsugu; Hattori, Norimichi; Saito, Bungo; Yanagisawa, Kouji; Harada, Hiroshi; Mori, Hiraku; Shiozawa, Eisuke; Nakamaki, Tsuyoshi

    2015-05-01

    In the present retrospective single-center study, we examined the efficacy and safety of eltrombopag, a thrombopoietin (TPO) -receptor agonist (TPO-RA), and found clinical factors associated with its efficacy in Japanese patients with chronic immune thrombocytopenia (ITP). According to the definition of a response, which is to attain a platelet count of more than 50,000/μL at least once during eltrombopag treatment, 42 enrolled patients were divided into two groups: responders (29 patients, 69%) and non-responders (13 patients, 31%). In analyses of the clinical and laboratory data of these two groups, we extracted two factors that are significantly associated with a better response to eltrombopag, which have not been recognized previously, namely, (1) an older age of patients at eltrombopag initiation (≥ 70 years old) and (2) normal or decreased cellularity of iliac bone marrow (BM) biopsy at diagnosis. The significance of patient age contradicts previous findings from studies in which the Caucasian population was the major focus. However, factors such as changes of pharmacokinetics might modulate the effects of eltrombopag in older patients in Japan because East Asians show higher bioavailability of eltrombopag by as-yet-unknown mechanisms. BM cellularity in ITP may represent an impairment and/or lower responsiveness of pluripotent hematopoietic stem cells, not limited to the megakaryocyte (MgK) -platelet axis, to endogenous TPO, because recent evidence shows that TPO-RA can successfully restore hematopoiesis in aplastic anemia. These results should be useful for the therapeutic use of TPO-RA for ITP and also related thrombocytopenia in Japan.

  12. Radionuclide surveillance of the allografted pancreas

    SciTech Connect

    George, E.A.; Salimi, Z.; Carney, K.; Castaneda, M.; Garvin, P.J.

    1988-04-01

    To determine the value of scintigraphy to detect posttransplantation complications of the allografted pancreas, we retrospectively reviewed 209 scintigrams obtained with /sup 99m/Tc-sulfur colloid (/sup 99m/Tc-SC) and /sup 99m/Tc-glucoheptonate (/sup 99m/Tc-GH). The scintigraphic studies were performed in 37 recipients of simultaneous renal and pancreatic allografts harvested from the same donor. /sup 99m/Tc-SC was used as an indicator of thrombotic vasculitis; pancreatic perfusion and blood-pool parameters were monitored with /sup 99m/Tc-GH. In 11 of the 37 recipients, scintigraphic abnormalities suggested posttransplantation infarction. Recurrent episodes of acute rejection of the pancreatic allograft, which always coincided with acute rejection of the renal allograft, were monitored in 24 recipients. Rejection-induced ischemic pancreatitis was suggested in 12 of the 24 recipients and persisted in 10 recipients for several weeks after improvement of renal allograft rejection. Pancreatic atrophy was suggested scintigraphically in 16 of the 24 recipients with recurrent episodes of rejection. Spontaneous pancreatic-duct obstruction and obstructive pancreatitis were associated with a scintigraphic pattern similar to that of rejection-induced ischemic pancreatitis. We concluded that the specific radionuclides used in this series are useful for the surveillance and assessment of posttransplantation pancreatic infarction, acute rejection, pancreatitis, and atrophy

  13. Transient mixed chimerism for allograft tolerance.

    PubMed

    Oura, Tetsu; Hotta, Kiyohiko; Cosimi, A B; Kawai, Tatsuo

    2015-04-01

    Mixed chimerism discovered in Freemartin cattle by Ray Owen 70 years ago paved the way for research on immune tolerance. Since his discovery, significant progress has been made in the effort to induce allograft tolerance via mixed chimerism in various murine models. However, induction of persistent mixed chimerism has proved to be extremely difficult in major histocompatibility complex mismatched humans. Chimerism induced in humans tends to either disappear or convert to full donor chimerism, depending on the intensity of the conditioning regimen. Nevertheless, our studies in both NHPs and humans have clearly demonstrated that renal allograft tolerance can be induced by transient mixed chimerism. Our studies have shown that solid organ allograft tolerance via transient mixed chimerism 1) requires induction of multilineage hematologic chimerism, 2) depends on peripheral regulatory mechanisms, rather than thymic deletion, for long-term maintenance, 3) is organ specific (kidney and lung but not heart allograft tolerance are feasible). A major advantage of tolerance induction via transient mixed chimerism is exclusion of the risk of graft-versus-host disease. Our ongoing studies are directed toward improving the consistency of tolerance induction, reducing the morbidity of the conditioning regimen, substituting clinically available agents, such as Belatacept for the now unavailable anti-CD2 monoclonal antibody, and extending the protocol to recipients of deceased donor allografts.

  14. Thrombotic microangiopathy in renal allografts

    PubMed Central

    Radha, S.; Tameem, Afroz; Sridhar, G.; Aiyangar, A.; Rajaram, K. G.; Prasad, R.; Kiran, K.

    2014-01-01

    Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation. It is a morphological expression of various etiological factors. In a renal allograft, TMA can occur de novo or be a recurrent disease. The aim of this study was to analyze the etiological factors and observe the changing trends of TMA with respect to emerging new etiological factors. We evaluated 131 graft biopsies over a period of 2½ years (2010-2012). All the renal biopsies were formalin fixed, paraffin embedded. Twenty serial sections were studied. Stains routinely used were Hematoxylin and Eosin, Periodic Acid Schiff, Massons Trichrome and Silver Methenamine stains. C4d by immunohistochemical method was done on all graft biopsies. Incidence of TMA in our series was 9.1%. Out of the 12 cases, five were associated with calcineurin inhibitor toxicity, three were diagnosed as acute antibody-mediated rejection, and two were recurrent haemolytic uremic syndrome. One patient developed haemolytic uremic syndrome on treatment with sirolimus and one patient was cytomegalovirus positive on treatment with ganciclovir, developed haemolytic uremic syndrome during treatment course. This study describes a spectrum of etiological factors for thrombotic mciroangiopathy ranging from common cause like calcineurin inhibitor toxicity to rare cause like ganciclovir induced TMA. PMID:24574627

  15. Thrombotic microangiopathy in renal allografts.

    PubMed

    Radha, S; Tameem, Afroz; Sridhar, G; Aiyangar, A; Rajaram, K G; Prasad, R; Kiran, K

    2014-01-01

    Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation. It is a morphological expression of various etiological factors. In a renal allograft, TMA can occur de novo or be a recurrent disease. The aim of this study was to analyze the etiological factors and observe the changing trends of TMA with respect to emerging new etiological factors. We evaluated 131 graft biopsies over a period of 2½ years (2010-2012). All the renal biopsies were formalin fixed, paraffin embedded. Twenty serial sections were studied. Stains routinely used were Hematoxylin and Eosin, Periodic Acid Schiff, Massons Trichrome and Silver Methenamine stains. C4d by immunohistochemical method was done on all graft biopsies. Incidence of TMA in our series was 9.1%. Out of the 12 cases, five were associated with calcineurin inhibitor toxicity, three were diagnosed as acute antibody-mediated rejection, and two were recurrent haemolytic uremic syndrome. One patient developed haemolytic uremic syndrome on treatment with sirolimus and one patient was cytomegalovirus positive on treatment with ganciclovir, developed haemolytic uremic syndrome during treatment course. This study describes a spectrum of etiological factors for thrombotic mciroangiopathy ranging from common cause like calcineurin inhibitor toxicity to rare cause like ganciclovir induced TMA.

  16. Cellular behaviour of hepatocyte-like cells from nude mouse bone marrow-derived mesenchymal stem cells on galactosylated poly(D,L-lactic-co-glycolic acid).

    PubMed

    Roh, Hyun; Yang, Dae Hyeok; Chun, Heung Jae; Khang, Gilson

    2015-07-01

    Previously, the galactosylation of poly(d,l-lactic-co-glycolic acid) (PLGA) surface was accomplished by grafting allylamine (AA), using inductively coupled plasma-assisted chemical vapour deposition (ICP-CVD) and conjugating lactobionic acid (LA) with AA via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide (EDC/NHS) activation for hepatic tissue-engineering purposes. As a continuation study, the cellular behaviour of hepatocyte-like cells (HLCs) on the surface of the galactosylated PLGA were investigated. Nude mouse bone marrow-derived mesenchymal stem cells (MSCs) were cultured under hepatogenic conditions and the differentiated cells were characterized by reverse-transcription polymerase chain reaction (RT-PCR), immunofluorescence and periodic acid-Schiff (PAS) staining. Galactosylated PLGA enhanced the proliferation rate of HLCs compared to the control; HLCs on the surface of the sample became aggregated and formed spheroids after 3 days of culture. A large number of cells on the surface of the sample exhibited increased liver-specific functional activities, such as albumin and urea secretions. In addition, multicellular spheroids in the sample strongly expressed phospholyated focal adhesion kinase (pFAK) (cell-matrix interactions), E-cadherin (cell-cell interactions) and connexin 32 (Cox32; gap junction).

  17. In situ expression of cytokines in human heart allografts.

    PubMed Central

    Van Hoffen, E.; Van Wichen, D.; Stuij, I.; De Jonge, N.; Klöpping, C.; Lahpor, J.; Van Den Tweel, J.; Gmelig-Meyling, F.; De Weger, R.

    1996-01-01

    Although allograft rejection, the major complication of human organ transplantation, has been extensively studied, little is known about the exact cellular localization of the cytokine expression inside the graft during rejection. Therefore, we used in situ hybridization and immunohistochemistry to study local cytokine mRNA and protein expression in human heart allografts, in relation to the phenotypical characteristics of the cellular infiltrate. Clear expression of mRNA for interleukin (IL)-6, IL-8, IL-9, and IL-10 and weak expression for IL-2, IL-4, IL-5, and tumor necrosis factor (TNF)-alpha was detected in biopsies exhibiting high rejection grades (grade 3A/B). Also at lower grades of rejection, mRNA for IL-6 and IL-9 was present. Some mRNA for IL-1 beta, TNF-beta, and interferon (IFN)-gamma was detected in only a few biopsies. Using immunohistochemistry, IL-2, IL-3, and IL-10 protein was detected in biopsies with high rejection grades, whereas few cells expressed IL-6, IL-8, and IFN-gamma. In biopsies with lower grades of rejection, a weaker expression of these cytokines was observed. IL-4 was hardly detected in any of the biopsies. The level of IL-12 expression was equal in all biopsies. Although mRNA expression of several cytokines was expressed at a low level compared with the protein level of those cytokines, there was a good correlation between localization of cytokine mRNA and protein. Expression of IL-2, IL-4, IL-5, TNF-alpha, and IFN-gamma was mainly detected in lymphocytes. IL-3, IL-6, IL-10, and IL-12 were not detected or not only detected in lymphocytes but also in other stromal elements (eg, macrophages). Macrophage production of IL-3 and IL-12 was confirmed by immunofluorescent double labeling with CD68. We conclude that cardiac allograft rejection is not simply regulated by T helper cell cytokine production, but other intragraft elements contribute considerably to this process. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8952534

  18. A case of primary renal allograft dysfunction due to myeloma cast nephropathy.

    PubMed

    Lingaraj, Umesh; Vankalakunti, Mahesha; Radhakrishnan, Hemachandar; Sreedhara, C G; Rajanna, Sunil

    2015-09-01

    We report a rare case of primary renal allograft dysfunction due to myeloma cast nephropathy in a patient with no overt clinical features of multiple myeloma preceding his transplantation. A 45-year-old man on hemodialysis for six months for end-stage kidney disease due to presumed chronic glomerulonephritis developed immediate graft dysfunction post-transplantation. The graft biopsy was diagnostic of myeloma cast nephropathy. Other criteria for lambda light chain multiple myeloma were fulfilled with immunofixation electrophoresis and bone marrow biopsy. He was treated with plasmapheresis, bortezomib and high-dose dexamethasone. However, the patient succumbed to septicemia on the 37 th post-operative day. This is probably the first report of primary renal allograft dysfunction due to myeloma cast nephropathy diagnosed within the first week post-transplanation in a patient with unrecognized multiple myeloma.

  19. Allograft rejection in cattle with bovine leukocyte adhesion deficiency.

    PubMed

    Müller, K E; Rutten, V P; Becker, C K; Hoek, A; Bernadina, W E; Wentink, G H; Figdor, C G

    1995-09-01

    In the present investigation cell-mediated immunity in animals with bovine leukocyte adhesion deficiency (BLAD) was studied by means of skin transplantation experiments. Autograft and allograft behaviour in animals with BLAD was compared with the behaviour of simultaneously transplanted autografts and allografts in healthy controls. Allograft survival time was prolonged in three BLAD cattle (28, 30, and 72 days) compared to six healthy controls (12-14 days). When transplantations were repeated on one animal with BLAD using skin grafts from the same donor, accelerated rejection was observed (allograft survival time decreased from 72 days at primary to 35 days at secondary and to 21 days at tertiary transplantation), suggesting the development of immunological memory. Graft-infiltrating lymphocytes that were obtained from allograft biopsies during the period of rejection, were shown to be from recipient origin (beta 2-integrin negative). Our findings demonstrate that, although prolonged allograft survival is observed in cattle with BLAD, skin allografts are ultimately rejected. PMID:8533316

  20. Bone graft materials in fixation of orthopaedic implants in sheep.

    PubMed

    Babiker, Hassan

    2013-07-01

    Bone graft is widely used within orthopaedic surgery especially in revision joint arthroplasty and spine fusion. The early implant fixation in the revision situation of loose joint prostheses is important for the long-term survival. Bone autograft has been considered as gold standard in many orthopaedic procedures, whereas allograft is the gold standard by replacement of extensive bone loss. However, the use of autograft is associated with donor site morbidity, especially chronic pain. In addition, the limited supply is a significant clinical challenge. Limitations in the use of allograft include the risk of bacterial contamination and disease transmission as well as non-union and poor bone quality. Other bone graft and substitutes have been considered as alternative in order to improve implant fixation. Hydroxyapatite and collagen type I composite (HA/Collagen) have the potential in mimicking skeletal bones. The osteoconductive properties of the composite might be improved by adding bone marrow aspirate (BMA), which can be harvested during surgery. Other alternatives to bone graft are demineralised bone matrix (DBM) and human cancellous bone (CB). DBM is prepared by acid extraction of human bone and includes bone collagen, morphogenetic proteins and growth factors. The combination of DBM with CB and with allograft might improve the healing potential of these grafts around non-cemented orthopaedic implants and thereby the implant fixation. Study I investigates the effect of HA/Collagen composite alone and in combination with BMA on the early fixation of porous coated titanium implants. In addition, the study compares also the effect of autograft with the gold standard allograft. By using a sheep model, the implants were inserted in the trabecular bone of femoral condyles. The test biomaterials were placed in a well defined peri-implant gap. After the observation period, the bone-implant specimens were harvested and evaluated mechanically by a destructive push

  1. Bone morphogenetic protein 15 and growth differentiation factor 9 expression in the ovary of European sea bass (Dicentrarchus labrax): cellular localization, developmental profiles, and response to unilateral ovariectomy.

    PubMed

    García-López, Ángel; Sánchez-Amaya, María Isabel; Halm, Silke; Astola, Antonio; Prat, Francisco

    2011-12-01

    Vertebrate oocytes actively contribute to follicle development by secreting a variety of growth factors, among which bone morphogenetic protein 15 (BMP15/Bmp15) and growth differentiation factor 9 (GDF9/Gdf9) have been paid particular attention. In the present study, we describe the cellular localization, the developmental profiles, and the response to unilateral ovariectomy (a procedure implying the surgical removal of one of the ovaries) of protein and mRNA steady-state levels of Bmp15 and Gdf9 in the ovary of European sea bass, an important fish species for marine aquaculture industry. In situ hybridization and immunohistochemistry demonstrated that the oocyte is the main production site of Bmp15 and Gdf9 in European sea bass ovary. During oocyte development, Bmp15 protein expression started to be detected only from the lipid vesicle stage onwards but not in primary pre-vitellogenic (i.e. perinucleolar) oocytes as the bmp15 mRNA already did. Gdf9 protein and gdf9 mRNA expression were both detected in primary perinucleolar oocytes and followed similar decreasing patterns thereafter. Unilateral ovariectomy induced a full compensatory growth of the remaining ovary in the 2-month period following surgery (Á. García-López, M.I. Sánchez-Amaya, C.R. Tyler, F. Prat 2011). The compensatory growth elicited different changes in the expression levels of mRNA and protein of both factors, although the involvement of Bmp15 and Gdf9 in the regulatory network orchestrating such process remains unclear at present. Altogether, our results establish a solid base for further studies focused on elucidating the specific functions of Bmp15 and Gdf9 during primary and secondary oocyte growth in European sea bass.

  2. Effects of complement activation on allograft injury

    PubMed Central

    Sheen, Joong Hyuk; Heeger, Peter S.

    2015-01-01

    Purpose of review To summarize the current knowledge regarding mechanisms linking the complement system to transplant injury, highlighting findings reported since 2013. Recent findings Building upon the documentation that complement activation is a pathogenic mediator of post-transplant ischemia-reperfusion (IR) injury, emerging evidence indicates blocking either the classical or lectin pathways attenuates IR injury in animal models. Immune cell-derived and locally activated complement, including intracellular C3 positively modulates allo-reactive T cell activation and expansion, while simultaneously inhibiting regulatory T cell induction and function, together promoting transplant rejection. While alloantibody-initiated complement activation directly injures target cells, complement-dependent signals activate endothelial cells to facilitate T cell dependent inflammation. Complement activation within allografts contributes to progressive chronic injury and fibrosis. Summary The complement cascade, traditionally considered relevant to transplantation only as an effector mechanism of antibody-initiated allograft injury, is now understood to damage the allograft through multiple mechanisms. Complement activation promotes post-transplant IR injury, formation and function of allo-antibody, differentiation and function of alloreactive T cells, and contributes to chronic progressive allograft failure. The recognition that complement impacts transplant injury at many levels provides a foundation for targeting complement as a therapy to prolong transplant survival and improve patient health. PMID:26132735

  3. Meniscal Allograft Transplantation: State of the Art.

    PubMed

    Trentacosta, Natasha; Graham, William C; Gersoff, Wayne K

    2016-06-01

    Meniscal allograft transplantation has evolved over the years to provide a state-of-the-art technique for the sports medicine surgeon to utilize in preserving contact mechanics and function of the knee in irreparable meniscal pathology. However, this procedure continues to spark considerable debate on proper tissue processing techniques, acceptable indications, methods of implantation, and potential long-term outcomes. PMID:27135295

  4. Acute colitis in the renal allograft recipient.

    PubMed Central

    Perloff, L J; Chon, H; Petrella, E J; Grossman, R A; Barker, C F

    1976-01-01

    Four renal allograft recipients with evidence of ischemic damage to the colon are presented and compared with 11 cases from 5 major series. Similarities in the patients included: deterioration of renal function, multiple immunosuppressive and antibiotic regimens, the use of cadaver renal allografts, and diagnostic and therapeutic measures requiring frequent enemas with barium and ion-exchange resins. Two of our patients underwent surgery for the removal of segments of necrotic colon after several weeks of fever and abdominal pain initially attributed to either acute rejection, viral infection, or pancreatitis. One patient had three days of melena and responded to non-operative therapy. The fourth patient developed ischemic colonic changes 10 weeks after allograft nephrectomy and was receiving no immunosuppression at the time. Broad spectrum antibiotics were used at various times in all patients. Early aggressive evaluation of gastrointestinal complaints--including barium enema, upper gastrointestinal series with small bowel follow-through, proctosigmoidoscopy or colonoscopy, and arteriography--is indicated, in view of the lethality of the complication of colonic ulceration. The clinical pictures presented emphasize the fact that recipients of renal allografts are commonly heir to many complications which may be considered rare in the normal population. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4a. Fig. 4b. PMID:1108814

  5. T-cell receptor Vbeta gene usage by lymphocytes infiltrating human renal allografts.

    PubMed

    Gecim, I E; Christmas, S E; Brew, R; Flanagan, B F; Wheatcroft, N J; Bakran, A; Sells, R A

    1992-01-01

    T cell lines have been derived from human kidney allograft biopsies using mitogenic stimulation. Southern blotting using a T-cell receptor (TCR) Cbeta probe revealed an oligoclonal pattern of rearranged bands in all 12 samples analysed. In some cases, differences in band patterns were noted between independent cultures from the same biopsy. Most T-cell clones derived from 2 biopsies showed different patterns of rearranged bands. The polymerase chain reaction (PCR) was used to study TCR Vbeta gene usage in allograft-derived T-cell cultures. This was more sensitive and more informative than Southern blotting and revealed that most TCR Vbeta genes were expressed in T cells from biopsies showing cellular rejection. The potential usefulness of this technique to quantify TCR V gene usage in allospecific T-cell populations is discussed.

  6. Factors Predicting Meniscal Allograft Transplantation Failure

    PubMed Central

    Parkinson, Ben; Smith, Nicholas; Asplin, Laura; Thompson, Peter; Spalding, Tim

    2016-01-01

    Background: Meniscal allograft transplantation (MAT) is performed to improve symptoms and function in patients with a meniscal-deficient compartment of the knee. Numerous studies have shown a consistent improvement in patient-reported outcomes, but high failure rates have been reported by some studies. The typical patients undergoing MAT often have multiple other pathologies that require treatment at the time of surgery. The factors that predict failure of a meniscal allograft within this complex patient group are not clearly defined. Purpose: To determine predictors of MAT failure in a large series to refine the indications for surgery and better inform future patients. Study Design: Cohort study; Level of evidence, 3. Methods: All patients undergoing MAT at a single institution between May 2005 and May 2014 with a minimum of 1-year follow-up were prospectively evaluated and included in this study. Failure was defined as removal of the allograft, revision transplantation, or conversion to a joint replacement. Patients were grouped according to the articular cartilage status at the time of the index surgery: group 1, intact or partial-thickness chondral loss; group 2, full-thickness chondral loss 1 condyle; and group 3, full-thickness chondral loss both condyles. The Cox proportional hazards model was used to determine significant predictors of failure, independently of other factors. Kaplan-Meier survival curves were produced for overall survival and significant predictors of failure in the Cox proportional hazards model. Results: There were 125 consecutive MATs performed, with 1 patient lost to follow-up. The median follow-up was 3 years (range, 1-10 years). The 5-year graft survival for the entire cohort was 82% (group 1, 97%; group 2, 82%; group 3, 62%). The probability of failure in group 1 was 85% lower (95% CI, 13%-97%) than in group 3 at any time. The probability of failure with lateral allografts was 76% lower (95% CI, 16%-89%) than medial allografts at

  7. Invasive Streptococcus pyogenes after allograft implantation--Colorado, 2003.

    PubMed

    2003-12-01

    Allograft tissues are used for various orthopedic procedures (e.g., ligament reconstruction, meniscal transplantation, and spinal surgery). In 2002, approximately one million allografts were distributed for transplantation (American Association of Tissue Banks [AATB], unpublished data, 2002). Recent reports of allograft-associated infections have prompted evaluation of the processing and quality-control methods employed by tissue processors. This report describes a case of invasive disease with Streptococcus pyogenes (i.e., group A streptococcus [GAS]), after reconstructive knee surgery using contaminated allograft tissue and provides recommendations to reduce the risk for allograft-associated infections. Although allograft infections are rare, they highlight the need for improved tissue evaluation and processing standards. PMID:14654764

  8. Comparison of Fusion Rates between Glycerol-Preserved and Frozen Composite Allografts in Cervical Fusion.

    PubMed

    Rodway, Ian; Gander, Julie

    2014-01-01

    Background. This retrospective, two cohort series study was designed to compare a room temperature, glycerol-preserved composite pinned bone allograft (G-CPBA) with the same graft type provided in a frozen state (F-CPBA) for use as a cervical interbody spacer in anterior cervical discectomy and fusion (ACDF). Methods. A comprehensive chart review was performed for 67 sequential patients that received either a F-CPBA or a G-CPBA and had at least one-year follow-up. Twenty-eight patients had received G-CPBA grafts and 37 patients had received F-CPBA grafts. Two additional 2-level patients had received one of each type of grafts. Results. At 3 months, 45.3% (29 of 64) of glycerol-preserved and 41.4% (29 of 70) of frozen allografts, respectively, were considered to be fused radiographically. At 12 months, 100% of both treatment groups (41 glycerol-preserved and 45 frozen) were considered fused. Fusion rates for G-CPBA were statistically similar to F-CPBA at both 3 and 12 months (P = 0.6535 and >0.999, resp.). There were no allograft related complications in either treatment group. Conclusions. 100% fusion rates were attained by both treatment groups at 12 months and were similar at short-term follow-up for all comparable levels. Level of Evidence. Level of evidence is III.

  9. Comparison of Fusion Rates between Glycerol-Preserved and Frozen Composite Allografts in Cervical Fusion

    PubMed Central

    Rodway, Ian; Gander, Julie

    2014-01-01

    Background. This retrospective, two cohort series study was designed to compare a room temperature, glycerol-preserved composite pinned bone allograft (G-CPBA) with the same graft type provided in a frozen state (F-CPBA) for use as a cervical interbody spacer in anterior cervical discectomy and fusion (ACDF). Methods. A comprehensive chart review was performed for 67 sequential patients that received either a F-CPBA or a G-CPBA and had at least one-year follow-up. Twenty-eight patients had received G-CPBA grafts and 37 patients had received F-CPBA grafts. Two additional 2-level patients had received one of each type of grafts. Results. At 3 months, 45.3% (29 of 64) of glycerol-preserved and 41.4% (29 of 70) of frozen allografts, respectively, were considered to be fused radiographically. At 12 months, 100% of both treatment groups (41 glycerol-preserved and 45 frozen) were considered fused. Fusion rates for G-CPBA were statistically similar to F-CPBA at both 3 and 12 months (P = 0.6535 and >0.999, resp.). There were no allograft related complications in either treatment group. Conclusions. 100% fusion rates were attained by both treatment groups at 12 months and were similar at short-term follow-up for all comparable levels. Level of Evidence. Level of evidence is III. PMID:27382618

  10. Experiences using IAEA Code of practice for radiation sterilization of tissue allografts: Validation and routine control

    NASA Astrophysics Data System (ADS)

    Hilmy, N.; Febrida, A.; Basril, A.

    2007-11-01

    Problems of tissue allografts in using International Standard (ISO) 11137 for validation of radiation sterilization dose (RSD) are limited and low numbers of uniform samples per production batch, those are products obtained from one donor. Allograft is a graft transplanted between two different individuals of the same species. The minimum number of uniform samples needed for verification dose (VD) experiment at the selected sterility assurance level (SAL) per production batch according to the IAEA Code is 20, i.e., 10 for bio-burden determination and the remaining 10 for sterilization test. Three methods of the IAEA Code have been used for validation of RSD, i.e., method A1 that is a modification of method 1 of ISO 11137:1995, method B (ISO 13409:1996), and method C (AAMI TIR 27:2001). This paper describes VD experiments using uniform products obtained from one cadaver donor, i.e., cancellous bones, demineralized bone powders and amnion grafts from one life donor. Results of the verification dose experiments show that RSD is 15.4 kGy for cancellous and demineralized bone grafts and 19.2 kGy for amnion grafts according to method A1 and 25 kGy according to methods B and C.

  11. The biomechanical behavior on the interface of tumor arthrosis/allograft prosthetic composite by finite element analysis

    NASA Astrophysics Data System (ADS)

    Chen, H. Z.; Jiang, W.; Zou, W.; Luo, J. M.; Chen, J. Y.; Tu, C. Q.; Xing, B. B.; Gu, Z. W.; Zhang, X. D.

    2008-11-01

    The biomechanical behavior of the uniting interface between the allograft bone and the autogenetic bone plays an important role in the treatment of the proximal femur massive defects with artificial tumor arthrosis/allograft prosthetic composite (TAAPC). According to the CT data of a patient, a 3D medical treatment model of TAAPC was established. Under the loads of 1.5 and 2.5 times standard body weight (70 kg), the mechanical behavior of the treatment model was analyzed by finite element analysis (FEA) for three typical healing periods. The results show that there are significant differences in the stress values and distribution in different healing periods. With healing of osteotomy, the hardness of the tissue of the uniting interface increases, the stress in uniting area was increased greatly and the stress concentration decreased. After cured the stress almost reached the level of normal bone. In the initial stage of healing, the healing training is not encouraged because there is an obvious risk of fracture of prosthesis and bone cement. In addition, porous hydroxyapatite (HA) ceramic used as bone tissue scaffold for this case, not only facilitates the generation of new bone, but also can avoid this risk caused by the non-uniting interface.

  12. Recirculation of indium-111-labeled lymphocytes in normal and allografted rats

    SciTech Connect

    Oluwole, S.; Satake, K.; Kuromoto, N.; Fawwaz, R.; Hardy, M.A.

    1983-11-01

    The kinetics of lymphocyte recirculation in normal and allografted rats with acute cardiac rejection was studied with indium-111 (In-111) labeled splenic lymphocytes in two groups of rats. Group 1 consisted of subgroups of normal Lewis rats infused with In-111 labeled unsensitized syngeneic cells (group 1a); ACI-sensitized syngeneic cells (group 1b); and ACI spleen cells (group 1c). Four rats from each subgroup were killed at 3, 6, 18, and 24 hr after cell infusion for blood, spleen, mesenteric lymph node (MLN), thymus, bone marrow (BM), liver, kidney, muscle, and heart scintillation counts. Group 2 consisted of Lewis recipients of ACI cardiac allografts infused with normal or with ACI-sensitized syngeneic splenic cells. Four rats from each subgroup were killed daily until rejection (day 7) for isotope counts of various organs. In ungrafted rats (group I), splenic accumulation of unsensitized syngeneic cells fell from 50% of the total injected dose/g tissue at 3 hr to 28% at 24 hr, whereas it rose from 12% at 3 hr to 39% at 24 hr in MLN. In contrast, the sensitized syngeneic and allogeneic cells homed preferentially to the spleen with insignificant accumulation in the MLN throughout the experiment. The BM and liver showed moderate accumulation while the thymus and nonlymphoid organs had low concentrations of labeled cells at all times. Splenic accumulation of unsensitized syngeneic cells in allografted rats (group II) showed a steep rise from day 1, reaching a peak at day 3, followed by a plateau--but sensitized cells demonstrated a peak on day 4 followed by a sharp decline until rejection. Accumulation of unsensitized cells in the MLN was significantly higher than that of sensitized cells throughout the study. There was a significant fall in radioactivity of BM, thymus, liver, and nonlymphoid organs from days 1-7, and the cardiac allograft demonstrated a reciprocal sharp rise in radioactivity.

  13. Transphyseal anterior cruciate ligament reconstruction in a skeletally immature knee using anterior tibialis allograft.

    PubMed

    Cho, Yool; Jang, Soo-Jin; Son, Jung-Hwan

    2011-05-18

    Anterior cruciate ligament (ACL) injury in the skeletally immature individual is being recognized with increasing frequency. Nonoperative treatment of ACL injuries in skeletally immature patients have not been favorable. Surgical treatment options for complete ACL tears include primary ligament repair, extraarticular tenodesis, transphyseal reconstruction, partial transphyseal reconstruction, and physeal-sparing reconstruction. The advantage of transphyseal reconstruction is placement of the graft tissue in an isometric position, which provides better results, according to the literature. The potential disadvantage is angular or limb-length discrepancy caused by physeal violation. Controversy exists in allograft selection about whether bone or soft tissue passes into physes. The use of standard tunnels provides reliable results, but carries the risk of iatrogenic growth disturbance from physeal injury.This article presents 4 cases of transphyseal ACL reconstruction using anterior tibialis allograft in skeletally immature patients that had satisfactory functional outcomes with no growth disturbances. This is the first report of transphyseal ACL reconstruction using anterior tibialis allograft in skeletally immature patients in the English-speaking literature. All patients underwent transphyseal ACL reconstruction using anterior tibialis tendon allograft. None of the patients had angular deformities. No early physeal arrest was measured between the preoperative and postoperative radiographs. At last follow-up, the results of the Lachman test were normal for 3 patients and nearly normal for 1 patient. All patients demonstrated full range of knee motion (comparing the reconstructed knee to the contralateral knee). The results of the pivot-shift test were normal for 3 patients and nearly normal for 1 patient. No patients reported giving way.

  14. Biomechanical Evaluation of Human Allograft Compression in Anterior Cruciate Ligament Reconstruction

    PubMed Central

    Lord, Breck; Yasen, Sam; Amis, Andrew; Wilson, Adrian

    2016-01-01

    Introduction: A common problem encountered during ACL reconstruction is asymmetry of proximal-distal graft diameter leading to tunnel upsizing and potential graft-tunnel mismatch. Human allografts are often oedematous, compounding this issue in the context of multi-ligament reconstructions. Tunnel upsizing reduces bone stock, increases the complexity of multi-bundle surgery and may compromise graft-osseous integration if cortical suspensory fixation is used. Graft compression provides uniform size, allowing easy passage into a smaller tunnel, potentially improving the ‘press-fit’ graft-osseous interaction whilst preserving bone stock. To our knowledge, no biomechanical evaluation of this increasing popular technique has been reported. Hypotheses: Graft compression would not cause any significant changes in the biomechanical properties of human allograft tendon that would be detrimental to the function of an ACL reconstruction. Compressed Bioclense® allograft will increase in size when soaked in Ringer’s solution at 36° improving the ‘press-fit’ within the bone socket, decreasing micro-motion at the graft-osseous interface following ACL reconstruction. Method: In-vitro laboratory study. Sixteen samples of Bioclense® treated peroneus longus allograft were quadrupled into GraftLink constructs randomly divided into control and compressed groups. Cross-sectional area (CSA) was determined using alginate moulds and specimens immersed, under tension, in Ringer’s solution at 36.5°. CSA was measured at 8 hours. A further 32 samples were randomised and evaluated under cyclic loading of 70N-220N (1020 cycles) followed by test to failure. A further 30 samples were quadrupled into GraftLink constructs and mounted within porcine femurs using suspensory fixation. High resolution videometer recorded motion at the graft-osseous interface under the same cyclic loading protocol. An independent samples t-test was used to compare changes in CSA whilst a one-way ANOVA was

  15. Total Knee Arthroplasty for Post-Traumatic Proximal Tibial Bone Defect: Three Cases Report

    PubMed Central

    Tigani, D; Dallari, D; Coppola, C; Ben Ayad, R; Sabbioni, G; Fosco, M

    2011-01-01

    Bone stock deficiency in primary as well as in revision total knee arthroplasty (TKA) represents a difficult problem to surgeon with regard to maintaining proper alignment of the implant components and in establishing a stable bone-implant interface. Different surgical procedures are available in these situations, for instances the use of bone cement, prosthetic augments, custom implant, and wire mesh with morsellized bone grafting and structural bone allograft. Structural allograft offers a numerous advantages as easy remodeling and felling cavitary or segmental defects, excellent biocompatibility, bone stock restoration and potential for ligamentous reattachment. In this article we report a short term result of three cases affected by severe segmental medial post/traumatic tibial plateau defect in arthritic knee, for which massive structural allograft reconstruction and primary total knee replacement were carried. The heights of the bone defect were between 27-33 mm and with moderate medio-lateral knee instability. Pre-operative AKS score in three cases was 30, 34 and 51 points consecutively and improved at the last follow-up to 83, 78 and 85 consecutively. No acute or chronic complication was observed. Last radiological exam referred no signs of prosthetic loosening, no secondary resorption of bone graft and well integrated graft to host bone. These results achieved in our similar three cases have confirmed that the structural bone allograft is a successful biological material to restore hemi-condylar segmental tibial bone defect when total knee replacement is indicated. PMID:21584202

  16. Procurement of hand and arm allografts.

    PubMed

    Cetrulo, Curtis L; Kovach, Stephen J

    2013-12-01

    Upper extremity transplantation has been at the forefront of vascularized composite allotransplantation. There have been more hand and upper extremity transplants than any other kinds of vascularized composite allotransplantation. However, it is a new and evolving field. Reconstructive surgeons are relative newcomers to the field of transplantation, and the procurement of upper extremity allografts has many subtleties that will differ depending on the intended recipient. However, there are certain principles that can be adhered to that this review serves to elucidate. PMID:24310234

  17. Procurement of hand and arm allografts.

    PubMed

    Cetrulo, Curtis L; Kovach, Stephen J

    2013-12-01

    Upper extremity transplantation has been at the forefront of vascularized composite allotransplantation. There have been more hand and upper extremity transplants than any other kinds of vascularized composite allotransplantation. However, it is a new and evolving field. Reconstructive surgeons are relative newcomers to the field of transplantation, and the procurement of upper extremity allografts has many subtleties that will differ depending on the intended recipient. However, there are certain principles that can be adhered to that this review serves to elucidate.

  18. Mouse kidney transplantation: models of allograft rejection.

    PubMed

    Tse, George H; Hesketh, Emily E; Clay, Michael; Borthwick, Gary; Hughes, Jeremy; Marson, Lorna P

    2014-01-01

    Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely replicates both the technical and pathological processes that occur in human renal transplantation. Although mouse models of allogeneic rejection in organs other than the kidney exist, and are more technically feasible, there is evidence that different organs elicit disparate rejection modes and dynamics, for instance the time course of rejection in cardiac and renal allograft differs significantly in certain strain combinations. This model is an attractive tool for many reasons despite its technical challenges. As inbred mouse strain haplotypes are well characterized it is possible to choose donor and recipient combinations to model acute allograft rejection by transplanting across MHC class I and II loci. Conversely by transplanting between strains with similar haplotypes a chronic process can be elicited were the allograft kidney develops interstitial fibrosis and tubular atrophy. We have modified the surgical technique to reduce operating time and improve ease of surgery, however a learning curve still needs to be overcome in order to faithfully replicate the model. This study will provide key points in the surgical procedure and aid the process of establishing this technique.

  19. Mouse Kidney Transplantation: Models of Allograft Rejection

    PubMed Central

    Clay, Michael; Borthwick, Gary; Hughes, Jeremy; Marson, Lorna P.

    2014-01-01

    Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely replicates both the technical and pathological processes that occur in human renal transplantation. Although mouse models of allogeneic rejection in organs other than the kidney exist, and are more technically feasible, there is evidence that different organs elicit disparate rejection modes and dynamics, for instance the time course of rejection in cardiac and renal allograft differs significantly in certain strain combinations. This model is an attractive tool for many reasons despite its technical challenges. As inbred mouse strain haplotypes are well characterized it is possible to choose donor and recipient combinations to model acute allograft rejection by transplanting across MHC class I and II loci. Conversely by transplanting between strains with similar haplotypes a chronic process can be elicited were the allograft kidney develops interstitial fibrosis and tubular atrophy. We have modified the surgical technique to reduce operating time and improve ease of surgery, however a learning curve still needs to be overcome in order to faithfully replicate the model. This study will provide key points in the surgical procedure and aid the process of establishing this technique. PMID:25350513

  20. Liver allograft pathology in liver/small bowel or multivisceral recipients.

    PubMed

    Tsamandas, A C; Furukawa, H; Abu-Elmagd, K; Todo, S; Demetris, A J; Lee, R G

    1996-07-01

    Combined liver/small bowel (LSB) and multivisceral (MV) transplantation represents an alternative treatment for patients with short-gut syndrome complicated by end-stage liver disease. However, the question of whether the addition of an intestinal allograft alters the pathologic features of the transplanted liver remains unanswered. We, therefore, evaluated the histologic features of 51 liver biopsy specimens from 13 LSB or MV recipients and compared them with a matched control group of specimens from recipients of isolated liver allografts. In general, the histologic alterations were comparable in the LSB/MV and control groups. The primary difference was that portal and sinusoidal neutrophilia accompanied acute cellular rejection in 10 (63%) of 16 LSB/MV specimens but none of the control specimens. Concurrent culture results were positive in 5 of the 10 cases: bacterial overgrowth of the intestinal allograft was found in 3 cases, and bacteremia in 2 other cases, 1 of which had also a positive liver culture. In contrast, these cultures (n = 7) were negative in the six LSB/MV cases of neutrophil-free acute cellular rejection. Neutrophilia was also present in 26 additional LSB/MV specimens, including instances of preservation injury, sepsis, impaired bile flow due to ampullary dysfunction, and one case without an underlying diagnosis, but its frequency did not significantly differ from that of corresponding control cases. An additional finding was the occurrence of a "fibrosing cholestatic" pattern of acquired hepatitis C in 10 specimens from 2 LSB/MV recipients. Acute cellular reaction-associated neutrophilia in LSB/MV recipients may reflect portal bacteremia resulting from bacterial overgrowth and translocation from the intestinal graft or represent simply a nonspecific hepatic response to intestinal inflammatory processes.

  1. Scaffold Design for Bone Regeneration

    PubMed Central

    Polo-Corrales, Liliana; Latorre-Esteves, Magda; Ramirez-Vick, Jaime E.

    2014-01-01

    The use of bone grafts is the standard to treat skeletal fractures, or to replace and regenerate lost bone, as demonstrated by the large number of bone graft procedures performed worldwide. The most common of these is the autograft, however, its use can lead to complications such as pain, infection, scarring, blood loss, and donor-site morbidity. The alternative is allografts, but they lack the osteoactive capacity of autografts and carry the risk of carrying infectious agents or immune rejection. Other approaches, such as the bone graft substitutes, have focused on improving the efficacy of bone grafts or other scaffolds by incorporating bone progenitor cells and growth factors to stimulate cells. An ideal bone graft or scaffold should be made of biomaterials that imitate the structure and properties of natural bone ECM, include osteoprogenitor cells and provide all the necessary environmental cues found in natural bone. However, creating living tissue constructs that are structurally, functionally and mechanically comparable to the natural bone has been a challenge so far. This focus of this review is on the evolution of these scaffolds as bone graft substitutes in the process of recreating the bone tissue microenvironment, including biochemical and biophysical cues. PMID:24730250

  2. Methods of reconstruction for bone defect after tumor excision: a review of alternatives.

    PubMed

    Nishida, Jun; Shimamura, Tadashi

    2008-08-01

    Bone defect is a common problem encountered in the treatment of musculoskeletal tumor surgery. Allograft is a commonly used technique to reconstruct a large osseous defect following tumor excision in the United States and some European countries, and relatively good results have been reported because of its biologic nature. However, with the use of an allograft, there are concerns of transmission of infectious diseases, immunological reactions, and social or religious refusal in some regions in the world. Under these circumstances, vascularized autogenous fibular or iliac bone grafts are commonly used techniques and bone lengthening techniques using external fixation have been reported recently. These procedures utilize viable bone. In addition to these procedures, some biological reconstructive techniques utilizing nonviable bone have been performed as surgical alternatives for allografts using treated recycling bone including irradiated or pasteurized resected bone graft and reconstruction using an autograft containing tumor treated by liquid nitrogen. Although each technique has its proper advantages and disadvantages, the clinical results are similar to the allograft, and numerous techniques are now available as reasonable alternatives for allografts.

  3. Non-invasive diffuse correlation tomography reveals spatial and temporal blood flow differences in murine bone grafting approaches

    PubMed Central

    Han, Songfeng; Proctor, Ashley R.; Vella, Joseph B.; Benoit, Danielle S. W.; Choe, Regine

    2016-01-01

    Longitudinal blood flow during murine bone graft healing was monitored non-invasively using diffuse correlation tomography. The system utilized spatially dense data from a scanning set-up, non-linear reconstruction, and micro-CT anatomical information. Weekly in vivo measurements were performed. Blood flow changes in autografts, which heal successfully, were localized to graft regions and consistent across mice. Poor healing allografts showed heterogeneous blood flow elevation and high inter-subject variabilities. Allografts with tissue-engineered periosteum showed responses intermediate to both autografts and allografts, consistent with healing observed. These findings suggest that spatiotemporal blood flow changes can be utilized to differentiate the degree of bone graft healing.

  4. Study of Osteoclast Adhesion to Cortical Bone Surfaces: A Correlative Microscopy Approach for Concomitant Imaging of Cellular Dynamics and Surface Modifications

    PubMed Central

    2015-01-01

    Bone remodeling relies on the coordinated functioning of osteoblasts, bone-forming cells, and osteoclasts, bone-resorbing cells. The effects of specific chemical and physical bone features on the osteoclast adhesive apparatus, the sealing zone ring, and their relation to resorption functionality are still not well-understood. We designed and implemented a correlative imaging method that enables monitoring of the same area of bone surface by time-lapse light microscopy, electron microscopy, and atomic force microscopy before, during, and after exposure to osteoclasts. We show that sealing zone rings preferentially develop around surface protrusions, with lateral dimensions of several micrometers, and ∼1 μm height. Direct overlay of sealing zone rings onto resorption pits on the bone surface shows that the rings adapt to pit morphology. The correlative procedure presented here is noninvasive and performed under ambient conditions, without the need for sample labeling. It can potentially be applied to study various aspects of cell-matrix interactions. PMID:26682493

  5. Clinical effectiveness of processed and unprocessed bone.

    PubMed

    Galea, G; Kearney, J N

    2005-06-01

    Bone allografts have been used clinically for a number of years. Understanding the biology of bone healing and the impact that bone banking has on this helps to improve the methodologies used in increasing the quality and safety of banked bone. Banked bone in its various forms has been used in a variety of surgical procedures, and although there is no doubt that it is clinically effective, most of the studies have been retrospective and non-randomized. The review attempts to summarize some of the data in this area and highlights some of the difficulties encountered in such work. Although there is no doubt that bone banking is nowadays better controlled, there are ever-increasing pressures to produce bone that is as safe as possible with the least impact on its effectiveness. This can only be achieved if the requirements of the providers and users of bone are better understood. PMID:15943701

  6. Metabolic bone diseases in kidney transplant recipients.

    PubMed

    Zhang, Rubin; Chouhan, Kanwaljit K

    2012-10-01

    Metabolic bone disease after kidney transplantation has a complex pathophysiology and heterogeneous histology. Pre-existing renal osteodystrophy may not resolve completely, but continue or evolve into a different osteodystrophy. Rapid bone loss immediately after transplant can persist, at a lower rate, for years to come. These greatly increase the risk of bone fracture and vertebral collapse. Each patient may have multiple risk factors of bone loss, such as steroids usage, hypogonadism, persistent hyperparathyroidism (HPT), poor allograft function, metabolic acidosis, hypophosphatemia, vitamin D deficiency, aging, immobility and chronic disease. Clinical management requires a comprehensive approach to address the underlying and ongoing disease processes. Successful prevention of bone loss has been shown with vitamin D, bisphosphonates, calcitonin as well as treatment of hypogonadism and HPT. Novel approach to restore the normal bone remodeling and improve the bone quality may be needed in order to effectively decrease bone fracture rate in kidney transplant recipients. PMID:24175250

  7. Clinical effectiveness of processed and unprocessed bone.

    PubMed

    Galea, G; Kearney, J N

    2005-06-01

    Bone allografts have been used clinically for a number of years. Understanding the biology of bone healing and the impact that bone banking has on this helps to improve the methodologies used in increasing the quality and safety of banked bone. Banked bone in its various forms has been used in a variety of surgical procedures, and although there is no doubt that it is clinically effective, most of the studies have been retrospective and non-randomized. The review attempts to summarize some of the data in this area and highlights some of the difficulties encountered in such work. Although there is no doubt that bone banking is nowadays better controlled, there are ever-increasing pressures to produce bone that is as safe as possible with the least impact on its effectiveness. This can only be achieved if the requirements of the providers and users of bone are better understood.

  8. Effect of Er:YAG laser holes on osteoinduction in demineralized rat calvarial allografts.

    PubMed

    O'Donnell, R J; Deutsch, T F; Flotte, R J; Lorente, C A; Tomford, W W; Mankin, H J; Schomacker, K T

    1996-01-01

    Massive cortical autografts and allografts have been found to incorporate into host bone very slowly and thus are subject to complications such as fatigue fracture and infection. In order to understand and improve the process of osteogenesis in these types of bone grafts, a new experimental model was developed using bone discs from rat calvaria prepared by demineralization and drilling of 0.5 mm diameter holes with a pulsed, 2.94 microns wavelength Erbium:Yttrium-Aluminum-Garnet laser. Four types of bone discs were analyzed: untreated (Type I), demineralized (Type II), laser-ablated (Type III), and laser-ablated then demineralized (Type IV). The discs were transplanted into a subcutaneous site in adult Sprague-Dawley rats and followed for as long as 6 weeks. Histologic analysis of the discs at weekly intervals with use of hematoxylin and eosin staining confirmed the presence of new bone growth in Type-II and Type-IV discs. The amount of new bone growth in each disc was estimated by determining the mineral x-ray attenuation coefficient, which is proportional to mineral density, from digitized radiographs of the discs. The results showed that the processes of demineralization (P < 0.001) and laser ablation with demineralization (p < 0.05) were both significant in enhancing new bone growth in this model. This study demonstrated that osteoinduction can be fostered in cortical bone through the processes of demineralization and laser ablation. To the extent that laser ablation may allow maintenance of structural integrity while altering the surface geometry in such a way as to promote ingrowth of new bone, this experimental model represents an advance in understanding how osteogenesis in cortical bone grafts might be improved. PMID:8618152

  9. Surgical techniques and radiological findings of meniscus allograft transplantation.

    PubMed

    Lee, Hoseok; Lee, Sang Yub; Na, Young Gon; Kim, Sung Kwan; Yi, Jae Hyuck; Lim, Jae Kwang; Lee, So Mi

    2016-08-01

    Meniscus allograft transplantation has been performed over the past 25 years to relieve knee pain and improve knee function in patients with an irreparable meniscus injury. The efficacy and safety of meniscus allograft transplantation have been established in numerous experimental and clinical researches. However, there is a lack of reviews to aid radiologists who are routinely interpreting images and evaluating the outcome of the procedures, and also meniscus allograft transplantation is not widely performed in most hospitals. This review focuses on the indications of the procedure, the different surgical techniques used for meniscus allograft transplantation according to the involvement of the lateral and medial meniscus, and the associated procedures. The postoperative radiological findings and surgical complications of the meniscus allograft transplantation are also described in detail.

  10. Comparison of structural allograft and traditional autograft technique in occipitocervical fusion: radiological and clinical outcomes from a single institution.

    PubMed

    Godzik, Jakub; Ravindra, Vijay M; Ray, Wilson Z; Schmidt, Meic H; Bisson, Erica F; Dailey, Andrew T

    2015-08-01

    OBJECT The authors' objectives were to compare the rate of fusion after occipitoatlantoaxial arthrodesis using structural allograft with the fusion rate from using autograft, to evaluate correction of radiographic parameters, and to describe symptom relief with each graft technique. METHODS The authors assessed radiological fusion at 6 and 12 months after surgery and obtained radiographic measurements of C1-2 and C2-7 lordotic angles, C2-7 sagittal vertical alignments, and posterior occipitocervical angles at preoperative, postoperative, and final follow-up examinations. Demographic data, intraoperative details, adverse events, and functional outcomes were collected from hospitalization records. Radiological fusion was defined as the presence of bone trabeculation and no movement between the graft and the occiput or C-2 on routine flexion-extension cervical radiographs. Radiographic measurements were obtained from lateral standing radiographs with patients in the neutral position. RESULTS At the University of Utah, 28 adult patients underwent occipitoatlantoaxial arthrodesis between 2003 and 2010 using bicortical allograft, and 11 patients were treated using iliac crest autograft. Mean follow-up for all patients was 20 months (range 1-108 months). Of the 27 patients with a minimum of 12 months of follow-up, 18 (95%) of 19 in the allograft group and 8 (100%) of 8 in the autograft group demonstrated evidence of bony fusion shown by imaging. Patients in both groups demonstrated minimal deterioration of sagittal vertical alignment at final follow-up. Operative times were comparable, but patients undergoing occipitocervical fusion with autograft demonstrated greater blood loss (316 ml vs 195 ml). One (9%) of 11 patients suffered a significant complication related to autograft harvesting. CONCLUSIONS The use of allograft in occipitocervical fusion allows a high rate of successful arthrodesis yet avoids the potentially significant morbidity and pain associated with

  11. Anterior cruciate ligament reconstruction with fresh-frozen patellar tendon allografts: sixty cases with 2 years' minimum follow-up.

    PubMed

    Nín, J R; Leyes, M; Schweitzer, D

    1996-01-01

    A prospective study was performed on 101 patients who underwent an arthroscopic anterior cruciate ligament (ACL) reconstruction with fresh-frozen patellar tendon allograft (bone-patellar tendon-bone). We present the results of the first 60 patients with a minimum follow-up of 2 years. Thirty-four were men and 26 women with a mean age of 23. In 45 patients, a postoperative arthroscopy was performed, and tissue biopsies of the reconstructed ACL were obtained. Patients were evaluated according to the International Knee Documentation Committee evaluation form. After a mean follow-up of 47 months, the overall results were normal or nearly normal in 85%. Under postoperative arthroscopy, the macroscopic appearance of the implant was similar to that of a normal ligament. The ACL allograft was covered with a normal, well-vascularized synovium. There were no cases of infection, disease transmission or tissue rejection. We conclude that the use of fresh-frozen patellar tendon allografts is a good method of ACL reconstruction.

  12. Alefacept promotes immunosuppression-free renal allograft survival in nonhuman primates via depletion of recipient memory T cells.

    PubMed

    Lee, S; Yamada, Y; Tonsho, M; Boskovic, S; Nadazdin, O; Schoenfeld, D; Cappetta, K; Atif, M; Smith, R-N; Cosimi, A B; Benichou, G; Kawai, T

    2013-12-01

    Renal allograft tolerance has been achieved in MHC-mismatched primates via nonmyeloablative conditioning beginning 6 days prior to planned kidney and donor bone marrow transplantation (DBMT). To extend the applicability of this approach to deceased donor transplantation, we recently developed a novel-conditioning regimen, the "delayed protocol" in which donor bone marrow (DBM) is transplanted several months after kidney transplantation. However, activation/expansion of donor-reactive CD8(+) memory T cells (TMEM) occurring during the interval between kidney and DBM transplantation impaired tolerance induction using this strategy. In the current study, we tested whether, Alefacept, a fusion protein which targets LFA-3/CD2 interactions and selectively depletes CD2(high) CD8(+) effector memory T cells (TEM) could similarly induce long-term immunosuppression-free renal allograft survival but avoid the deleterious effects of anti-CD8 mAb treatment. We found that Alefacept significantly delayed the expansion of CD2(high) cells including CD8(+) TEM while sparing naïve CD8(+) T and NK cells and achieved mixed chimerism and long-term immunosuppression-free renal allograft survival. In conclusion, elimination of CD2(high) T cells represents a promising approach to prevent electively the expansion/activation of donor-reactive TEM and promotes tolerance induction via the delayed protocol mixed chimerism approach.

  13. Anterior cruciate ligament reconstruction with fresh-frozen patellar tendon allografts: sixty cases with 2 years' minimum follow-up.

    PubMed

    Nín, J R; Leyes, M; Schweitzer, D

    1996-01-01

    A prospective study was performed on 101 patients who underwent an arthroscopic anterior cruciate ligament (ACL) reconstruction with fresh-frozen patellar tendon allograft (bone-patellar tendon-bone). We present the results of the first 60 patients with a minimum follow-up of 2 years. Thirty-four were men and 26 women with a mean age of 23. In 45 patients, a postoperative arthroscopy was performed, and tissue biopsies of the reconstructed ACL were obtained. Patients were evaluated according to the International Knee Documentation Committee evaluation form. After a mean follow-up of 47 months, the overall results were normal or nearly normal in 85%. Under postoperative arthroscopy, the macroscopic appearance of the implant was similar to that of a normal ligament. The ACL allograft was covered with a normal, well-vascularized synovium. There were no cases of infection, disease transmission or tissue rejection. We conclude that the use of fresh-frozen patellar tendon allografts is a good method of ACL reconstruction. PMID:8961227

  14. Histopathological features of bone regeneration in a canine segmental ulnar defect model

    PubMed Central

    2014-01-01

    Background Today, finding an ideal biomaterial to treat the large bone defects, delayed unions and non-unions remains a challenge for orthopaedic surgeions and researchers. Several studies have been carried out on the subject of bone regeneration, each having its own advantages. The present study has been designed in vivo to evaluate the effects of cellular auto-transplantation of tail vertebrae on healing of experimental critical bone defect in a dog model. Methods Six indigenous breeds of dog with 32 ± 3.6 kg average weight from both sexes (5 males and 1 female) received bilateral critical-sized ulnar segmental defects. After determining the health condition, divided to 2 groups: The Group I were kept as control I (n = 1) while in Group II (experimental group; n = 5) bioactive bone implants were inserted. The defects were implanted with either autogeneic coccygeal bone grafts in dogs with 3-4 cm diaphyseal defects in the ulna. Defects were stabilized with internal plate fixation, and the control defects were not stabilized. Animals were euthanized at 16 weeks and analyzed by histopathology. Results Histological evaluation of this new bone at sixteen weeks postoperatively revealed primarily lamellar bone, with the formation of new cortices and normal-appearing marrow elements. And also reformation cortical compartment and reconstitution of marrow space were observed at the graft-host interface together with graft resorption and necrosis responses. Finally, our data were consistent with the osteoconducting function of the tail autograft. Conclusions Our results suggested that the tail vertebrae autograft seemed to be a new source of autogenous cortical bone in order to supporting segmental long bone defects in dogs. Furthermore, cellular autotransplantation was found to be a successful replacement for the tail vertebrae allograft bone at 3-4 cm segmental defects in the canine mid- ulna. Clinical application using graft expanders or bone

  15. Sterilization of skin allografts by ionizing radiation.

    PubMed

    Bourroul, Selma Cecília; Herson, Marisa Roma; Pino, Eddy; Matho, Monica Beatriz

    2002-11-01

    The skin has a fundamental role in the viability of human body. In the case of extensive wounds, skin allografts provide an alternative to cover temporarily the damaged areas. After donor screening and preservation in glycerol 85%, the skin can be stored in a Skin Bank. Glycerol at this concentration has a bacteriostatic effect after certain time of preservation. On the other hand, skin sterilization by ionizing radiation may reduce the quarentine period for transplantation in patients. The objective of this work was to evaluate allograft sterilization using two sources of ionizing radiation. Through the analysis of stress-strain, it was intended to verify possible effects of the radiation on the structure of preserved grafts. Three groups of skin samples were selected. The first group was maintained in the initial conditions, not irradiated. The second was exposed to cobalt-60, while the third one was irradiated using an Dynamitron Accelerator JOB188 electron beam. The irradiation dose was 25 kGy for both tests. Both irradiation sources, and the Instron Universal Machine used for biomechanical experiments, are installed at the Centro de Tecnologia das Radiações/Instituto de Pesquisas Energéticas e Nucleares (São Paulo, Brazil). According to the preliminary results, biomechanical characteristics of the samples irradiated seem to be maintained with regard to the non irradiated group.

  16. Teriparatide therapy enhances devitalized femoral allograft osseointegration and biomechanics in a murine model.

    PubMed

    Reynolds, David G; Takahata, Masahiko; Lerner, Amy L; O'Keefe, Regis J; Schwarz, Edward M; Awad, Hani A

    2011-03-01

    Despite the remarkable healing potential of long bone fractures, traumatic injuries that result in critical defects require challenging reconstructive limb sparing surgery. While devitalized allografts are the gold standard for these procedures, they are prone to failure due to their limited osseointegration with the host. Thus, the quest for adjuvants to enhance allograft healing remains a priority for this unmet clinical need. To address this, we investigated the effects of daily systemic injections of 40 μg/kg teriparatide (recombinant human parathyroid hormone) on the healing of devitalized allografts used to reconstruct critical femoral defects (4mm) in C57Bl/6 mice. The femurs were evaluated at 4 and 6 weeks using micro CT, histology, and torsion testing. Our findings demonstrated that teriparatide induced prolonged cartilage formation at the graft-host junction at 4 weeks, which led to enhanced trabeculated bone callus formation and remarkable graft-host integration at 6-weeks. Moreover, we observed a significant 2-fold increase in normalized callus volume (1.04 ± 0.3 vs. 0.54 ± 0.14 mm³/mm; p < 0.005), and Union Ratio (0.28 ± 0.07 vs. 0.13 ± 0.09; p < 0.005), compared to saline treated controls at 6-weeks. Teriparatide treatment significantly increased the torsional rigidity (1175 ± 311 versus 585 ± 408 N.mm²) and yield torque (10.5 ± 4.2 versus 6.8 ± 5.5 N.mm) compared to controls. Interestingly, the Union Ratio correlated significantly with the yield torque and torsional rigidity (R²=0.59 and R²=0.77, p < 0.001, respectively). These results illustrate the remarkable potential of teriparatide as an adjuvant therapy for allograft repair in a mouse model of massive femoral defect reconstruction, and warrant further investigation in a larger animal model at longer time intervals to justify future clinical trials for PTH therapy in limb sparing reconstructive procedures.

  17. Autograft versus allograft in anterior cruciate ligament reconstruction

    PubMed Central

    Kan, Shun-Li; Yuan, Zhi-Fang; Ning, Guang-Zhi; Yang, Bo; Li, Hai-Liang; Sun, Jing-Cheng; Feng, Shi-Qing

    2016-01-01

    Abstract Background: Anterior cruciate ligament (ACL) reconstruction is considered as the standard surgical procedure for the treatment of ACL tear. However, there is a crucial controversy in terms of whether to use autograft or allograft in ACL reconstruction. The purpose of this meta-analysis is to compare autograft with allograft for patients undergoing ACL reconstruction. Methods: PubMed, EMBASE, and the Cochrane Library were searched for randomized controlled trials that compared autograft with allograft in ACL reconstruction up to January 31, 2016. The relative risk or mean difference with 95% confidence interval was calculated using either a fixed- or random-effects model. The risk of bias for individual studies according to the Cochrane Handbook. The trial sequential analysis was used to test the robustness of our findings and get more conservative estimates. Results: Thirteen trials were included, involving 1636 participants. The results of this meta-analysis indicated that autograft brought about lower clinical failure, better overall International Knee Documentation Committee (IKDC) level, better pivot-shift test, better Lachman test, greater Tegner score, and better instrumented laxity test (P < 0.05) than allograft. Autograft was not statistically different from allograft in Lysholm score, subjective IKDC score, and Daniel 1-leg hop test (P > 0.05). Subgroup analyses demonstrated that autograft was superior to irradiated allograft for patients undergoing ACL reconstruction in clinical failure, Lysholm score, pivot-shift test, Lachman test, Tegner score, instrumented laxity test, and subjective IKDC score (P < 0.05). Moreover, there were no significant differences between autograft and nonirradiated allograft. Conclusions: Autograft is superior to irradiated allograft for patients undergoing ACL reconstruction concerning knee function and laxity, but there are no significant differences between autograft and nonirradiated allograft. However

  18. Acute and Chronic Allograft Dysfunction in Kidney Transplant Recipients.

    PubMed

    Goldberg, Ryan J; Weng, Francis L; Kandula, Praveen

    2016-05-01

    Allograft dysfunction after a kidney transplant is often clinically asymptomatic and is usually detected as an increase in serum creatinine level with corresponding decrease in glomerular filtration rate. The diagnostic evaluation may include blood tests, urinalysis, transplant ultrasonography, radionuclide imaging, and allograft biopsy. Whether it occurs early or later after transplant, allograft dysfunction requires prompt evaluation to determine its cause and subsequent management. Acute rejection, medication toxicity from calcineurin inhibitors, and BK virus nephropathy can occur early or later. Other later causes include transplant glomerulopathy, recurrent glomerulonephritis, and renal artery stenosis.

  19. Altered Composition of Bone as Triggered by Irradiation Facilitates the Rapid Erosion of the Matrix by Both Cellular and Physicochemical Processes

    PubMed Central

    Green, Danielle E.; Adler, Benjamin J.; Chan, Meilin Ete; Lennon, James J.; Acerbo, Alvin S.; Miller, Lisa M.; Rubin, Clinton T.

    2013-01-01

    Radiation rapidly undermines trabecular architecture, a destructive process which proceeds despite a devastated cell population. In addition to the ‘biologically orchestrated’ resorption of the matrix by osteoclasts, physicochemical processes enabled by a damaged matrix may contribute to the rapid erosion of bone quality. 8w male C57BL/6 mice exposed to 5 Gy of Cs137 γ-irradiation were compared to age-matched control at 2d, 10d, or 8w following exposure. By 10d, irradiation had led to significant loss of trabecular bone volume fraction. Assessed by reflection-based Fourier transform infrared imaging (FTIRI), chemical composition of the irradiated matrix indicated that mineralization had diminished at 2d by −4.3±4.8%, and at 10d by −5.8±3.2%. These data suggest that irradiation facilitates the dissolution of the matrix through a change in the material itself, a conclusion supported by a 13.7±4.5% increase in the elastic modulus as measured by nanoindentation. The decline in viable cells within the marrow of irradiated mice at 2d implies that the immediate collapse of bone quality and inherent increased risk of fracture is not solely a result of an overly-active biologic process, but one fostered by alterations in the material matrix that predisposes the material to erosion. PMID:23741433

  20. [Current treatment situation and progress on bone defect of collapsed tibial plateau fractures].

    PubMed

    Luo, Chang-qi; Fang, Yue; Tu, Chong-qi; Yang, Tian-fu

    2016-02-01

    Characteristics of collapsed tibial plateau fracture determines that the joint surface must remain anatomical reduction,line of force in tibial must exist and internal fixation must be strong. However, while renewing articular surface smoothness, surgeons have a lot of problems in dealing with bone defect under the joint surface. Current materials used for bone defect treatment include three categories: autologous bone, allograft bone and bone substitutes. Some scholars think that autologous bone grafts have a number of drawbacks, such as increasing trauma, prolonged operation time, the limited source, bone area bleeding,continuous pain, local infection and anesthesia,but most scholars believe that the autologous cancellous bone graft is still the golden standard. Allograft bone has the ability of bone conduction, but the existence of immune responses, the possibility of a virus infection, and the limited source of the allograft cannot meet the clinical demands. Likewise, bone substitutes have the problem that osteogenesis does not match with degradation in rates. Clinical doctors can meet the demand of the patient's bone graft according to patient's own situation and economic conditions. PMID:27141793

  1. Dysplasia Epiphysealis Hemimelica Treated with Osteochondral Allograft: A Case Report

    PubMed Central

    Anthony, Chris A.; Wolf, Brian R.

    2015-01-01

    Background Dysplasia epiphysealis hemimelica (DEH), or Trevor's disease, is a developmental disorder of the pediatric skeleton characterized by asymmetric osteochondral overgrowth. Methods We present the case of a five year old boy with a two year history of right knee pain and evidence of DEH on imaging who underwent initial arthroscopic resection of his lesion with subsequent recurrence. The patient then underwent osteochondral allograft revision surgery and was asymptomatic at two year follow-up with a congruent joint surface. Results To our knowledge, this is the first reported case of a DEH lesion treated with osteochondral allograft and also the youngest reported case of osteochondral allograft placement in the literature. Conclusions Osteochondral allograft may be a viable option in DEH and other deformities of the pediatric knee. Level of Evidence Level V PMID:26361443

  2. Polyetheretherketone (PEEK) cage filled with cancellous allograft in anterior cervical discectomy and fusion

    PubMed Central

    Liao, Jen-Chung; Chen, Wen-Jer; Chen, Lih-Huei

    2007-01-01

    From July 2004 to June 2005, 19 patients with 25 discs underwent anterior cervical discectomy and interbody fusion (ACDF) in which polyetheretherketone (PEEK) cages were filled with freeze-dried cancellous allograft bone. This kind of bone graft was made from femoral condyle that was harvested during total knee arthroplasty. Patient age at surgery was 52.9 (28–68) years. All patients were followed up at least 1 year. We measured the height of the disc and segmental sagittal angulation by pre-operative and post-operative radiographs. CT scan of the cervical spine at 1 year was used to evaluate fusion rates. Odom's criteria were used to assess the clinical outcome. All interbody disc spaces achieved successful union at 1-year follow-up. The use of a PEEK cage was found to increase the height of the disc immediately after surgery (5.0 mm pre-operatively, 7.3 mm immediately post-operatively). The final disc height was 6.2 mm, and the collapse of the disc height was 1.1 mm. The segmental lordosis also increased after surgery (2.0° pre-operatively, 6.6° immediately post-operatively), but the mean loss of lordosis correction was 3.3° at final follow-up. Seventy-four percent of patients (14/19) exhibited excellent/good clinical outcomes. Analysis of the results indicated the cancellous allograft bone-filled PEEK cage used in ACDF is a good choice for patients with cervical disc disease, and avoids the complications of harvesting iliac autograft. PMID:17639386

  3. Altering adsorbed proteins or cellular gene expression in bone-metastatic cancer cells affects PTHrP and Gli2 without altering cell growth.

    PubMed

    Page, Jonathan M; Merkel, Alyssa R; Ruppender, Nazanin S; Guo, Ruijing; Dadwal, Ushashi C; Cannonier, Shellese; Basu, Sandip; Guelcher, Scott A; Sterling, Julie A

    2015-09-01

    The contents of this data in brief are related to the article titled "Matrix Rigidity Regulates the Transition of Tumor Cells to a Bone-Destructive Phenotype through Integrin β3 and TGF-β Receptor Type II". In this DIB we will present our supplemental data investigating Integrin expression, attachment of cells to various adhesion molecules, and changes in gene expression in multiple cancer cell lines. Since the interactions of Integrins with adsorbed matrix proteins are thought to affect the ability of cancer cells to interact with their underlying substrates, we examined the expression of Integrin β1, β3, and β5 in response to matrix rigidity. We found that only Iβ3 increased with increasing substrate modulus. While it was shown that fibronectin greatly affects the expression of tumor-produced factors associated with bone destruction (parathyroid hormone-related protein, PTHrP, and Gli2), poly-l-lysine, vitronectin and type I collagen were also analyzed as potential matrix proteins. Each of the proteins was independently adsorbed on both rigid and compliant polyurethane films which were subsequently used to culture cancer cells. Poly-l-lysine, vitronectin and type I collagen all had negligible effects on PTHrP or Gli2 expression, but fibronectin was shown to have a dose dependent effect. Finally, altering the expression of Iβ3 demonstrated that it is required for tumor cells to respond to the rigidity of the matrix, but does not affect other cell growth or viability. Together these data support the data presented in our manuscript to show that the rigidity of bone drives Integrinβ3/TGF-β crosstalk, leading to increased expression of Gli2 and PTHrP.

  4. Compensatory cellular reactions to nonsteroidal anti-inflammatory drugs on osteogenic differentiation in canine bone marrow-derived mesenchymal stem cells.

    PubMed

    Oh, Namgil; Kim, Sangho; Hosoya, Kenji; Okumura, Masahiro

    2014-05-01

    The suppressive effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the bone healing process have remained controversial, since no clinical data have clearly shown the relationship between NSAIDs and bone healing. The aim of this study was to assess the compensatory response of canine bone marrow-derived mesenchymal stem cells (BMSCs) to several classes of NSAIDs, including carprofen, meloxicam, indomethacin and robenacoxib, on osteogenic differentiation. Each of the NSAIDs (10 µM) was administered during 20 days of the osteogenic process with human recombinant IL-1β (1 ng/ml) as an inflammatory stimulator. Gene expression of osteoblast differentiation markers (alkaline phosphatase and osteocalcin), receptors of PGE2 (EP2 and EP4) and enzymes for prostaglandin (PG) E2 synthesis (COX-1, COX-2, cPGES and mPGES-1) was measured by using quantitative reverse transcription-polymerase chain reaction. Protein production levels of alkaline phosphatase, osteocalcin and PGE2 were quantified using an alkaline phosphatase activity assay, osteocalcin immunoassay and PGE2 immunoassay, respectively. Histologic analysis was performed using alkaline phosphatase staining, von Kossa staining and alizarin red staining. Alkaline phosphatase and calcium deposition were suppressed by all NSAIDs. However, osteocalcin production showed no significant suppression by NSAIDs. Gene expression levels of PGE2-related receptors and enzymes were upregulated during continuous treatment with NSAIDs, while certain channels for PGE2 synthesis were utilized differently depending on the kind of NSAIDs. These data suggest that canine BMSCs have a compensatory mechanism to restore PGE2 synthesis, which would be an intrinsic regulator to maintain differentiation of osteoblasts under NSAID treatment. PMID:24419976

  5. Comparison of contamination of femoral heads and pre-processed bone chips during hip revision arthroplasty.

    PubMed

    Mathijssen, N M C; Sturm, P D; Pilot, P; Bloem, R M; Buma, P; Petit, P L; Schreurs, B W

    2013-12-01

    With bone impaction grafting, cancellous bone chips made from allograft femoral heads are impacted in a bone defect, which introduces an additional source of infection. The potential benefit of the use of pre-processed bone chips was investigated by comparing the bacterial contamination of bone chips prepared intraoperatively with the bacterial contamination of pre-processed bone chips at different stages in the surgical procedure. To investigate baseline contamination of the bone grafts, specimens were collected during 88 procedures before actual use or preparation of the bone chips: in 44 procedures intraoperatively prepared chips were used (Group A) and in the other 44 procedures pre-processed bone chips were used (Group B). In 64 of these procedures (32 using locally prepared bone chips and 32 using pre-processed bone chips) specimens were also collected later in the procedure to investigate contamination after use and preparation of the bone chips. In total, 8 procedures had one or more positive specimen(s) (12.5 %). Contamination rates were not significantly different between bone chips prepared at the operating theatre and pre-processed bone chips. In conclusion, there was no difference in bacterial contamination between bone chips prepared from whole femoral heads in the operating room and pre-processed bone chips, and therefore, both types of bone allografts are comparable with respect to risk of infection.

  6. Deceased donor skin allograft banking: Response and utilization

    PubMed Central

    Gore, Madhuri A.; De, Anuradha S.

    2010-01-01

    Background: In the absence of xenograft and biosynthetic skin substitutes, deceased donor skin allografts is a feasible option for saving life of patient with extensive burn injury in our country. Aims: The first deceased donor skin allograft bank in India became functional at Lokmanya Tilak Municipal (LTM) medical college and hospital on 24th April 2000. The response of Indian society to this new concept of skin donation after death and the pattern of utilization of banked allografts from 2000 to 2010 has been presented in this study. Settings and Design: This allograft skin bank was established by the department of surgery. The departments of surgery and microbiology share the responsibility of smooth functioning of the bank. Materials and Methods: The response in terms of number of donations and the profile of donors was analyzed from records. Pattern and outcome of allograft utilization was studied from specially designed forms. Results: During these ten years, 262 deceased donor skin allograft donations were received. The response showed significant improvement after counselling was extended to the community. Majority of the donors were above 70 years of age and procurement was done at home for most. Skin allografts from 249 donors were used for 165 patients in ten years. The outcome was encouraging with seven deaths in 151 recipients with burn injuries. Conclusions: Our experience shows that the Indian society is ready to accept the concept of skin donation after death. Use of skin allografts is life saving for large burns. We need to prepare guidelines for the establishment of more skin banks in the country. PMID:21321645

  7. A Case of Intraparenchymal Pseudoaneurysms in Kidney Allograft.

    PubMed

    Lorentz, Liam Antony; Hlabangana, Linda Tebogo; Davies, Malcom

    2016-01-01

    BACKGROUND Percutaneous needle biopsy is routinely performed for renal allograft management. Vascular complications of the procedure include pseudoaneurysm and arterio-venous fistulae formation. Delayed diagnosis of these complications is due to their mostly asymptomatic and indolent nature. CASE REPORT We present a case of extensive intraparenchymal pseudoaneurysm formation within the inferior pole of the allograft, diagnosed two years following the most recent biopsy procedure. CONCLUSIONS Renal pseudoaneurysms may only be diagnosed years after their formation as they are typically asymptomatic. PMID:27510594

  8. Metaphyseal bone loss in revision knee arthroplasty.

    PubMed

    Ponzio, Danielle Y; Austin, Matthew S

    2015-12-01

    The etiology of bone loss encountered during revision total knee arthroplasty (TKA) is often multifactorial and can include stress shielding, osteolysis, osteonecrosis, infection, mechanical loss due to a grossly loose implant, and iatrogenic loss at the time of implant resection. Selection of the reconstructive technique(s) to manage bone deficiency is determined by the location and magnitude of bone loss, ligament integrity, surgeon experience, and patient factors including the potential for additional revision, functional demand, and comorbidities. Smaller, contained defects are reliably managed with bone graft, cement augmented with screw fixation, or modular augments. Large metaphyseal defects require more extensive reconstruction such as impaction bone grafting with or without mesh augmentation, prosthetic augmentation, use of bulk structural allografts, or use of metaphyseal cones or sleeves. While each technique has advantages and disadvantages, the most optimal method for reconstruction of large metaphyseal bone defects during revision TKA is not clearly established. PMID:26362647

  9. The Spectrum of Renal Allograft Failure

    PubMed Central

    Chand, Sourabh; Atkinson, David; Collins, Clare; Briggs, David; Ball, Simon; Sharif, Adnan; Skordilis, Kassiani; Vydianath, Bindu; Neil, Desley; Borrows, Richard

    2016-01-01

    Background Causes of “true” late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. Methods We evaluated all unselected graft failures from 2008–2014 (n = 171; 0–36 years post-transplantation) by contemporary classification of indication biopsies “proximate” to failure, DSA assessment, clinical and biochemical data. Results The spectrum of graft failure changed markedly depending on the timing of allograft failure. Failures within the first year were most commonly attributed to technical failure, acute rejection (with T-cell mediated rejection [TCMR] dominating antibody-mediated rejection [ABMR]). Failures beyond a year were increasingly dominated by ABMR and ‘interstitial fibrosis with tubular atrophy’ without rejection, infection or recurrent disease (“IFTA”). Cases of IFTA associated with inflammation in non-scarred areas (compared with no inflammation or inflammation solely within scarred regions) were more commonly associated with episodes of prior rejection, late rejection and nonadherence, pointing to an alloimmune aetiology. Nonadherence and late rejection were common in ABMR and TCMR, particularly Acute Active ABMR. Acute Active ABMR and nonadherence were associated with younger age, faster functional decline, and less hyalinosis on biopsy. Chronic and Chronic Active ABMR were more commonly associated with Class II DSA. C1q-binding DSA, detected in 33% of ABMR episodes, were associated with shorter time to graft failure. Most non-biopsied patients were DSA-negative (16/21; 76.1%). Finally, twelve losses to recurrent disease were seen (16%). Conclusion This data from an unselected population identifies IFTA alongside ABMR as a very important cause of true late graft failure, with nonadherence-associated TCMR as a phenomenon in some patients. It highlights clinical and immunological characteristics of ABMR subgroups, and should inform clinical practice and

  10. Maxillary sinus augmentation using recombinant bone morphogenetic protein-2/acellular collagen sponge in combination with a mineralized bone replacement graft: a report of three cases.

    PubMed

    Tarnow, Dennis P; Wallace, Stephen S; Testori, Tiziano; Froum, Stuart J; Motroni, Alessandro; Prasad, Hari S

    2010-04-01

    The objective of the following case reports was to assess whether mineralized bone replacement grafts (eg, xenografts and allografts) could be added to recombinant human bone morphogenetic protein-2/acellular collagen sponge (rhBMP-2/ACS) in an effective manner that would: (1) reduce the graft shrinkage observed when using rhBMP-2/ACS alone, (2) reduce the volume and dose of rhBMP-2 required, and (3) preserve the osteoinductivity that rhBMP-2/ACS has shown when used alone. The primary outcome measures were histomorphometric analysis of vital bone production and analysis of serial computed tomographic scans to determine changes in bone graft density and stability. Over the 6-month course of this investigation, bone graft densities tended to increase (moreso with the xenograft than the allograft). The increased density in allograft cases was likely the result of both compression of the mineralized bone replacement graft and vital bone formation, seen histologically. Loss of volume was greater with the four-sponge dose than the two-sponge dose because of compression and resorption of the sponges. Vital bone formation in the allograft cases ranged from 36% to 53% but, because of the small sample size, it was not possible to determine any significant difference between the 5.6 mL (four-sponge) dose and the 2.8 mL (two-sponge) dose. Histology revealed robust new woven bone formation with only minimal traces of residual allograft, which appeared to have undergone accelerated remodeling or rhBMP-2-mediated resorption. PMID:20228973

  11. Role of anti-vimentin antibodies in allograft rejection.

    PubMed

    Rose, Marlene L

    2013-11-01

    Production of anti-vimentin antibodies (AVA) after solid organ transplantation are common. Although classically thought to be expressed mainly within the cytosol, recent evidence demonstrates that extracellular or cell surface expression of vimentin is not unusual. This review examines the evidence to assess whether AVA contribute to allograft pathology. Clinical studies suggest that AVA are associated with cardiac allograft vasculopathy in heart transplant recipients. Studies in non-human primates confirm that production of AVA after renal and heart transplantation are not inhibited by Cyclosporine. Experimental studies have demonstrated that mice pre-immunised with vimentin undergo accelerated acute rejection and vascular intimal occlusion of cardiac allografts. Adoptive transfer of hyperimmune sera containing AVA into B-cell-knock-out mice caused accelerated rejection of allografted hearts, this is clear evidence that antibodies to vimentin accelerate rejection. AVA act in concert with the alloimmune response and AVA do not damage syngeneic or native heart allografts. Confocal microscopy of allografted organs in vimentin immunised mice shows extensive expression of vimentin on endothelial cells, apoptotic leukocytes and platelet/leukocyte conjugates, co-localising with C4d. One explanation for the ability of AVA to accelerate rejection would be fixation of complement within the graft and subsequent pro-inflammatory effects; there may also be interactions with platelets within the vasculature.

  12. Musculoskeletal allograft risks and recalls in the United States.

    PubMed

    Mroz, Thomas E; Joyce, Michael J; Steinmetz, Michael P; Lieberman, Isador H; Wang, Jeffrey C

    2008-10-01

    There have been several improvements to the US tissue banking industry over the past decade. Tissue banks had limited active government regulation until 1993, at which time the US Food and Drug Administration began regulatory oversight because of reports of disease transmission from allograft tissues. Reports in recent years of disease transmission associated with the use of allografts have further raised concerns about the safety of such implants. A retrospective review of allograft recall data was performed to analyze allograft recall by tissue type, reason, and year during the period from January 1994 to June 30, 2007. During the study period, more than 96.5% of all allograft tissues recalled were musculoskeletal. The reasons underlying recent musculoskeletal tissue recalls include insufficient or improper donor evaluation, contamination, recipient infection, and positive serologic tests. Infectious disease transmission following allograft implantation may occur if potential donors are not adequately evaluated or screened serologically during the prerecovery phase and if the implant is not sterilized before implantation. PMID:18832599

  13. Expression of granzyme A and B proteins by cytotoxic lymphocytes involved in acute renal allograft rejection.

    PubMed

    Kummer, J A; Wever, P C; Kamp, A M; ten Berge, I J; Hack, C E; Weening, J J

    1995-01-01

    Granzymes A and B are serine-proteinases stored in the granules of activated cytotoxic T-lymphocytes and natural killer (NK) cells. Expression of granzymes in tissues can be used as an activation marker for cytotoxic cells. Using mAbs specific for human granzyme A or B in immunohistochemical staining techniques we investigated expression of granzyme A and B by lymphocytes infiltrating acutely rejected renal allografts. Twelve core needle biopsies were taken from ten different patients during an episode of acute rejection. Eleven biopsies contained high numbers of granzyme A and B positive lymphocytes infiltrating tubular epithelium, and vascular and glomerular structures. In one patient infiltrating lymphocytes did not express granzyme A and only low amounts of granzyme B. No correlation was found between the number of granzyme positive cells and the severity of the rejection as classified by conventional histological criteria. In one tissue specimen from a patient with a renal allograft without signs of rejection, the number of granzyme positive cells was much lower compared to that of the transplant group. In spite of the presence of a marked inflammatory infiltrate, no granzyme positive cells were detected in renal biopsies from patients with various inflammatory, not transplant-related, renal diseases. Phenotypic analysis showed that granzymes A and B were expressed by CD56+ NK cells and CD3+ cells, representing cytotoxic T-lymphocytes. Thus, this study demonstrates that granzyme A and B protein-expressing lymphocytes infiltrate the kidney allografts during an acute cellular rejection but not in several other inflammatory renal diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. The Macrophage-depleting Agent Clodronate Promotes Durable Hematopoietic Chimerism and Donor-specific Skin Allograft Tolerance in Mice

    PubMed Central

    Li, Zhanzhuo; Xu, Xin; Feng, Xingmin; Murphy, Philip M.

    2016-01-01

    Hematopoietic chimerism is known to promote donor-specific organ allograft tolerance; however, clinical translation has been impeded by the requirement for toxic immunosuppression and large doses of donor bone marrow (BM) cells. Here, we investigated in mice whether durable chimerism might be enhanced by pre-treatment of the recipient with liposomal clodronate, a macrophage depleting agent, with the goal of vacating BM niches for preferential reoccupation by donor hematopoietic stem cells (HSC). We found that liposomal clodronate pretreatment of C57BL/6 mice permitted establishment of durable hematopoietic chimerism when the mice were given a low dose of donor BM cells and transient immunosuppression. Moreover, clodronate pre-treatment increased durable donor-specific BALB/c skin allograft tolerance. These results provide proof-of-principle that clodronate is effective at sparing the number of donor BM cells required to achieve durable hematopoietic chimerism and donor-specific skin allograft tolerance and justify further development of a tolerance protocol based on this principle. PMID:26917238

  15. Role of donor lymphoid cells in the transfer of allograft tolerance

    SciTech Connect

    Pierce, G.E.; Watts, L.M.

    1985-12-01

    Tolerance to murine skin allografts across a MHC disparity was induced by conditioning primary hosts with sublethal fractionated total-body irradiation (FTBI) and transfusion of allogeneic bone marrow (BM). Tolerance could be adoptively transferred to secondary hosts conditioned by FTBI with infusion of spleen cells from hosts bearing intact skin allografts greater than 60 days. Tolerance could not be transferred by tolerant host spleen (THS) preparations from which cells of the donor genotype had been deleted by cytotoxic alloantisera. Deletion of host genotype cells, however, did not diminish the capability of THS to transfer tolerance. All of the tolerizing activity of THS appeared to reside within cells of the donor genotype. Small numbers of normal donor spleen cells could induce tolerance in FTBI hosts but only at the expense of very high mortality, in contrast to the low mortality observed with tolerizing injections of allogeneic donor cells from THS or injections of normal semiallogeneic F1 hybrid spleen cells. If an active immune response is responsible for tolerance induction/transfer in this model, allogeneic donor lymphoid cells derived from BM, in contrast to donor spleen cells, must be capable of mounting this response without concomitant severe GVHD. In future experiments, cells of donor genotype can be isolated from THS and purified in sufficient numbers to compare their tolerizing efficiency vs. that of normal donor cells, detect possible suppression of normal host cell alloreactivity in vitro and identify the donor cell phenotypes involved.

  16. Resident tissue-specific mesenchymal progenitor cells contribute to fibrogenesis in human lung allografts.

    PubMed

    Walker, Natalie; Badri, Linda; Wettlaufer, Scott; Flint, Andrew; Sajjan, Uma; Krebsbach, Paul H; Keshamouni, Venkateshwar G; Peters-Golden, Marc; Lama, Vibha N

    2011-06-01

    Fibrotic obliteration of the small airways leading to progressive airflow obstruction, termed bronchiolitis obliterans syndrome (BOS), is the major cause of poor outcomes after lung transplantation. We recently demonstrated that a donor-derived population of multipotent mesenchymal stem cells (MSCs) can be isolated from the bronchoalveolar lavage (BAL) fluid of human lung transplant recipients. Herein, we study the organ specificity of these cells and investigate the role of local mesenchymal progenitors in fibrogenesis after lung transplantation. We demonstrate that human lung allograft-derived MSCs uniquely express embryonic lung mesenchyme-associated transcription factors with a 35,000-fold higher expression of forkhead/winged helix transcription factor forkhead box (FOXF1) noted in lung compared with bone marrow MSCs. Fibrotic differentiation of MSCs isolated from normal lung allografts was noted in the presence of profibrotic mediators associated with BOS, including transforming growth factor-β and IL-13. MSCs isolated from patients with BOS demonstrated increased expression of α-SMA and collagen I when compared with non-BOS controls, consistent with a stable in vivo fibrotic phenotype. FOXF1 mRNA expression in the BAL cell pellet correlated with the number of MSCs in the BAL fluid, and myofibroblasts present in the fibrotic lesions expressed FOXF1 by in situ hybridization. These data suggest a key role for local tissue-specific, organ-resident, mesenchymal precursors in the fibrogenic processes in human adult lungs.

  17. Segmental pancreatic allograft survival in baboons treated with combined irradiation and cyclosporine: a preliminary report

    SciTech Connect

    du Toit, D.F.; Heydenrych, J.J.; Smit, B.; Louw, G.; Zuurmond, T.; Laker, L.; Els, D.; Weideman, A.; Wolfe-Coote, S.; van der Merwe, E.A.

    1985-04-01

    The present study was undertaken to evaluate the effectiveness of cyclosporine (CS) alone, total lymphoid irradiation (TLI) alone, and CS in combination with total body irradiation (TBI) in suppressing segmental pancreatic allograft rejection in totally pancreatectomized outbred chacma baboons. The administration of CS 25 mg/kg/day and 50 mg/ kg/day resulted in mean graft survival of 21.5 days and 24.5 days, respectively. CS 85 mg/kg/day resulted in median graft survival of 9 days. There was a wide daily fluctuation of CS serum trough levels exhibited between primates receiving the same oral dose. TBI in excess of 300 rads resulted in irreversible bone marrow suppression. Modest results were achieved in recipients of TBI-76 rads (38 x 2 rads), with median graft survival of 21 days, results not different from recipients treated with CS. TLI recipients of 600 rads (150 x 4 rads) resulted in median pancreatic graft survival of 16 days. TBI together with oral CS administration exhibited no synergistic or additive effect and a single peroperative donor-specific blood transfusion did not enhance pancreatic allograft survival in this model. However, of 10 primates receiving TBI 100 rads (50 x 2 rads) and CS 25 mg/kg/day administered orally indefinitely, four remained normoglycemic for more than 60 days. TBI 100 rads (50 x 2 rads) together with oral and parenteral CS resulted in necrotizing enterocolitis in four of six recipients.

  18. Nonallograft osteoconductive bone graft substitutes.

    PubMed

    Bucholz, Robert W

    2002-02-01

    An estimated 500,000 to 600,000 bone grafting procedures are done annually in the United States. Approximately (1/2) of these surgeries involve spinal arthrodesis whereas 35% to 40% are used for general orthopaedic applications. Synthetic bone graft substitutes currently represent only 10% of the bone graft market, but their share is increasing as experience and confidence in their use are accrued. Despite 15 to 20 years of clinical experience with various synthetic substitutes, there have been few welldesigned, controlled clinical trials of these implants. Synthetic bone graft substitutes consist of hydroxyapatite, tricalcium phosphate, calcium sulfate, or a combination of these minerals. Their fabrication technique, crystallinity, pore dimensions, mechanical properties, and resorption rate vary. All synthetic porous substitutes share numerous advantages over autografts and allografts including their unlimited supply, easy sterilization, and storage. However, the degree to which the substitute provides an osteoconductive structural framework or matrix for new bone ingrowth differs among implants. Disadvantages of ceramic implants include brittle handling properties, variable rates of resorption, poor performance in diaphyseal defects, and potentially adverse effects on normal bone remodeling. These inherent weaknesses have refocused their primary use to bone graft extenders and carriers for pharmaceuticals. The composition, histologic features, indications, and clinical experience of several of the synthetic bone graft substitutes approved for orthopaedic use in the United States are reviewed. PMID:11937865

  19. Synergistic effects of combined immunosuppressive modulation. I. Unresponsiveness to dendritic cell-depleted renal allografts in dogs exposed to total-lymphoid irradiation

    SciTech Connect

    Rapaport, F.T.; Meek, A.; Miura, S.; Hayashi, R.; Arnold, A.N.; Strober, S.

    1988-04-01

    Attenuation of the allogeneic stimulus provided by dendritic cells (DC) was achieved by irradiation of the donors, followed by their reconstitution with bone marrow from the prospective DLA-identical recipient. Following long-term (131-187 days) recovery free of graft-versus-host (GVH) disease, the chimeric kidneys were placed into the corresponding recipients; such allografts were rejected at 55, 55, and 60 days, respectively. Four other recipients were conditioned with 1750-1790 cgy of total lymphoid irradiation (TLI) and were then given a similar chimeric kidney from the corresponding partner. These allografts currently survive for 296, 295, 290, and 252 days, respectively. A third group of four dogs was exposed to TLI prior to transplantation of a normal DLA-identical kidney. These grafts were rejected at 20, 42, 46, and 242 days, respectively. Thirteen DLA-identical renal allografts transplanted into normal dogs survived for 13-38 days (mean survival time = 28.6 days). Depletion of allogeneic DC alone, or TLI alone, produced relative prolongations in allograft survival in canine recipients. Combined use of these two modalities, however, resulted in long-term allogeneic unresponsiveness in the recipients.

  20. Nitration and Inactivation of Manganese Superoxide Dismutase in Chronic Rejection of Human Renal Allografts

    NASA Astrophysics Data System (ADS)

    MacMillan-Crow, L. A.; Crow, John P.; Kerby, Jeffrey D.; Beckman, Joseph S.; Thompson, John A.

    1996-10-01

    Inflammatory processes in chronic rejection remain a serious clinical problem in organ transplantation. Activated cellular infiltrate produces high levels of both superoxide and nitric oxide. These reactive oxygen species interact to form peroxynitrite, a potent oxidant that can modify proteins to form 3-nitrotyrosine. We identified enhanced immunostaining for nitrotyrosine localized to tubular epithelium of chronically rejected human renal allografts. Western blot analysis of rejected tissue demonstrated that tyrosine nitration was restricted to a few specific polypeptides. Immunoprecipitation and amino acid sequencing techniques identified manganese superoxide dismutase, the major antioxidant enzyme in mitochondria, as one of the targets of tyrosine nitration. Total manganese superoxide dismutase protein was increased in rejected kidney, particularly in the tubular epithelium; however, enzymatic activity was significantly decreased. Exposure of recombinant human manganese superoxide dismutase to peroxynitrite resulted in a dose-dependent (IC50 = 10 μ M) decrease in enzymatic activity and concomitant increase in tyrosine nitration. Collectively, these observations suggest a role for peroxynitrite during development and progression of chronic rejection in human renal allografts. In addition, inactivation of manganese superoxide dismutase by peroxynitrite may represent a general mechanism that progressively increases the production of peroxynitrite, leading to irreversible oxidative injury to mitochondria.

  1. Obligatory role for interleukin-13 in obstructive lesion development in airway allografts.

    PubMed

    Lama, Vibha N; Harada, Hiroaki; Badri, Linda N; Flint, Andrew; Hogaboam, Cory M; McKenzie, Andrew; Martinez, Fernando J; Toews, Galen B; Moore, Bethany B; Pinsky, David J

    2006-07-01

    The pathogenesis of bronchiolitis obliterans (BO), a common and devastating obliterative disorder of small airways following lung transplantation, remains poorly understood. Lesions are characterized in their early stages by lymphocyte influx that evolves into dense fibrotic infiltrates. Airway specimens taken from patients with histological BO revealed infiltrating myofibroblasts, which strongly expressed the signaling chain of the high affinity interleukin-13 (IL-13) receptor IL-13Ralpha1. Because IL-13 has proinflammatory and profibrotic actions, a contributory role for IL-13 in BO development was examined using murine models of orthotopic and heterotopic tracheal transplantation. Compared with airway isografts, allografts exhibited a significant increase in relative IL-13 mRNA and protein levels. Allogeneic tracheas transplanted into IL-13-deficient mice were protected from BO in both transplant models. Flow cytometric analysis of orthotopic transplant tissue digests revealed markedly fewer infiltrating mononuclear phagocytes and CD3(+) T lymphocytes in IL-13-deficient recipients. Furthermore, protection from luminal obliteration, collagen deposition, and myofibroblast infiltration was observed in heterotopic airways transplanted into the IL-13(-/-) recipients. Transforming growth factor-beta1 expression was significantly decreased in tracheal allografts into IL-13(-/-) recipients, compared to wild-type counterparts. These human and murine data implicate IL-13 as a critical effector cytokine driving cellular recruitment and subsequent fibrosis in clinical and ex-perimental BO.

  2. Apoptosis and expression of cytotoxic T lymphocyte effector molecules in renal allografts.

    PubMed

    Olive, C; Cheung, C; Falk, M C

    1999-03-01

    Cytotoxic T lymphocyte (CTL) mediated apoptosis is thought to play a major role in the rejection of renal allografts following transplantation, however, the CTL effector mechanism that is primarily responsible for immunological rejection is unknown. The two major effector pathways of CTL killing which lead to apoptosis involve the Fas/Fas ligand (Fas L) lytic pathway, and the perforin/granzyme degranulation pathway. The expression of CTL effector molecules which influence these pathways include Fas, Fas L and TiA-1 (cytotoxic granule protein). This study has investigated apoptosis by in situ terminal deoxytransferase-catalysed DNA nick end labelling (TUNEL), and the expression of CTL effector molecules by immunohistochemistry, in renal allograft biopsies obtained from patients following kidney transplantation. Renal biopsies were classified into three histological groups; acute cellular rejection, chronic rejection, or no rejection. The extent of T-cell infiltration of renal tissues was assessed by immunohistochemical staining with an anti-CD3 monoclonal antibody. Numerous TUNEL positive cells were detected in all transplant biopsies examined; these consisted mainly of renal tubular cells and infiltrating cells, with some TUNEL positive cells also detected in the glomeruli. In the case of normal kidney tissue, renal cells also stained positive for TUNEL but there was no lymphocytic infiltration. There was significantly more T-cell infiltration observed in acute rejection biopsies compared to the no rejection biopsies. In the case of Fas L expression, there was little expression in all three biopsy groups, apart from one case of chronic rejection. Conversely, although there were no significant differences in TiA-1 expression between the three biopsy groups, TiA-1 expression was more prominent in acute rejection biopsies. Furthermore, Fas expression was significantly decreased in acute rejection biopsies when compared to those of chronic and no rejection in which Fas

  3. Apoptotic tubular cell death during acute renal allograft rejection.

    PubMed

    Wever, P C; Aten, J; Rentenaar, R J; Hack, C E; Koopman, G; Weening, J J; ten Berge, I J

    1998-01-01

    Tubular cells are important targets during acute renal allograft rejection and induction of apoptosis might be a mechanism of tubular cell destruction. Susceptibility to induction of apoptosis is regulated by the homologous Bcl-2 and Bax proteins. Expression of Bcl-2 and Bax is regulated by p53, which down-regulates expression of Bcl-2, while simultaneously up-regulating expression of Bax. We studied apoptotic tubular cell death in 10 renal allograft biopsies from transplant recipients with acute rejection by in situ end-labelling and the DNA-binding fluorochrome propidium iodide. Tubular expression of p53, Bcl-2 and Bax was studies by immunohistochemistry. Five renal allograft biopsies from transplant recipients with uncomplicated clinical course and histologically normal renal tissue present in nephrectomy specimens from 4 patients with renal adenocarcinoma served as control specimens. Apoptotic cells and apoptotic bodies were detected in tubular epithelia and tubular lumina in 9 out of 10 acute rejection biopsies. In control renal tissue, apoptotic cells were detected in 1 biopsy only. Compared to control renal tissue, acute renal allograft rejection was, furthermore, associated with a shift in the ratio of Bcl-2 to Bax in favour of Bax in tubular epithelia and increased expression of p53 in tubular nuclei. These observations demonstrate that apoptosis contributes in part to tubular cell destruction during acute renal allograft rejection. In accordance, the shift in the ratio of Bcl-2 to Bax in favour of Bax indicates increased susceptibility of tubular epithelia to induction of apoptosis. The expression of p53 in tubular nuclei during acute renal allograft rejection indicates the presence of damaged DNA, which can be important in initiation of part of the observed apoptosis. These findings elucidate part of the mechanisms controlling apoptotic tubular cell death during acute renal allograft rejection.

  4. Acute Delamination of Commercially Available Decellularized Osteochondral Allograft Plugs: A Report of Two Cases.

    PubMed

    Degen, Ryan M; Tetreault, Danielle; Mahony, Greg T; Williams, Riley J

    2016-10-01

    Articular cartilage injuries, and corresponding surgical procedures, are occurring with increasing frequency as identified by a review of recent surgical trends. Concerns have grown in recent years regarding the longevity of results following microfracture, with a shift toward cartilage restoration procedures in recent years. This case report describes 2 cases of acute failure following the use of commercially available osteochondral allograft plugs used for the treatment of osteochondral defects of the distal femur. In both cases the chondral surface of the plug delaminated from the underlying cancellous bone, resulting in persistent pain and swelling requiring reoperation and removal of the loose fragments. Caution should be employed when considering use of these plugs for the treatment of osteochondral lesions, as similar outcomes have not been noted with other cartilage restoration techniques. PMID:27688840

  5. CD8+IL-17+ T Cells Mediate Neutrophilic Airway Obliteration in T-bet–Deficient Mouse Lung Allograft Recipients

    PubMed Central

    Dodd-o, Jeffrey M.; Coon, Tiffany A.; Miller, Hannah L.; Ganguly, Sudipto; Popescu, Iulia; O'Donnell, Christopher P.; Cardenes, Nayra; Levine, Melanie; Rojas, Mauricio; Weathington, Nathaniel M.; Zhao, Jing; Zhao, Yutong; McDyer, John F.

    2015-01-01

    Acute cellular rejection is a known risk factor for the development of obliterative bronchiolitis, which limits the long-term survival of lung transplant recipients. However, the T cell effector mechanisms in both of these processes remain incompletely understood. Using the mouse orthotopic lung transplant model, we investigated whether C57BL/6 T-bet−/− recipients of major histocompatibility complex (MHC)-mismatched BALB/c lung grafts develop rejection pathology and allospecific cytokine responses that differ from wild-type mice. T-bet−/− recipients demonstrated vigorous allograft rejection at 10 days, characterized by neutrophilic inflammation and predominantly CD8+ T cells producing allospecific IL-17 and/or IFN-γ, in contrast to IFN-γ–dominant responses in WT mice. CD4+ T cells produced IL-17 but not IFN-γ responses in T-bet−/− recipients, in contrast to WT controls. Costimulation blockade using anti-CD154 Ab significantly reduced allospecific CD8+IFN-γ+ responses in both T-bet−/− and WT mice but had no attenuating effect on lung rejection pathology in T-bet−/− recipients or on the development of obliterative airway inflammation that occurred only in T-bet−/− recipients. However, neutralization of IL-17A significantly attenuated costimulation blockade–resistant rejection pathology and airway inflammation in T-bet−/− recipients. In addition, CXCL1 (neutrophil chemokine) was increased in T-bet−/− allografts, and IL-17 induced CXCL1 from mouse lung epithelial cells in vitro. Taken together, our data show that T-bet–deficient recipients of complete MHC-mismatched lung allografts develop costimulation blockade–resistant rejection characterized by neutrophilia and obliterative airway inflammation that is predominantly mediated by CD8+IL-17+ T cells. Our data support T-bet–deficient mouse recipients of lung allografts as a viable animal model to study the immunopathogenesis of small airway injury in lung transplantation

  6. Effects of Lycium barbarum Polysaccharides on Apoptosis, Cellular Adhesion, and Oxidative Damage in Bone Marrow Mononuclear Cells of Mice Exposed to Ionizing Radiation Injury

    PubMed Central

    Zhou, Jing; Pang, Hua; Li, Wenbo; Liu, Qiong; Xu, Lu; Liu, Qian; Liu, Ying

    2016-01-01

    Lycium barbarum has been used for more than 2500 years as a traditional herb and food in China. We investigated the effects of Lycium barbarum polysaccharides (LBP) on apoptosis, oxidative damage, and expression of adhesion molecules in bone marrow mononuclear cells (BMNC) of mice injured by ionizing radiation. Kunming mice were exposed to X-rays; then mice in the LBP groups were continuously injected with various concentrations of LBP intraperitoneally for 14 days. Mice in the control group were continuously injected with normal saline (NS) by the same route for 14 days. A normal group was set up. After 1, 7, and 14 days of treatment, mice were killed and BMNC were extracted. Cell cycle, apoptosis, and the expression of adhesion molecules CD44 and CD49d were detected by flow cytometry. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were identified by colorimetric analyses. LBP significantly decreased the percentage of G0/G1 phase, apoptosis, MDA level, and expression of CD44 and CD49d and distinctly increased the activity of SOD. LBP showed a protective effect on BMNC against ionizing radiation-induced apoptosis and oxidative damage and altered the expression of adhesion molecule. PMID:27314019

  7. p53/p21 Pathway involved in mediating cellular senescence of bone marrow-derived mesenchymal stem cells from systemic lupus erythematosus patients.

    PubMed

    Gu, Zhifeng; Jiang, Jinxia; Tan, Wei; Xia, Yunfei; Cao, Haixia; Meng, Yan; Da, Zhanyun; Liu, Hong; Cheng, Chun

    2013-01-01

    Our and other groups have found that bone marrow-derived mesenchymal stem cells (BM-MSCs) from systemic lupus erythematosus (SLE) patients exhibited senescent behavior and are involved in the pathogenesis of SLE. Numerous studies have shown that activation of the p53/p21 pathway inhibits the proliferation of BM-MSCs. The aim of this study was to determine whether p53/p21 pathway is involved in regulating the aging of BM-MSCs from SLE patients and the underlying mechanisms. We further confirmed that BM-MSCs from SLE patients showed characteristics of senescence. The expressions of p53 and p21 were significantly increased, whereas levels of Cyclin E, cyclin-dependent kinase-2, and phosphorylation of retinoblastoma protein were decreased in the BM-MSCs from SLE patients and knockdown of p21 expression reversed the senescent features of BM-MSCs from SLE patients. Our results demonstrated that p53/p21 pathway played an important role in the senescence process of BM-MSCs from SLE.

  8. Suppression of MicroRNA-203 improves survival of rat bone marrow mesenchymal stem cells through enhancing PI3K-induced cellular activation.

    PubMed

    Liu, Tao; Fu, Nan-Nan; Song, Hong-Li; Wang, Yu-Liang; Wu, Ben-Juan; Shen, Zhong-Yang

    2014-03-23

    As a group of heterogeneous multipotent cells, mesenchymal stem cells (MSCs) have potential in treatment of a variety of clinical diseases. However, the low survival of the transplanted MSCs reduced their therapeutic effects. In this study, we revealed that rno-miR-203 suppressed activity and colony formation and enhanced apoptosis of the rat bone marrow-derived MSCs (BM-MSCs). Using bioinformatics analysis, we found a potential miR-203 binding site within rat phosphatidylinositol 3-kinase (PI3K) 3'UTR, and fluorescent reporter experiments validated the direct and negative regulation of PI3K expression by miR-203 through this site. Ectopic expression of PI3K rescued BM-MSCs from depressed activity induced by miR-203, and suppression of PI3K attenuated the increased BM-MSCs activity by miR-203 inhibitor treatment. Moreover, miR-203 blocking partly protected BM-MSCs from impairment caused by low nutrition. We conclude that inhibition of endogenous miR-203 elevated PI3K expression, which may strengthen PI3K/Akt pathway and promote BM-MSCs activity and survival. © 2014 IUBMB Life, 2014.

  9. Competition between clonal plasma cells and normal cells for potentially overlapping bone marrow niches is associated with a progressively altered cellular distribution in MGUS vs myeloma.

    PubMed

    Paiva, B; Pérez-Andrés, M; Vídriales, M-B; Almeida, J; de las Heras, N; Mateos, M-V; López-Corral, L; Gutiérrez, N C; Blanco, J; Oriol, A; Hernández, M T; de Arriba, F; de Coca, A G; Terol, M-J; de la Rubia, J; González, Y; Martín, A; Sureda, A; Schmidt-Hieber, M; Schmitz, A; Johnsen, H E; Lahuerta, J-J; Bladé, J; San-Miguel, J F; Orfao, A

    2011-04-01

    Disappearance of normal bone marrow (BM) plasma cells (PC) predicts malignant transformation of monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM) into symptomatic multiple myeloma (MM). The homing, behavior and survival of normal PC, but also CD34(+) hematopoietic stem cells (HSC), B-cell precursors, and clonal PC largely depends on their interaction with stromal cell-derived factor-1 (SDF-1) expressing, potentially overlapping BM stromal cell niches. Here, we investigate the distribution, phenotypic characteristics and competitive migration capacity of these cell populations in patients with MGUS, SMM and MM vs healthy adults (HA) aged >60 years. Our results show that BM and peripheral blood (PB) clonal PC progressively increase from MGUS to MM, the latter showing a slightly more immature immunophenotype. Of note, such increased number of clonal PC is associated with progressive depletion of normal PC, B-cell precursors and CD34(+) HSC in the BM, also with a parallel increase in PB. In an ex vivo model, normal PC, B-cell precursors and CD34(+) HSC from MGUS and SMM, but not MM patients, were able to abrogate the migration of clonal PC into serial concentrations of SDF-1. Overall, our results show that progressive competition and replacement of normal BM cells by clonal PC is associated with more advanced disease in patients with MGUS, SMM and MM. PMID:21252988

  10. Cellular compatibility of a gamma-irradiated modified siloxane-poly(lactic acid)-calcium carbonate hybrid membrane for guided bone regeneration.

    PubMed

    Takeuchi, Naoshi; Machigashira, Miho; Yamashita, Daisuke; Shirakata, Yoshinori; Kasuga, Toshihiro; Noguchi, Kazuyuki; Ban, Seiji

    2011-01-01

    A bi-layered silicon-releasable membrane consisting of a siloxane-poly(lactic acid) (PLA)-vaterite hybrid material (Si-PVH) microfiber mesh and a PLA microfiber mesh has been developed by an electrospinning method for guided bone regeneration (GBR) application. The bi-layered membrane was modified to a three-laminar structure by sandwiching an additional PLA microfiber mesh between the Si-PVH and PLA microfiber meshes (Si-PVH/PLA membrane). In this study, the influence of gamma irradiation, used for sterilization, on biological properties of the Si-PVH/PLA membrane was evaluated with osteoblasts and fibroblasts. After gamma irradiation, while the average molecular weight of the Si-PVH/PLA membrane decreased, the Si-PVH/PLA membrane promoted cell proliferation and differentiation (alkaline phosphatase activity and calcification) of osteoblasts, compared with the poly(lactide-co-glycolide) membrane. These results suggest that the gamma-irradiated Si-PVH/PLA membrane is biocompatible with both fibroblasts and osteoblasts, and may have an application for GBR. PMID:21946495

  11. Auto Bone Banking: Innovative Method for Bone Preservation

    PubMed Central

    M, Desai Mohan; R, Biraris Sandeep; M, Wade Roshan

    2014-01-01

    Introduction: Bone grafting is an integral part of orthopaedic surgery; the use of bone graft is increasing consistently in traumatology and also in complex revision surgeries of hip and knee arthroplasties. Considering this fact there is a need for some way to find solution for a bone graft which has more osteoinduction, osteoconduction as well as osteogenecity and also reduced rates of graft rejection and transmission of infections. All these qualities are found in autogenous bone graft. We hereby put forward a innovative method of bone preservation by using patients own femoral head and preserving it in patients own iliac pouch and making it available for future use. Case Report: From 2008 to 2012, total 17 numbers of operated sides were included in this method; patients had femoral neck fracture, osteoarthritis or avascular necrosis of femoral head and who underwent either hemi or total hip arthroplasty. Intraoperatively the resected femoral head was preserved in iliac pouch on ipsilateral side. This integrates with the native bone and additional bone graft would be made available for future use. We did not get opportunity to use the stored auograft. Conclusion: This is very innovative concept for preserving patient’s autogenous femoral head for future use. As conventional allograft relies upon screening procedure for infections, proper storage facilities and are expensive. PMID:27298993

  12. Arthroscopic posterior cruciate ligament reconstruction with allograft versus autograft

    PubMed Central

    Sun, Xiujiang; Zhang, Jianfeng; Qu, Xiaoyi

    2015-01-01

    Introduction The aim of the study was to compare and analyze retrospectively the outcomes of arthroscopic posterior cruciate ligament reconstruction with autograft versus allograft. Material and methods Seventy-one patients who underwent arthroscopic posterior cruciate ligament reconstruction with an autograft or allograft met our inclusion criteria. There were 36 patients in the autograft group and 35 patients in the allograft group. All the patients were evaluated by physical examination and a functional ligament test. Comparative analysis was done in terms of operation time, incision length, fever time, postoperative infection rate, incidence of numbness and dysesthesia around the incision, as well as a routine blood test. Results The average follow-up of the autograft group was 3.2 ±0.2 years and that of the allograft group was 3.3 ±0.6 years; there was no significant difference (p > 0.05). No differences existed in knee range of motion, Lysholm scores, International Knee Documentation Committee standard evaluation form and Tegner activity score at final follow-up (p > 0.05), except that patients in the allograft group had a shorter operation time and incision length and a longer fever time (p < 0.05). We found a difference in posterior drawer test and KT-2000 arthrometer assessment (p < 0.05). The posterior tibia displacement averaged 3.8 ±1.5 mm in the autograft group and 4.8 ±1.7 mm in the allograft group (p < 0.05). The incidence of numbness and dysesthesia around the incision in the autograft group was higher than that in the allograft group (p < 0.05). There was no infection postoperatively. The white blood cells and neutrophils in the allograft group increased more than those in the autograft group postoperatively (p < 0.05). Conclusions Both groups of patients had satisfactory outcomes after the operation. However, in the instrumented posterior laxity test, the autograft gave better results than the allograft. No differences in functional scores

  13. Severe adult burn survivors. What information about skin allografts?

    PubMed Central

    Gaucher, Sonia; Duchange, Nathalie; Jarraya, Mohamed; Magne, Jocelyne; Rochet, Jean-Michel; Stéphanazzi, Jean; Hervé, Christian; Moutel, Grégoire

    2013-01-01

    Background and objective During the acute phase of a severe burn, surgery is an emergency. In this situation, human skin allografts constitute an effective temporary skin substitute. However, information about the use of human tissue can not be given to the patients because most of the allografted patients are unconscious due to their injury. Objective This study explored the restitution of information on skin donation to patients who have been skin allografted and who have survived their injury. Method A qualitative study was conducted due to the limited number of patients in ability to be interviewed according to our medical and psychological criteria. Results and discussion Twelve patients who had been treated between 2002 and 2008 were interviewed. Our results show that 10 of them ignored that they had received skin allografts. One of the two patients who knew that they had received allografts knew that skin had been harvested from deceased donor. All patients expressed that there is no information that should not be delivered. They also expressed their relief to have had the opportunity to discuss their case and at being informed during their interview. Their own experience impacted their view in favor of organ and tissue donation. PMID:23229877

  14. Significant prolongation of segmental pancreatic allograft survival in two species

    SciTech Connect

    Du Toit, D.F.; Heydenrych, J.J.

    1988-06-01

    A study was conducted to assess the suppression of segmental pancreatic allograft rejection by cyclosporine (CSA) alone in baboons and dogs, and subtotal marrow irradiation (TL1) alone and TL 1 in combination with CSA in baboons. Total pancreatectomy in the dog and primate provided a reliable diabetic model, induced an absolute deficiency of insulin and was uniformly lethal if not treated. Continuous administration of CSA in baboons resulted in modest allograft survival. As in baboons, dogs receiving CSA 25 mg/kg/d rendered moderate graft prolongation but a dose of 40 mg/kg/d resulted in significant graft survival (greater than 100 days) in 5 of 8 allograft recipients. Irradiation alone resulted in minimal baboon pancreatic allograft survival of 20 baboons receiving TL1 1,000 rad and CSA, 3 had graft survival greater than of 100 days. Of 15 baboons receiving TL1 800 rad and CSA, 6 had graft survival of greater than 100 days. In conclusion, CSA administration in dogs and TL1 in combination with CSA in baboons resulted in highly significant segmental pancreatic allograft survival.

  15. Oral hydrogen water prevents chronic allograft nephropathy in rats.

    PubMed

    Cardinal, Jon S; Zhan, Jianghua; Wang, Yinna; Sugimoto, Ryujiro; Tsung, Allan; McCurry, Kenneth R; Billiar, Timothy R; Nakao, Atsunori

    2010-01-01

    Reactive oxygen species (ROS) contribute to the development of interstitial fibrosis and tubular atrophy seen in chronic allograft nephropathy (CAN). As molecular hydrogen gas can act as a scavenger of ROS, we tested the effect of treatment with hydrogen water (HW) in a model of kidney transplantation, in which allografts from Lewis rats were orthotopically transplanted into Brown Norway recipients that had undergone bilateral nephrectomy. Molecular hydrogen was dissolved in water and recipients were given HW from day 0 until day 150. Rats that were treated with regular water (RW) gradually developed proteinuria and their creatinine clearance declined, ultimately leading to graft failure secondary to CAN. In contrast, treatment with HW improved allograft function, slowed the progression of CAN, reduced oxidant injury and inflammatory mediator production, and improved overall survival. Inflammatory signaling pathways, such as mitogen-activated protein kinases, were less activated in renal allografts from HW-treated rats as compared with RW-treated rats. Hence, oral HW is an effective antioxidant and antiinflammatory agent that prevented CAN, improved survival of rat renal allografts, and may be of therapeutic value in the setting of transplantation. PMID:19907413

  16. Predicting the development of cardiac allograft vasculopathy.

    PubMed

    Seki, Atsuko; Fishbein, Michael C

    2014-01-01

    Cardiac transplantation is a lifesaving therapy for patients with end-stage cardiovascular disease. There has been remarkable progress in controlling acute rejection, and the early survival rate after the heart transplantation has significantly improved. Cardiac allograft vasculopathy (CAV) is one of the common causes of death and a major limiting factor for long-term graft survival years after heart transplantation. CAV is a progressive occlusion of arteries and veins of the transplanted heart. CAV is often clinically silent because of the denervation of the transplanted heart. CAV tends to be found at an advanced stage of disease, including myocardial infarction (MI), congestive heart failure, arrhythmia, and/or sudden cardiac death. Because of the serious sequelae of CAV, risk factors, prevention, and prediction of CAV have been investigated. Despite the effort by many researchers, the pathogenesis is not yet completely understood. There are a number of both immune and nonimmune factors in the donor and recipient that are related to the development of CAV. In addition, several biomarkers in blood and tissue are found to correlate with the presence of CAV, and that may be able to predict CAV. Here, we review the pathology, pathogenesis, risk factors, diagnosis, and the potential for prediction of CAV. PMID:24972526

  17. Bone Marrow–Derived Stromal Cell Therapy in Cirrhosis: Clinical Evidence, Cellular Mechanisms, and Implications for the Treatment of Hepatocellular Carcinoma

    SciTech Connect

    Vainshtein, Jeffrey M.; Kabarriti, Rafi; Mehta, Keyur J.; Roy-Chowdhury, Jayanta; Guha, Chandan

    2014-07-15

    Current treatment options for hepatocellular carcinoma (HCC) are often limited by the presence of underlying liver disease. In patients with liver cirrhosis, surgery, chemotherapy, and radiation therapy all carry a high risk of hepatic complications, ranging from ascites to fulminant liver failure. For patients receiving radiation therapy, cirrhosis dramatically reduces the already limited radiation tolerance of the liver and represents the most important clinical risk factor for the development of radiation-induced liver disease. Although improvements in conformal radiation delivery techniques have improved our ability to safely irradiate confined areas of the liver to increasingly higher doses with excellent local disease control, patients with moderate-to-severe liver cirrhosis continue to face a shortage of treatment options for HCC. In recent years, evidence has emerged supporting the use of bone marrow–derived stromal cells (BMSCs) as a promising treatment for liver cirrhosis, with several clinical studies demonstrating sustained improvement in clinical parameters of liver function after autologous BMSC infusion. Three predominant populations of BMSCs, namely hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells, seem to have therapeutic potential in liver injury and cirrhosis. Preclinical studies of BMSC transplantation have identified a range of mechanisms through which these cells mediate their therapeutic effects, including hepatocyte transdifferentiation and fusion, paracrine stimulation of hepatocyte proliferation, inhibition of activated hepatic stellate cells, enhancement of fibrolytic matrix metalloproteinase activity, and neovascularization of regenerating liver. By bolstering liver function in patients with underlying Child's B or C cirrhosis, autologous BMSC infusion holds great promise as a therapy to improve the safety, efficacy, and utility of surgery, chemotherapy, and hepatic radiation therapy in the treatment

  18. Differential gene expression pattern in biopsies with renal allograft pyelonephritis and allograft rejection.

    PubMed

    Oghumu, Steve; Nori, Uday; Bracewell, Anna; Zhang, Jianying; Bott, Cherri; Nadasdy, Gyongyi M; Brodsky, Sergey V; Pelletier, Ronald; Satoskar, Abhay R; Nadasdy, Tibor; Satoskar, Anjali A

    2016-09-01

    Differentiating acute pyelonephritis (APN) from acute rejection (AR) in renal allograft biopsies can sometimes be difficult because of overlapping clinical and histologic features, lack of positive urine cultures,and variable response to antibiotics. We wanted to study differential gene expression between AR and APN using biopsy tissue. Thirty-three biopsies were analyzed using NanoString multiplex platform and PCR (6 transplant baseline biopsies, 8 AR, 15 APN [8 culture positive, 7 culture negative], and 4 native pyelonephritis [NP]). Additional 22 biopsies were tested by PCR to validate the results. CXCL9, CXCL10, CXCL11, and IDO1 were the top differentially expressed genes, upregulated in AR. Lactoferrin (LTF) and CXCL1 were higher in APN and NP. No statistically significant difference in transcript levels was seen between culture-positive and culture-negative APN biopsies. Comparing the overall mRNA signature using Ingenuity pathway analysis, interferon-gamma emerged as the dominant upstream regulator in AR and allograft APN, but not in NP (which clustered separately). Our study suggests that chemokine pathways in graft APN may differ from NP and in fact resemble AR, due to a component of alloreactivity, resulting in variable response to antibiotic treatment. Therefore, cautious addition of steroids might help in resistant cases of graft APN.

  19. Postextraction ridge preservation and augmentation with mineralized allograft with or without recombinant human platelet-derived growth factor BB (rhPDGF-BB): a consecutive case series.

    PubMed

    Wallace, Stephen C; Snyder, Mark B; Prasad, Hari

    2013-01-01

    In an attempt to reduce postextraction alveolar bone resorption, ridge preservation and augmentation procedures have become standard-of-care treatment following tooth removal. This consecutive case series compares histologic and histomorphometric bone regenerative findings at 4 months following grafting for ridge preservation and augmentation in intact sockets and sockets with buccal wall defects. Sites were treated with mineralized allograft alone (control) or in combination with 0.3 mg/mL recombinant human platelet-derived growth factor BB (rhPDGF-BB) (test). Sites were allowed to heal for 4 months and then re-entered for trephine core biopsy and implant placement. At the end of 4 months, the mean percent remaining mineralized allograft was statistically significantly less in the test group than in the control group. The difference in mean percent vital bone between the groups showed a strong trend toward greater bone formation for the test group (41.8%) compared to the control group (32.5%) at the end of 4 months. Addition of growth factor signaling molecules to current grafting procedures may lead to accelerated bone regeneration, making it possible to successfully place implants at earlier time points. PMID:23998156

  20. Septic arthritis with Staphylococcus lugdunensis following arthroscopic ACL revision with BPTB allograft.

    PubMed

    Mei-Dan, Omer; Mann, Gideon; Steinbacher, Gilbert; Ballester, Soleda J; Cugat, Ramon Bertomeu; Alvarez, Pedro Diaz

    2008-01-01

    Septic arthritis following anterior cruciate ligament reconstruction is an uncommon but a serious complication resulting in six times greater hospital costs than that of uncomplicated ACL surgery and an inferior postoperative activity level. Promptly initiating a specific antibiotic therapy is the most critical treatment, followed by open or arthroscopic joint decompression, debridement and lavage. Staphylococcus lugdunensis is a coagulase-negative staphylococcus predominantly infecting the skin and soft tissue. The few reported cases of bone and joint infections by S. lugdunensis indicate that the clinical manifestations were severe, the diagnosis elusive, and the treatment difficult. If the microbiology laboratory does not use the tube coagulase (long) test to confirm the slide coagulase test result, the organism might be misidentified as Staphylococcus aureus. S. lugdunensis is more virulent than other coagulase-negative staphylococcus; in many clinical situations it behaves like S. aureus, further increasing the confusion and worsening the expected outcome. S. lugdunensis is known to cause infective endocarditis with a worse outcome, septicemia, deep tissue infection, vascular and joint prosthesis infection, osteomyelitis, discitis, breast abscess, urine tract infections, toxic shock and osteitis pubis. We present the first case report in the literature of septic arthritis with S. lugdunensis following arthroscopic ACL revision with bone-patellar-tendon-bone allograft.

  1. Septic arthritis with Staphylococcus lugdunensis following arthroscopic ACL revision with BPTB allograft.

    PubMed

    Mei-Dan, Omer; Mann, Gideon; Steinbacher, Gilbert; Ballester, Soleda J; Cugat, Ramon Bertomeu; Alvarez, Pedro Diaz

    2008-01-01

    Septic arthritis following anterior cruciate ligament reconstruction is an uncommon but a serious complication resulting in six times greater hospital costs than that of uncomplicated ACL surgery and an inferior postoperative activity level. Promptly initiating a specific antibiotic therapy is the most critical treatment, followed by open or arthroscopic joint decompression, debridement and lavage. Staphylococcus lugdunensis is a coagulase-negative staphylococcus predominantly infecting the skin and soft tissue. The few reported cases of bone and joint infections by S. lugdunensis indicate that the clinical manifestations were severe, the diagnosis elusive, and the treatment difficult. If the microbiology laboratory does not use the tube coagulase (long) test to confirm the slide coagulase test result, the organism might be misidentified as Staphylococcus aureus. S. lugdunensis is more virulent than other coagulase-negative staphylococcus; in many clinical situations it behaves like S. aureus, further increasing the confusion and worsening the expected outcome. S. lugdunensis is known to cause infective endocarditis with a worse outcome, septicemia, deep tissue infection, vascular and joint prosthesis infection, osteomyelitis, discitis, breast abscess, urine tract infections, toxic shock and osteitis pubis. We present the first case report in the literature of septic arthritis with S. lugdunensis following arthroscopic ACL revision with bone-patellar-tendon-bone allograft. PMID:17684731

  2. Biomaterial scaffolds for treating osteoporotic bone

    PubMed Central

    Sterling, Julie A.

    2014-01-01

    Healing fractures resulting from osteoporosis or cancer remains a significant clinical challenge. In these populations, healing is often impaired not only due to age and disease, but also by other therapeutic interventions such as radiation, steroids, and chemotherapy. Despite substantial improvements in the treatment of osteoporosis over the few decades, osteoporotic fractures are still a major clinical challenge in the elderly population due to impaired healing. Similar fractures with impaired healing are also prevalent in cancer patients, especially those with tumor growing in bone. Treatment options for cancer patients are further complicated by the fact that bone anabolic therapies are contraindicated in patients with tumors. Therefore, many patients undergo surgery to repair the fracture, and bone grafts are often used to stabilize orthopaedic implants and provide a scaffold for ingrowth of new bone. Both synthetic and naturally occurring biomaterials have been investigated as bone grafts for repair of osteoporotic fractures, including calcium phosphate bone cements, resorbable polymers, and allograft or autograft bone. In order to re-establish normal bone repair, bone grafts have been augmented with anabolic agents, such as mesenchymal stem cells (MSC) or recombinant human bone morphogenetic protein-2 (rhBMP2). These developing approaches to bone grafting are anticipated to improve the clinical management of osteoporotic and cancer-induced fractures. PMID:24458428

  3. Bone Grafts

    MedlinePlus

    A bone graft transplants bone tissue. Surgeons use bone grafts to repair and rebuild diseased bones in your hips, knees, ... fractures or cancers. Once your body accepts the bone graft, it provides a framework for growth of new, ...

  4. Bone Diseases

    MedlinePlus

    ... avoid smoking and drinking too much alcohol. Bone diseases can make bones easy to break. Different kinds ... break Osteogenesis imperfecta makes your bones brittle Paget's disease of bone makes them weak Bones can also ...

  5. Technique of Open Reduction and Internal Fixation of Comminuted Proximal Humerus Fractures With Allograft Femoral Head Metaphyseal Reconstruction.

    PubMed

    Parada, Stephen A; Makani, Amun; Stadecker, Monica J; Warner, Jon J P

    2015-10-01

    Proximal humerus fractures are common injuries that can require operative treatment. Different operative techniques are available, but the hallmark of fixation for 3- and 4-part fractures is a locking-plate-and-screw construct. Despite advances in this technology, obtaining anatomical reduction and fracture union can be difficult, and complications (eg, need for revision) are not uncommon. These issues can be addressed by augmenting the fixation with an endosteally placed fibular allograft. Although biomechanical and clinical results have been good, the technique can lead to difficulties in future revision to arthroplasty, a common consequence of failed open reduction and internal fixation. The technique described, an alternative to placing a long endosteal bone graft, uses a trapezoidal, individually sized pedestal of allograft femoral head to facilitate the reduction and healing of the humeral head and tuberosity fragments in a displaced 3- or 4-part fracture of the proximal humerus. It can be easily incorporated with any plate-and-screw construct and does not necessitate placing more than 1 cm of bone into the humeral intramedullary canal, limiting the negative effects on any future revision to arthroplasty.

  6. BATF inhibition prevent acute allograft rejection after cardiac transplantation

    PubMed Central

    Yang, Bo; He, Fan; Dai, Chen; Tan, Rumeng; Ma, Dongxia; Wang, Zhimin; Zhang, Bo; Feng, Jincheng; Wei, Lai; Zhu, Hua; Chen, Zhishui

    2016-01-01

    Acute allograft rejection is a serious and life-threatening complication of organ transplantation. Th17 cells induced inflammation has been described to play an important role in allograft rejection. Since there is a plenty of evidence indicating that transcriptional factor BATF regulates the differentiation of Th17 and follicular T helper cells both in vitro and in vivo, we investigated whether is BATF involved in acute rejection and allograft survival by injecting lentivirus containing BATF shRNA through tail vein before the cardiac transplantation operation. We found that the allograft survival time of the mice treated with BATF shRNA was significantly prolonged compared with that of negative shRNA treated group and the control group. Further pathological analysis revealed that the BATF shRNA treatment group had significantly lower rejection degree than the negative shRNA group, while there was no significant difference between the negative shRNA group and the control group. Furthermore, flow cytometry analysis and quantitative polymerase chain reaction and enzyme-linked immuno sorbent assay were used to determine the proportion of T helper cells, the expression of specific transcription factor and the inflammatory cytokines respectively. Data showed that BATF regulated Th17 and Treg responses during allograft rejection. And BATF inhibition led to reduction of the expression level of Rorγ-t and enhancement of the Foxp-3. In addition, cytokines IL-17A and IL-4 were found decreased. This may indicate BATF as a novel therapy target for treatment of acute allograft rejection. PMID:27648151

  7. BATF inhibition prevent acute allograft rejection after cardiac transplantation.

    PubMed

    Yang, Bo; He, Fan; Dai, Chen; Tan, Rumeng; Ma, Dongxia; Wang, Zhimin; Zhang, Bo; Feng, Jincheng; Wei, Lai; Zhu, Hua; Chen, Zhishui

    2016-01-01

    Acute allograft rejection is a serious and life-threatening complication of organ transplantation. Th17 cells induced inflammation has been described to play an important role in allograft rejection. Since there is a plenty of evidence indicating that transcriptional factor BATF regulates the differentiation of Th17 and follicular T helper cells both in vitro and in vivo, we investigated whether is BATF involved in acute rejection and allograft survival by injecting lentivirus containing BATF shRNA through tail vein before the cardiac transplantation operation. We found that the allograft survival time of the mice treated with BATF shRNA was significantly prolonged compared with that of negative shRNA treated group and the control group. Further pathological analysis revealed that the BATF shRNA treatment group had significantly lower rejection degree than the negative shRNA group, while there was no significant difference between the negative shRNA group and the control group. Furthermore, flow cytometry analysis and quantitative polymerase chain reaction and enzyme-linked immuno sorbent assay were used to determine the proportion of T helper cells, the expression of specific transcription factor and the inflammatory cytokines respectively. Data showed that BATF regulated Th17 and Treg responses during allograft rejection. And BATF inhibition led to reduction of the expression level of Rorγ-t and enhancement of the Foxp-3. In addition, cytokines IL-17A and IL-4 were found decreased. This may indicate BATF as a novel therapy target for treatment of acute allograft rejection. PMID:27648151

  8. BATF inhibition prevent acute allograft rejection after cardiac transplantation

    PubMed Central

    Yang, Bo; He, Fan; Dai, Chen; Tan, Rumeng; Ma, Dongxia; Wang, Zhimin; Zhang, Bo; Feng, Jincheng; Wei, Lai; Zhu, Hua; Chen, Zhishui

    2016-01-01

    Acute allograft rejection is a serious and life-threatening complication of organ transplantation. Th17 cells induced inflammation has been described to play an important role in allograft rejection. Since there is a plenty of evidence indicating that transcriptional factor BATF regulates the differentiation of Th17 and follicular T helper cells both in vitro and in vivo, we investigated whether is BATF involved in acute rejection and allograft survival by injecting lentivirus containing BATF shRNA through tail vein before the cardiac transplantation operation. We found that the allograft survival time of the mice treated with BATF shRNA was significantly prolonged compared with that of negative shRNA treated group and the control group. Further pathological analysis revealed that the BATF shRNA treatment group had significantly lower rejection degree than the negative shRNA group, while there was no significant difference between the negative shRNA group and the control group. Furthermore, flow cytometry analysis and quantitative polymerase chain reaction and enzyme-linked immuno sorbent assay were used to determine the proportion of T helper cells, the expression of specific transcription factor and the inflammatory cytokines respectively. Data showed that BATF regulated Th17 and Treg responses during allograft rejection. And BATF inhibition led to reduction of the expression level of Rorγ-t and enhancement of the Foxp-3. In addition, cytokines IL-17A and IL-4 were found decreased. This may indicate BATF as a novel therapy target for treatment of acute allograft rejection.

  9. A Case of Intraparenchymal Pseudoaneurysms in Kidney Allograft

    PubMed Central

    Lorentz, Liam Antony; Hlabangana, Linda Tebogo; Davies, Malcolm

    2016-01-01

    Patient: Male, 31 Final Diagnosis: Intraparenchymal pseudo-aneurysms in kidney transplant Symptoms: Asymptomatic Medication: — Clinical Procedure: Percutaneous renal biopsy Specialty: Transplantology Objective: Diagnostic/therapeutic accidents Background: Percutaneous needle biopsy is routinely performed for renal allograft management. Vascular complications of the procedure include pseudoaneurysm and arterio-venous fistulae formation. Delayed diagnosis of these complications is due to their mostly asymptomatic and indolent nature. Case Report: We present a case of extensive intraparenchymal pseudoaneurysm formation within the inferior pole of the allograft, diagnosed two years following the most recent biopsy procedure. Conclusions: Renal pseudoaneurysms may only be diagnosed years after their formation as they are typically asymptomatic. PMID:27510594

  10. Rare presentations of cytomegalovirus infection in renal allograft recipients.

    PubMed

    Ardalan, Mohammadreza

    2012-01-01

    Cytomegalovirus is the most common viral infection after kidney transplantation. Clinical presentations of cytomegalovirus infection range from asymptomatic infection to organ-specific involvement. Most symptomatic infections manifest as fever and cytopenia. The gastrointestinal tract is the most common site of tissue-invasive infection, often presenting as diarrhea or gastrointestinal bleeding. Gastrointestinal obstruction, perforation, thrombosis of large gastrointestinal veins, splenic artery thrombosis, and pancreatitis are rare gastrointestinal presentations of cytomegalovirus infection. Renal-allograft ureteral stricture and skin involvement are other rare presentations of cytomegalovirus infection. hemophagocytic syndrome, thrombotic microangiopathy, adrenal insufficiency, and renal allograft artery stenosis are other rare symptoms of cytomegalovirus infection.

  11. Improved osteoconduction of cortical bone grafts by biodegradable foam coating.

    PubMed

    Lewandrowski, K U; Bondre, S P; Gresser, J D; Wise, D L; Tomford, W W; Trantolo, D J

    1999-01-01

    Alteration of the geometrical surface configuration of cortical bone allografts may improve incorporation into host bone. A porous biodegradable coating that would maintain immediate structural recovery and subsequently allow normal graft healing and remodeling by promoting bony ingrowth could provide an osteoconductive surface scaffold. We investigated the feasibility of augmenting cortical bone grafts with osteoconductive biodegradable polymeric scaffold coatings. Three types of bone grafts were prepared: Type I--cortical bone without coating (control), Type II--cortical bone coated with PLGA-foam, Type III--cortical bone coated with PPF-foam. The grafts were implanted into the rat tibial metaphysis (16 animals for each type of bone graft). Post-operatively the animals were sacrificed at 2 weeks and 4 weeks (8 animals for each type of bone graft at each time point). Histologic and histomorphometric analysis of grafts showed that the amount of new bone forming around the foam-coated grafts was significantly higher than in the control group (uncoated; p < 0.02). Although both foam formulations were initially equally osteoconductive, PLGA-based foam coatings appeared to have degraded at two weeks postoperatively, whereas PPF-based foam coatings were still present at 4 weeks postoperatively. While significant resorption was present in control allografts with little accompanying reactive new bone formation, PLGA-coated bone grafts showed evidence of bone resorption and subsequent bony ingrowth earlier than those coated with PPF-based foams suggesting that PPF-coated cortical bone grafts were longer protected against host reactions resulting in bone resorption.

  12. Coverage of gingival recession defects using acellular dermal matrix allograft with or without beta-tricalcium phosphate.

    PubMed

    Okubo, Nobuki; Fujita, Takahisa; Ishii, Yoshihito; Ota, Mikio; Shibukawa, Yoshihiro; Yamada, Satoru

    2013-01-01

    The aim of this study was to investigate the effect of beta-tricalcium phosphate (β-TCP) particles in combination with acellular dermal matrix (ADM) allograft in gingival recession. Experimental gingival recession defects were created in beagle dogs and randomly assigned to one of the following groups: ADM, ADM + β-TCP, or coronally positioned flap (CPF; control). Tissues were histologically examined at 4, 8, or 16 weeks following treatment. A greater thickness of gingiva was observed at the sites treated in both the ADM + β-TCP and ADM groups than in the CPF group. The ADM + β-TCP group showed a statistically significant increase in both new bone and cementum formations compared to the ADM group. The results suggest that the combination of β-TCP and ADM is more effective in promoting new bone and cementum formations than ADM graft alone. PMID:21862508

  13. Simultaneous Osteoperiosteal Autologous Iliac Crest Graft and Lateral Meniscus Allograft Transplantation for Osteochondral Lesion with Bony Defect and Lateral Discoid Meniscus Tear.

    PubMed

    Lee, Dhong Won; Kim, Jin Goo; Ha, Jeong Ku; Kim, Woo Jong

    2016-06-01

    The optimal treatment for combined osteochondritis dissecans (OCD) with considerable bony defect of the lateral femoral condyle (LFC) and torn discoid lateral meniscus is unclear. We present a case of a 15-year-old female who was a gymnast and had a large OCD lesion in the LFC combined with deficiency of the lateral meniscus. The patient underwent the "one-step" technique of osteoperiosteal autologous iliac crest graft and lateral meniscus allograft transplantation after a failure of meniscectomy with repair at another hospital. Twenty-four months postoperatively, clinical results were significantly improved. Follow-up imaging tests and second-look arthroscopy showed well incorporated structured bone graft and fibrous cartilage regeneration as well as stabilized lateral meniscus allograft. She could return to her sport without any pain or swelling. This "one-step" surgical technique is worth considering as a joint salvage procedure for massive OCD lesions with torn discoid lateral meniscus. PMID:27274475

  14. Simultaneous Osteoperiosteal Autologous Iliac Crest Graft and Lateral Meniscus Allograft Transplantation for Osteochondral Lesion with Bony Defect and Lateral Discoid Meniscus Tear.

    PubMed

    Lee, Dhong Won; Kim, Jin Goo; Ha, Jeong Ku; Kim, Woo Jong

    2016-06-01

    The optimal treatment for combined osteochondritis dissecans (OCD) with considerable bony defect of the lateral femoral condyle (LFC) and torn discoid lateral meniscus is unclear. We present a case of a 15-year-old female who was a gymnast and had a large OCD lesion in the LFC combined with deficiency of the lateral meniscus. The patient underwent the "one-step" technique of osteoperiosteal autologous iliac crest graft and lateral meniscus allograft transplantation after a failure of meniscectomy with repair at another hospital. Twenty-four months postoperatively, clinical results were significantly improved. Follow-up imaging tests and second-look arthroscopy showed well incorporated structured bone graft and fibrous cartilage regeneration as well as stabilized lateral meniscus allograft. She could return to her sport without any pain or swelling. This "one-step" surgical technique is worth considering as a joint salvage procedure for massive OCD lesions with torn discoid lateral meniscus.

  15. Simultaneous Osteoperiosteal Autologous Iliac Crest Graft and Lateral Meniscus Allograft Transplantation for Osteochondral Lesion with Bony Defect and Lateral Discoid Meniscus Tear

    PubMed Central

    Lee, Dhong Won; Ha, Jeong Ku; Kim, Woo Jong

    2016-01-01

    The optimal treatment for combined osteochondritis dissecans (OCD) with considerable bony defect of the lateral femoral condyle (LFC) and torn discoid lateral meniscus is unclear. We present a case of a 15-year-old female who was a gymnast and had a large OCD lesion in the LFC combined with deficiency of the lateral meniscus. The patient underwent the "one-step" technique of osteoperiosteal autologous iliac crest graft and lateral meniscus allograft transplantation after a failure of meniscectomy with repair at another hospital. Twenty-four months postoperatively, clinical results were significantly improved. Follow-up imaging tests and second-look arthroscopy showed well incorporated structured bone graft and fibrous cartilage regeneration as well as stabilized lateral meniscus allograft. She could return to her sport without any pain or swelling. This "one-step" surgical technique is worth considering as a joint salvage procedure for massive OCD lesions with torn discoid lateral meniscus. PMID:27274475

  16. In vitro cartilage tissue engineering using cancellous bone matrix gelatin as a biodegradable scaffold.

    PubMed

    Yang, Bo; Yin, Zhanhai; Cao, Junling; Shi, Zhongli; Zhang, Zengtie; Song, Hongxing; Liu, Fuqiang; Caterson, Bruce

    2010-08-01

    In this study, we constructed tissue-engineered cartilage using allogeneic cancellous bone matrix gelatin (BMG) as a scaffold. Allogeneic BMG was prepared by sequential defatting, demineralization and denaturation. Isolated rabbit chondrocytes were seeded onto allogeneic cancellous BMG, and cell-BMG constructs were harvested after 1, 3 and 6 weeks for evaluation by hematoxylin and eosin staining for overall morphology, toluidine blue for extracellular matrix (ECM) proteoglycans, immunohistochemical staining for collagen type II and a transmission electron microscope for examining cellular microstructure on BMG. The prepared BMG was highly porous with mechanical strength adjustable by duration of demineralization and was easily trimmed for tissue repair. Cancellous BMG showed favorable porosity for cell habitation and metabolism material exchange with larger pore sizes (100-500 microm) than in cortical BMG (5-15 microm), allowing cell penetration. Cancellous BMG also showed good biocompatibility, which supported chondrocyte proliferation and sustained their differentiated phenotype in culture for up to 6 weeks. Rich and evenly distributed cartilage ECM proteoglycans and collagen type II were observed around chondrocytes on the surface and inside the pores throughout the cancellous BMG. Considering the large supply of banked bone allografts and relatively convenient preparation, our study suggests that allogeneic cancellous BMG is a promising scaffold for cartilage tissue engineering.

  17. Biomaterials and bone mechanotransduction

    NASA Technical Reports Server (NTRS)

    Sikavitsas, V. I.; Temenoff, J. S.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    2001-01-01

    Bone is an extremely complex tissue that provides many essential functions in the body. Bone tissue engineering holds great promise in providing strategies that will result in complete regeneration of bone and restoration of its function. Currently, such strategies include the transplantation of highly porous scaffolds seeded with cells. Prior to transplantation the seeded cells are cultured in vitro in order for the cells to proliferate, differentiate and generate extracellular matrix. Factors that can affect cellular function include the cell-biomaterial interaction, as well as the biochemical and the mechanical environment. To optimize culture conditions, good understanding of these parameters is necessary. The new developments in bone biology, bone cell mechanotransduction, and cell-surface interactions are reviewed here to demonstrate that bone mechanotransduction is strongly influenced by the biomaterial properties.

  18. Multi-variety bone bank in China.

    PubMed

    Li, Dan; Bi, Long; Meng, Guo-Lin; Liu, Min; Jin, Jing; Liu, Yin; Wang, Zhen; Liu, Jian; Hu, Yun-Yu

    2010-08-01

    This is a descriptive report of the establishment and operation of a Chinese bone bank, though not a typical one. While being engaged in collection, processing and storage of allogeneic tissues, the bone bank to which the author belongs concurrently develops and produces new, non-human derived, graft materials. Among others is reconstituted bone xenograft (RBX) which possesses strong osteoinductive capability without evoking immune rejection. Hence, its appellation "multi-variety bone bank," which was established by Dr. Hu Yunyu in 1990, the first of its kind in China. There are several salient features discriminating this bone bank from others. At this hospital-based non-profit institution, allograft hemi-joints are freshly prepared and distributed deep-frozen, instead of being freeze-dried on an industrialized basis for convenient transportation. The former has much more superior biological and mechanical properties as compared with the latter. However, allogeneic tissues are sometimes in short supply due to limited number of donors and the risk of some potential donors carrying viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). New graft materials, including reconstituted bone xenograft (RBX), were developed that serve as a supplement to allografts. RBX has been successfully used in clinical practice for the management of old fractures, nonunions and bone defects, most notably of contaminated, infected open fractures and osteomyelitis with the use of anti-infective reconstituted bone xenograft (ARBX). Additionally the multi-variety bone bank serves as a training base for educating professional personnel and researchers (postgraduates) in theories and technologies of tissue banking. Up to now, eighteen special technical staff members and approximately sixty senior researchers have been trained at this institution.

  19. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder.

    PubMed

    Seifert, Michael E; Hruska, Keith A

    2016-03-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy.

  20. The Kidney-Vascular-Bone Axis in the Chronic Kidney Disease-Mineral Bone Disorder.

    PubMed

    Seifert, Michael E; Hruska, Keith A

    2016-03-01

    The last 25 years have been characterized by dramatic improvements in short-term patient and allograft survival after kidney transplantation. Long-term patient and allograft survival remains limited by cardiovascular disease and chronic allograft injury, among other factors. Cardiovascular disease remains a significant contributor to mortality in native chronic kidney disease as well as cardiovascular mortality in chronic kidney disease more than doubles that of the general population. The chronic kidney disease (CKD)-mineral bone disorder (MBD) is a syndrome recently coined to embody the biochemical, skeletal, and cardiovascular pathophysiology that results from disrupting the complex systems biology between the kidney, skeleton, and cardiovascular system in native and transplant kidney disease. The CKD-MBD is a unique kidney disease-specific syndrome containing novel cardiovascular risk factors, with an impact reaching far beyond traditional notions of renal osteodystrophy and hyperparathyroidism. This overview reviews current knowledge of the pathophysiology of the CKD-MBD, including emerging concepts surrounding the importance of circulating pathogenic factors released from the injured kidney that directly cause cardiovascular disease in native and transplant chronic kidney disease, with potential application to mechanisms of chronic allograft injury and vasculopathy. PMID:26356179

  1. Coronary Collaterals Predict Improved Survival and Allograft Function in Patients with Coronary Allograft Vasculopathy

    PubMed Central

    Lavine, Kory J.; Sintek, Marc; Novak, Eric; Ewald, Gregory; Geltman, Edward; Joseph, Susan; Pfeifer, John; Mann, Douglas

    2013-01-01

    Background Despite improvements in the care of patients who have received cardiac transplants, coronary allograft vasculopathy (CAV) remains the most prevalent cause of late allograft failure and cardiac mortality. Few proven therapies are available for this important disease. The presence of coronary collaterals imparts a favorable prognosis in patients with native ischemic heart disease; however, the impact of collaterals in CAV is unknown. Methods and results To determine whether the development of coronary collaterals is associated with improved outcomes in patients with CAV, we performed a retrospective analysis of patients followed in the heart transplant program at Barnes Jewish Hospital from 1994–2008. The primary endpoints included all cause mortality and the composite of all cause mortality, retransplantation, and inotrope dependence. We screened 493 patients and identified 59 (12%) subjects with moderate to severe CAV. Angiographically visible coronary collaterals were present in 34 (57%) subjects. Kaplan-Meier and Cox multivariable analyses revealed that patients with collaterals had reduced incidence of all cause mortality HR 0.20, p<0.001 and the composite endpoint HR 0.17, p<0.001. In addition, patients with collaterals had less severe heart failure symptoms as measured by NYHA class. Immunostaining of biopsy specimens revealed that among patients with CAV, the presence of coronary collaterals correlated with increased microvascular density, reduced fibrosis and lower LVEDP. Conclusions Together, these data demonstrate that the presence of coronary collaterals predicts a favorable prognosis in patients with CAV and suggests that interventions aimed at promoting collateral and microvascular growth may serve as effective therapies for this disease. PMID:23709657

  2. [Integration properties of bone substitute materials. Experimental studies on animals].

    PubMed

    Günther, K P; Scharf, H P; Pesch, H J; Puhl, W

    1998-02-01

    In order to avoid the potential risks of disease transmission in allograft surgery, numerous substitute materials have been described. As the biological response to implant materials is different, we undertook the following study to assess type and amount of bone ingrowth in CaP-ceramics. 105 cylindrical bone defects with a diameter of 5.4 mm were created surgically in the femoral condyles of 53 skeletal mature NZW rabbits. The defects were filled with crushed coralline hydroxyapatite (HA) implants (n = 21), synthetically produced hydroxyapatite (n = 21) and surface-modified alpha-Tricalciumphosphate (TCP) grains (n = 21). 21 defects were left empty and other drill holes were filled with rabbit cancellous bone cylinders (n = 21) after 3 months of cryopreservation at -78 degrees C without sterilization. Following observation periods of 2, 4, 6, 8, 12, 26 and 52 weeks the femoral condyles were harvested for histological evaluation and quantitative analysis of bone ingrowth. Woven bone formation at implant periphery can be observed in all substances as early as 2 weeks postoperatively. At 4-week-intervals cryopreserved allografts show new bone apposition on surfaces of necrotic trabeculae and graft-host junctions by a predominantly osteoblastic reaction at the periphery of all cylinders, while in HA- and TCP-grains early bone formation in the center of drill holes is detectable as well. There is a direct contact between HA-/TCP-particles and newly formed bone without fibrous tissue formation at the implant surfaces. Central new bone formation in rabbit allografts can be observed after 6 to 8 weeks together with a secondary osteoclastic resorption of necrotic transplant trabeculae. The result of this remodeling process is a complete degradation of transplant cylinders with reorganization of vital trabeculae oriented in a mature pattern after 12 to 26 weeks. In contrast the HA- and TCP-implants did not show any signs of resorption. PMID:9530667

  3. Functional Immune Anatomy of the Liver-As an Allograft.

    PubMed

    Demetris, A J; Bellamy, C O C; Gandhi, C R; Prost, S; Nakanuma, Y; Stolz, D B

    2016-06-01

    The liver is an immunoregulatory organ in which a tolerogenic microenvironment mitigates the relative "strength" of local immune responses. Paradoxically, necro-inflammatory diseases create the need for most liver transplants. Treatment of hepatitis B virus, hepatitis C virus, and acute T cell-mediated rejection have redirected focus on long-term allograft structural integrity. Understanding of insults should enable decades of morbidity-free survival after liver replacement because of these tolerogenic properties. Studies of long-term survivors show low-grade chronic inflammatory, fibrotic, and microvascular lesions, likely related to some combination of environment insults (i.e. abnormal physiology), donor-specific antibodies, and T cell-mediated immunity. The resultant conundrum is familiar in transplantation: adequate immunosuppression produces chronic toxicities, while lightened immunosuppression leads to sensitization, immunological injury, and structural deterioration. The "balance" is more favorable for liver than other solid organ allografts. This occurs because of unique hepatic immune physiology and provides unintended benefits for allografts by modulating various afferent and efferent limbs of allogenic immune responses. This review is intended to provide a better understanding of liver immune microanatomy and physiology and thereby (a) the potential structural consequences of low-level, including allo-antibody-mediated injury; and (b) how liver allografts modulate immune reactions. Special attention is given to the microvasculature and hepatic mononuclear phagocytic system.

  4. Urine Proteomics to Detect Biomarkers for Chronic Allograft Dysfunction

    PubMed Central

    Quintana, Luís F.; Solé-Gonzalez, Amanda; Kalko, Susana G.; Bañon-Maneus, Elisenda; Solé, Manel; Diekmann, Fritz; Gutierrez-Dalmau, Alex; Abian, Joaquin; Campistol, Josep M.

    2009-01-01

    Despite optimal immunosuppressive therapy, more than 50% of kidney transplants fail because of chronic allograft dysfunction. A noninvasive means to diagnose chronic allograft dysfunction may allow earlier interventions that could improve graft half-life. In this proof-of-concept study, we used mass spectrometry to analyze differences in the urinary polypeptide patterns of 32 patients with chronic allograft dysfunction (14 with pure interstitial fibrosis and tubular atrophy and 18 with chronic active antibody-mediated rejection) and 18 control subjects (eight stable recipients and 10 healthy control subjects). Unsupervised hierarchical clustering showed good segregation of samples in groups corresponding mainly to the four biomedical conditions. Moreover, the composition of the proteome of the pure interstitial fibrosis and tubular atrophy group differed from that of the chronic active antibody-mediated rejection group, and an independent validation set confirmed these results. The 14 protein ions that best discriminated between these two groups correctly identified 100% of the patients with pure interstitial fibrosis and tubular atrophy and 100% of the patients with chronic active antibody-mediated rejection. In summary, this study establishes a pattern for two histologic lesions associated with distinct graft outcomes and constitutes a first step to designing a specific, noninvasive diagnostic tool for chronic allograft dysfunction. PMID:19056874

  5. Tuberculosis in a renal allograft recipient presenting with intussusception.

    PubMed

    Mohapatra, A; Basu, G; Sen, I; Asirvatham, R; Michael, J S; Pulimood, A B; John, G T

    2012-01-01

    Extra-pulmonary tuberculosis (TB) is more common in renal allograft recipients and may present with dissemination or an atypical features. We report a renal allograft recipient with intestinal TB presenting 3 years after transplantation with persistent fever, weight loss, diarrhea, abdominal pain and mass in the abdomen with intestinal obstruction. He was diagnosed to be having an ileocolic intussusception which on resection showed a granulomatous inflammation with presence of acid-fast bacilli (AFB) typical of Mycobacterium tuberculosis. In addition, AFB was detected in the tracheal aspirate, indicating dissemination. He received anti-TB therapy (ATT) from the fourth postoperative day. However, he developed a probable immune reconstitution inflammatory syndrome (IRIS) with multiorgan failure and died on 11(th) postoperative day. This is the first report of intestinal TB presenting as intussusception in a renal allograft recipient. The development of IRIS after starting ATT is rare in renal allograft recipients. This report highlights the need for a high index of suspicion for diagnosing TB early among renal transplant recipients and the therapeutic dilemma with overwhelming infection and development of IRIS upon reduction of immunosuppression and starting ATT.

  6. Recurrence of Acute Page Kidney in a Renal Transplant Allograft

    PubMed Central

    Zayas, Carlos; Mulloy, Laura; Jagadeesan, Muralidharan

    2016-01-01

    Acute Page Kidney (APK) phenomenon is a rare cause of secondary hypertension, mediated by activation of renin-angiotensin-aldosterone system (RAAS). Timely intervention is of great importance to prevent any end organ damage from hypertension. We present a unique case of three episodes of APK in the same renal transplant allograft. PMID:27725836

  7. Identification and treatment of cyclosporine-associated allograft thrombosis

    SciTech Connect

    Schlanger, R.E.; Henry, M.L.; Sommer, B.G.; Ferguson, R.M.

    1986-08-01

    Endothelial injury associated with cyclosporine (CSA) therapy in the absence of rejection has resulted in irreversible intrarenal allograft thrombosis and transplant loss. Indium 111 (/sup 111/In)-labeled platelet scanning is an effective way to identify those transplants that are at risk for acute loss. Two hundred prospective /sup 111/In scans were obtained (100 on allografts with normal function and 100 with transplant dysfunction of all causes). /sup 111/In scans in patients with dose-dependent CSA nephrotoxicity (N = 58) and biopsy proved acute rejection (N = 22) were negative. Grossly abnormal scans (three to eight times greater than hepatic uptake) were noted in nine recipients identified as having a hemolytic uremic-like syndrome associated with CSA use. Accelerated allograft functional loss was irreversible in six patients despite stopping CSA, systemic anticoagulation, increased steroids and antilymphocyte globulin, and infusion of fresh-frozen plasma. Three patients with grossly positive /sup 111/In scans and clinical and laboratory parameters consistent with this syndrome were treated with cessation of CSA and intra-arterial infusion of streptokinase into the renal allograft followed by systemic heparinization. Normal transplant function was regained and continues at 1, 7, and 8 months after transplant. /sup 111/In-labeled platelet scanning can noninvasively identify this syndrome of CSA-associated arteriopathy and allow for early therapy to reverse it. Intrarenal arterial streptokinase therapy is a successful way to treat acute CSA-associated arteriopathy.

  8. Bioactive scaffold for bone tissue engineering: An in vivo study

    NASA Astrophysics Data System (ADS)

    Livingston, Treena Lynne

    Massive bone loss of the proximal femur is a common problem in revision cases of total hip implants. Allograft is typically used to reconstruct the site for insertion of the new prosthesis. However, for long term fixation and function, it is desirable that the allograft becomes fully replaced by bone tissue and aids in the regeneration of bone to that site. However, allograft use is typically associated with delayed incorporation and poor remodeling. Due to these profound limitations, alternative approaches are needed. Tissue engineering is an attractive approach to designing improved graft materials. By combining osteogenic activity with a resorbable scaffold, bone formation can be stimulated while providing structure and stability to the limb during incorporation and remodeling of the scaffold. Porous, surface modified bioactive ceramic scaffolds (pSMC) have been developed which stimulate the expression of the osteoblastic phenotype and production of bone-like tissue in vitro. The scaffold and two tissue-engineered constructs, osteoprogenitor cells seeded onto scaffolds or cells expanded in culture to form bone tissue on the scaffolds prior to implantation, were investigated in a long bone defect model. The rate of incorporation was assessed. Both tissue-engineered constructs stimulated bone formation and comparable repair at 2 weeks. In a rat femoral window defect model, bone formation increased over time for all groups in concert with scaffold resorption, leading to a 40% increase in bone and 40% reduction of the scaffold in the defect by 12 weeks. Both tissue-engineered constructs enhanced the rate of mechanical repair of long bones due to better bony union with the host cortex. Long bones treated with tissue engineered constructs demonstrated a return in normal torsional properties by 4 weeks as compared to 12 weeks for long bones treated with pSMC. Culture expansion of cells to produce bone tissue in vitro did not accelerate incorporation over the treatment

  9. Biomaterials and bone.

    PubMed

    Pili, Daniele; Tranquilli Leali, Paolo

    2011-04-01

    The healing process of bone is influenced by several biochemical, biomechanics, cellular, hormonal and pathological mechanisms. The ideal biomaterials should therefore guarantee the same mechanisms and be able to "heal". At present we do not have such materials at our disposal. We can anyway select among several biomaterials with different characteristics to best suit our need. In this paper we will overview some of the biomaterials used today in bone surgery with regard to their main biological properties as well as their compatibility.

  10. [Many issues about bone quality].

    PubMed

    Saito, Mitsuru

    2012-06-01

    According to the present definition of osteoporosis, bone mineral density, architecture, and tissue material properties are important factors in determining bone strength. Bone matrix consists of a two-phase composite material in which the mineral phase provides stiffness and collagen provide tensile strength and ductility. The proposed determinants of bone strength at the material level are the degree of mineralization of basic structure units, microdamage accumulation, and collagen cross-link formation. These are regulated by cellular activities, tissue turnover rate, and the levels of oxidative stress and glycation. In this review, I describe the concerns regarding bone qualities. PMID:22653026

  11. Non-Invasive Monitoring of Temporal and Spatial Blood Flow during Bone Graft Healing Using Diffuse Correlation Spectroscopy

    PubMed Central

    Han, Songfeng; Hoffman, Michael D.; Proctor, Ashley R.; Vella, Joseph B.; Mannoh, Emmanuel A.; Barber, Nathaniel E.; Kim, Hyun Jin; Jung, Ki Won; Benoit, Danielle S. W.; Choe, Regine

    2015-01-01

    Vascular infiltration and associated alterations in microvascular blood flow are critical for complete bone graft healing. Therefore, real-time, longitudinal measurement of blood flow has the potential to successfully predict graft healing outcomes. Herein, we non-invasively measure longitudinal blood flow changes in bone autografts and allografts using diffuse correlation spectroscopy in a murine femoral segmental defect model. Blood flow was measured at several positions proximal and distal to the graft site before implantation and every week post-implantation for a total of 9 weeks (autograft n = 7 and allograft n = 10). Measurements of the ipsilateral leg with the graft were compared with those of the intact contralateral control leg. Both autografts and allografts exhibited an initial increase in blood flow followed by a gradual return to baseline levels. Blood flow elevation lasted up to 2 weeks in autografts, but this duration varied from 2 to 6 weeks in allografts depending on the spatial location of the measurement. Intact contralateral control leg blood flow remained at baseline levels throughout the 9 weeks in the autograft group; however, in the allograft group, blood flow followed a similar trend to the graft leg. Blood flow difference between the graft and contralateral legs (ΔrBF), a parameter defined to estimate graft-specific changes, was elevated at 1–2 weeks for the autograft group, and at 2–4 weeks for the allograft group at the proximal and the central locations. However, distal to the graft, the allograft group exhibited significantly greater ΔrBF than the autograft group at 3 weeks post-surgery (p < 0.05). These spatial and temporal differences in blood flow supports established trends of delayed healing in allografts versus autografts. PMID:26625352

  12. CD8 T-cell recognition of acquired alloantigen promotes acute allograft rejection

    PubMed Central

    Harper, Simon J. F.; Ali, Jason M.; Wlodek, Elizabeth; Negus, Marg C.; Harper, Ines G.; Chhabra, Manu; Qureshi, M. Saeed; Mallik, Mekhola; Bolton, Eleanor; Bradley, J. Andrew; Pettigrew, Gavin J.

    2015-01-01

    Adaptive CD8 T-cell immunity is the principal arm of the cellular alloimmune response, but its development requires help. This can be provided by CD4 T cells that recognize alloantigen “indirectly,” as self-restricted allopeptide, but this process remains unexplained, because the target epitopes for CD4 and CD8 T-cell recognition are “unlinked” on different cells (recipient and donor antigen presenting cells (APCs), respectively). Here, we test the hypothesis that the presentation of intact and processed MHC class I alloantigen by recipient dendritic cells (DCs) (the “semidirect” pathway) allows linked help to be delivered by indirect-pathway CD4 T cells for generating destructive cytotoxic CD8 T-cell alloresponses. We show that CD8 T-cell–mediated rejection of murine heart allografts that lack hematopoietic APCs requires host secondary lymphoid tissue (SLT). SLT is necessary because within it, recipient dendritic cells can acquire MHC from graft parenchymal cells and simultaneously present it as intact protein to alloreactive CD8 T cells and as processed peptide alloantigen for recognition by indirect-pathway CD4 T cells. This enables delivery of essential help for generating cytotoxic CD8 T-cell responses that cause rapid allograft rejection. In demonstrating the functional relevance of the semidirect pathway to transplant rejection, our findings provide a solution to a long-standing conundrum as to why SLT is required for CD8 T-cell allorecognition of graft parenchymal cells and suggest a mechanism by which indirect-pathway CD4 T cells provide help for generating effector cytotoxic CD8 T-cell alloresponses at late time points after transplantation. PMID:26420874

  13. Porous poly(propylene fumarate) foam coating of orthotopic cortical bone grafts for improved osteoconduction.

    PubMed

    Lewandrowski, Kai-Uwe; Bondre, Shrikar; Hile, David D; Thompson, Benjamin M J; Wise, Donald L; Tomford, William W; Trantolo, Debra J

    2002-12-01

    A porous biodegradable scaffold coating for perforated and demineralized cortical bone allografts could maintain immediate structural recovery and subsequently allow normal healing and remodeling by promoting bony ingrowth and avoiding accelerated graft resorption. This new type of osteoconductive surface modification should improve allograft incorporation by promoting new bone growth throughout the biodegradable scaffold, hence encasing the graft with the recipient's own bone. We investigated the feasibility of augmenting orthotopically transplanted cortical bone grafts with osteoconductive biodegradable polymeric scaffold coatings. Five types of bone grafts were prepared: type I, untreated fresh-frozen cortical bone grafts (negative control); type II, perforated and partially demineralized cortical bone grafts without additional coating (positive control); type III, perforated and partially demineralized cortical bone coated with a low-porosity poly(propylene fumarate) (PPF) foam; type IV, perforated and partially demineralized cortical bone coated with a medium-porosity PPF foam; and type V, perforated and partially demineralized cortical bone coated with a high-porosity PPF foam. Grafts were implanted into the rat tibial diaphysis. Fixation was achieved with an intramedullary threaded K-wire. Two sets of animals were operated on. Animals were killed in groups of eight with one set being killed 12 weeks, and the other 16 weeks, postoperatively. Radiographic, histologic, and histomorphometric analyses of grafts showed that the amount of new bone forming around the foam-coated grafts was significantly higher than that in the type I control group (uncoated) or that in type II group (perforated and partially demineralized cortical bone grafts). Although all foam formulations appeared initially equally osteoconductive, histologic evaluation of medium-porosity PPF foam-based coatings appeared to result in a sustained response 16 weeks postoperatively. Significant

  14. Kidney retransplantation for BK virus nephropathy with active viremia without allograft nephrectomy.

    PubMed

    Huang, Jingbo; Danovitch, Gabriel; Pham, Phuong-Thu; Bunnapradist, Suphamai; Huang, Edmund

    2015-12-01

    BK virus nephropathy is an important cause of kidney allograft failure. Retransplantation has been successfully performed for patients with previous allograft loss due to BK virus nephropathy; however, whether allograft nephrectomy and viral clearance are required prior to retransplantation is controversial. Some recent studies have suggested that retransplantion can be successfully achieved without allograft nephrectomy if viremia is cleared prior to retransplant. The only published experience of successful retransplantation in the presence of active viremia occurred in the presence of concomitant allograft nephrectomy of the failing kidney. In this report, we describe a case of successful repeat kidney transplant in a patient with high-grade BK viremia and fulminant hepatic failure without concomitant allograft nephrectomy performed under the setting of a simultaneous liver-kidney transplant.

  15. Structural allograft and cemented long-stem prosthesis for complex revision hip arthroplasty: use of a trochanteric claw plate improves final hip function

    PubMed Central

    Lemoine, Camille Thevenin; Kerboull, Marcel; Courpied, Jean Pierre

    2007-01-01

    Extensive bone loss raises formidable challenges in total hip revision. The aim of this study was to evaluate the results of reconstruction using a cemented long-stem and massive structural allograft implanted in a filleted proximal femur, with and without the use of a trochanteric claw plate. Between 1988 and 2001, 44 revisions were performed in 42 patients. After a transtrochanteric approach, the femur was cut longitudinally. A long, cemented Charnley-type prosthesis was used, and flaps of the residual femur were folded around the allograft. The greater trochanter was reinserted with wires in all revisions, and with both wires and a claw plate in 20 revisions. Mean follow-up was 7.15 years (range: 3–16); seven patients, died and four were lost to follow-up. The follow-up exceeded five years in 34 patients. The major complication was nonunion of the greater trochanter, which occurred in 25 cases. Six dislocations, one recurrence of infection, two mechanical loosening, and two fractures below the stem were also recorded. The use of a trochanteric claw plate significantly improved final hip stability, even in patients with nonunion. Femoral reconstruction with a massive structural allograft is reliable and long-lived, and serious complications and long-term resorption are uncommon. The use of a trochanteric claw plate significantly improves final hip stability. Level of evidence: Therapeutic study, level III (retrospective comparative study). PMID:18008098

  16. Current trends and future perspectives of bone substitute materials - from space holders to innovative biomaterials.

    PubMed

    Kolk, Andreas; Handschel, Jörg; Drescher, Wolf; Rothamel, Daniel; Kloss, Frank; Blessmann, Marco; Heiland, Max; Wolff, Klaus-Dietrich; Smeets, Ralf

    2012-12-01

    An autologous bone graft is still the ideal material for the repair of craniofacial defects, but its availability is limited and harvesting can be associated with complications. Bone replacement materials as an alternative have a long history of success. With increasing technological advances the spectrum of grafting materials has broadened to allografts, xenografts, and synthetic materials, providing material specific advantages. A large number of bone-graft substitutes are available including allograft bone preparations such as demineralized bone matrix and calcium-based materials. More and more replacement materials consist of one or more components: an osteoconductive matrix, which supports the ingrowth of new bone; and osteoinductive proteins, which sustain mitogenesis of undifferentiated cells; and osteogenic cells (osteoblasts or osteoblast precursors), which are capable of forming bone in the proper environment. All substitutes can either replace autologous bone or expand an existing amount of autologous bone graft. Because an understanding of the properties of each material enables individual treatment concepts this review presents an overview of the principles of bone replacement, the types of graft materials available, and considers future perspectives. Bone substitutes are undergoing a change from a simple replacement material to an individually created composite biomaterial with osteoinductive properties to enable enhanced defect bridging.

  17. Imaging-based diagnosis of acute renal allograft rejection

    PubMed Central

    Thölking, Gerold; Schuette-Nuetgen, Katharina; Kentrup, Dominik; Pawelski, Helga; Reuter, Stefan

    2016-01-01

    Kidney transplantation is the best available treatment for patients with end stage renal disease. Despite the introduction of effective immunosuppressant drugs, episodes of acute allograft rejection still endanger graft survival. Since efficient treatment of acute rejection is available, rapid diagnosis of this reversible graft injury is essential. For diagnosis of rejection, invasive core needle biopsy of the graft is the “gold-standard”. However, biopsy carries the risk of significant graft injury and is not immediately feasible in patients taking anticoagulants. Therefore, a non-invasive tool assessing the whole organ for specific and fast detection of acute allograft rejection is desirable. We herein review current imaging-based state of the art approaches for non-invasive diagnostics of acute renal transplant rejection. We especially focus on new positron emission tomography-based as well as targeted ultrasound-based methods. PMID:27011915

  18. Total lymphoid irradiation for treatment of intractable cardiac allograft rejection

    SciTech Connect

    Hunt, S.A.; Strober, S.; Hoppe, R.T.; Stinson, E.B. )

    1991-03-01

    The ability of postoperative total lymphoid irradiation to reverse otherwise intractable cardiac allograft rejection was examined in a group of 10 patients in whom conventional rejection therapy (including pulsed steroids and monoclonal or polyclonal anti-T-cell antibody therapy) had failed to provide sustained freedom from rejection. Follow-up periods range from 73 to 1119 days since the start of total lymphoid irradiation. No patient died or sustained serious morbidity because of the irradiation. Three patients have had no further rejection (follow-up periods, 105 to 365 days). Two patients died--one in cardiogenic shock during the course of total lymphoid irradiation, the other with recurrent rejection caused by noncompliance with his medical regimen. Total lymphoid irradiation appears to be a safe and a moderately effective immunosuppressive modality for 'salvage' therapy of cardiac allograft rejection unresponsive to conventional therapy.

  19. The safe and effective use of allograft tissue--an update.

    PubMed

    Barbour, Scott A; King, Warren

    2003-01-01

    The use of allograft tissue in orthopaedic surgery has increased tremendously over the last several years. Tissue availability, reduced surgical times, and lack of donor site morbidity are attractive characteristics to surgeons and patients alike. Although complications, such as disease transmission, are relatively uncommon when using allograft tissue, they do occur. This article will review the literature concerning the safe and effective use of allograft tissue, as well as present four case reports of Clostridium septicum infection caused by implantation of contaminated allograft tissue.

  20. Prolongation of segmental and pancreaticoduodenal allografts in the primate with total-lymphoid irradiation and cyclosporine

    SciTech Connect

    Du Toit, D.F.; Heydenrych, J.J.; Smit, B.; Louw, G.; Zuurmond, T.; Els, D.; Du Toit, L.B.; Weideman, A.; Davids, H.; van der Merwe, E.

    1987-09-01

    The prolongation of segmental and pancreaticoduodenal allografts (PDA) by total lymphoid irradiation (TLI) and in combination with cyclosporine (CsA) was assessed in a well established total pancreatectomy, diabetic, primate transplantation model. Pancreatic transplantation was performed in 119 pancreatectomized baboons (Papio ursinus). Of a total of 109 allografts performed, 71 were segmental allografts (open duct drainage) and 38 PDA. Of 119 graft recipients, 10 received segmental pancreatic autografts. TLI and CsA administered separately to segmental allograft recipients resulted in modest allograft survival and indefinite graft survival was not observed. 8 of 17 (47%) segmental allograft recipients that received TLI and CsA had graft survival beyond 100 days, indicating highly significant pancreatic allograft survival. All long-term segmental allograft recipients were rendered normoglycemic (plasma glucose less than 8 mmol/L) by this immunosuppressive regimen. In contrast, poor results were observed in PDA recipients treated with TLI and CsA. Mean survival in 18 treated PDA recipients was 23.8 days, 8 survived longer than 20 days (44.4%), and 1 greater than 100 days (5.5%). Despite treatment, early rejection of the duodenum in PDA recipients frequently resulted in necrosis and perforation and contributed to a high morbidity and mortality. This study indicates that, in contrast to the significant prolongation of segmental allografts by TLI and CsA, poor immunosuppression was achieved by this regimen in PDA recipients and was associated with a high morbidity and mortality caused by early rejection of the duodenum.

  1. Immunomodulation of vascular endothelium: Effects of ultraviolet B irradiation on vein allograft rejection

    SciTech Connect

    Marin, M.L.; Hardy, M.A.; Gordon, R.E.; Reemtsma, K.; Benvenisty, A.I. )

    1990-01-01

    Prosthetic grafts of vein allografts are inadequate as small-diameter vessel substitutes. We have applied ultraviolet B (UVB) irradiation to modulate the immunogenicity of vein allografts to avoid immunologic injury. The veins of male ACI rats were irradiated with UVB (60 mJ/cm2) in situ and transplanted to male ACI rats (autografts) and female Lewis rats (allografts). Nonirradiated veins served as controls. At 4, 7, 14, and 28 days, all grafts were patent and were studied for morphologic changes by scanning electron microscopy and for immunogold labeling of major histocompatibility complex class II antigen expression. In autografts, scanning electron microscopy demonstrated minimal endothelial loss after grafting, regardless of UVB irradiation. Untreated allografts showed severe endothelial injury 4, 7, and 14 days after transplantation. UVB irradiation of veins protected allografts from injury to the endothelium and basement membrane. Major histocompatibility complex class II-positive endothelial cells were not seen in autografts but were seen in 40% of cells 4 days after transplantation in untreated allografts. UVB-treated allografts showed MHC class II antigen expression labeling of 20% of the endothelial cells. Barr body analysis demonstrated the donor origin of these endothelial cells. UVB irradiation of rat vein allografts prolongs endothelial survival while decreasing endothelial surface expression of class II antigens. These data suggest that modification of vein immunogenicity with UVB irradiation may permit functional survival of small-vessel allografts without chronic immunosuppression.

  2. The safe and effective use of allograft tissue--an update.

    PubMed

    Barbour, Scott A; King, Warren

    2003-01-01

    The use of allograft tissue in orthopaedic surgery has increased tremendously over the last several years. Tissue availability, reduced surgical times, and lack of donor site morbidity are attractive characteristics to surgeons and patients alike. Although complications, such as disease transmission, are relatively uncommon when using allograft tissue, they do occur. This article will review the literature concerning the safe and effective use of allograft tissue, as well as present four case reports of Clostridium septicum infection caused by implantation of contaminated allograft tissue. PMID:12975205

  3. Quantitative podocyte parameters predict human native kidney and allograft half-lives

    PubMed Central

    Naik, Abhijit S.; Afshinnia, Farsad; Cibrik, Diane; Hodgin, Jeffrey B.; Zhang, Min; Kikuchi, Masao; Wickman, Larysa; Samaniego, Milagros; Bitzer, Markus; Wiggins, Jocelyn E.; Ojo, Akinlolu; Li, Yi; Wiggins, Roger C.

    2016-01-01

    BACKGROUND. Kidney function decreases with age. A potential mechanistic explanation for kidney and allograft half-life has evolved through the realization that linear reduction in glomerular podocyte density could drive progressive glomerulosclerosis to impact both native kidney and allograft half-lives. METHODS. Predictions from podometrics (quantitation of podocyte parameters) were tested using independent pathologic, functional, and outcome data for native kidneys and allografts derived from published reports and large registries. RESULTS. With age, native kidneys exponentially develop glomerulosclerosis, reduced renal function, and end-stage kidney disease, projecting a finite average kidney life span. The slope of allograft failure rate versus age parallels that of reduction in podocyte density versus age. Quantitative modeling projects allograft half-life at any donor age, and rate of podocyte detachment parallels the observed allograft loss rate. CONCLUSION. Native kidneys are designed to have a limited average life span of about 100–140 years. Allografts undergo an accelerated aging-like process that accounts for their unexpectedly short half-life (about 15 years), the observation that older donor age is associated with shorter allograft half-life, and the fact that long-term allograft survival has not substantially improved. Podometrics provides potential readouts for these processes, thereby offering new approaches for monitoring and intervention. FUNDING: National Institutes of Health. PMID:27280173

  4. 21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system....

  5. 21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system....

  6. 21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system....

  7. 21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system....

  8. 21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system....

  9. The effects of immunosuppression and anticoagulation on fibrin deposition and swelling in rat cardiac allografts.

    PubMed

    Christmas, S E; Jasani, M K; Jayson, M I

    1987-01-01

    Rat cardiac allograft recipients were injected with radiolabeled human fibrinogen at intervals after transplantation. There was a progressive increase in tracer accumulation within graft ventricles, peaking at the time of rejection at about 30-fold that within syngeneic grafts. Protein extraction experiments indicated that ca. 90% of tracer was present as cross-linked fibrin at the time of rejection. Exudation within rejecting allografts was nearly threefold that in syngeneic grafts. The weight of allografts at different times after transplantation increased in close concordance with fibrin deposition. Pharmacologically immunosuppressed recipients showed negligible fibrin deposition and swelling whereas "B" rats and thoracic-duct-lymph-drained recipients showed moderate allograft swelling in the absence of significant fibrin deposition or rejection. The decreased fibrin deposition was not a result of depressed plasma clotting factor levels. B rats reconstituted with thoracic duct lymphocytes still had reduced allograft fibrin deposition in the presence of normal amounts of swelling and exudation. The anticoagulants warfarin and heparin greatly decreased allograft fibrin but were almost without effect on allograft swelling, exudation, and rejection. The possible participation of infiltrating macrophages in allograft fibrin deposition is discussed. Unlike cutaneous delayed hypersensitivity reactions, normal amounts of fibrin deposition appear not to be essential for full cardiac allograft rejection.

  10. Bone and the immune system.

    PubMed

    Gruber, H E

    1991-07-01

    There are several lines of evidence which provide support for an important relationship between immune cells and bone. Clinical studies of immunodeficiency syndromes have shown that abnormalities in bone shape are evident on x-rays, and peculiarities in the structure of the growth plate have been identified by histopathology. Studies of bone histology, and quantitation of cellular abnormalities, are scarce. Abnormalities in bone turnover, have, however, been identified in the nude mouse model. Many lines of evidence derived from in vitro bone studies have shown that lymphokines and monokines can influence bone formation and bone resorption. Some clinical studies of postmenopausal osteoporosis have indicated the possible presence of immune cell changes in this condition. Although several hypotheses have been formed regarding the exact mechanisms of the effect of immune cytokine on bone, this is clearly a very large area of study and there is a need for additional carefully controlled experiments with special emphasis on bone cells and bone matrix, especially in the human. As knowledge progresses regarding immunology and hematology, a clearer understanding of the lineages of the osteoblast and osteoclast will emerge and we will better understand how specialized bone cells interact with and react to their immune cell neighbors in the bone marrow and to immune system signals. These findings will have especially important implications for the local bone loss seen in rheumatoid arthritis, periodontal disease, and chronic osteomyelitis. PMID:2068116

  11. Transcutaneous Raman spectroscopy for assessing progress of bone-graft incorporation in bone reconstruction and repair

    NASA Astrophysics Data System (ADS)

    Okagbare, Paul I.; Esmonde-White, Francis W. L.; Goldstein, Steven A.; Morris, Michael D.

    2011-03-01

    Allografts and other bone-grafts are frequently used for a variety of reconstructive approaches in orthopaedic surgery. However, successful allograft incorporation remains uncertain. Consequently, there is significant need for methods to monitor the fate of these constructs. Only few noninvasive methods can fully assess the progress of graft incorporation and to provide information on the metabolic status of the graft, such as the mineral and matrix composition of the regenerated-tissue that may provide early indications of graft success or failure. For example, Computed-tomography and MRI provide information on the morphology of the graft/host interface. Limited information is also available from DXA. To address this challenge, we present here the implementation of a noninvasive Raman spectroscopy technique for in-vivo assessment of allograft incorporation in animal-model. In an animal use committee approved osseointegration experiment, a 3mm defect is created in rat's tibia. The defect is reconstructed using auto or allograft and Raman spectra are collected at several time-points during healing using an array of optical-fibers in contact with the skin of the rat over the tibia while the rat is anaesthetized. The array allows excitation and collection of Raman spectra through the skin at various positions around the tibia. Raman parameters such as mineral/matrix, carbonate/phosphate and cross-linking are recovered and monitored. The system is calibrated against locally-constructed phantoms that mimic the morphology, optics and spectroscopy of the rat. This new technology provides a non-invasive method for in-vivo assessment of bone-graft incorporation in animal-models and can be adapted for similar study in human subjects.

  12. Regulatory oversight in the United States of vascularized composite allografts.

    PubMed

    Glazier, Alexandra K

    2016-06-01

    Vascularized composite allograft (VCA) transplantation is a medically acceptable treatment for the reconstruction of major tissue loss. The advent of VCA transplantation has spurred regulatory and policy development in the United States to address the multiple clinical, ethical and legal issues that must be considered for the practice of VCA donation and transplantation to develop within the existing framework of public trust and transparency vital to the success of donation and transplantation. PMID:26284312

  13. Orthotopic bone transplantation in mice. III. Methods of reducing the immune response and their effect on healing

    SciTech Connect

    Kliman, M.; Halloran, P.F.; Lee, E.; Esses, S.; Fortner, P.; Langer, F.

    1981-01-01

    Various methods of reducing the immune response to allogeneic bone grafts, either by pretreating the graft or by immunosuppressing the recipient, were compared. Tibial grafts from B10.D2 mice, either untreated or pretreated in various ways, were transplanted into B10 recipients. The antibody response was followed and the extent of bone healing at 4 months was assessed. Pretreatment of the graft by X-irradiation, freezing, or by incubation in alloantisera (either anti-H-2 or anti-Ia) reduced or abolished the immunogenicity of the graft. Immunosuppression of the recipient with methotrexate or antilymphocyte serum (ALS) also greatly depressed the antibody response. But when healing was assessed, none of these treatments except ALS improved the delayed healing of the bone allografts. The reason for this failure was probably that X-irradiation, freezing, alloantiserum pretreatment, and methotrexate all interfered with bone healing directly, whereas ALS did not. We conclude that many methods will reduce the immune response to allogeneic bone, but that only ALS will improve the healing of the allogeneic bone. Furthermore, as a corollary to the observation that pretreatment with anti-Ia serum markedly reduced the immunogenicity of bone allografts, we conclude that much of the immunogenicity of bone allografts is attributable to a population of Ia-positive cells.

  14. Donor apoptotic lymphocyte transfusion-induced liver allograft tolerance by up-regulation of CD4(+)CD25(+) regulatory T cells in peripheral blood.

    PubMed

    Cheng, J; Zhou, L; Qin, Y S; Wang, Y; Xie, H Y; Feng, X W; Zheng, S S

    2009-11-01

    Uptake of apoptotic cells by antigen-presenting cells (APC) may be involved in tolerance maintenance with an immunoregulatory role. The aim of this study was to evaluate the consequences of preoperative transfusion of donor apoptotic lymphocytes on survival of orthotopic liver transplantations (OLT). OLT was performed between Lewis (donor) and Brown Norway (BN recipient) inbred rats using a double-cuff technique. Apoptotic splenic lymphocytes induced by ultraviolet-C (UVC) irradiation were infused intravenously at 7 days before OLT. Changes in regulatory T cells in blood were determined using flow cytometry. UVC irradiated lymphocytes were sensitive and effective, as evidenced by increased peripheral blood CD4(+)CD25(+) T cells compared with recipients that received infusion of untreated donor lymphocytes or a control. Apoptotic lymphocyte transfusion prolonged hepatic allograft survival, with significantly lower histological stages of inflammation and cellular infiltration than in untreated allografts. Our results demonstrated that donor apoptotic cells promoted allograft acceptance and up-regulated CD4(+)CD25(+) regulatory T cells (Treg) in blood.

  15. Quiescent interplay between inducible nitric oxide synthase and tumor necrosis factor-alpha: influence on transplant graft vasculopathy in renal allograft dysfunction.

    PubMed

    Elahi, Maqsood M; Matata, Bashir M; Hakim, Nadey S

    2006-06-01

    A healthy endothelium is essential for vascular homeostasis, and preservation of endothelial cell function is critical for maintaining transplant allograft function. Damage to the microvascular endothelial cells is now regarded as a characteristic feature of acute vascular rejection, an important predictor of graft loss. It is also linked with transplant vasculopathy, often associated with chronic allograft nephropathy. Large bursts of nitric oxide in infiltrating monocytes/macrophages modulated by inducible nitric oxide synthase are considered pivotal in driving this mechanism. Indeed, it has been shown recently that increased circulating levels of tumor necrosis factor-alpha in the rejecting kidneys are largely responsible for triggering inducible nitric oxide synthase expression. This in turn suggests that several structural and functional features of graft rejection could be mediated by tumor necrosis factor-alpha. Despite the large body of evidence that supports immunologic involvement, knowledge concerning the cellular and biochemical mechanisms for nephritic cell dysfunction and death is incomplete. The role of tumor necrosis factor-alpha in mediating pathophysiological activity of inducible nitric oxide synthase during transplant vasculopathy remains contentious. Here, we discuss the effect of inducible nitric oxide synthase and tumor necrosis factor-alpha interaction on progressive damage to glomerular and vascular structures during renal allograft rejection. Selective inhibition of inducible nitrous oxide synthase and tumor necrosis factor-alpha as a potential therapy for ameliorating endothelial dysfunction and transplant graft vasculopathy is also discussed.

  16. Significance of urinary proteome pattern in renal allograft recipients.

    PubMed

    Suhail, Sufi M

    2014-01-01

    Urinary proteomics is developing as a platform of urinary biomarkers of immense potential in recent years. The definition of urinary proteome in the context of renal allograft and characterization of different proteome patterns in various graft dysfunctions have led to the development of a distinct science of this noninvasive tool. Substantial numbers of studies have shown that different renal allograft disease states, both acute and chronic, could portray unique urinary proteome pattern enabling early diagnosis of graft dysfunction and proper manipulation of immunosuppressive strategy that could impact graft prognosis. The methodology of the urinary proteome is nonetheless not more complex than that of other sophisticated assays of conventional urinary protein analysis. Moreover, the need for a centralized database is also felt by the researchers as more and more studies have been presenting their results from different corners and as systems of organizing these newly emerging data being developed at international and national levels. In this context concept of urinary proteomics in renal allograft recipients would be of significant importance in clinical transplantation.

  17. Renal allograft tuberculosis with infected lymphocele transmitted from the donor.

    PubMed

    Al-Nesf, Maryam Ali; Al-Ani, Omar Isam; Al-Ani, Ahmed Abdul-Rahman; Rashed, Awad Hamed

    2014-03-01

    Transmission of tuberculosis (TB) from a donor through renal transplantation is a rare incident. We are reporting a 53-year-old Qatari woman diagnosed with renal allograft TB infection. The disease was confirmed by isolation of Mycobacterium tuberculosis from fluid from the lymphocele and demonstration of caseating granuloma in graft biopsy with acid-fast bacilli seen on Ziehl-Neelsen staining. The diagnosis was made quite early post-transplantation. The presence of the granuloma, which is unusual with patients on intensive immunosuppressant medications, suggests that transmission of the infection occurred from the donor rather than from the activation of latent infection. In reviewing the literature, we found ten case reports of TB in transplanted kidney with transmission of TB infection from the donor. The presence of TB in lymphocele in association with the infected transplant by TB, to the best of our knowledge, was reported only once in the literature. Our case had unfavorable outcome and ended by renal allograft nephrectomy and hemodialysis. We are presenting this case of TB infection of renal allograft and lymphocele diagnosed early post-transplantation transmitted from the donor and pertinent review from the literature.

  18. Significance of urinary proteome pattern in renal allograft recipients.

    PubMed

    Suhail, Sufi M

    2014-01-01

    Urinary proteomics is developing as a platform of urinary biomarkers of immense potential in recent years. The definition of urinary proteome in the context of renal allograft and characterization of different proteome patterns in various graft dysfunctions have led to the development of a distinct science of this noninvasive tool. Substantial numbers of studies have shown that different renal allograft disease states, both acute and chronic, could portray unique urinary proteome pattern enabling early diagnosis of graft dysfunction and proper manipulation of immunosuppressive strategy that could impact graft prognosis. The methodology of the urinary proteome is nonetheless not more complex than that of other sophisticated assays of conventional urinary protein analysis. Moreover, the need for a centralized database is also felt by the researchers as more and more studies have been presenting their results from different corners and as systems of organizing these newly emerging data being developed at international and national levels. In this context concept of urinary proteomics in renal allograft recipients would be of significant importance in clinical transplantation. PMID:24757556

  19. Biomechanical Strength of Large Diaphyseal Deep-frozen Allografts.

    PubMed

    Nather, A; Goh, J C

    2000-01-01

    The aim of this paper is to study the biomechanical strength of deep-frozen allografts as they heal. Twenty-eight adult cats were used with the tibia as the experimental model site. Deep-frozen allografts stored at -80 degrees C were used to reconstruct a large tibial defect (at least two-thirds of the diaphysis). An intra-medullary rod was used for fixation. The healing was studied by X-ray at observation periods of 4, 6, 8, 12, 16, 24 and 36 weeks. Post-transplantation biomechanical testing was performed using the Shimadzu Universal Testing Machine DCS series with a torsion test device of 50 kg force metre. Parameters studied included maximum torque, torsional stiffness and energy of absorption. The transplanted grafts were compared to the mechanical properties of the internal controls of the normal opposite tibia of each cat. The results of the mechanical tests demonstrated that deep-frozen allografts did not regain normal strength. At nine months, only about 60% of normal torque strength and about 80% of normal torsional stiffness was achieved. Clinically, it is important to employ strong and rigid internal fixation using intra-medullary nailing rather than plating to allow for immediate mobilisation and reduce the rate of graft fracture.

  20. Non-invasive diffuse correlation tomography reveals spatial and temporal blood flow differences in murine bone grafting approaches

    PubMed Central

    Han, Songfeng; Proctor, Ashley R.; Vella, Joseph B.; Benoit, Danielle S. W.; Choe, Regine

    2016-01-01

    Longitudinal blood flow during murine bone graft healing was monitored non-invasively using diffuse correlation tomography. The system utilized spatially dense data from a scanning set-up, non-linear reconstruction, and micro-CT anatomical information. Weekly in vivo measurements were performed. Blood flow changes in autografts, which heal successfully, were localized to graft regions and consistent across mice. Poor healing allografts showed heterogeneous blood flow elevation and high inter-subject variabilities. Allografts with tissue-engineered periosteum showed responses intermediate to both autografts and allografts, consistent with healing observed. These findings suggest that spatiotemporal blood flow changes can be utilized to differentiate the degree of bone graft healing. PMID:27699097

  1. Fabrication of cellular materials

    NASA Astrophysics Data System (ADS)

    Prud'homme, Robert K.; Aksay, Ilhan A.; Garg, Rajeev

    1996-02-01

    Nature uses cellular materials in applications requiring strength while, simultaneously, minimizing raw materials requirements. Minimizing raw materials is efficient both in terms of the energy expended by the organism to synthesize the structure and in terms of the strength- to-weight ratio of the structure. Wood is the most obvious example of cellular bio-materials, and it is the focus of other presentations in this symposium. The lightweight bone structure of birds is another excellent example where weight is a key criterion. The anchoring foot of the common muscle [Mytilus edulis] whereby it attaches itself to objects is a further example of a biological system that uses a foam to fill space and yet conserve on raw materials. In the case of the muscle the foam is water filled and the foot structure distributes stress over a larger area so that the strength of the byssal thread from which it is suspended is matched to the strength of interfacial attachment of the foot to a substrate. In these examples the synthesis and fabrication of the cellular material is directed by intercellular, genetically coded, biochemical reactions. The resulting cell sizes are microns in scale. Cellular materials at the next larger scale are created by organisms at the next higher level of integration. For example an African tree frog lays her eggs in a gas/fluid foam sack she builds on a branch overhanging a pond. The outside of the foam sack hardens in the sun and prevents water evaporation. The foam structure minimizes the amount of fluid that needs to be incorporated into the sack and minimizes its weight. However, as far as the developing eggs are concerned, they are in an aqueous medium, i.e. the continuous fluid phase of the foam. After precisely six days the eggs hatch, and the solidified outer wall re-liquefies and dumps the emerging tadpoles into the pond below. The bee honeycomb is an example of a cellular material with exquisite periodicity at millimeter length scales. The

  2. Prevention of allograft rejection in heart transplantation through concurrent gene silencing of TLR and Kinase signaling pathways

    PubMed Central

    Wang, Hongmei; Zhang, Xusheng; Zheng, Xiufen; Lan, Zhu; Shi, Jun; Jiang, Jifu; Zwiep, Terry; Li, Qing; Quan, Douglas; Zhang, Zhu-Xu; Min, Weiping

    2016-01-01

    Toll-like receptors (TLRs) act as initiators and conductors responsible for both innate and adaptive immune responses in organ transplantation. The mammalian target of rapamycin (mTOR) is one of the most critical signaling kinases that affects broad aspects of cellular functions including metabolism, growth, and survival. Recipients (BALB/c) were treated with MyD88, TRIF and mTOR siRNA vectors, 3 and 7 days prior to heart transplantation and 7, 14 and 21 days after transplantation. After siRNA treatment, recipients received a fully MHC-mismatched C57BL/6 heart. Treatment with mTOR siRNA significantly prolonged allograft survival in heart transplantation. Moreover, the combination of mTOR siRNA with MyD88 and TRIF siRNA further extended the allograft survival; Flow cytometric analysis showed an upregulation of FoxP3 expression in spleen lymphocytes and a concurrent downregulation of CD40, CD86 expression, upregulation of PD-L1 expression in splenic dendritic cells in MyD88, TRIF and mTOR treated mice. There is significantly upregulated T cell exhaustion in T cells isolated from tolerant recipients. This study is the first demonstration of preventing immune rejection of allogeneic heart grafts through concurrent gene silencing of TLR and kinase signaling pathways, highlighting the therapeutic potential of siRNA in clinical transplantation. PMID:27659428

  3. Plasma cell-rich acute rejection of the renal allograft: A distinctive morphologic form of acute rejection?

    PubMed

    Gupta, R; Sharma, A; Mahanta, P J; Agarwal, S K; Dinda, A K

    2012-05-01

    This study was aimed at evaluating the clinicopathologic features of plasma cell-rich acute rejection (PCAR) of renal allograft and comparing them with acute cellular rejection (ACR), non-plasma cell-rich type. During a 2-year period, eight renal allograft biopsies were diagnosed as PCAR (plasma cells >10% of interstitial infiltrate). For comparison, 14 biopsies with ACR were included in the study. Detailed pretransplant data, serum creatinine at presentation, and other clinical features of all these cases were noted. Renal biopsy slides were reviewed and relevant immunohistochemistry performed for characterization of plasma cell infiltrate. The age range and duration of transplantation to diagnosis of acute rejection were comparable in both the groups. Histologically, the proportion of interstitial plasma cells, mean interstitial inflammation, and tubulitis score were higher in the PCAR group compared with cases with ACR. A significant difference was found in the outcome at last follow-up, being worse in patients with PCAR. This study shows that PCAR portends a poor outcome compared with ACR, with comparable Banff grade of rejection. Due to its rarity and recent description, nephrologists and renal pathologists need to be aware of this entity.

  4. BENIGN BONE TUMORS AND TUMOR-LIKE BONE LESIONS: TREATMENT UPDATE AND NEW TRENDS

    PubMed Central

    Nogueira Drumond, José Marcos

    2015-01-01

    The treatment of benign bone tumors (BBT) and tumor-like bone lesions (TBL) has observed the introduction of new drugs, such as intravenous bisphosphonates, which have ossified bone lesions caused by fibrous dysplasia. Aneurismal bone cyst has been treated with sclerosing agents by percutaneous injection, yielding good results. Adjuvants allow joint salvage, maintenance of movements and function, with low rates of recurrence. Among them, the most used ones are bone cement (PMMA), phenol, nitrogen-based cryotherapy, hydrogen peroxide, ethanol and radiotherapy. New methods of treatment include thermal ablation with radiofrequency and laser, mainly utilized for treating osteoid osteoma. Arthroscopy allows resection of benign intra-joint lesions and assists the surgery of subchondral tumors. A great advance is the utilization of synthetic bone substitutes, which are a mixture of osteoinductive growth factors and osteoconductive ceramics, and have presented comparable results to autogenous bone grafts. There is a recent trend for closed treatments, with percutaneous injection of demineralized bone matrix (DBM) and calcium sulfate. Autogenous cancellous bone graft remains as the gold standard. Vascularized fibula graft, on the other hand, incorporates faster in the treatment of large destructive lesions. Also, allogenic cortical support allows structural augmentation for aggressive tumors. Freeze-dried allografts are used to fill contained defects and as expanders of autografts. Joint endoprosthesis may be used in large destructive lesions of the distal femur, hip and shoulder. PMID:27004184

  5. The mechanically stable steam sterilization of bone grafts.

    PubMed

    Draenert, G F; Delius, M

    2007-03-01

    Bone allografts are the standard material used in augmentative bone surgery. However, steam-sterilized bone has a low mechanical stability and limited ossification based on low strain-adapted bone remodelling. Here we describe a new technique which allows the bone to be autoclaved without losing its mechanical stability and osteoconductivity. The compression strength of the new material was compared with steam-sterilized and fresh bone based on mechanical testing using bone cylinders (n=30/group). Allogeneic new material and fresh bone were press-fit implanted into rabbit patellar grooves and examined under fluorescent light and conventional microscopy. Initial healing was assessed after 30 d (n=5/group). Osseous integration and remodelling was studied after 100 d (n=12/group). Steam-sterilized bone showed no mechanical stability, whereas the new material was stiff and had compression curves similar to fresh bone; both groups showed equal degrees of direct ossification after 30 d, advanced bony ingrowth and remodelling after 100 d, and similar ingrowth depths on histomorphometric analysis. The new method preserved the stiffness and osteoconductivity of bone after steam sterilization, and microstructure, mineralization, and composition were conserved. This technique could be useful for bone banking in Third World countries.

  6. [Bone bank management using a thermal disinfection system (Lobator SD-1). A critical analysis].

    PubMed

    Hofmann, C; von Garrel, T; Gotzen, L

    1996-07-01

    In the study presented on 380 allogenic bone donations from living and organ donors, we analyzed the safety of allograft handling bone-band documentation, logistics and costs. For transplant treatment we routinely used a thermal disinfection system (Lobator SD-1). From 380 allograft donors, 400 bone transplants were gained. The rejection rate was 12.2%. After thermal disinfection for 1 h at 80 degrees C, the grafts were cryopreserved at -80 degrees C and released from the bone bank for potential transplantation after 14-16 days. Five of 730 microbiological specimens showed bacterial contamination after thermal graft decontamination. The bacterial species found on the allografts normally have an inactivation temperature under 80 degrees C. Therefore, only secondary contamination can explain the positive bacteriological test results. With reform of the health care system the economical aspects of bone banking have triggered more interest. The cost for one bone transplant released from the bone bank was 424.75 DM: the overall cost for the bone bank in one year was 75,076 DM. Laboratory (58.2%) and material costs (22.5%) were the major factors. Personnel costs and apparatus costs were relatively low (< 20%). With introduction of the thermal disinfection system (Lobator SD-1) into the bone bank, the safety of allogenic bone transplants was greatly improved. Clinical and serological donor screening must be performed according to international bone bank directives. Considering the low rejection rate and the short turnover rate, the economical costs could be reduced. Using an appropriate disinfection system (thermal disinfection at 80 degrees C), laboratory tests covering venereal diseases, malaria and cytomegalia are no longer required. Also, secondary HIV testing of living donors can be omitted without reducing the safety of the transplant.

  7. Biologic and clinical aspects of integration of different bone substitutes in oral surgery: a literature review.

    PubMed

    Zizzari, Vincenzo Luca; Zara, Susi; Tetè, Giulia; Vinci, Raffaele; Gherlone, Enrico; Cataldi, Amelia

    2016-10-01

    Many bone substitutes have been proposed for bone regeneration, and researchers have focused on the interactions occurring between grafts and host tissue, as the biologic response of host tissue is related to the origin of the biomaterial. Bone substitutes used in oral and maxillofacial surgery could be categorized according to their biologic origin and source as autologous bone graft when obtained from the same individual receiving the graft; homologous bone graft, or allograft, when harvested from an individual other than the one receiving the graft; animal-derived heterologous bone graft, or xenograft, when derived from a species other than human; and alloplastic graft, made of bone substitute of synthetic origin. The aim of this review is to describe the most commonly used bone substitutes, according to their origin, and to focus on the biologic events that ultimately lead to the integration of a biomaterial with the host tissue.

  8. [Custom-made artificial bones fabricated by an inkjet printing technology].

    PubMed

    Igawa, Kazuyo; Chung, Ung-il; Tei, Yuichi

    2008-12-01

    Although current treatment modalities for bone defects include autograft, allograft, and artificial bone substitutes, they have problems concerning invasiveness, safety, and performance, respectively, calling for development of innovative artificial bones with better handling and mechanical strength, better control of external and internal structures, and better biodegradability and osteo-inductive ability. We propose to fabricate novel high performance artificial bones using 3D inkjet printer based on the image data of bone deformity. Shape precisely fitting to the deformity, internal structure facilitating cell invasion, and good biodegradability are achieved. Bioactive substances can be incorporated by printing in combination with drug delivery system to induce bone regeneration at desired locations. These osteo-inductive artificial bones will help efficiently treat various types of bone deformity in a less invasive and safe manner.

  9. Living Bones, Strong Bones

    NASA Video Gallery

    In this classroom activity, engineering, nutrition, and physical activity collide when students design and build a healthy bone model of a space explorer which is strong enough to withstand increas...

  10. Bone Tumor

    MedlinePlus

    ... most common types of primary bone cancer are: • Multiple myeloma. Multiple myeloma is the most common primary bone cancer. It ... Any bone can be affected by this cancer. Multiple myeloma affects approximately six people per 100,000 each ...

  11. Bone Cancer

    MedlinePlus

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  12. Both rejection and tolerance of allografts can occur in the absence of secondary lymphoid tissues.

    PubMed

    Kant, Cavit D; Akiyama, Yoshinobu; Tanaka, Katsunori; Shea, Susan; Yamada, Yohei; Connolly, Sarah E; Marino, Jose; Tocco, Georges; Benichou, Gilles

    2015-02-01

    In this study, we showed that aly/aly mice, which are devoid of lymph nodes and Peyer's patches, acutely rejected fully allogeneic skin and heart grafts. They mounted potent inflammatory direct alloresponses but failed to develop indirect alloreactivity after transplantation. Remarkably, skin allografts also were rejected acutely by splenectomized aly/aly (aly/aly-spl(-)) mice devoid of all secondary lymphoid organs. In these recipients, the rejection was mediated by alloreactive CD8(+) T cells presumably primed in the bone marrow. In contrast, cardiac transplants were not rejected by aly/aly-spl(-) mice. Actually, aly/aly-spl(-) mice that spontaneously accepted a heart allotransplant and displayed donor-specific tolerance also accepted skin grafts from the same, but not a third-party, donor via a mechanism involving CD4(+) regulatory T cells producing IL-10 cytokine. Therefore, direct priming of alloreactive T cells, as well as rejection and regulatory tolerance of allogeneic transplants, can occur in recipient mice lacking secondary lymphoid organs.

  13. Recurrent 2,8-dihydroxyadenine nephropathy: a rare but preventable cause of renal allograft failure

    PubMed Central

    Zaidan, Mohamad; Palsson, Runolfur; Gall, Emilie Cornec-Le; Garstka, Antoine; Maggiore, Umberto; Deteix, Patrice; Battista, Michele; Gagné, Eve-Reine; Ceballos-Picot, Irène; Van Huyen, Jean-Paul Duong; Legendre, Christophe; Daudon, Michel; Edvardsson, Vidar O.; Knebelmann, Bertrand

    2015-01-01

    Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive enzyme defect of purine metabolism that usually manifests as 2,8-dihydroxyadenine (2,8-DHA) nephrolithiasis and more rarely chronic kidney disease. The disease is most often misdiagnosed and can recur in the renal allograft. We analyzed 9 patients with recurrent 2,8-DHA crystalline nephropathy, in all of whom the diagnosis had been missed prior to renal transplantation. The diagnosis was established for a median of 5 (range, 1.5–312) weeks following the transplant procedure. Patients had delayed graft function (n=2), acute-on-chronic (n=5) or acute (n=1) allograft dysfunction, whereas one patient had normal graft function at the time of diagnosis. Analysis of allograft biopsies showed birefringent 2,8-DHA crystals in renal tubular lumens, within tubular epithelial cells and interstitium. Fourier transformed infrared microscopy confirmed the diagnosis in all cases, which was further supported by 2,8-DHA crystalluria, undetectable erythrocyte APRT enzyme activity, and genetic testing. With allopurinol therapy, the allograft function improved (n=7), remained stable (n=1), or worsened (n=1). At last follow-up, 2 patients had experienced allograft loss and 5 had persistent chronic allograft dysfunction. 2,8-DHA nephropathy is a rare but underdiagnosed and preventable disorder that can recur in the renal allograft and may lead to allograft loss. PMID:25307253

  14. Spleen tyrosine kinase contributes to acute renal allograft rejection in the rat.

    PubMed

    Ramessur Chandran, Sharmila; Tesch, Greg H; Han, Yingjie; Woodman, Naomi; Mulley, William R; Kanellis, John; Blease, Kate; Ma, Frank Y; Nikolic-Paterson, David J

    2015-02-01

    Kidney allografts induce strong T-cell and antibody responses which mediate acute rejection. Spleen tyrosine kinase (Syk) is expressed by most leucocytes, except mature T cells, and is involved in intracellular signalling following activation of the Fcγ-receptor, B-cell receptor and some integrins. A role for Syk signalling has been established in antibody-dependent native kidney disease, but little is known of Syk in acute renal allograft rejection. Sprague-Dawley rats underwent bilateral nephrectomy and received an orthotopic Wistar renal allograft. Recipient rats were treated with a Syk inhibitor (CC0482417, 30 mg/kg/bid), or vehicle, from 1 h before surgery until being killed 5 days later. Vehicle-treated recipients developed severe allograft failure with marked histologic damage in association with dense leucocyte infiltration (T cells, macrophages, neutrophils and NK cells) and deposition of IgM, IgG and C3. Immunostaining identified Syk expression by many infiltrating leucocytes. CC0482417 treatment significantly improved allograft function and reduced histologic damage, although allograft injury was still clearly evident. CC0482417 failed to prevent T-cell infiltration and activation within the allograft. However, CC0482417 significantly attenuated acute tubular necrosis, infiltration of macrophages and neutrophils and thrombosis of peritubular capillaries. In conclusion, this study identifies a role for Syk in acute renal allograft rejection. Syk inhibition may be a useful addition to T-cell-based immunotherapy in renal transplantation.

  15. B cells assist allograft rejection in the deficiency of protein kinase c-theta.

    PubMed

    Yan, Wenwei; Xu, Rui; Ma, Lian Li; Han, Wei; Geevarghese, Sunil K; Williams, Phillip E; Sciammas, Roger; Chong, Anita S; Yin, Deng Ping

    2013-09-01

    We have previously shown that mice deficient in protein kinase C theta (PKCθ) have the ability to reject cardiac allografts, but are susceptible to tolerance induction. Here we tested role of B cells in assisting alloimmune responses in the absence of PKCθ. Mouse cardiac allograft transplantations were performed from Balb/c (H-2d) to PKCθ knockout (PKCθ(-/-)), PKCθ and B cell double-knockout (PBDK, H-2b) mice and wild-type (WT) C57BL/6 (H-2b) mice. PBDK mice spontaneously accepted the allografts with the inhibition of NF-κB activation in the donor cardiac allograft. Anti-B cell antibody (rituximab) significantly delayed allograft rejection in PKCθ(-/-), but not in WT mice. Co-transfer of PKCθ(-/-) T plus PKCθ(-/-) B cells or primed sera triggered allograft rejection in Rag1(-/-) mice, and only major histocompatibility complex class II-enriched B cells, but not class I-enriched B cells, were able to promote rejection. This, together with the inability of PKCθ(-/-) and CD28(-/-) double-deficient (PCDK) mice to acutely reject allografts, suggested that an effective cognate interaction between PKCθ(-/-) T and B cells for acute rejection is CD28 molecule dependent. We conclude that T-B cell interactions synergize with PKCθ(-/-) T cells to mediate acute allograft rejection.

  16. Monitoring of human liver and kidney allograft tolerance: a tissue/histopathology perspective.

    PubMed

    Demetris, Anthony J; Lunz, John G; Randhawa, Parmjeet; Wu, Tong; Nalesnik, Michael; Thomson, Angus W

    2009-01-01

    Several factors acting together have recently enabled clinicians to seriously consider whether chronic immunosuppression is needed in all solid organ allograft recipients. This has prompted a dozen or so centers throughout the world to prospectively wean immunosuppression from conventionally treated liver allograft recipients. The goal is to lessen the impact of chronic immunosuppression and empirically identify occasional recipients who show operational tolerance, defined as gross phenotype of tolerance in the presence of an immune response and/or immune deficit that has little or no significant clinical impact. Rare operationally tolerant kidney allograft recipients have also been identified, usually by single case reports, but only a couple of prospective weaning trials in conventionally treated kidney allograft recipients have been attempted and reported. Pre- and postweaning allograft biopsy monitoring of recipients adds a critical dimension to these trials, not only for patient safety but also for determining whether events in the allografts can contribute to a mechanistic understanding of allograft acceptance. The following is based on a literature review and personal experience regarding the practical and scientific aspects of biopsy monitoring of potential or actual operationally tolerant human liver and kidney allograft recipients where the goal, intended or attained, was complete withdrawal of immunosuppression.

  17. Dehydrated Amniotic Membrane Allograft for Treatment of Chronic Leg Ulcers in Patients With Multiple Comorbidities: A Case Series

    PubMed Central

    Barr, Stephen M.

    2016-01-01

    Cellular and/or tissue-based products (CTPs) are emerging treatment options for chronic non-healing wounds. Dehydrated amniotic membrane allograft (DAMA) was used in 7 patients whose wounds had not responded adequately to standard and adjuvant therapies; four VLUs, 2 surgical wounds, and 1 DFU. Patients had multiple comorbidities, including 2 with autoimmune disorders (CREST syndrome and systemic lupus erythematosus). Patients received 3–8 applications of DAMA at weekly to biweekly intervals (average, 5.4 applications). Complete wound healing was observed in 6 of 7 patients during study period, with an average time to closure of 7.9 weeks. Closure was achieved in 3 of 7 patients after 3 DAMA applications. In the patient with CREST syndrome who did not completely close, DAMA reduced the area and volume by nearly 50% and later went on to closure. These cases suggest that DAMA is a viable option for recalcitrant DFUs, VLUs, and surgical wounds. PMID:27104144

  18. Strontium in the bone-implant interface.

    PubMed

    Vestermark, Marianne Toft

    2011-05-01

    Total hip replacement surgery is being performed on an increasingly large part of the population and at increasingly younger age. Because we live and stay physically active longer, and since hip replacement surgery has become quite successful, the treatment is being offered to progressively more patients. Unfortunately, about 17% of hip replacement surgeries currently involve revisions. Consequently, the longevity of both the primary and revision implant is an issue and warrants further investigation. Implants undergoing early instability or even subsidence correlate with an increased risk of aseptic loosening, subsequently requiring revision. Thus, the goal is early fixation by osseointegration of the implant. For revision implants, this is an even greater challenge since an allograft is often needed during surgery to obtain immediate stability of the implant. Bone grafts are rapidly resorbed. Thus, instability of the prosthesis may develop before new bone formation is well established and can mechanically secure the prosthesis. Strontium is a dual action drug; being both bone anabolic and anti-catabolic. In the form of strontiumranelate, it is used in the treatment of osteoporosis. Strontium may potentially improve the early osseointegration and fixation of implants. This dissertation consists of three studies investigating the effect of strontium at the bone-implant interface. The questions were firstly, what is the optimal delivery method for strontium to the interface, and secondly, can strontium exercise its dual action at the interface? The studies were performed in a cementless, experimental gap model in canine. The effects of strontium were evaluated by histomorphometrical analysis of the osseointegration and mechanical push-out test of implant fixation. Different stereological methods were used for the histomorphometrical analysis of each study. The methods used were reviewed critically and found valid. Study I compared a 5% strontium

  19. Management of Humeral and Glenoid Bone Loss in Recurrent Glenohumeral Instability

    PubMed Central

    Rusen, Jamie; Leiter, Jeff; Chahal, Jaskarndip; MacDonald, Peter

    2014-01-01

    Recurrent shoulder instability and resultant glenoid and humeral head bone loss are not infrequently encountered in the population today, specifically in young, athletic patients. This review on the management of bone loss in recurrent glenohumeral instability discusses the relevant shoulder anatomy that provides stability to the shoulder joint, relevant history and physical examination findings pertinent to recurrent shoulder instability, and the proper radiological imaging choices in its workup. Operative treatments that can be used to treat both glenoid and humeral head bone loss are outlined. These include coracoid transfer procedures and allograft/autograft reconstruction at the glenoid, as well as humeral head disimpaction/humeroplasty, remplissage, humeral osseous allograft reconstruction, rotational osteotomy, partial humeral head arthroplasty, and hemiarthroplasty on the humeral side. Clinical outcomes studies reporting general results of these techniques are highlighted. PMID:25136461

  20. Meniscal allograft transplantation--part I: background, results, graft selection and preservation, and surgical considerations.

    PubMed

    Rijk, Paul C

    2004-09-01

    Removal of the meniscus leads to progressive degenerative arthritis of the knee on a long-term basis. Therefore, meniscal allograft transplantation has been proposed as an alternative to meniscectomy. Although several experimental and clinical studies have documented that meniscal allografts show capsular ingrowth in meniscectomized knees, it remains to be established whether meniscal allograft transplantation can prevent degenerative changes after meniscectomy. Part 1 of this Current Concepts review will discuss the function, anatomy, and composition of the meniscus, followed by the history of surgery of meniscal tears and the healing of meniscal allografts in experimental and clinical studies. In addition, issues concerning preservation techniques, immunological reactions, sizing, disease transmission, indications, surgical technique, graft fixation, rehabilitation, and complications, will be taken into consideration. It can be concluded that the use of meniscal allografts in clinical practice has progressed to a point where relief of pain may be expected for the short-term.

  1. Abdominal aortic aneurysm repair in patient with a renal allograft: a case report.

    PubMed

    Kim, Hyung-Kee; Ryuk, Jong-Pil; Choi, Hyang Hee; Kwon, Sang-Hwy; Huh, Seung

    2009-02-01

    Renal transplant recipients requiring aortic reconstruction due to abdominal aortic aneurysm (AAA) pose a unique clinical problem. The concern during surgery is causing ischemic injury to the renal allograft. A variety of strategies for protection of the renal allograft during AAA intervention have been described including a temporary shunt, cold renal perfusion, extracorporeal bypass, general hypothermia, and endovascular stent-grafting. In addition, some investigators have reported no remarkable complications of the renal allograft without any specific measures. We treated a case of AAA in a patient with a renal allograft using a temporary aortofemoral shunt with good result. Since this technique is safe and effective, it should be considered in similar patients with AAA and previously placed renal allografts.

  2. Meniscal allograft transplantation--part I: background, results, graft selection and preservation, and surgical considerations.

    PubMed

    Rijk, Paul C

    2004-09-01

    Removal of the meniscus leads to progressive degenerative arthritis of the knee on a long-term basis. Therefore, meniscal allograft transplantation has been proposed as an alternative to meniscectomy. Although several experimental and clinical studies have documented that meniscal allografts show capsular ingrowth in meniscectomized knees, it remains to be established whether meniscal allograft transplantation can prevent degenerative changes after meniscectomy. Part 1 of this Current Concepts review will discuss the function, anatomy, and composition of the meniscus, followed by the history of surgery of meniscal tears and the healing of meniscal allografts in experimental and clinical studies. In addition, issues concerning preservation techniques, immunological reactions, sizing, disease transmission, indications, surgical technique, graft fixation, rehabilitation, and complications, will be taken into consideration. It can be concluded that the use of meniscal allografts in clinical practice has progressed to a point where relief of pain may be expected for the short-term. PMID:15346115

  3. Microgravity and bone cell mechanosensitivity.

    PubMed

    Klein-Nulend, J; Bacabac, R G; Veldhuijzen, J P; Van Loon, J J W A

    2003-01-01

    The capacity of bone tissue to alter its mass and structure in response to mechanical demands has long been recognized but the cellular mechanisms involved remained poorly understood. Bone not only develops as a structure designed specifically for mechanical tasks, but it can adapt during life toward more efficient mechanical performance. Mechanical adaptation of bone is a cellular process and needs a biological system that senses the mechanical loading. The loading information must then be communicated to the effector cells that form new bone or destroy old bone. The in vivo operating cell stress derived from bone loading is likely the flow of interstitial fluid along the surface of osteocytes and lining cells. The response of bone cells in culture to fluid flow includes prostaglandin (PG) synthesis and expression of prostaglandin G/H synthase inducible cyclooxygenase (COX-2). Cultured bone cells also rapidly produce nitric oxide (NO) in response to fluid flow as a result of activation of endothelial nitric oxide synthase (ecNOS), which enzyme also mediates the adaptive response of bone tissue to mechanical loading. Earlier studies have shown that the disruption of the actin-cytoskeleton abolishes the response to stress, suggesting that the cytoskeleton is involved in cellular mechanotransduction. Microgravity, or better near weightlessness, is associated with the loss of bone in astronauts, and has catabolic effects on mineral metabolism in bone organ cultures. This might be explained as resulting from an exceptional form of disuse under near weightlessness conditions. However, under near weightlessness conditions the assembly of cytoskeletal elements may be altered since it has been shown that the direction of the gravity vector determines microtubular pattern formation in vivo. We found earlier that the transduction of mechanical signals in bone cells also involves the cytoskeleton and is related to PGE2 production. Therefore it is possible that the

  4. Microgravity and bone cell mechanosensitivity

    NASA Astrophysics Data System (ADS)

    Klein-Nulend, J.; Bacabac, R. G.; Veldhuijzen, J. P.; Van Loon, J. J. W. A.

    2003-10-01

    The capacity of bone tissue to alter its mass and structure in response to mechanical demands has long been recognized but the cellular mechanisms involved remained poorly understood. Bone not only develops as a structure designed specifically for mechanical tasks, but it can adapt during life toward more efficient mechanical performance. Mechanical adaptation of bone is a cellular process and needs a biological system that senses the mechanical loading. The loading information must then be communicated to the effector cells that form new bone or destroy old bone. The in vivo operating cell stress derived from bone loading is likely the flow of interstitial fluid along the surface of osteocytes and lining cells. The response of bone cells in culture to fluid flow includes prostaglandin (PG) synthesis and expression of prostaglandin G/H synthase inducible cyclooxygenase (COX-2). Cultured bone cells also rapidly produce nitric oxide (NO) in response to fluid flow as a result of activation of endothelial nitric oxide synthase (ecNOS), which enzyme also mediates the adaptive response of bone tissue to mechanical loading. Earlier studies have shown that the disruption of the actin-cytoskeleton abolishes the response to stress, suggesting that the cytoskeleton is involved in cellular mechanotransduction. Microgravity, or better near weightlessness, is associated with the loss of bone in astronauts, and has catabolic effects on mineral metabolism in bone organ cultures. This might be explained as resulting from an exceptional form of disuse under near weightlessness conditions. However, under near weightlessness conditions the assembly of cytoskeletal elements may be altered since it has been shown that the direction of the gravity vector determines microtubular pattern formation in vivo. We found earlier that the transduction of mechanical signals in bone cells also involves the cytoskeleton and is related to PGEZ production. Therefore it is possible that the

  5. Lymphocyte migration patterns in organ allograft recipients.

    PubMed

    Kupiec-Weglinski, J W; Tilney, N L

    1989-04-01

    A central tenet of immunology is the observation, made 30 years ago, that lymphocytes recirculate continuously between peripheral blood and lymphoid tissues. In recent years, the subject of lymphocyte migration, both under physiological conditions and in states of alloresponsiveness, has become more enigmatic. It lies outside most current topics of immunological investigations, labelling and tracing techniques are problematic, and many experimental findings are phenomenological and difficult to interpret. Indeed, our overall knowledge of the functional differences between the various host lymphoid compartments and their constituent cell populations remains rudimentary. However, as understanding increases regarding the host immunological events responding to an antigenic stimulus such as a graft, with growing definition of the distinctive and interconnecting roles of lymphocyte subpopulations and their products acting on each other to produce graft destruction, the conceptual importance of lymphocyte migration again is becoming obvious. This role includes many facets of immunity such as the effects of antigen specificity, immunologic memory, differential behavior of recirculating or sessile populations, and local and systemic contact between antigen and effector cells. It has become evident that lymphocytes migrate in a non-random and highly dynamic fashion determined by a range of specific and non-specific factors; in the setting of organ transplantation, patterns are profoundly affected by the interrelated cellular and humoral components of the immunological cascade which may lead either to graft rejection or to its prolongation in untreated and immunologically modified recipients, respectively. Thus, the traffic of lymphocytes throughout host lymphoid and non-lymphoid compartments and their activity within these compartments should be considered an integral part of the host immunomodulation triggered by transplantation of histoincompatible tissue. Gradual filling

  6. Bone and bone turnover.

    PubMed

    Crofton, Patricia M

    2009-01-01

    Children with cancer are exposed to multiple influences that may adversely affect bone health. Some treatments have direct deleterious effects on bone whilst others may have indirect effects mediated through various endocrine abnormalities. Most clinical outcome studies have concentrated on survivors of acute lymphoblastic leukaemia (ALL). There is now good evidence that earlier treatment protocols that included cranial irradiation with doses of 24 Gy or greater may result in growth hormone deficiency and low bone mineral density (BMD) in the lumbar spine and femoral neck. Under current protocols, BMD decreases during intensive chemotherapy and fracture risk increases. Although total body BMD may eventually return to normal after completion of chemotherapy, lumbar spine trabecular BMD may remain low for many years. The implications for long-term fracture risk are unknown. Risk factors for low BMD include high dose methotrexate, higher cumulative doses of glucocorticoids, male gender and low physical activity. BMD outcome in non-ALL childhood cancers has been less well studied but there is evidence that survivors of childhood brain or bone tumours, and survivors of bone marrow transplants for childhood malignancy, all have a high risk of long-term osteopenia. Long-term follow-up is required, with appropriate treatment of any endocrine abnormalities identified.

  7. Evaluation and utility of new CE marked containers (CELLFLEX-MacoPharma) for bone bank.

    PubMed

    Villalba, R; Fornés, G; Dueñas, R; García, A; Ariza, A; Gómez-Villagrán, J L

    2004-01-01

    In order to guarantee the required level of quality for our Bone &Tissue Banking, we evaluated a new CE marked container (CELLFLEX MacoPharma), for packing, transport, processing and storage of bones for therapeutic use. The use of CE marked containers is mandatory for organ and tissue containers (Medical Device Directive 93/42). We carried out a three-phase study: (1)Evaluation, (2) Implementation, (3)Audit The product was evaluated for the following criteria:Dash mechanical resistance, Dash air tightness, Dash fragility, Dash capacity. No damage was observed after the storage period, even after immersion in liquid nitrogen. No breakages were observed after provoked impact tests (pots dropped onto the floor). The pot capacity evaluation showed that the inner pot volume (approximately 500 ml) permits adequate storage of tendons and the majority of bone allografts. In conclusion, this evaluation has shown that the CELLFLEX kit is suitable for long duration preservation of bone allografts even at very low temperature conditions (vapour phase nitrogen). Its format and structure permit preservation of most bone allografts. PMID:15591830

  8. The effect of supercritical carbon dioxide sterilization on the anisotropy of bovine cortical bone.

    PubMed

    Russell, Nicholas; Rives, Alain; Pelletier, Matthew H; Wang, Tian; Walsh, William R

    2015-03-01

    Bone allografts are used to replace bone that has been removed or to augment bone tissue in a number of clinical scenarios. In order to minimize the risk of infection and immune response, the bone is delipidated and terminally sterilized prior to implantation. The optimal method for bone graft sterilization has been the topic of considerable research and debate. Recently, supercritical carbon dioxide (SCCO(2)) treatments have been shown to terminally sterilize bone against a range of bacteria and viruses. This study aimed to evaluate the effect of these SCCO(2) treatments on the anisotropic mechanical properties of cortical bone. Adult bovine cortical cubes were prepared and treated using SCCO(2) and a range of common processing additives (ethanol, peracetic acid and hydrogen peroxide). The bone was mechanically tested in uniaxial compression in the axial, radial and tangential orientations. Ultimate stress, strain, elastic modulus, energy and stiffness were evaluated. This study found that SCCO(2) treatment without additive did not alter the ultimate stress, stiffness or energy to failure depreciably in any orientation. The addition of sterilants peracetic acid and hydrogen peroxide also preserved mechanical function, with no deleterious effect on stress or stiffness. This study highlights the expediency of SCCO(2) treatment for bone allograft processing as terminal sterilization can be achieved while maintaining the intrinsic mechanical properties of the graft.

  9. The effect of supercritical carbon dioxide sterilization on the anisotropy of bovine cortical bone.

    PubMed

    Russell, Nicholas; Rives, Alain; Pelletier, Matthew H; Wang, Tian; Walsh, William R

    2015-03-01

    Bone allografts are used to replace bone that has been removed or to augment bone tissue in a number of clinical scenarios. In order to minimize the risk of infection and immune response, the bone is delipidated and terminally sterilized prior to implantation. The optimal method for bone graft sterilization has been the topic of considerable research and debate. Recently, supercritical carbon dioxide (SCCO(2)) treatments have been shown to terminally sterilize bone against a range of bacteria and viruses. This study aimed to evaluate the effect of these SCCO(2) treatments on the anisotropic mechanical properties of cortical bone. Adult bovine cortical cubes were prepared and treated using SCCO(2) and a range of common processing additives (ethanol, peracetic acid and hydrogen peroxide). The bone was mechanically tested in uniaxial compression in the axial, radial and tangential orientations. Ultimate stress, strain, elastic modulus, energy and stiffness were evaluated. This study found that SCCO(2) treatment without additive did not alter the ultimate stress, stiffness or energy to failure depreciably in any orientation. The addition of sterilants peracetic acid and hydrogen peroxide also preserved mechanical function, with no deleterious effect on stress or stiffness. This study highlights the expediency of SCCO(2) treatment for bone allograft processing as terminal sterilization can be achieved while maintaining the intrinsic mechanical properties of the graft. PMID:24737303

  10. Denosumab for bone diseases: translating bone biology into targeted therapy.

    PubMed

    Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

    2011-12-01

    Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

  11. Function of osteocytes in bone.

    PubMed

    Aarden, E M; Burger, E H; Nijweide, P J

    1994-07-01

    Although the structural design of cellular bone (i.e., bone containing osteocytes that are regularly spaced throughout the bone matrix) dates back to the first occurrence of bone as a tissue in evolution, and although osteocytes represent the most abundant cell type of bone, we know as yet little about the role of the osteocyte in bone metabolism. Osteocytes descend from osteoblasts. They are formed by the incorporation of osteoblasts into the bone matrix. Osteocytes remain in contact with each other and with cells on the bone surface via gap junction-coupled cell processes passing through the matrix via small channels, the canaliculi, that connect the cell body-containing lacunae with each other and with the outside world. During differentiation from osteoblasts to mature osteocyte the cells lose a large part of their cell organelles. Their cell processes are packed with microfilaments. In this review we discuss the various theories on osteocyte function that have taken in consideration these special features of osteocytes. These are 1) osteocytes are actively involved in bone turnover; 2) the osteocyte network is through its large cell-matrix contact surface involved in ion exchange; and 3) osteocytes are the mechanosensory cells of bone and play a pivotal role in functional adaptation of bone. In our opinion, especially the last theory offers an exciting concept for which some biomechanical, biochemical, and cell biological evidence is already available and which fully warrants further investigations.

  12. Generation of suppressive blood cells for control of allograft rejection.

    PubMed

    Kleist, Christian; Sandra-Petrescu, Flavius; Jiga, Lucian; Dittmar, Laura; Mohr, Elisabeth; Greil, Johann; Mier, Walter; Becker, Luis E; Lang, Peter; Opelz, Gerhard; Terness, Peter

    2015-05-01

    Our previous studies in rats showed that incubation of monocytic dendritic cells (DCs) with the chemotherapeutic drug mitomycin C (MMC) renders the cells immunosuppressive. Donor-derived MMC-DCs injected into the recipient prior to transplantation prolonged heart allograft survival. Although the generation of DCs is labour-intensive and time-consuming, peripheral blood mononuclear cells (PBMCs) can be easily harvested. In the present study, we analyse under which conditions DCs can be replaced by PBMCs and examine their mode of action. When injected into rats, MMC-incubated donor PBMCs (MICs) strongly prolonged heart allograft survival. Removal of monocytes from PBMCs completely abrogated their suppressive effect, indicating that monocytes are the active cell population. Suppression of rejection was donor-specific. The injected MICs migrated into peripheral lymphoid organs and led to an increased number of regulatory T-cells (Tregs) expressing cluster of differentiation (CD) markers CD4 and CD25 and forkhead box protein 3 (FoxP3). Tolerance could be transferred to syngeneic recipients with blood or spleen cells. Depletion of Tregs from tolerogenic cells abrogated their suppressive effect, arguing for mediation of immunosuppression by CD4⁺CD25⁺FoxP3⁺ Tregs. Donor-derived MICs also prolonged kidney allograft survival in pigs. MICs generated from donor monocytes were applied for the first time in humans in a patient suffering from therapy-resistant rejection of a haploidentical stem cell transplant. We describe, in the present paper, a simple method for in vitro generation of suppressor blood cells for potential use in clinical organ transplantation. Although the case report does not allow us to draw any conclusion about their therapeutic effectiveness, it shows that MICs can be easily generated and applied in humans.

  13. Characteristics of Cardiac Allograft Vasculopathy Induced by Immunomodulation in the Miniature Swine

    PubMed Central

    Akashima, Tomohiro; Terasaki, Takamitsu; Wada, Yuko; Ito-Amano, Midori; Suzuki, Jun-ichi; Isobe, Mitsuaki

    2014-01-01

    Purpose: We aimed to develop swine cardiac transplantation model for study of cardiac allograft vasculopathy (CAV) and to characterize the mechanisms of its formation. Methods: Heterotropic cardiac transplantation was performed in swine leukocyte antigen mismatched miniature swine, and CAV was induced by immunomodulation by cyclosporine A (CyA). Histology and immunohistochemistry were performed to identify cellular components of CAV. Fluorescence in situ hybridization (FISH) was developed for detection of 1 and Y-chromosome for identification of cell origin in the female donor to the male recipient heart transplantation model. Results: CAV was successfully developed by immunomodulation of CyA. Severity of CAV revealed more prominent in the distal epicardial coronary arteries than proximal coronary arteries. Phenotype of the SMCs proliferated in the intimal thickening of CAV were mostly embryonal/secretory type. Our new chromosome specific probes for FISH method were useful for discrimination of sex of each cell, and proliferated SMCs were revealed to be mainly donor origin. Conclusion: CAV mimicking human heart transplantation can be developed by appropriate immunomodulation in the swine. In swine CAV, proliferated SMCs seen in the intimal thickening were demonstrated to be from the donor origin. PMID:24747545

  14. Postradiation atrophy of mature bone

    SciTech Connect

    Ergun, H.; Howland, W.J.

    1980-01-01

    The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.

  15. Human flexor tendon tissue engineering: revitalization of biostatic allograft scaffolds.

    PubMed

    Woon, Colin Y L; Farnebo, Simon; Schmitt, Taliah; Kraus, Armin; Megerle, Kai; Pham, Hung; Yan, Xinrui; Gambhir, Sanjiv S; Chang, James

    2012-12-01

    Cadaveric tendon allografts form a readily available and underutilized source of graft material. Because of their material properties, allografts are biomechanically and biologically superior to synthetic scaffolds. However, before clinical use, allografts must undergo decellularization to reduce immunogenicity and oxidation to increase porosity, leaving a nonvital biostatic scaffold. Ex vivo seeding, or revitalization, is thought to hasten graft incorporation and stimulate intrinsic tendon healing, permitting early mobilization and return to function. In this study, we examined physical and biochemical augmentation methods, including scaffold surface scoring (physical) and rehydration of lyophilized scaffolds in serum (biochemical). Scaffolds were divided into four groups: (1) scored scaffolds, (2) lyophilized scaffolds rehydrated in fetal calf serum (FCS), (3) scaffolds both scored and rehydrated in FCS, and (4) control scaffolds. Scaffolds were reseeded with adipose-derived stem cells (ADSCs). Reseeding efficacy was quantified by a live cell and total cell assays and qualified histologically with hematoxylin and eosin, live/dead and SYTO green nucleic acid stains, TUNEL apoptosis stains, procollagen stains, and transmission electron microscopy. Scaffold-seeded cell viability at up to 2 weeks in vitro and up to 4 weeks in vivo was demonstrated with bioluminescent imaging of scaffolds seeded with luciferase-positive ADSCs. The effect of seeding on scaffold biomechanical properties was demonstrated with evaluation of ultimate tensile stress (UTS) and an elastic modulus (EM). We found that scaffold surface scoring led to an increase in live and total cell attachment and penetration (MTS assay, p<0.001 and DNA assay, p=0.003, respectively). Histology confirmed greater total cell number in both construct core and surface in scored compared with unscored constructs. Cells reseeded on scored constructs displayed reduced apoptosis, persistent procollagen production, and

  16. Combined PCR and Q-RT-PCR technique for detecting chimerism in a non-human Primate vascularized osteomyocutaneous allografts model.

    PubMed

    Jiang, J; Wang, J; Zhong, F; Chen, G; Li, Y; Zheng, X X

    2016-01-01

    Face transplantation and other composite tissue transplantation (CTA) are permissive to transplantation tolerance. The real reason, that composite tissue containing bone achieves transplantation immune tolerance more easily than the composite tissue without the bone is not clear. The chimerism may be the main mechanism in the progress of inducing the transplantation tolerance by CTA. We currently have established a non-human Primate Vascularized Osteomyocutaneous Allografts Model. To test the chimerism which comes from donor after the transplantation, we developed a method which combined reverse transcription polymerase chain reaction (RT-PCR) and real-time quantitative PCR (qRT-PCR) technique using primers specific for Macaca fascicularis sex determination region on the Y chromosome (SRY) gene. With the method, we estimated the level of the chimerism. PMID:27453269

  17. Efficacy of a small cell-binding peptide coated hydroxyapatite substitute on bone formation and implant fixation in sheep.

    PubMed

    Ding, Ming; Andreasen, Christina M; Dencker, Mads L; Jensen, Anders E; Theilgaard, Naseem; Overgaard, Søren

    2015-04-01

    Cylindrical critical size defects were created at the distal femoral condyles bilaterally of eight female adult sheep. Titanium implants with 2-mm concentric gaps were inserted and the gaps were filled with one of the four materials: allograft; a synthetic 15-amino acid cell-binding peptide coated hydroxyapatite (ABM/P-15); hydroxyapatite + βtricalciumphosphate+ Poly-Lactic-Acid (HA/βTCP-PDLLA); or ABM/P-15+HA/βTCP-PDLLA. After nine weeks, bone-implant blocks were harvested and sectioned for micro-CT scanning, push-out test, and histomorphometry. Significant bone formation and implant fixation could be observed in all four groups. Interestingly, the microarchitecture of the ABM/P-15 group was significantly different from the control group. Tissue volume fraction and thickness were significantly greater in the ABM/P-15 group than in the allograft group. Bone formation and bone ingrowth to porous titanium implant were not significantly different among the four groups. The ABM/P-15 group had similar shear mechanical properties on implant fixation as the allograft group. Adding HA/βTCP-PDLLA to ABM/P-15 did not significantly change these parameters. This study revealed that ABM/P-15 had significantly bone formation in concentric gap, and its enhancements on bone formation and implant fixation were at least as good as allograft. It is suggested that ABM/P-15 might be a good alternative biomaterial for bone implant fixation in this well-validated critical-size defect gap model in sheep. Nevertheless, future clinical researches should focus on prospective, randomized, controlled trials in order to fully elucidate whether ABM/P-15 could be a feasible candidate for bone substitute material in orthopedic practices.

  18. Microgravity and Bone Cell Mechanosensitivity

    NASA Astrophysics Data System (ADS)

    Klein-Nulend, J.; Bacabac, R.; Veldhuijzen, J.; van Loon, J.

    The capacity of bone tissue to alter its mass and structure in response to mechanical demands has long been recognized but the cellular mechanisms involved remained poorly understood. Bone not only develops as a structure designed specifically for mechanical tasks, but it can adapt during life toward more efficient mechanical performance. Mechanical adaptation of bone is a cellular process and needs a biological system that senses the mechanical loading. The loading information must then be communicated to the effector cells that form new bone or destroy old bone.The in vivo operating cell stress derived from bone loading is likely flow of interstitial fluid along the surface of osteocytes and lining cells. The response of bone cells in culture to fluid flow includes prostaglandin (PG) synthesis and expression of prostaglandin G/H synthase inducible cyclooxygenase (COX-2). Cultured bone cells also rapidly produce nitric oxide (NO) in response to fluid flow as a result of activation of endothelial nitric oxide synthase (ecNOS), which enzyme also mediates the adaptive response of bone tissue to mechanical loading. Disruption of the actin-cytoskeleton abolishes the response to stress, suggesting that the cytoskeleton is involved in cellular mechanotransduction.Microgravity, or better near weightlessness, has catabolic effects on the skeleton of astronauts, and on mineral metabolism in bone organ cultures. This might be explained as resulting from an exceptional form of disuse under near weightlessness conditions. However, under near weightlessness conditions the assembly of cytoskeletal elements may be altered since it has been shown that the direction of the gravity vector determines microtubular pattern formation in vivo. We found that the transduction of mechanical signals in bone cells also involves the cytoskeleton and is related to PGE2 production. Therefore it is possible that the mechanosensitivity of bone cells is altered under near weightlessness conditions

  19. Increased BK viremia and progression to BK-virus nephropathy following high-dose intravenous immunoglobulin for acute cellular rejection.

    PubMed

    Boonyapredee, Maytee; Knight, Kendral; Little, Dustin

    2014-06-01

    BK virus nephropathy and cellular rejection are common causes of allograft dysfunction in renal transplant recipients. The two can be difficult to distinguish on allograft biopsy and can be present simultaneously. Management of the patient with coexistent BK infection and rejection is complicated by the conflicting ideals of decreasing immunosuppression to treat the former and increasing immunosuppression to treat the latter. The authors present the case of a 57-year-old renal transplant recipient who underwent allograft biopsy 8 weeks post-transplant for evaluation of increased serum creatinine in the setting of BK viremia (BKV). Biopsy revealed Banff classification 1b acute cellular rejection, with insufficient evidence to diagnose BK virus-associated nephropathy. The patient was administered intravenous immune globulin (IVIG), with no other changes in immunosuppressive therapy. Plasma and urine BK increased exponentially following IVIG administration, and allograft function further deteriorated. Repeat biopsy showed overt BK viral nephropathy, and BKV and creatinine decreased only after reduction in immunosuppression and initiation of leflunomide. Although case series have suggested a potential role for IVIG in the setting of BK infection, further study is needed to define the safety and efficacy of this approach.

  20. Bone scanning.

    PubMed

    Greenfield, L D; Bennett, L R

    1975-03-01

    Scanning is based on the uptake of a nuclide by the crystal lattice of bone and is related to bone blood flow. Cancer cells do not take up the tracer. Normally, the scan visualizes the highly vascular bones. Scans are useful and are indicated in metastatic bone disease, primary bone tumors, hematologic malignancies and some non-neoplastic diseases. The scan is more sensitive than x-ray in the detection of malignant diseases of the skeleton. PMID:1054210

  1. Chondroblastoma with secondary aneurysmal bone cyst of the capitate.

    PubMed

    Sato, Eiichi; Ichikawa, Jiro; Ando, Takashi; Sato, Nobutaka; Kawasaki, Tomonori; Haro, Hirotaka

    2014-05-01

    Chondroblastoma is a benign tumor that typically arises in the epiphysis of a long bone. There have been only 2 reported cases of chondroblastoma involving the capitate. This is the first report of chondroblastoma with secondary aneurysmal bone cyst involving the capitate. A 33-year-old man presented with a 3-year history of pain and swelling of the right wrist. Radiography as well as computed tomography showed a radiolucent area and no matrix calcification within the capitate. Magnetic resonance imaging revealed a homogeneous signal that was low on T1-weighted images and high on T2-weighted images and showed only slight enhancement. On the basis of imaging findings, the authors chose excisional biopsy. The bone tumor in the capitate was explored through a dorsal approach by dividing the extensor tendons. After repeated curettages, bone graft substitute using allograft bone was packed into the capitate. Histologically, the authors diagnosed this tumor as a chondroblastoma with a secondary aneurysmal bone cyst. At the final 2-year follow-up, there was evidence of bone union, full range of motion, and recovery and no evidence of recurrence. Although the recurrence of chondroblastoma is occasionally reported, the principal treatment is intralesional curettage and bone graft. High-speed burring, phenol, bone cement, and cryosurgery have been reported to reduce local recurrence. Complete excision of the carpal bone seems to be overtreatment.

  2. Chondroblastoma with secondary aneurysmal bone cyst of the capitate.

    PubMed

    Sato, Eiichi; Ichikawa, Jiro; Ando, Takashi; Sato, Nobutaka; Kawasaki, Tomonori; Haro, Hirotaka

    2014-05-01

    Chondroblastoma is a benign tumor that typically arises in the epiphysis of a long bone. There have been only 2 reported cases of chondroblastoma involving the capitate. This is the first report of chondroblastoma with secondary aneurysmal bone cyst involving the capitate. A 33-year-old man presented with a 3-year history of pain and swelling of the right wrist. Radiography as well as computed tomography showed a radiolucent area and no matrix calcification within the capitate. Magnetic resonance imaging revealed a homogeneous signal that was low on T1-weighted images and high on T2-weighted images and showed only slight enhancement. On the basis of imaging findings, the authors chose excisional biopsy. The bone tumor in the capitate was explored through a dorsal approach by dividing the extensor tendons. After repeated curettages, bone graft substitute using allograft bone was packed into the capitate. Histologically, the authors diagnosed this tumor as a chondroblastoma with a secondary aneurysmal bone cyst. At the final 2-year follow-up, there was evidence of bone union, full range of motion, and recovery and no evidence of recurrence. Although the recurrence of chondroblastoma is occasionally reported, the principal treatment is intralesional curettage and bone graft. High-speed burring, phenol, bone cement, and cryosurgery have been reported to reduce local recurrence. Complete excision of the carpal bone seems to be overtreatment. PMID:24810829

  3. Bone Targeted Therapies for Bone Metastasis in Breast Cancer

    PubMed Central

    Razaq, Wajeeha

    2013-01-01

    Cancer metastasis to the bone develops commonly in patients with various malignancies, and is a major cause of morbidity and diminished quality of life in many affected patients. Emerging treatments for metastatic bone disease have arisen from advances in our understanding of the unique cellular and molecular mechanisms that contribute to the bone metastasis. The tendency of cancer cells to metastasize to bone is probably the end result of many factors including vascular pathways, the highly vascular nature of the bone marrow (which increases the probability that cancer cells will be deposited in bone marrow capillaries), and molecular characteristics of the cancer cells that allow them to adapt to the bone marrow microenvironment. The goals of treating osseous metastases are manifold. Proper treatment can lead to significant improvements in pain control and function, and maintain skeletal integrity. The treatment plan requires a multidisciplinary approach. Widespread metastatic disease necessitates systemic therapy, while a localized problem is best managed with surgery, external beam radiotherapy, or both. Patients with bone metastasis can have prolonged survival, and proper management can have a significant impact on their quality of life. We will review the factors in this article that are promising molecular bone-targeted therapies or will be likely targets for future therapeutic intervention to restore bone remodeling and suppress tumor growth. PMID:26237142

  4. T cell requirements for the rejection of renal allografts bearing an isolated class I MHC disparity

    PubMed Central

    1990-01-01

    This study has examined the cellular and humoral responses underlying the rejection of rat renal allografts bearing an isolated RT1Aa class I MHC disparity. RT1Aa disparate kidneys were rejected promptly by high responder RT1u but not by low responder RT1c recipients (median survival time 10 d and greater than 100 d, respectively). The magnitude and phenotype of the cellular infiltrate were similar in rejecting and nonrejecting RT1Aa disparate kidneys. Paradoxically, graft infiltrating cells and spleen cells from RT1u recipients showed minimal ability to lyse donor strain lymphoblasts in vitro, whereas effector cells from RT1c recipients showed modest levels of cytotoxicity. Injection of RT1u rats with MRC OX8 mAb was highly effective at selectively depleting CD8+ cells from graft recipients but had no effect in prolonging the survival of RT1Aa disparate grafts despite the complete absence of CD8+ cells from the graft infiltrate, which included numerous CD4+ T cells and macrophages. RT1u, but not RT1c, recipients mounted a strong alloantibody response against RT1Aa disparate kidneys. Immune serum obtained from RT1u recipients that had rejected a RT1Aa disparate graft was able, when injected into cyclosporin-treated RT1u recipients, to restore their ability to reject a RT1Aa, but not a third-party RT1c, kidney. These results suggest that CD8+ cells in general and CD8+ cytotoxic effector cells in particular are unnecessary for the rapid rejection of RT1Aa class I disparate kidney grafts by high responder RT1u recipients. By implication, CD4+ T cells alone are sufficient to cause prompt rejection of such grafts and they may do so by providing T cell help for the generation of alloantibody. PMID:2258695

  5. Hydroxyapatite crystals as a bone graft substitute in benign lytic lesions of bone

    PubMed Central

    Gupta, Anil Kumar; Kumar, Praganesh; Keshav, Kumar; Singh, Anant

    2015-01-01

    Background: Bone grafts are required to fill a cavity created after curettage of benign lytic lesions of the bone. To avoid the problems associated at donor site with autologous bone graft, we require allograft or bone graft substitutes. We evaluated the healing of lytic lesions after hydroxyapatite (HA) grafting by serial radiographs. Materials and Methods: Forty cases of benign lytic lesions of bone were managed by simple curettage and grafting using HA blocks. Commercially available HA of bovine origin (Surgiwear Ltd., Shahjahanpur, India) was used for this purpose. Mean duration of followup was 34.8 months (range 12–84 months). Mean patient age was 19.05 years (range 3–55 years). Radiological staging of graft incorporation was done as per criteria of Irwin et al. 2001. Results: In our series, two cases were in stage I. A total of 11 cases were in stage II and 27 were in stage III. Graft incorporation was radiologically complete by 15 months. Clinical recovery was observed before radiological healing. The average time taken to return to preoperative function was 3 months. Recurrence was observed in giant cell tumor (n = 3) and chondromyxoid fibroma (n = 1). There was no incidence of graft rejection, collapse, growth plate disturbances or antigenic response. Conclusions: We conclude that calcium HA is biologically acceptable bone graft substitute in the management of benign lytic lesions of bone. PMID:26806973

  6. Calcium Phosphate Based Three-Dimensional Cold Plotted Bone Scaffolds for Critical Size Bone Defects

    PubMed Central

    Bergmann, Christian J. D.; Odekerken, Jim C. E.; Welting, Tim J. M.; Jungwirth, Franz; Devine, Declan; Bouré, Ludovic; Zeiter, Stephan; van Rhijn, Lodewijk W.; Telle, Rainer; Fischer, Horst; Emans, Pieter J.

    2014-01-01

    Bone substitutes, like calcium phosphate, are implemented more frequently in orthopaedic surgery to reconstruct critical size defects, since autograft often results in donor site morbidity and allograft can transmit diseases. A novel bone cement, based on β-tricalcium phosphate, polyethylene glycol, and trisodium citrate, was developed to allow the rapid manufacturing of scaffolds, by extrusion freeform fabrication, at room temperature. The cement composition exhibits good resorption properties and serves as a basis for customised (e.g., drug or growth factor loaded) scaffolds for critical size bone defects. In vitro toxicity tests confirmed proliferation and differentiation of ATDC5 cells in scaffold-condi