Brief reports: regional anesthesia needles can introduce ultrasound gel into tissues.

PubMed

Belavy, David

2010-09-01

Anesthesiologists may insert needles through ultrasound gel when performing ultrasound-guided regional anesthesia. In this study, it was determined whether needles carry gel into tissues. Ultrasound gel dyed blue was applied to pork rashers. Tuohy and short-bevel needles were passed through the gel and pork. The needles were then assessed for the presence of ultrasound gel. All needles, including those with stylets, carried gel and tissue within the lumen. Ultrasound gel may be injected around (and perhaps in) nerves during regional anesthesia procedures. Studies are needed to determine the implications of this practice.

Infant phantom head circuit board for EEG head phantom and pediatric brain simulation

NASA Astrophysics Data System (ADS)

Almohsen, Safa

The infant's skull differs from an adult skull because of the characteristic features of the human skull during early development. The fontanels and the conductivity of the infant skull influence surface currents, generated by neurons, which underlie electroencephalography (EEG) signals. An electric circuit was built to power a set of simulated neural sources for an infant brain activity simulator. Also, in the simulator, three phantom tissues were created using saline solution plus Agarose gel to mimic the conductivity of each layer in the head [scalp, skull brain]. The conductivity measurement was accomplished by two different techniques: using the four points' measurement technique, and a conductivity meter. Test results showed that the optimized phantom tissues had appropriate conductivities to simulate each tissue layer to fabricate a physical head phantom. In this case, the best results should be achieved by testing the electrical neural circuit with the sample physical model to generate simulated EEG data and use that to solve both the forward and the inverse problems for the purpose of localizing the neural sources in the head phantom.

Gel phase formation in dilute triblock copolyelectrolyte complexes

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

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chainmore » aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.« less

Gel phase formation in dilute triblock copolyelectrolyte complexes

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

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chainmore » aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Finally, our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.« less

Gel phase formation in dilute triblock copolyelectrolyte complexes

DOE PAGES

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.; ...

2017-02-23

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chainmore » aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Finally, our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.« less

Gel Phase Formation in Dilute Triblock Copolyelectrolyte Complexes

NASA Astrophysics Data System (ADS)

Srivastava, Samanvaya; Andreev, Marat; Prabhu, Vivek; de Pablo, Juan; Tirrell, Matthew

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at extremely low polymer concentrations (<1 % by mass) has been observed in scattering experiments and molecular dynamics simulations. In contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing polymer concentrations, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assemblies of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously upon solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chain aggregates in early stages of triblock copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries not only contribute to our fundamental understanding of the structure and pathways of complexation driven assemblies, but also raise intriguing prospects for formation of gel structures at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.

Gel phase formation in dilute triblock copolyelectrolyte complexes

NASA Astrophysics Data System (ADS)

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.; Goldfeld, David J.; Mao, Jun; Heller, William T.; Prabhu, Vivek M.; de Pablo, Juan J.; Tirrell, Matthew V.

2017-02-01

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chain aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.

In vitro mechanical fatigue behavior of poly-ɛ-caprolactone macroporous scaffolds for cartilage tissue engineering: Influence of pore filling by a poly(vinyl alcohol) gel.

PubMed

Panadero, J A; Vikingsson, L; Gomez Ribelles, J L; Lanceros-Mendez, S; Sencadas, V

2015-07-01

Polymeric scaffolds used in regenerative therapies are implanted in the damaged tissue and submitted to repeated loading cycles. In the case of articular cartilage engineering, an implanted scaffold is typically subjected to long-term dynamic compression. The evolution of the mechanical properties of the scaffold during bioresorption has been deeply studied in the past, but the possibility of failure due to mechanical fatigue has not been properly addressed. Nevertheless, the macroporous scaffold is susceptible to failure after repeated loading-unloading cycles. In this work fatigue studies of polycaprolactone scaffolds were carried by subjecting the scaffold to repeated compression cycles in conditions simulating the scaffold implanted in the articular cartilage. The behavior of the polycaprolactone sponge with the pores filled with a poly(vinyl alcohol) gel simulating the new formed tissue within the pores was compared with that of the material immersed in water. Results were analyzed with Morrow's criteria for failure and accurate fittings are obtained just up to 200 loading cycles. It is also shown that the presence of poly(vinyl alcohol) increases the elastic modulus of the scaffolds, the effect being more pronounced with increasing the number of freeze/thawing cycles. © 2014 Wiley Periodicals, Inc.

Fabrication of micro-alginate gel tubes utilizing micro-gelatin fibers

NASA Astrophysics Data System (ADS)

Sakaguchi, Katsuhisa; Arai, Takafumi; Shimizu, Tatsuya; Umezu, Shinjiro

2017-05-01

Tissues engineered utilizing biofabrication techniques have recently been the focus of much attention, because these bioengineered tissues have great potential to improve the quality of life of patients with various hard-to-treat diseases. Most tissues contain micro-tubular structures including blood vessels, lymphatic vessels, and bile canaliculus. Therefore, we bioengineered a micro diameter tube using alginate gel to coat the core gelatin gel. Micro-gelatin fibers were fabricated by the coacervation method and then coated with a very thin alginate gel layer by dipping. A micro diameter alginate tube was produced by dissolving the core gelatin gel. Consequently, these procedures led to the formation of micro-alginate gel tubes of various shapes and sizes. This biofabrication technique should contribute to tissue engineering research fields.

3D conformal MRI-controlled transurethral ultrasound prostate therapy: validation of numerical simulations and demonstration in tissue-mimicking gel phantoms.

PubMed

Burtnyk, Mathieu; N'Djin, William Apoutou; Kobelevskiy, Ilya; Bronskill, Michael; Chopra, Rajiv

2010-11-21

MRI-controlled transurethral ultrasound therapy uses a linear array of transducer elements and active temperature feedback to create volumes of thermal coagulation shaped to predefined prostate geometries in 3D. The specific aims of this work were to demonstrate the accuracy and repeatability of producing large volumes of thermal coagulation (>10 cc) that conform to 3D human prostate shapes in a tissue-mimicking gel phantom, and to evaluate quantitatively the accuracy with which numerical simulations predict these 3D heating volumes under carefully controlled conditions. Eleven conformal 3D experiments were performed in a tissue-mimicking phantom within a 1.5T MR imager to obtain non-invasive temperature measurements during heating. Temperature feedback was used to control the rotation rate and ultrasound power of transurethral devices with up to five 3.5 × 5 mm active transducer elements. Heating patterns shaped to human prostate geometries were generated using devices operating at 4.7 or 8.0 MHz with surface acoustic intensities of up to 10 W cm(-2). Simulations were informed by transducer surface velocity measurements acquired with a scanning laser vibrometer enabling improved calculations of the acoustic pressure distribution in a gel phantom. Temperature dynamics were determined according to a FDTD solution to Pennes' BHTE. The 3D heating patterns produced in vitro were shaped very accurately to the prostate target volumes, within the spatial resolution of the MRI thermometry images. The volume of the treatment difference falling outside ± 1 mm of the target boundary was, on average, 0.21 cc or 1.5% of the prostate volume. The numerical simulations predicted the extent and shape of the coagulation boundary produced in gel to within (mean ± stdev [min, max]): 0.5 ± 0.4 [-1.0, 2.1] and -0.05 ± 0.4 [-1.2, 1.4] mm for the treatments at 4.7 and 8.0 MHz, respectively. The temperatures across all MRI thermometry images were predicted within -0.3 ± 1.6 °C and 0.1 ± 0.6 °C, inside and outside the prostate respectively, and the treatment time to within 6.8 min. The simulations also showed excellent agreement in regions of sharp temperature gradients near the transurethral and endorectal cooling devices. Conformal 3D volumes of thermal coagulation can be precisely matched to prostate shapes with transurethral ultrasound devices and active MRI temperature feedback. The accuracy of numerical simulations for MRI-controlled transurethral ultrasound prostate therapy was validated experimentally, reinforcing their utility as an effective treatment planning tool.

Tunable Mechanical Behavior of Synthetic Organogels as Biofidelic Tissue Simulants

DTIC Science & Technology

2013-01-01

leather , silicone elastomers, soap, lard, and clay (Appleby- Thomas et al., 2011; Jussila et al., 2005; Merkle et al., 2008). In most cases, the tissue...and throughout all experiments reported herein. 2.2. Rheology To measure the shear storage modulus G′, loss modulus G″, and loss tangent tan δ (i.e...magnitude and rate dependence of G′, G″, and tan δ Solvent has a significant impact on the modulus of these gels in two ways: (1) the solvent will

A new prospect in magnetic nanoparticle-based cancer therapy: Taking credit from mathematical tissue-mimicking phantom brain models.

PubMed

Saeedi, Mostafa; Vahidi, Omid; Goodarzi, Vahabodin; Saeb, Mohammad Reza; Izadi, Leila; Mozafari, Masoud

2017-11-01

Distribution patterns/performance of magnetic nanoparticles (MNPs) was visualized by computer simulation and experimental validation on agarose gel tissue-mimicking phantom (AGTMP) models. The geometry of a complex three-dimensional mathematical phantom model of a cancer tumor was examined by tomography imaging. The capability of mathematical model to predict distribution patterns/performance in AGTMP model was captured. The temperature profile vs. hyperthermia duration was obtained by solving bio-heat equations for four different MNPs distribution patterns and correlated with cell death rate. The outcomes indicated that bio-heat model was able to predict temperature profile throughout the tissue model with a reasonable precision, to be applied for complex tissue geometries. The simulation results on the cancer tumor model shed light on the effectiveness of the studied parameters. Copyright © 2017 Elsevier Inc. All rights reserved.

Significant degradability enhancement in multilayer coating of polycaprolactone-bioactive glass/gelatin-bioactive glass on magnesium scaffold for tissue engineering applications

NASA Astrophysics Data System (ADS)

Yazdimamaghani, Mostafa; Razavi, Mehdi; Vashaee, Daryoosh; Pothineni, Venkata Raveendra; Rajadas, Jayakumar; Tayebi, Lobat

2015-05-01

Magnesium (Mg) is a promising candidate to be used in medical products especially as bone tissue engineering scaffolds. The main challenge for using Mg in biomedical applications is its high degradation rate in the body. For this reason, in this study, a multilayer polymeric layer composed of polycaprolactone (PCL) and gelatin (Gel) reinforced with bioactive glass (BaG) particles has been applied on the surface of Mg scaffolds. The materials characteristics of uncoated Mg scaffold, Mg scaffold coated only with PCL-BaG and Mg scaffold coated with PCL-BaG and Gel-BaG have been analyzed and compared in detail. Scanning electron microscope (SEM) equipped with energy dispersive spectroscopy (EDS), and Fourier transform infrared spectroscopy (FTIR) were utilized for microstructural studies. In vitro bioactivity and biodegradation evaluations were carried out by submerging the scaffolds in simulated body fluid (SBF) at pre-determined time points. The results demonstrated that Mg scaffold coated with PCL-BaG and Gel-BaG exhibited significant improvement in biodegradability.

The Consolidation Behavior of Silk Hydrogels

PubMed Central

Kluge, Jonathan A.; Rosiello, Nicholas C.; Leisk, Gary G.; Kaplan, David L.; Dorfmann, A. Luis

2010-01-01

Hydrogels have mechanical properties and structural features that are similar to load bearing soft tissues including intervertebral disc and articular cartilage, and can be implanted for tissue restoration or for local release of therapeutic factors. To help predict their performance, mechanical characterization and mathematical modeling are available methods for use in tissue engineering and drug delivery settings. In this study, confined compression creep tests were performed on silk hydrogels, over a range of concentrations, to examine the phenomenological behavior of the gels under a physiological loading scenario. Based on the observed behavior, we show that the time-dependent response can be explained by a consolidation mechanism, and modeled using Biot’s poroelasticity theory. Two observations are in strong support of this modeling framework, namely, the excellent numerical agreement between increasing load step creep data and the linear Terzaghi theory, and the similar values obtained from numerical simulations and direct measurements of the permeability coefficient. The higher concentration gels (8% and 12% w/v) clearly show a strain-stiffening response to creep loading with increasing loads, while the lower concentration gel (4% w/v) does not. A nonlinear elastic constitutive formulation is employed to account for the stiffening. Furthermore, an empirical formulation is used to represent the deformation-dependent permeability. PMID:20142112

Pharmacodynamic Activity of Dapivirine and Maraviroc Single Entity and Combination Topical Gels for HIV-1 Prevention.

PubMed

Dezzutti, Charlene S; Yandura, Sarah; Wang, Lin; Moncla, Bernard; Teeple, Elizabeth A; Devlin, Brid; Nuttall, Jeremy; Brown, Elizabeth R; Rohan, Lisa C

2015-11-01

Dapivirine (DPV), a non-nucleoside reverse transcriptase inhibitor, and maraviroc (MVC), a CCR5 antagonist, were formulated into aqueous gels designed to prevent mucosal HIV transmission. 0.05% DPV, 0.1% MVC, 0.05% DPV/0.1% MVC and placebo gels were evaluated for pH, viscosity, osmolality, and in vitro release. In vitro assays and mucosal tissues were used to evaluate anti-HIV activity. Viability (Lactobacilli only) and epithelial integrity in cell lines and mucosal tissues defined safety. The gels were acidic and viscous. DPV gel had an osmolality of 893 mOsm/kg while the other gels had an osmolality of <100 mOsm/kg. MVC release was similar from the single and combination gels (~5 μg/cm(2)/min(1/2)), while DPV release was 10-fold less from the single as compared to the combination gel (0.4331 μg/cm(2)/min(1/2)). Titrations of the gels showed 10-fold more drug was needed to protect ectocervical than colonic tissue. The combination gel showed ~10- and 100-fold improved activity as compared to DPV and MVC gel, respectively. All gels were safe. The DPV/MVC gel showed a benefit blocking HIV infection of mucosal tissue compared to the single entity gels. Combination products with drugs affecting unique steps in the viral replication cycle would be advantageous for HIV prevention.

Mechanotransduction mechanisms in growing spherically structured tissues

NASA Astrophysics Data System (ADS)

Littlejohns, Euan; Dunlop, Carina M.

2018-04-01

There is increasing experimental interest in mechanotransduction in multi-cellular tissues as opposed to single cells. This is driven by a growing awareness of the importance of physiologically relevant three-dimensional culture and of cell–cell and cell–gel interactions in directing growth and development. The paradigm biophysical technique for investigating tissue level mechanobiology in this context is to grow model tissues in artificial gels with well-defined mechanical properties. These studies often indicate that the stiffness of the encapsulating gel can significantly alter cellular behaviours. We demonstrate here potential mechanisms linking tissue growth with stiffness-mediated mechanotransduction. We show how tissue growth in gel systems generates points at which there is a significant qualitative change in the cellular stress and strain experienced. We show analytically how these potential switching points depend on the mechanical properties of the constraining gel and predict when they will occur. Significantly, we identify distinct mechanisms that act separately in each of the stress and strain fields at different times. These observations suggest growth as a potential physical mechanism coupling gel stiffness with cellular mechanotransduction in three-dimensional tissues. We additionally show that non-proliferating areas, in the case that the constraining gel is soft compared with the tissue, will expand and contract passively as a result of growth. Central compartment size is thus seen to not be a reliable indicator on its own for growth initiation or active behaviour.

Experimental determination of the effect of detector size on profile measurements in narrow photon beams.

PubMed

Pappas, E; Maris, T G; Papadakis, A; Zacharopoulou, F; Damilakis, J; Papanikolaou, N; Gourtsoyiannis, N

2006-10-01

The aim of this work is to investigate experimentally the detector size effect on narrow beam profile measurements. Polymer gel and magnetic resonance imaging dosimetry was used for this purpose. Profile measurements (Pm(s)) of a 5 mm diameter 6 MV stereotactic beam were performed using polymer gels. Eight measurements of the profile of this narrow beam were performed using correspondingly eight different detector sizes. This was achieved using high spatial resolution (0.25 mm) two-dimensional measurements and eight different signal integration volumes A X A X slice thickness, simulating detectors of different size. "A" ranged from 0.25 to 7.5 mm, representing the detector size. The gel-derived profiles exhibited increased penumbra width with increasing detector size, for sizes >0.5 mm. By extrapolating the gel-derived profiles to zero detector size, the true profile (Pt) of the studied beam was derived. The same polymer gel data were also used to simulate a small-volume ion chamber profile measurement of the same beam, in terms of volume averaging. The comparison between these results and actual corresponding small-volume chamber profile measurements performed in this study, reveal that the penumbra broadening caused by both volume averaging and electron transport alterations (present in actual ion chamber profile measurements) is a lot more intense than that resulted by volume averaging effects alone (present in gel-derived profiles simulating ion chamber profile measurements). Therefore, not only the detector size, but also its composition and tissue equivalency is proved to be an important factor for correct narrow beam profile measurements. Additionally, the convolution kernels related to each detector size and to the air ion chamber were calculated using the corresponding profile measurements (Pm(s)), the gel-derived true profile (Pt), and convolution theory. The response kernels of any desired detector can be derived, allowing the elimination of the errors associated with narrow beam profile measurements.

Equivalent of a cartilage tissue for simulations of laser-induced temperature fields

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

Kondyurin, A V; Sviridov, A P

2008-07-31

The thermal and optical properties of polyacrylamide hydrogels and cartilages are studied by the method of IR laser radiometry. The thermal diffusivity, heat capacity, and the effective absorption coefficient at a wavelength of 1.56 {mu}m measured for polyacrylamide gel with 70% water content and the degree of cross-linking 1:9 and for the nasal septum cartilage proved to be close. This allows the use of polyacrylamide hydrogels as equivalents of cartilages in simulations of laser-induced temperature fields. (biophotonics)

Pharmacodynamic activity of Dapivirine and Maraviroc single entity and combination topical gels for HIV-1 prevention

PubMed Central

Dezzutti, Charlene S.; Yandura, Sarah; Wang, Lin; Moncla, Bernard; Teeple, Elizabeth A.; Devlin, Brid; Nuttall, Jeremy; Brown, Elizabeth R.; Rohan, Lisa C.

2015-01-01

Purpose Dapivirine (DPV), a non-nucleoside reverse transcriptase inhibitor, and maraviroc (MVC), a CCR5 antagonist, were formulated into aqueous gels designed to prevent mucosal HIV transmission. Methods 0.05% DPV, 0.1% MVC, 0.05% DPV/0.1% MVC and placebo gels were evaluated for pH, viscosity, osmolality, and in vitro release. In vitro assays and mucosal tissues were used to evaluate anti-HIV activity. Viability (Lactobacilli only) and epithelial integrity in cell lines and mucosal tissues defined safety. Results The gels were acidic and viscous. DPV gel had an osmolality of 893 mOsm/kg while the other gels had an osmolality of <100 mOsm/kg. MVC release was similar from the single and combination gels (~5 μg/cm2/min1/2), while DPV release was 10-fold less from the single as compared to the combination gel (0.4331 μg/cm2/min1/2). Titrations of the gels showed 10-fold more drug was needed to protect ectocervical than colonic tissue. The combination gel showed ~10- and 100-fold improved activity as compared to DPV and MVC gel, respectively. All gels were safe. Conclusions The DPV/MVC gel showed a benefit blocking HIV infection of mucosal tissue compared to the single entity gels. Combination products with drugs affecting unique steps in the viral replication cycle would be advantageous for HIV prevention. PMID:26078001

A Phase 1 Trial to Assess the Safety, Acceptability, Pharmacokinetics, and Pharmacodynamics of a Novel Dapivirine Vaginal Film.

PubMed

Bunge, Katherine E; Dezzutti, Charlene S; Rohan, Lisa C; Hendrix, Craig W; Marzinke, Mark A; Richardson-Harman, Nicola; Moncla, Bernard J; Devlin, Brid; Meyn, Leslie A; Spiegel, Hans M L; Hillier, Sharon L

2016-04-15

Films may deliver antiretroviral drugs efficiently to mucosal tissues. In this first in-human trial of a vaginal film for delivering the nonnucleoside reverse transcriptase inhibitor dapivirine, safety, pharmacokinetics, and pharmacodynamics of film and gel formulations were compared with placebo. Sixty-one healthy HIV-negative women were randomized to daily dapivirine (0.05%) or placebo gel, or dapivirine (1.25 mg) or placebo film for seven days. The proportion of participants experiencing grade 2 and higher adverse events related to study product were compared. Plasma dapivirine concentrations were quantified. Paired cervical and vaginal tissue biopsies obtained ∼2 hours after the last dose were measured for tissue drug concentration and exposed to HIV in an ex vivo challenge assay. Two grade 2 related adverse events occurred in the placebo film group. Women randomized to gel and film products had 4 log10 higher of dapivirine in cervical and vaginal tissues than plasma. Although gel and film users had comparable plasma dapivirine concentrations, tissue concentrations of dapivirine were 3-5 times higher in the gel users when compared with film users. HIV replication in the ex vivo challenge assay was significantly reduced in vaginal tissues from women randomized to dapivirine film or gel; furthermore, tissue drug concentrations were highly correlated with HIV protection. Women rated the film more comfortable with less leakage but found it more difficult to insert than gel. Both film and gel delivered dapivirine at concentrations sufficient to block HIV ex vivo. This proof-of-concept study suggests film formulations for microbicides merit further investigation.

Hydroxyapatite-coated double network hydrogel directly bondable to the bone: Biological and biomechanical evaluations of the bonding property in an osteochondral defect.

PubMed

Wada, Susumu; Kitamura, Nobuto; Nonoyama, Takayuki; Kiyama, Ryuji; Kurokawa, Takayuki; Gong, Jian Ping; Yasuda, Kazunori

2016-10-15

We have developed a novel hydroxyapatite (HAp)-coated double-network (DN) hydrogel (HAp/DN gel). The purpose of this study was to determine details of the cell and tissue responses around the implanted HAp/DN gel and to determine how quickly and strongly the HAp/DN gel bonds to the bone in a rabbit osteochondral defect model. Immature osteoid tissue was formed in the space between the HAp/DN gel and the bone at 2weeks, and the osteoid tissue was mineralized at 4weeks. The push-out load of the HAp/DN gel averaged 37.54N and 42.15N at 4 and 12weeks, respectively, while the push-out load of the DN gel averaged less than 5N. The bonding area of the HAp/DN gel to the bone was above 80% by 4weeks, and above 90% at 12weeks. This study demonstrated that the HAp/DN gel enhanced osseointegration at an early stage after implantation. The presence of nanoscale structures in addition to osseointegration of HAp promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Recent studies have reported the development of various hydrogels that are sufficiently tough for application as soft supporting tissues. However, fixation of hydrogels on bone surfaces with appropriate strength is a great challenge. We have developed a novel, tough hydrogel hybridizing hydroxyapatite (HAp/DN gel), which is directly bondable to the bone. The present study demonstrated that the HAp/DN gel enhanced osseointegration in the early stage after implantation. The presence of nanoscale structures in addition to the osseointegration ability of hydroxyapatite promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Comparative Testis Tissue Proteomics Using 2-Dye Versus 3-Dye DIGE Analysis.

PubMed

Holland, Ashling

2018-01-01

Comparative tissue proteomics aims to analyze alterations of the proteome in response to a stimulus. Two-dimensional difference gel electrophoresis (2D-DIGE) is a modified and advanced form of 2D gel electrophoresis. DIGE is a powerful biochemical method that compares two or three protein samples on the same analytical gel, and can be used to establish differentially expressed protein levels between healthy normal and diseased pathological tissue sample groups. Minimal DIGE labeling can be used via a 2-dye system with Cy3 and Cy5 or a 3-dye system with Cy2, Cy3, and Cy5 to fluorescently label samples with CyDye flours pre-electrophoresis. DIGE circumvents gel-to-gel variability by multiplexing samples to a single gel and through the use of a pooled internal standard for normalization. This form of quantitative high-resolution proteomics facilitates the comparative analysis and evaluation of tissue protein compositions. Comparing tissue groups under different conditions is crucially important for advancing the biomedical field by characterization of cellular processes, understanding pathophysiological development and tissue biomarker discovery. This chapter discusses 2D-DIGE as a comparative tissue proteomic technique and describes in detail the experimental steps required for comparative proteomic analysis employing both options of 2-dye and 3-dye DIGE minimal labeling.

3D printing of microtube in solid phantom to simulate tissue oxygenation and perfusion (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lv, Xiang; Xue, Yue; Wang, Haili; Shen, Shu Wei; Zhou, Ximing; Liu, Guangli; Dong, Erbao; Xu, Ronald X.

2017-03-01

Tissue-simulating phantoms with interior vascular network may facilitate traceable calibration and quantitative validation of many medical optical devices. However, a solid phantom that reliably simulates tissue oxygenation and blood perfusion is still not available. This paper presents a new method to fabricate hollow microtubes for blood vessel simulation in solid phantoms. The fabrication process combines ultraviolet (UV) rapid prototyping technique with fluid mechanics of a coaxial jet flow. Polydimethylsiloxane (PDMS) and a UV-curable polymer are mixed at the designated ratio and extruded through a coaxial needle device to produce a coaxial jet flow. The extruded jet flow is quickly photo-polymerized by ultraviolet (UV) light to form vessel-simulating solid structures at different sizes ranging from 700 μm to 1000 μm. Microtube structures with adequate mechanical properties can be fabricated by adjusting material compositions and illumination intensity. Curved, straight and stretched microtubes can be formed by adjusting the extrusion speed of the materials and the speed of the 3D printing platform. To simulate vascular structures in biologic tissue, we embed vessel-simulating microtubes in a gel wax phantom of 10 cm x10 cm x 5 cm at the depth from 1 to 2 mm. Bloods at different oxygenation and hemoglobin concentration levels are circulated through the microtubes at different flow rates in order to simulate different oxygenation and perfusion conditions. The simulated physiologic parameters are detected by a tissue oximeter and a laser speckle blood flow meter respectively and compared with the actual values. Our experiments demonstrate that the proposed 3D printing process is able to produce solid phantoms with simulated vascular networks for potential applications in medical device calibration and drug delivery studies.

A new sol-gel process for producing Na(2)O-containing bioactive glass ceramics.

PubMed

Chen, Qi-Zhi; Li, Yuan; Jin, Li-Yu; Quinn, Julian M W; Komesaroff, Paul A

2010-10-01

The sol-gel process of producing SiO(2)-CaO bioactive glasses is well established, but problems remain with the poor mechanical properties of the amorphous form and the bioinertness of its crystalline counterpart. These properties may be improved by incorporating Na(2)O into bioactive glasses, which can result in the formation of a hard yet biodegradable crystalline phase from bioactive glasses when sintered. However, production of Na(2)O-containing bioactive glasses by sol-gel methods has proved to be difficult. This work reports a new sol-gel process for the production of Na(2)O-containing bioactive glass ceramics, potentially enabling their use as medical implantation materials. Fine powders of 45S5 (a Na(2)O-containing composition) glass ceramic have for the first time been successfully synthesized using the sol-gel technique in aqueous solution under ambient conditions, with the mean particle size being approximately 5 microm. A comparative study of sol-gel derived S70C30 (a Na(2)O-free composition) and 45S5 glass ceramic materials revealed that the latter possesses a number of features desirable in biomaterials used for bone tissue engineering, including (i) the crystalline phase Na(2)Ca(2)Si(3)O(9) that couples good mechanical strength with satisfactory biodegradability, (ii) formation of hydroxyapatite, which may promote good bone bonding and (iii) cytocompatibility. In contrast, the sol-gel derived S70C30 glass ceramic consisted of a virtually inert crystalline phase CaSiO(3). Moreover, amorphous S70C30 largely transited to CaCO(3) with minor hydroxyapatite when immersed in simulated body fluid under standard tissue culture conditions. In conclusion, sol-gel derived Na(2)O-containing glass ceramics have significant advantages over related Na(2)O-free materials, having a greatly improved combination of mechanical capability and biological absorbability. 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Integration of Fricke gel dosimetry with Ag nanoparticles for experimental dose enhancement determination in theranostics.

PubMed

Vedelago, J; Mattea, F; Valente, M

2018-03-01

The use and implementation of nanoparticles in medicine has grown exponentially in the last twenty years. Their main applications include drug delivery, theranostics, tissue engineering and magneto function. Dosimetry techniques can take advantage of inorganic nanoparticles properties and their combination with gel dosimetry techniques could be used as a first step for their later inclusion in radio-diagnostics or radiotherapy treatments. The present study presents preliminary results of properly synthesized and purified silver nanoparticles integration with Fricke gel dosimeters. Used nanoparticles presented mean sizes ranging from 2 to 20 nm, with a lognormal distribution. Xylenol orange concentration in Fricke gel dosimeter was adjust in order to allow sample's optical readout, accounting nanoparticles plasmon. Dose enhancement was assessed irradiating dosimeters setting X-ray beams energies below and above silver K-edge. Monte Carlo simulations were used to estimate the dose enhancement in the experiments and compare with the trend obtained in the experimental results. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fluctuations and differential contraction during regeneration of Hydra vulgaris tissue toroids

NASA Astrophysics Data System (ADS)

Krahe, Michael; Wenzel, Iris; Lin, Kao-Nung; Fischer, Julia; Goldmann, Joseph; Kästner, Markus; Fütterer, Claus

2013-03-01

We studied regenerating bilayered tissue toroids dissected from Hydra vulgaris polyps and relate our macroscopic observations to the dynamics of force-generating mesoscopic cytoskeletal structures. Tissue fragments undergo a specific toroid-spheroid folding process leading to complete regeneration towards a new organism. The time scale of folding is too fast for biochemical signalling or morphogenetic gradients, which forced us to assume purely mechanical self-organization. The initial pattern selection dynamics was studied by embedding toroids into hydro-gels, allowing us to observe the deformation modes over longer periods of time. We found increasing mechanical fluctuations which break the toroidal symmetry, and discuss the evolution of their power spectra for various gel stiffnesses. Our observations are related to single-cell studies which explain the mechanical feasibility of the folding process. In addition, we observed switching of cells from a tissue bound to a migrating state after folding failure as well as in tissue injury. We found a supra-cellular actin ring assembled along the toroid's inner edge. Its contraction can lead to the observed folding dynamics as we could confirm by finite element simulations. This actin ring in the inner cell layer is assembled by myosin-driven length fluctuations of supra-cellular F-actin bundles (myonemes) in the outer cell layer. This paper is dedicated to Malcolm Steinberg.

Methods of Manufacturing Bioactive Gels from Extracellular Matrix Material

NASA Technical Reports Server (NTRS)

Janis, Abram D. (Inventor); Kentner, Kimberly A. (Inventor); Stuart, Katherine A. (Inventor)

2014-01-01

The present invention is directed to methods of manufacturing bioactive gels from ECM material, i.e., gels which retain bioactivity, and can serve as scaffolds for preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction. The manufacturing methods take advantage of a new recognition that bioactive gels from ECM material can be created by digesting particularized ECM material in an alkaline environment and neutralizing to provide bioactive gels.

Methods of Manufacturing Bioactive Gels from Extracellular Matrix Material

NASA Technical Reports Server (NTRS)

Kentner, Kimberly A. (Inventor); Stuart, Katherine A. (Inventor); Janis, Abram D. (Inventor)

2015-01-01

The present invention is directed to methods of manufacturing bioactive gels from ECM material, i.e., gels which retain bioactivity, and can serve as scaffolds for preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction. The manufacturing methods take advantage of a new recognition that bioactive gels from ECM material can be created by digesting particularized ECM material in an alkaline environment and neutralizing to provide bioactive gels.

Methods of Manufacturing Bioactive Gels from Extracellular Matrix Material

NASA Technical Reports Server (NTRS)

Kentner, Kimberly A. (Inventor); Stuart, Katherine A. (Inventor); Janis, Abram D. (Inventor)

2016-01-01

The present invention is directed to methods of manufacturing bioactive gels from ECM material, i.e., gels which retain bioactivity, and can serve as scaffolds for preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction. The manufacturing methods take advantage of a new recognition that bioactive gels from ECM material can be created by digesting particularized ECM material in an alkaline environment and neutralizing to provide bioactive gels.

Methods of Manufacturing Bioactive Gels from Extracellular Matrix Material

NASA Technical Reports Server (NTRS)

Kentner, Kimberly (Inventor); Janis, Abram D. (Inventor); Stuart, Katherine A. (Inventor)

2017-01-01

The present invention is directed to methods of manufacturing bioactive gels from ECM material, i.e., gels which retain bioactivity, and can serve as scaffolds for preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction. The manufacturing methods take advantage of a new recognition that bioactive gels from ECM material can be created by digesting particularized ECM material in an alkaline environment and neutralizing to provide bioactive gels.

Fibrin gel improves tissue ingrowth and cell differentiation in human immature premolars implanted in rats.

PubMed

Ruangsawasdi, Nisarat; Zehnder, Matthias; Weber, Franz E

2014-02-01

In pulpless immature human premolars implanted in rodents, this study investigated whether fibrin gel offered advantages over leaving the root canal empty regarding soft tissue ingrowth and cell differentiation. Root canals of extracted human immature premolars (n = 12) were accessed and then irrigated with 5% sodium hypochlorite followed by 17% ethylenediaminetetraacetic acid. Root canals were then either left empty or filled with a fibrin gel (n = 6 each) before being placed subcutaneously on top of the calvarial bone of rats (1 tooth per rat) for 12 weeks. After sacrifice, teeth were histologically assessed. Tissue ingrowth was quantified and compared between groups using the Mann-Whitney U test (P < .05). Cells adhering to the pulp canal wall were immunohistochemically screened for the presence of bone sialoprotein (BSP) and dentin sialoprotein (DSP). More tissue grew into the pulp space when teeth were filled with fibrin gel (P < .05). The presence of fibrin gel affected not only the extent of tissue ingrowth but also tissue morphology and differentiation of cells contacting the dentinal wall. In the fibrin gel group, newly formed tissue was similar to normal pulp, constituted of inner pulp, cell-rich zone, cell-free zone, and an apparent odontoblast layer, which stained positive for BSP and DSP. Newly formed blood vessels were also more abundant compared with the initially empty root canals. Under the conditions of this study, fibrin gel improved cell infiltration and cell-dentin interaction. Both are necessary for pulp tissue regeneration. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Modeling mechanical interactions between cancerous mammary acini

NASA Astrophysics Data System (ADS)

Wang, Jeffrey; Liphardt, Jan; Rycroft, Chris

2015-03-01

The rules and mechanical forces governing cell motility and interactions with the extracellular matrix of a tissue are often critical for understanding the mechanisms by which breast cancer is able to spread through the breast tissue and eventually metastasize. Ex vivo experimentation has demonstrated the the formation of long collagen fibers through collagen gels between the cancerous mammary acini responsible for milk production, providing a fiber scaffolding along which cancer cells can disorganize. We present a minimal mechanical model that serves as a potential explanation for the formation of these collagen fibers and the resultant motion. Our working hypothesis is that cancerous cells induce this fiber formation by pulling on the gel and taking advantage of the specific mechanical properties of collagen. To model this system, we employ a new Eulerian, fixed grid simulation method to model the collagen as a nonlinear viscoelastic material subject to various forces coupled with a multi-agent model to describe individual cancer cells. We find that these phenomena can be explained two simple ideas: cells pull collagen radially inwards and move towards the tension gradient of the collagen gel, while being exposed to standard adhesive and collision forces.

Numerical Study on Focusing of Ultrasounds in Microbubble-enhanced HIFU

NASA Astrophysics Data System (ADS)

Matsumoto, Yoichiro; Okita, Kohei; Takagi, Shu

2011-11-01

The injection of microbubbles into the target tissue enhances tissue heating in High-Intensity Focused Ultrasound therapy, via inertial cavitation. The control of the inertial cavitation is required to achieve the efficient tissue ablation. Microbubbles between a transducer and a target disturb the ultrasound propagation depending on the conditions. A method to clear such microbubbles has been proposed by Kajiyama et al. [Physics Procedia 3 (2010) 305-314]. In the method, the irradiation of intense ultrasounds with a burst waveform fragmentize microbubbles in the pathways before the irradiation of ultrasounds for tissue heating. The vitro experiment using a gel containing microbubbles has showed that the method enables to heat the target correctly by controlling the microbubble distribution. Following the experiment, we simulate the focusing of ultrasounds through a mixture containing microbubbles with considering the size and number density distributions in space. The numerical simulation shows that the movement of the heating region from the transducer side to the target by controlling the microbubble distributions. The numerical results elucidate well the experimental ones.

Tissue temperature distribution measurement by MRI and laser immunology for cancer treatment

NASA Astrophysics Data System (ADS)

Chen, Yichao; Gnyawali, Surya C.; Wu, Feng; Liu, Hong; Tesiram, Yasvir A.; Abbott, Andrew; Towner, Rheal A.; Chen, Wei R.

2007-02-01

In cancer treatment and immune response enhancement research, Magnetic Resonance Imaging (MRI) is an ideal method for non-invasive, three-dimensional temperature measurement. We used a 7.1-Tesla magnetic resonance imager for ex vivo tissues and small animal to determine temperature distribution of target tissue during laser irradiation. The feasibility of imaging is approved with high spatial resolution and high signal-noise- ratio. Tissue-simulating gel phantom gel, biological tissues, and tumor-bearing animals were used in the experiments for laser treatment and MR imaging. Thermal couple measurement of temperature in target samples was used for system calibration. An 805-nm laser was used to irradiate the samples with a laser power in the range of 1 to 2.5 watts. Using the MRI system and a specially developed processing algorithm, a clear temperature distribution matrix in the target tissue and surrounding tissue was obtained. The temperature profiles show that the selective laser photothermal effect could result in tissue temperature elevation in a range of 10 to 45 °C. The temperature resolution of the measurement was about 0.37°C including the total system error. The spatial resolution was 0.4 mm (128x128 pixels with field of view of 5.5x5.5 cm). The temperature distribution provided in vivo thermal information and future reference for optimizing dye concentration and irradiation parameters to achieve optimal thermal effects in cancer treatment.

A Phase 1 trial to assess the safety, acceptability, pharmacokinetics and pharmacodynamics of a novel dapivirine vaginal film

PubMed Central

Bunge, Authors: Katherine E.; Dezzutti, Charlene S.; Rohan, Lisa C.; Hendrix, Craig W.; Marzinke, Mark A.; Richardson-Harman, Nicola; Moncla, Bernard J.; Devlin, Brid; Meyn, Leslie A.; M.L.Spiegel, Hans; Hillier, Sharon L.

2016-01-01

Background Films may deliver antiretroviral drugs efficiently to mucosal tissues. In this first in-human trial of a vaginal film for delivering the non-nucleoside reverse transcriptase inhibitor dapivirine, safety, pharmacokinetics, and pharmacodynamics of film and gel formulations were compared to placebo. Methods 61 healthy HIV negative women were randomized to daily dapivirine (0.05%) or placebo gel, or dapivirine (1.25mg) or placebo film for seven days. The proportion of participants experiencing Grade 2 and higher adverse events related to study product were compared. Plasma dapivirine concentrations were quantified. Paired cervical and vaginal tissue biopsies obtained ∼2 hours following the last dose were measured for tissue drug concentration and exposed to HIV in an ex vivo challenge assay. Results Two Grade 2 related AEs occurred in the placebo film group. Women randomized to gel and film products had 4 log10 higher of dapivirine in cervical and vaginal tissues than plasma. While gel and film users had comparable plasma dapivirine concentrations, tissue concentrations of dapivirine were 3 to 5 times higher in the gel users when compared to film users. HIV replication in the ex vivo challenge assay was significantly reduced in vaginal tissues from women randomized to dapivirine film or gel; furthermore, tissue drug concentrations were highly correlated with HIV protection. Women rated the film more comfortable with less leakage, but found it more difficult to insert than gel. Discussion Both film and gel delivered dapivirine at concentrations sufficient to block HIV ex vivo. This proof of concept study suggests film formulations for microbicides merit further investigation. PMID:26565716

Extraction and Assembly of Tissue-Derived Gels for Cell Culture and Tissue Engineering

PubMed Central

Uriel, Shiri; Labay, Edwardine; Francis-Sedlak, Megan; Moya, Monica L.; Weichselbaum, Ralph R.; Ervin, Natalia; Cankova, Zdravka

2009-01-01

Interactions with the extracellular matrix (ECM) play an important role in regulating cell function. Cells cultured in, or on, three-dimensional ECM recapitulate similar features to those found in vivo that are not present in traditional two-dimensional culture. In addition, both natural and synthetic materials containing ECM components have shown promise in a number of tissue engineering applications. Current materials available for cell culture and tissue engineering do not adequately reflect the diversity of ECM composition between tissues. In this paper, a method is presented for extracting solutions of proteins and glycoproteins from soft tissues and inducing assembly of these proteins into gels. The extracts contain ECM proteins specific to the tissue source with low levels of intracellular molecules. Gels formed from the tissue-derived extracts have nanostructure similar to ECM in vivo and can be used to culture cells as both a thin substrate coating and a thick gel. This technique could be used to assemble hydrogels with varying composition depending upon the tissue source, hydrogels for three-dimensional culture, as scaffolds for tissue engineering therapies, and to study cell–matrix interactions. PMID:19115821

Silk-fibrin/hyaluronic acid composite gels for nucleus pulposus tissue regeneration.

PubMed

Park, Sang-Hyug; Cho, Hongsik; Gil, Eun Seok; Mandal, Biman B; Min, Byoung-Hyun; Kaplan, David L

2011-12-01

Scaffold designs are critical for in vitro culture of tissue-engineered cartilage in three-dimensional environments to enhance cellular differentiation for tissue engineering and regenerative medicine. In the present study we demonstrated silk and fibrin/hyaluronic acid (HA) composite gels as scaffolds for nucleus pulposus (NP) cartilage formation, providing both biochemical support for NP outcomes as well as fostering the retention of size of the scaffold during culture due to the combined features of the two proteins. Passage two (P2) human chondrocytes cultured in 10% serum were encapsulated within silk-fibrin/HA gels. Five study groups with fibrin/HA gel culture (F/H) along with varying silk concentrations (2% silk gel only, fibrin/HA gel culture with 1% silk [F/H+1S], 1.5% silk [F/H+1.5S], and 2% silk [F/H+2S]) were cultured in serum-free chondrogenic defined media (CDM) for 4 weeks. Histological examination with alcian blue showed a defined chondrogenic area at 1 week in all groups that widened homogenously until 4 weeks. In particular, chondrogenic differentiation observed in the F/H+1.5S had no reduction in size throughout the culture period. The results of biochemical and molecular biological evaluations supported observations made during histological examination. Mechanical strength measurements showed that the silk mixed gels provided stronger mechanical properties for NP tissue than fibrin/HA composite gels in CDM. This effect could potentially be useful in the study of in vitro NP tissue engineering as well as for clinical implications for NP tissue regeneration.

Silk-Fibrin/Hyaluronic Acid Composite Gels for Nucleus Pulposus Tissue Regeneration

PubMed Central

Park, Sang-Hyug; Cho, Hongsik; Gil, Eun Seok; Mandal, Biman B.; Min, Byoung-Hyun

2011-01-01

Scaffold designs are critical for in vitro culture of tissue-engineered cartilage in three-dimensional environments to enhance cellular differentiation for tissue engineering and regenerative medicine. In the present study we demonstrated silk and fibrin/hyaluronic acid (HA) composite gels as scaffolds for nucleus pulposus (NP) cartilage formation, providing both biochemical support for NP outcomes as well as fostering the retention of size of the scaffold during culture due to the combined features of the two proteins. Passage two (P2) human chondrocytes cultured in 10% serum were encapsulated within silk-fibrin/HA gels. Five study groups with fibrin/HA gel culture (F/H) along with varying silk concentrations (2% silk gel only, fibrin/HA gel culture with 1% silk [F/H+1S], 1.5% silk [F/H+1.5S], and 2% silk [F/H+2S]) were cultured in serum-free chondrogenic defined media (CDM) for 4 weeks. Histological examination with alcian blue showed a defined chondrogenic area at 1 week in all groups that widened homogenously until 4 weeks. In particular, chondrogenic differentiation observed in the F/H+1.5S had no reduction in size throughout the culture period. The results of biochemical and molecular biological evaluations supported observations made during histological examination. Mechanical strength measurements showed that the silk mixed gels provided stronger mechanical properties for NP tissue than fibrin/HA composite gels in CDM. This effect could potentially be useful in the study of in vitro NP tissue engineering as well as for clinical implications for NP tissue regeneration. PMID:21736446

Traction force microscopy of engineered cardiac tissues.

PubMed

Pasqualini, Francesco Silvio; Agarwal, Ashutosh; O'Connor, Blakely Bussie; Liu, Qihan; Sheehy, Sean P; Parker, Kevin Kit

2018-01-01

Cardiac tissue development and pathology have been shown to depend sensitively on microenvironmental mechanical factors, such as extracellular matrix stiffness, in both in vivo and in vitro systems. We present a novel quantitative approach to assess cardiac structure and function by extending the classical traction force microscopy technique to tissue-level preparations. Using this system, we investigated the relationship between contractile proficiency and metabolism in neonate rat ventricular myocytes (NRVM) cultured on gels with stiffness mimicking soft immature (1 kPa), normal healthy (13 kPa), and stiff diseased (90 kPa) cardiac microenvironments. We found that tissues engineered on the softest gels generated the least amount of stress and had the smallest work output. Conversely, cardiomyocytes in tissues engineered on healthy- and disease-mimicking gels generated significantly higher stresses, with the maximal contractile work measured in NRVM engineered on gels of normal stiffness. Interestingly, although tissues on soft gels exhibited poor stress generation and work production, their basal metabolic respiration rate was significantly more elevated than in other groups, suggesting a highly ineffective coupling between energy production and contractile work output. Our novel platform can thus be utilized to quantitatively assess the mechanotransduction pathways that initiate tissue-level structural and functional remodeling in response to substrate stiffness.

Evaluating the angiogenic potential of a novel temperature-sensitive gel scaffold derived from porcine skeletal muscle tissue.

PubMed

Zhang, Di; Tan, Qiu-Wen; Luo, Jing-Cong; Lv, Qing

2018-06-11

Our previous study fabricated decellularized porcine muscle tissues (DPMTs) and demonstrated that DPMTs with few cell residues possess highly preserved protein components and good biocompatibility. In the physical state, skeletal muscle equips an abundant vascular network due to the vast demand of energy from aerobic metabolism. Vascular bioactive factors which are rich in skeletal muscle tissues may contribute to the angiogenic effect of DPMTs. However, implanting DPMTs in vivo in a less invasive way is unfeasible. Hence, the purpose of this study was to fabricate DPMTs into hydrogel and investigate the effects of DPMT gel on promoting neovessel formation in vitro and in vivo. The results demonstrated that the surface topographies of the DPMT gel were looser and more homogeneous than the DPMTs. The rates of retained VEGF, bFGF, and PDGF-BB in DPMT gel were almost half of the corresponding content in fresh skeletal muscle tissues. Human umbilical endothelial cells displayed better proliferation ability and enhanced the formation of neovascular loops when seeded on DPMT gel compared to small intestinal submucosa gels at the same concentration of 2% (W/V). Furthermore, the increased neovessel formation was detected after subcutaneous injection of DPMT gel. Taken together, these findings suggested that DPMT gel may possess the potential of promoting neovascular formation.

Sustained subconjunctival protein delivery using a thermosetting gel delivery system.

PubMed

Rieke, Erin R; Amaral, Juan; Becerra, S Patricia; Lutz, Robert J

2010-02-01

An effective treatment modality for posterior eye diseases would provide prolonged delivery of therapeutic agents, including macromolecules, to eye tissues using a safe and minimally invasive method. The goal of this study was to assess the ability of a thermosetting gel to deliver a fluorescently labeled protein, Alexa 647 ovalbumin, to the choroid and retina of rats following a single subconjunctival injection of the gel. Additional experiments were performed to compare in vitro to in vivo ovalbumin release rates from the gel. The ovalbumin content of the eye tissues was monitored by spectrophotometric assays of tissue extracts of Alexa 647 ovalbumin from dissected sclera, choroid, and retina at time points ranging from 2 h to 14 days. At the same time points, fluorescence microscopy images of tissue samples were also obtained. Measurement of intact ovalbumin was verified by LDS-PAGE analysis of the tissue extract solutions. In vitro release of Alexa 488 ovalbumin into 37 degrees C PBS solutions from ovalbumin-loaded gel pellets was also monitored over time by spectrophotometric assay. In vivo ovalbumin release rates were determined by measurement of residual ovalbumin extracted from gel pellets removed from rat eyes at various time intervals. Our results indicate that ovalbumin concentrations can be maintained at measurable levels in the sclera, choroid, and retina of rats for up to 14 days using the thermosetting gel delivery system. The concentration of ovalbumin exhibited a gradient that decreased from sclera to choroid and to retina. The in vitro release rate profiles were similar to the in vivo release profiles. Our findings suggest that the thermosetting gel system may be a feasible method for safe and convenient sustained delivery of proteins to choroidal and retinal tissue in the posterior segments of the eye.

Sustained Subconjunctival Protein Delivery Using a Thermosetting Gel Delivery System

PubMed Central

2010-01-01

Purpose: An effective treatment modality for posterior eye diseases would provide prolonged delivery of therapeutic agents, including macromolecules, to eye tissues using a safe and minimally invasive method. The goal of this study was to assess the ability of a thermosetting gel to deliver a fluorescently labeled protein, Alexa 647 ovalbumin, to the choroid and retina of rats following a single subconjunctival injection of the gel. Additional experiments were performed to compare in vitro to in vivo ovalbumin release rates from the gel. Methods: The ovalbumin content of the eye tissues was monitored by spectrophotometric assays of tissue extracts of Alexa 647 ovalbumin from dissected sclera, choroid, and retina at time points ranging from 2 h to 14 days. At the same time points, fluorescence microscopy images of tissue samples were also obtained. Measurement of intact ovalbumin was verified by LDS-PAGE analysis of the tissue extract solutions. In vitro release of Alexa 488 ovalbumin into 37°C PBS solutions from ovalbumin-loaded gel pellets was also monitored over time by spectrophotometric assay. In vivo ovalbumin release rates were determined by measurement of residual ovalbumin extracted from gel pellets removed from rat eyes at various time intervals. Results: Our results indicate that ovalbumin concentrations can be maintained at measurable levels in the sclera, choroid, and retina of rats for up to 14 days using the thermosetting gel delivery system. The concentration of ovalbumin exhibited a gradient that decreased from sclera to choroid and to retina. The in vitro release rate profiles were similar to the in vivo release profiles. Conclusions: Our findings suggest that the thermosetting gel system may be a feasible method for safe and convenient sustained delivery of proteins to choroidal and retinal tissue in the posterior segments of the eye. PMID:20148655

[Treatment of postburn and postoperative cicatrices using karipaine cream preparations and karipaine ultra gel].

PubMed

Zhernov, O A; Osadcha, O I; Zhernov, A O; Nazarenko, V M; Staskevych, S V

2011-07-01

Peculiarities of the burn wound course and the cicatricial tissue formation are shown. Clinical efficacy of application of cream Karipaine and gel Karipaine Ultra was proved, witnessed by improvement of the cell to tissue interaction as well as the connective tissue metabolism and the cicatricial tissue reconstruction.

[Accuracy Check of Monte Carlo Simulation in Particle Therapy Using Gel Dosimeters].

PubMed

Furuta, Takuya

2017-01-01

Gel dosimeters are a three-dimensional imaging tool for dose distribution induced by radiations. They can be used for accuracy check of Monte Carlo simulation in particle therapy. An application was reviewed in this article. An inhomogeneous biological sample placing a gel dosimeter behind it was irradiated by carbon beam. The recorded dose distribution in the gel dosimeter reflected the inhomogeneity of the biological sample. Monte Carlo simulation was conducted by reconstructing the biological sample from its CT image. The accuracy of the particle transport by Monte Carlo simulation was checked by comparing the dose distribution in the gel dosimeter between simulation and experiment.

Development of In Vitro Embryo Production System Using Collagen Matrix Gel Attached with Vascular Endothelial Growth Factor Derived from Interleukin-1 Beta-Treated Porcine Endometrial Tissue.

PubMed

Han, Hye-In; Lee, Sang-Hee; Park, Choon-Keun

2017-07-01

The aim of this study was to establish an embryo culture system using collagen gel attached with vascular endothelial growth factor (VEGF) derived from interleukin-1 beta (IL-1β)-treated endometrial tissues from pigs. Endometria were separated from the porcine uterus at the follicular phase of the estrous cycle and were cultured with IL-1β. The collagen gels coincubated with IL-1β-treated endometria (C, without endometrial tissue; CE, with endometrial tissue; and CEI, IL-1β-treated endometrial tissue) were used for embryo culture. We found that, compared with the comparable figures in the control group, prostaglandin synthase-2 (PTGS-2) mRNA was increased in IL-1β-treated endometrial tissue (p < 0.05). The VEGF protein was not observed in collagen gel coincubated without endometrial tissue (C); however, it was detected in collagen gels coincubated with endometrial tissue (CE and CEI). The embryo cleavage rates and blastocyst formation did not differ among the treatment groups. The proportion of blastocysts did not differ among the groups. However, the number of blastocyst cells was significantly (p < 0.05) higher in the CEI group than in the other groups. These results clarify the effects of the intrauterine environment on preimplantation embryos and may be useful in research on the effects of extracellular matrix- and cytokine-treated endometrial tissue on embryo development.

Neural stem cell proliferation and differentiation in the conductive PEDOT-HA/Cs/Gel scaffold for neural tissue engineering.

PubMed

Wang, Shuping; Guan, Shui; Xu, Jianqiang; Li, Wenfang; Ge, Dan; Sun, Changkai; Liu, Tianqing; Ma, Xuehu

2017-09-26

Engineering scaffolds with excellent electro-activity is increasingly important in tissue engineering and regenerative medicine. Herein, conductive poly(3,4-ethylenedioxythiophene) doped with hyaluronic acid (PEDOT-HA) nanoparticles were firstly synthesized via chemical oxidant polymerization. A three-dimensional (3D) PEDOT-HA/Cs/Gel scaffold was then developed by introducing PEDOT-HA nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. HA, as a bridge, not only was used as a dopant, but also combined PEDOT into the Cs/Gel via chemical crosslinking. The PEDOT-HA/Cs/Gel scaffold was used as a conductive substrate for neural stem cell (NSC) culture in vitro. The results demonstrated that the PEDOT-HA/Cs/Gel scaffold had excellent biocompatibility for NSC proliferation and differentiation. 3D confocal fluorescence images showed cells attached on the channel surface of Cs/Gel and PEDOT-HA/Cs/Gel scaffolds with a normal neuronal morphology. Compared to the Cs/Gel scaffold, the PEDOT-HA/Cs/Gel scaffold not only promoted NSC proliferation with up-regulated expression of Ki67, but also enhanced NSC differentiation into neurons and astrocytes with up-regulated expression of β tubulin-III and GFAP, respectively. It is expected that this electro-active and bio-active PEDOT-HA/Cs/Gel scaffold will be used as a conductive platform to regulate NSC behavior for neural tissue engineering.

SU-E-T-102: Determination of Dose Distributions and Water-Equivalence of MAGIC-F Polymer Gel for 60Co and 192Ir Brachytherapy Sources

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

Quevedo, A; Nicolucci, P

2014-06-01

Purpose: Analyse the water-equivalence of MAGIC-f polymer gel for {sup 60}Co and {sup 192}Ir clinical brachytherapy sources, through dose distributions simulated with PENELOPE Monte Carlo code. Methods: The real geometry of {sup 60} (BEBIG, modelo Co0.A86) and {sup 192}192Ir (Varian, model GammaMed Plus) clinical brachytherapy sources were modelled on PENELOPE Monte Carlo simulation code. The most probable emission lines of photons were used for both sources: 17 emission lines for {sup 192}Ir and 12 lines for {sup 60}. The dose distributions were obtained in a cubic water or gel homogeneous phantom (30 × 30 × 30 cm{sup 3}), with themore » source positioned in the middle of the phantom. In all cases the number of simulation showers remained constant at 10{sup 9} particles. A specific material for gel was constructed in PENELOPE using weight fraction components of MAGIC-f: wH = 0,1062, wC = 0,0751, wN = 0,0139, wO = 0,8021, wS = 2,58×10{sup −6} e wCu = 5,08 × 10{sup −6}. The voxel size in the dose distributions was 0.6 mm. Dose distribution maps on the longitudinal and radial direction through the centre of the source were used to analyse the water-equivalence of MAGIC-f. Results: For the {sup 60} source, the maximum diferences in relative doses obtained in the gel and water were 0,65% and 1,90%, for radial and longitudinal direction, respectively. For {sup 192}Ir, the maximum difereces in relative doses were 0,30% and 1,05%, for radial and longitudinal direction, respectively. The materials equivalence can also be verified through the effective atomic number and density of each material: Zef-MAGIC-f = 7,07 e .MAGIC-f = 1,060 g/cm{sup 3} and Zef-water = 7,22. Conclusion: The results showed that MAGIC-f is water equivalent, consequently being suitable to simulate soft tissue, for Cobalt and Iridium energies. Hence, gel can be used as a dosimeter in clinical applications. Further investigation to its use in a clinical protocol is needed.« less

Noninvasive spectral imaging of skin chromophores based on multiple regression analysis aided by Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Nishidate, Izumi; Wiswadarma, Aditya; Hase, Yota; Tanaka, Noriyuki; Maeda, Takaaki; Niizeki, Kyuichi; Aizu, Yoshihisa

2011-08-01

In order to visualize melanin and blood concentrations and oxygen saturation in human skin tissue, a simple imaging technique based on multispectral diffuse reflectance images acquired at six wavelengths (500, 520, 540, 560, 580 and 600nm) was developed. The technique utilizes multiple regression analysis aided by Monte Carlo simulation for diffuse reflectance spectra. Using the absorbance spectrum as a response variable and the extinction coefficients of melanin, oxygenated hemoglobin, and deoxygenated hemoglobin as predictor variables, multiple regression analysis provides regression coefficients. Concentrations of melanin and total blood are then determined from the regression coefficients using conversion vectors that are deduced numerically in advance, while oxygen saturation is obtained directly from the regression coefficients. Experiments with a tissue-like agar gel phantom validated the method. In vivo experiments with human skin of the human hand during upper limb occlusion and of the inner forearm exposed to UV irradiation demonstrated the ability of the method to evaluate physiological reactions of human skin tissue.

Macroporous Hydrogel Scaffolds for Three-Dimensional Cell Culture and Tissue Engineering.

PubMed

Fan, Changjiang; Wang, Dong-An

2017-10-01

Hydrogels have been promising candidate scaffolds for cell delivery and tissue engineering due to their tissue-like physical properties and capability for homogeneous cell loading. However, the encapsulated cells are generally entrapped and constrained in the submicron- or nanosized gel networks, seriously limiting cell growth and tissue formation. Meanwhile, the spatially confined settlement inhibits attachment and spreading of anchorage-dependent cells, leading to their apoptosis. In recent years, macroporous hydrogels have attracted increasing attention in use as cell delivery vehicles and tissue engineering scaffolds. The introduction of macropores within gel scaffolds not only improves their permeability for better nutrient transport but also creates space/interface for cell adhesion, proliferation, and extracellular matrix deposition. Herein, we will first review the development of macroporous gel scaffolds and outline the impact of macropores on cell behaviors. In the first part, the advantages and challenges of hydrogels as three-dimensional (3D) cell culture scaffolds will be described. In the second part, the fabrication of various macroporous hydrogels will be presented. Third, the enhancement of cell activities within macroporous gel scaffolds will be discussed. Finally, several crucial factors that are envisaged to propel the improvement of macroporous gel scaffolds are proposed for 3D cell culture and tissue engineering.

A bio-inspired, microchanneled hydrogel with controlled spacing of cell adhesion ligands regulates 3D spatial organization of cells and tissue.

PubMed

Lee, Min Kyung; Rich, Max H; Lee, Jonghwi; Kong, Hyunjoon

2015-07-01

Bioactive hydrogels have been extensively studied as a platform for 3D cell culture and tissue regeneration. One of the key desired design parameters is the ability to control spatial organization of biomolecules and cells and subsequent tissue in a 3D matrix. To this end, this study presents a simple but advanced method to spatially organize microchanneled, cell adherent gel blocks and non-adherent ones in a single construct. This hydrogel system was prepared by first fabricating a bimodal hydrogel in which the microscale, alginate gel blocks modified with cell adhesion peptides containing Arg-Gly-Asp sequence (RGD peptides), and those free of RGD peptides, were alternatingly presented. Then, anisotropically aligned microchannels were introduced by uniaxial freeze-drying of the bimodal hydrogel. The resulting gel system could drive bone marrow stromal cells to adhere to and differentiate into neuron and glial cells exclusively in microchannels of the alginate gel blocks modified with RGD peptides. Separately, the bimodal gel loaded with microparticles releasing vascular endothelial growth factor stimulated vascular growth solely into microchannels of the RGD-alginate gel blocks in vivo. These results were not attained by the bimodal hydrogel fabricated to present randomly oriented micropores. Overall, the bimodal gel system could regulate spatial organization of nerve-like tissue or blood vessels at sub-micrometer length scale. We believe that the hydrogel assembly demonstrated in this study will be highly useful in developing a better understanding of diverse cellular behaviors in 3D tissue and further improve quality of a wide array of engineered tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

Detecting De-gelation through Tissue Using Magnetically Modulated Optical Nanoprobes (MagMOONs)

PubMed Central

Nguyen, KhanhVan T.; Anker, Jeffrey N.

2014-01-01

Alginate gels are widely used for drug delivery and implanted devices. The rate at which these gels break down is important for controlling drug release. Since the de-gelation may be different in vivo, monitoring this process in situ is essential. However, it is challenging to monitor the gel through tissue due to optical scattering and tissue autofluorescence. Herein we describe a method to detect through tissue the chemically-induced changes in viscosity and de-gelation process of alginate gels using magnetically modulated optical nanoprobes (MagMOONs). The MagMOONs are fluorescent magnetic microspheres coated with a thin layer of opaque metal on one hemisphere. The metal layer prevents excitation and emission light from passing through one side of the MagMOONs, which creates orientation-dependent fluorescence intensity. The magnetic particles also align in an external magnetic field and give blinking signals when they rotate to follow an external modulated magnetic field. The blinking signals from these MagMOONs are distinguished from background autofluorescence and can be tracked on a single particle level in the absence of tissue, or for an ensemble average of particles blinking through tissue. When these MagMOONs are dispersed in calcium alginate gel, they become sensors for detecting gel degradation upon addition of either ammonium ion or alginate lyase. Our results show MagMOONs start blinking approximately 10 minutes after 2 mg/mL alginate lyase addition and this blinking is clearly detected even through up to 4 mm chicken breast. This approach can potentially be employed to detect bacterial biofilm formation on medical implants by sensing specific proteases that either activate a related function or regulate biofilm formation. It can also be applied to other biosensors and drug delivery systems based on enzyme-catalyzed breakdown of gel components. PMID:26273129

Detecting De-gelation through Tissue Using Magnetically Modulated Optical Nanoprobes (MagMOONs).

PubMed

Nguyen, KhanhVan T; Anker, Jeffrey N

2014-12-15

Alginate gels are widely used for drug delivery and implanted devices. The rate at which these gels break down is important for controlling drug release. Since the de-gelation may be different in vivo , monitoring this process in situ is essential. However, it is challenging to monitor the gel through tissue due to optical scattering and tissue autofluorescence. Herein we describe a method to detect through tissue the chemically-induced changes in viscosity and de-gelation process of alginate gels using magnetically modulated optical nanoprobes (MagMOONs). The MagMOONs are fluorescent magnetic microspheres coated with a thin layer of opaque metal on one hemisphere. The metal layer prevents excitation and emission light from passing through one side of the MagMOONs, which creates orientation-dependent fluorescence intensity. The magnetic particles also align in an external magnetic field and give blinking signals when they rotate to follow an external modulated magnetic field. The blinking signals from these MagMOONs are distinguished from background autofluorescence and can be tracked on a single particle level in the absence of tissue, or for an ensemble average of particles blinking through tissue. When these MagMOONs are dispersed in calcium alginate gel, they become sensors for detecting gel degradation upon addition of either ammonium ion or alginate lyase. Our results show MagMOONs start blinking approximately 10 minutes after 2 mg/mL alginate lyase addition and this blinking is clearly detected even through up to 4 mm chicken breast. This approach can potentially be employed to detect bacterial biofilm formation on medical implants by sensing specific proteases that either activate a related function or regulate biofilm formation. It can also be applied to other biosensors and drug delivery systems based on enzyme-catalyzed breakdown of gel components.

Subsurface thermal behaviour of tissue mimics embedded with large blood vessels during plasmonic photo-thermal therapy.

PubMed

Paul, Anup; Narasimhan, Arunn; Das, Sarit K; Sengupta, Soujit; Pradeep, Thalappil

2016-11-01

The purpose of this study was to understand the subsurface thermal behaviour of a tissue phantom embedded with large blood vessels (LBVs) when exposed to near-infrared (NIR) radiation. The effect of the addition of nanoparticles to irradiated tissue on the thermal sink behaviour of LBVs was also studied. Experiments were performed on a tissue phantom embedded with a simulated blood vessel of 2.2 mm outer diameter (OD)/1.6 mm inner diameter (ID) with a blood flow rate of 10 mL/min. Type I collagen from bovine tendon and agar gel were used as tissue. Two different nanoparticles, gold mesoflowers (AuMS) and graphene nanostructures, were synthesised and characterised. Energy equations incorporating a laser source term based on multiple scattering theories were solved using finite element-based commercial software. The rise in temperature upon NIR irradiation was seen to vary according to the position of the blood vessel and presence of nanoparticles. While the maximum rise in temperature was about 10 °C for bare tissue, it was 19 °C for tissue embedded with gold nanostructures and 38 °C for graphene-embedded tissues. The axial temperature distribution predicted by computational simulation matched the experimental observations. A different subsurface temperature distribution has been obtained for different tissue vascular network models. The position of LBVs must be known in order to achieve optimal tissue necrosis. The simulation described here helps in predicting subsurface temperature distributions within tissues during plasmonic photo-thermal therapy so that the risks of damage and complications associated with in vivo experiments and therapy may be avoided.

Robotic multimodality stereotactic brain tissue identification: work in progress

NASA Technical Reports Server (NTRS)

Andrews, R.; Mah, R.; Galvagni, A.; Guerrero, M.; Papasin, R.; Wallace, M.; Winters, J.

1997-01-01

Real-time identification of tissue would improve procedures such as stereotactic brain biopsy (SBX), functional and implantation neurosurgery, and brain tumor excision. To standard SBX equipment has been added: (1) computer-controlled stepper motors to drive the biopsy needle/probe precisely; (2) multiple microprobes to track tissue density, detect blood vessels and changes in blood flow, and distinguish the various tissues being penetrated; (3) neural net learning programs to allow real-time comparisons of current data with a normative data bank; (4) three-dimensional graphic displays to follow the probe as it traverses brain tissue. The probe can differentiate substances such as pig brain, differing consistencies of the 'brain-like' foodstuff tofu, and gels made to simulate brain, as well as detect blood vessels imbedded in these substances. Multimodality probes should improve the safety, efficacy, and diagnostic accuracy of SBX and other neurosurgical procedures.

Comparison of Dapivirine Vaginal Gel and Film Formulation Pharmacokinetics and Pharmacodynamics (FAME 02B).

PubMed

Robinson, Jennifer A; Marzinke, Mark A; Bakshi, Rahul P; Fuchs, Edward J; Radebaugh, Christine L; Aung, Wutyi; Spiegel, Hans M L; Coleman, Jenell S; Rohan, Lisa C; Hendrix, Craig W

2017-04-01

While preexposure prophylaxis with oral tenofovir/emtricitabine reduces HIV acquisition rates, poor adherence to and acceptability of vaginal gels and the potential for evolving drug resistance have led to development of vaginal film formulations and other antiretroviral drugs, respectively, including the non-nucleoside reverse transcriptase inhibitor dapivirine. In this two-arm crossover study of a novel fast-dissolving dapivirine film and a previously studied semisolid dapivirine gel, 10 healthy women received a single 1.25 mg vaginal dose of each study product; one withdrew after the first dose. Clinical, pharmacokinetic, and antiviral pharmacodynamic assessments (ex vivo HIV-BaL challenge of tissue explants) were performed over 168 h postdose. Six of ten participants experienced mild to moderate adverse effects, similar between products, with no severe adverse events or adverse events attributed to study products. There were no statistically significant differences in plasma, cervicovaginal fluid (CVF), or cervical tissue dapivirine concentrations between the gel and film (all p > .05). CVF dapivirine concentrations were 1.5 and 6 log 10 greater than tissue and plasma concentrations, respectively (p < .001). Both film and gel demonstrated reduced cervical tissue infectivity after ex vivo HIV challenge 5 h postdose, compared to baseline and 72-h postdose biopsies (p < .05 for gel, p = .06 for film). There was no difference in ex vivo explant HIV challenge between gel and film. The dapivirine film and gel performed similarly in terms of tolerability, pharmacokinetics, and antiviral effect. Dapivirine film may provide an alternative to pharmacokinetically comparable dapivirine gel formulations. Effectiveness remains to be tested.

The effects of scaffold architecture and fibrin gel addition on tendon cell phenotype.

PubMed

Pawelec, K M; Wardale, R J; Best, S M; Cameron, R E

2015-01-01

Development of tissue engineering scaffolds relies on careful selection of pore architecture and chemistry of the cellular environment. Repair of skeletal soft tissue, such as tendon, is particularly challenging, since these tissues have a relatively poor healing response. When removed from their native environment, tendon cells (tenocytes) lose their characteristic morphology and the expression of phenotypic markers. To stimulate tendon cells to recreate a healthy extracellular matrix, both architectural cues and fibrin gels have been used in the past, however, their relative effects have not been studied systematically. Within this study, a combination of collagen scaffold architecture, axial and isotropic, and fibrin gel addition was assessed, using ovine tendon-derived cells to determine the optimal strategy for controlling the proliferation and protein expression. Scaffold architecture and fibrin gel addition influenced tendon cell behavior independently in vitro. Addition of fibrin gel within a scaffold doubled cell number and increased matrix production for all architectures studied. However, scaffold architecture dictated the type of matrix produced by cells, regardless of fibrin addition. Axial scaffolds, mimicking native tendon, promoted a mature matrix, with increased tenomodulin, a marker for mature tendon cells, and decreased scleraxis, an early transcription factor for connective tissue. This study demonstrated that both architectural cues and fibrin gel addition alter cell behavior and that the combination of these signals could improve clinical performance of current tissue engineering constructs.

Mitomycin C dissolved in a reversible thermosetting gel: target tissue concentrations in the rabbit eye.

PubMed

Ichien, K; Yamamoto, T; Kitazawa, Y; Oguri, A; Ando, H; Kondo, Y

1997-01-01

To determine whether a new, reversible thermosetting gel enhances mitomycin C transfer to target ocular tissues in the rabbit eye. A 0.1 ml solution of mitomycin C containing 0.22 microgram, 2.9 micrograms, or 28 micrograms of the agent dissolved in a reversible thermosetting gel consisting of methylcellulose, citric acid, and polyethylene glycol was injected subconjunctivally in 30 New Zealand albino rabbits. Scleral and conjunctival tissues were excised at 0.5, 1, 2, 4, or 24 hours after the injection and mitomycin C concentrations in these tissues were determined by high performance liquid chromatography. The concentration over time was approximated to a single exponential curve, and initial mitomycin C concentrations, time constants, and half life values were determined. Finally, the areas under the curves (AUCs) between 0.5 and 24 hours were calculated. The mitomycin C concentrations in the target tissues were dose dependent and decreased rapidly over 24 hours. Both the initial mitomycin C concentrations as well as AUCs in these eyes treated with mitomycin C, dissolved in a reversible thermosetting gel, were higher than those in eyes treated similarly in a previous study in which the gel was not used. Applied subconjunctivally in the rabbit eye, mitomycin C dissolved in the reversible thermosetting gel enhanced transfer of the agent to the sclera and the conjunctiva.

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

PubMed Central

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

2013-01-01

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

Method to reduce non-specific tissue heating of small animals in solenoid coils.

PubMed

Kumar, Ananda; Attaluri, Anilchandra; Mallipudi, Rajiv; Cornejo, Christine; Bordelon, David; Armour, Michael; Morua, Katherine; Deweese, Theodore L; Ivkov, Robert

2013-01-01

Solenoid coils that generate time-varying or alternating magnetic fields (AMFs) are used in biomedical devices for research, imaging and therapy. Interactions of AMF and tissue produce eddy currents that deposit power within tissue, thus limiting effectiveness and safety. We aim to develop methods that minimise excess heating of mice exposed to AMFs for cancer therapy experiments. Numerical and experimental data were obtained to characterise thermal management properties of water using a continuous, custom water jacket in a four-turn simple solenoid. Theoretical data were obtained with method-of-moments (MoM) numerical field calculations and finite element method (FEM) thermal simulations. Experimental data were obtained from gel phantoms and mice exposed to AMFs having amplitude >50 kA/m and frequency of 160 kHz. Water has a high specific heat and thermal conductivity, is diamagnetic, polar, and nearly transparent to magnetic fields. We report at least a two-fold reduction of temperature increase from gel phantom and animal models when a continuous layer of circulating water was placed between the sample and solenoid, compared with no water. Thermal simulations indicate the superior efficiency in thermal management by the developed continuous single chamber cooling system over a double chamber non-continuous system. Further reductions of heating were obtained by regulating water temperature and flow for active cooling. These results demonstrate the potential value of a contiguous layer of circulating water to permit sustained exposure to high intensity alternating magnetic fields at this frequency for research using small animal models exposed to AMFs.

Method to reduce non-specific tissue heating of small animals in solenoid coils

PubMed Central

KUMAR, ANANDA; ATTALURI, ANILCHANDRA; MALLIPUDI, RAJIV; CORNEJO, CHRISTINE; BORDELON, DAVID; ARMOUR, MICHAEL; MORUA, KATHERINE; DEWEESE, THEODORE L.; IVKOV, ROBERT

2014-01-01

Purpose Solenoid coils that generate time-varying or alternating magnetic fields (AMFs) are used in biomedical devices for research, imaging and therapy. Interactions of AMF and tissue produce eddy currents that deposit power within tissue, thus limiting effectiveness and safety. We aim to develop methods that minimise excess heating of mice exposed to AMFs for cancer therapy experiments. Materials and methods Numerical and experimental data were obtained to characterise thermal management properties of water using a continuous, custom water jacket in a four-turn simple solenoid. Theoretical data were obtained with method-of-moments (MoM) numerical field calculations and finite element method (FEM) thermal simulations. Experimental data were obtained from gel phantoms and mice exposed to AMFs having amplitude >50kA/m and frequency of 160 kHz. Results Water has a high specific heat and thermal conductivity, is diamagnetic, polar, and nearly transparent to magnetic fields. We report at least a two-fold reduction of temperature increase from gel phantom and animal models when a continuous layer of circulating water was placed between the sample and solenoid, compared with no water. Thermal simulations indicate the superior efficiency in thermal management by the developed continuous single chamber cooling system over a double chamber non-continuous system. Further reductions of heating were obtained by regulating water temperature and flow for active cooling. Conclusions These results demonstrate the potential value of a contiguous layer of circulating water to permit sustained exposure to high intensity alternating magnetic fields at this frequency for research using small animal models exposed to AMFs. PMID:23402327

Hyaluronic acid gel distribution pattern in periocular area with high-resolution ultrasound imaging.

PubMed

Goh, Alice S; Kohn, Jocelyne C; Rootman, Daniel B; Lin, Joseph L; Goldberg, Robert A

2014-05-01

High-resolution ultrasound (HRUS) is a useful tool in defining anatomic and dynamic soft tissue relationships in the periocular area. It also allows visualization of hyaluronic acid (HA) gel within the soft tissue. The authors investigate the difference in the distribution pattern between 2 HA fillers in the periocular tissue using HRUS. The charts of 10 patients who underwent periocular injection using HA gel filler and were subsequently examined with HRUS were reviewed. Half of the patients (n = 5) were treated with Restylane-L (Medicis Aesthetics, Inc, Scottsdale, Arizona) and the remaining 5 with Belotero Balance (Merz Aesthetics, Inc, San Mateo, California). Ultrasonographic evaluation (Logiq p6; GE Healthcare, Waukesha, Washington) was performed before and immediately after HA filler injection. The HA appears as a hypoechoic image within the soft tissue plane on HRUS. Restylane-L filler formed a localized hypoechoic image within the tissue, with some spread into bubbles or pearl-like configuration. Belotero Balance spread more widely into the tissue plane and diffused into an elongated or spindle-shaped hypoechoic image. Our preliminary data suggest that HA gel fillers with differing production technologies show distinct spread and distribution patterns in the periocular tissues on HRUS examination.

Quantifying white matter tract diffusion parameters in the presence of increased extra-fiber cellularity and vasogenic edema

PubMed Central

Chiang, Chia-Wen; Wang, Yong; Sun, Peng; Lin, Tsen-Hsuan; Trinkaus, Kathryn; Cross, Anne H.; Song, Sheng-Kwei

2014-01-01

The effect of extra-fiber structural and pathological components confounding diffusion tensor imaging (DTI) computation was quantitatively investigated using data generated by both Monte-Carlo simulations and tissue phantoms. Increased extent of vasogenic edema, by addition of various amount of gel to fixed normal mouse trigeminal nerves or by increasing non-restricted isotropic diffusion tensor components in Monte-Carlo simulations, significantly decreased fractional anisotropy (FA), increased radial diffusivity, while less significantly increased axial diffusivity derived by DTI. Increased cellularity, mimicked by graded increase of the restricted isotropic diffusion tensor component in Monte-Carlo simulations, significantly decreased FA and axial diffusivity with limited impact on radial diffusivity derived by DTI. The MC simulation and tissue phantom data were also analyzed by the recently developed diffusion basis spectrum imaging (DBSI) to simultaneously distinguish and quantify the axon/myelin integrity and extra-fiber diffusion components. Results showed that increased cellularity or vasogenic edema did not affect the DBSI-derived fiber FA, axial or radial diffusivity. Importantly, the extent of extra-fiber cellularity and edema estimated by DBSI correlated with experimentally added gel and Monte-Carlo simulations. We also examined the feasibility of applying 25-direction diffusion encoding scheme for DBSI analysis on coherent white matter tracts. Results from both phantom experiments and simulations suggested that the 25-direction diffusion scheme provided comparable DBSI estimation of both fiber diffusion parameters and extra-fiber cellularity/edema extent as those by 99-direction scheme. An in vivo 25-direction DBSI analysis was performed on experimental autoimmune encephalomyelitis (EAE, an animal model of human multiple sclerosis) optic nerve as an example to examine the validity of derived DBSI parameters with post-imaging immunohistochemistry verification. Results support that in vivo DBSI using 25-direction diffusion scheme correctly reflect the underlying axonal injury, demyelination, and inflammation of optic nerves in EAE mice. PMID:25017446

Development of a Searchable Database of Cryoablation Simulations for Use in Treatment Planning.

PubMed

Boas, F Edward; Srimathveeravalli, Govindarajan; Durack, Jeremy C; Kaye, Elena A; Erinjeri, Joseph P; Ziv, Etay; Maybody, Majid; Yarmohammadi, Hooman; Solomon, Stephen B

2017-05-01

To create and validate a planning tool for multiple-probe cryoablation, using simulations of ice ball size and shape for various ablation probe configurations, ablation times, and types of tissue ablated. Ice ball size and shape was simulated using the Pennes bioheat equation. Five thousand six hundred and seventy different cryoablation procedures were simulated, using 1-6 cryoablation probes and 1-2 cm spacing between probes. The resulting ice ball was measured along three perpendicular axes and recorded in a database. Simulated ice ball sizes were compared to gel experiments (26 measurements) and clinical cryoablation cases (42 measurements). The clinical cryoablation measurements were obtained from a HIPAA-compliant retrospective review of kidney and liver cryoablation procedures between January 2015 and February 2016. Finally, we created a web-based cryoablation planning tool, which uses the cryoablation simulation database to look up the probe spacing and ablation time that produces the desired ice ball shape and dimensions. Average absolute error between the simulated and experimentally measured ice balls was 1 mm in gel experiments and 4 mm in clinical cryoablation cases. The simulations accurately predicted the degree of synergy in multiple-probe ablations. The cryoablation simulation database covers a wide range of ice ball sizes and shapes up to 9.8 cm. Cryoablation simulations accurately predict the ice ball size in multiple-probe ablations. The cryoablation database can be used to plan ablation procedures: given the desired ice ball size and shape, it will find the number and type of probes, probe configuration and spacing, and ablation time required.

The cryoablation of lung tissue using liquid nitrogen in gel and in the ex vivo pig lung.

PubMed

Nomori, Hiroaki; Yamazaki, Ikuo; Kondo, Toshiya; Kanno, Masaya

2017-02-01

To examine the efficiency of cryoablation using liquid nitrogen in lung tissue, we measured the size and temperature distribution of the frozen area (iceball) in gel and in the ex vivo pig lungs. Cryoprobes with diameters of 2.4 and 3.4 mm (2.4D and 3.4D, respectively) were used. Three temperature sensors were positioned at the surface of the cryoprobe and at distances of 0.5 and 1.5 cm from the cryoprobe. The ex vivo pig lungs were perfused with 37 °C saline and inflated using ventilator to simulate in vivo lung conditions. In gel, the 2.4D and 3.4D probes made iceballs of 3.9 ± 0.1 and 4.8 ± 0.3 cm in diameter, respectively, and the temperature at 1.5 cm from those probes reached -32 ± 8 and -53 ± 5 °C, respectively. In the pig lung, the 2.4D and 3.4D probes made iceballs of 5.2 ± 0.1 and 5.5 ± 0.4 cm in diameter, respectively, and the temperature at 1.5 cm from these probes reached -49 ± 5 and -58 ± 3 °C, respectively. Liquid nitrogen cryoablation using both 2.4D and 3.4D probes made iceballs that were of sufficient size, and effective temperatures were reached in both gel and the ex vivo pig lung.

Comparison of Dapivirine Vaginal Gel and Film Formulation Pharmacokinetics and Pharmacodynamics (FAME 02B)

PubMed Central

Marzinke, Mark A.; Bakshi, Rahul P.; Fuchs, Edward J.; Radebaugh, Christine L.; Aung, Wutyi; Spiegel, Hans M.L.; Coleman, Jenell S.; Rohan, Lisa C.; Hendrix, Craig W.

2017-01-01

Abstract While preexposure prophylaxis with oral tenofovir/emtricitabine reduces HIV acquisition rates, poor adherence to and acceptability of vaginal gels and the potential for evolving drug resistance have led to development of vaginal film formulations and other antiretroviral drugs, respectively, including the non-nucleoside reverse transcriptase inhibitor dapivirine. In this two-arm crossover study of a novel fast-dissolving dapivirine film and a previously studied semisolid dapivirine gel, 10 healthy women received a single 1.25 mg vaginal dose of each study product; one withdrew after the first dose. Clinical, pharmacokinetic, and antiviral pharmacodynamic assessments (ex vivo HIV-BaL challenge of tissue explants) were performed over 168 h postdose. Six of ten participants experienced mild to moderate adverse effects, similar between products, with no severe adverse events or adverse events attributed to study products. There were no statistically significant differences in plasma, cervicovaginal fluid (CVF), or cervical tissue dapivirine concentrations between the gel and film (all p > .05). CVF dapivirine concentrations were 1.5 and 6 log10 greater than tissue and plasma concentrations, respectively (p < .001). Both film and gel demonstrated reduced cervical tissue infectivity after ex vivo HIV challenge 5 h postdose, compared to baseline and 72-h postdose biopsies (p < .05 for gel, p = .06 for film). There was no difference in ex vivo explant HIV challenge between gel and film. The dapivirine film and gel performed similarly in terms of tolerability, pharmacokinetics, and antiviral effect. Dapivirine film may provide an alternative to pharmacokinetically comparable dapivirine gel formulations. Effectiveness remains to be tested. PMID:27809557

SU-E-T-130: Dosimetric Evaluation of Tissue Equivalent Gel Dosimeter Using Saccharide in Radiotherapy System

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

Cho, Y; Lee, D; Jung, H

2014-06-01

Purpose: In this study, the dose responses of the MAGIC gel with various concentrations and type of saccharide are examined to clarify the roles of mono and disaccharide in the polymerization process. Then we focused on the tissue equivalence and dose sensitivity of MAGIC gel dosimeters. Methods: The gel is composed of HPLC, 8% gelatin, 2 × 10-3 M L-ascorbic acid, 1.8 × 10-2 M hydroquinone, 8 × 10-5 M copper(II)sulfate and 9% methacrylic acid, new polymer gels are synthesized by adding glucose(monosaccharide), sucrose(disaccharide) and urea in the concentration range of 5∼35%. For irradiation of the gel, cesium-137 gamma-ray irradiatormore » was used, radiation dose was delivered from 5∼50 Gy. MRI images of the gel were acquired by using a 3.0 T MRI system. Results: When saccharide and urea were added, the O/C, O/N and C/N ratios agreed with those of soft tissue with 1.7%. The dose-response of glucose and sucrose gel have slope-to-intercept ratio of 0.044 and 0.283 respectively. The slope-to-ratio is one important determinant of gel sensitivity. R-square values of glucose and sucrose gel dosimeters were 0.984 and 0.994 respectively. Moreover when urea were added, the slope-to-intercept ratio is 0.044 and 0.073 respectively. R-square values of mono and disaccharide gel were 0.973 and 0.989 respectively. When a saccharide is added into the MAGIC gel dosimeter, dose sensitivity is increased. However when urea were added, dose sensitivity is slightly decreased. Conclusion: In this study, it was possible to obtain the following conclusions by looking at the dose response characteristics after adding mono-, di-saccharide and urea to a MAGIC gel dosimeter. Saccharide was a tendency of increasing dose sensitivity with disaccharide. Sa.ccharide is cost effective, safe, soft tissue equivalent, and can be used under various experimental conditions, making it a suitable dosimeter for some radiotherapy applications.« less

Encapsulation of Mesenchymal Stem Cells Improves Vascularization of Alginate-Based Scaffolds.

PubMed

Steiner, Dominik; Lingens, Lara; Fischer, Laura; Köhn, Katrin; Detsch, Rainer; Boccaccini, Aldo R; Fey, Tobias; Greil, Peter; Weis, Christian; Beier, Justus P; Horch, Raymund E; Arkudas, Andreas

2018-05-09

Vascularization of bioartificial tissues can be significantly enhanced by the generation of an arteriovenous (AV) loop. Besides the surgical vascularization, the choice of the scaffold and the applied cells are indispensable cofactors. The combination of alginate dialdehyde and gelatin (ADA-GEL) and mesenchymal stem cells (MSCs) is a promising approach with regard to biocompatibility, biodegradation, as well as de novo tissue formation. In this study, we targeted the investigation of the vascularization of ADA-GEL with and in the absence of encapsulated MSCs in the AV loop model. A Teflon chamber filled with ADA-GEL microcapsules was placed in the groin of Lewis rats and an AV loop was placed into the chamber. Group A encompassed the ADA-GEL without MSCs, whereas group B contained 2 × 10 6 DiI-labeled MSCs/mL ADA-GEL. Four weeks postoperatively, tissue formation and vascularization were investigated by histology and microcomputed tomography. We were able to prove vascularization originating from the AV loop in both groups with statistically significant more vessels in group B containing MSCs. Moreover, encapsulated MSCs promoted biodegradation of the ADA-GEL microcapsules. In the present study, we were able to demonstrate for the first time, the successful vascularization of ADA-GEL microcapsules by means of the AV loop. Furthermore, ADA-GEL displayed a good biocompatibility and encapsulation of MSCs into ADA-GEL microcapsule-enhanced vascularization as well as biodegradation.

Mechanics of a two-fiber model with one nested fiber network, as applied to the collagen-fibrin system.

PubMed

Nedrelow, David S; Bankwala, Danesh; Hyypio, Jeffrey D; Lai, Victor K; Barocas, Victor H

2018-05-01

The mechanical behavior of collagen-fibrin (col-fib) co-gels is both scientifically interesting and clinically relevant. Collagen-fibrin networks are a staple of tissue engineering research, but the mechanical consequences of changes in co-gel composition have remained difficult to predict or even explain. We previously observed fundamental differences in failure behavior between collagen-rich and fibrin-rich co-gels, suggesting an essential change in how the two components interact as the co-gel's composition changes. In this work, we explored the hypothesis that the co-gel behavior is due to a lack of percolation by the dilute component. We generated a series of computational models based on interpenetrating fiber networks. In these models, the major network component percolated the model space but the minor component did not, instead occupying a small island embedded within the larger network. Each component was assigned properties based on a fit of single-component gel data. Island size was varied to match the relative concentrations of the two components. The model predicted that networks rich in collagen, the stiffer component, would roughly match pure-collagen gel behavior with little additional stress due to the fibrin, as seen experimentally. For fibrin-rich gels, however, the model predicted a smooth increase in the overall network strength with added collagen, as seen experimentally but not consistent with an additive parallel model. We thus conclude that incomplete percolation by the low-concentration component of a co-gel is a major determinant of its macroscopic properties, especially if the low-concentration component is the stiffer component. Models for the behavior of fibrous networks have useful applications in many different fields, including polymer science, textiles, and tissue engineering. In addition to being important structural components in soft tissues and blood clots, these protein networks can serve as scaffolds for bioartificial tissues. Thus, their mechanical behavior, especially in co-gels, is both interesting from a materials science standpoint and significant with regard to tissue engineering. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Molecular simulation of the swelling of polyelectrolyte gels by monovalent and divalent counterions

PubMed Central

Yin, De-Wei; Horkay, Ferenc; Douglas, Jack F.; de Pablo, Juan J.

2008-01-01

Permanently crosslinked polyelectrolyte gels are known to undergo discontinuous first-order volume phase transitions, the onset of which may be caused by a number of factors. In this study we examine the volumetric properties of such polyelectrolyte gels in relation to the progressive substitution of monovalent counterions by divalent counterions as the gels are equilibrated in solvents of different dielectric qualities. We compare the results of coarse-grained molecular dynamics simulations of polyelectrolyte gels with previous experimental measurements by others on polyacrylate gels. The simulations show that under equilibrium conditions there is an approximate cancellation between the electrostatic contribution and the counterion excluded-volume contribution to the osmotic pressure in the gel-solvent system; these two contributions to the osmotic pressure have, respectively, energetic and entropic origins. The finding of such a cancellation between the two contributions to the osmotic pressure of the gel-solvent system is consistent with experimental observations that the swelling behavior of polyelectrolyte gels can be described by equations of state for neutral gels. Based on these results, we show and explain that a modified form of the Flory–Huggins model for nonionic polymer solutions, which accounts for neither electrostatic effects nor counterion excluded-volume effects, fits both experimental and simulated data for polyelectrolyte gels. The Flory–Huggins interaction parameters obtained from regression to the simulation data are characteristic of ideal polymer solutions, whereas the experimentally obtained interaction parameters, particularly that associated with the third virial coefficient, exhibit a significant departure from ideality, leading us to conclude that further enhancements to the simulation model, such as the inclusion of excess salt, the allowance for size asymmetric electrolytes, or the use of a distance-dependent solvent dielectricity model, may be required. Molecular simulations also reveal that the condensation of divalent counterions onto the polyelectrolyte network backbone occurs preferentially over that of monovalent counterions. PMID:19045224

Molecular simulation of the swelling of polyelectrolyte gels by monovalent and divalent counterions.

PubMed

Yin, De-Wei; Horkay, Ferenc; Douglas, Jack F; de Pablo, Juan J

2008-10-21

Permanently crosslinked polyelectrolyte gels are known to undergo discontinuous first-order volume phase transitions, the onset of which may be caused by a number of factors. In this study we examine the volumetric properties of such polyelectrolyte gels in relation to the progressive substitution of monovalent counterions by divalent counterions as the gels are equilibrated in solvents of different dielectric qualities. We compare the results of coarse-grained molecular dynamics simulations of polyelectrolyte gels with previous experimental measurements by others on polyacrylate gels. The simulations show that under equilibrium conditions there is an approximate cancellation between the electrostatic contribution and the counterion excluded-volume contribution to the osmotic pressure in the gel-solvent system; these two contributions to the osmotic pressure have, respectively, energetic and entropic origins. The finding of such a cancellation between the two contributions to the osmotic pressure of the gel-solvent system is consistent with experimental observations that the swelling behavior of polyelectrolyte gels can be described by equations of state for neutral gels. Based on these results, we show and explain that a modified form of the Flory-Huggins model for nonionic polymer solutions, which accounts for neither electrostatic effects nor counterion excluded-volume effects, fits both experimental and simulated data for polyelectrolyte gels. The Flory-Huggins interaction parameters obtained from regression to the simulation data are characteristic of ideal polymer solutions, whereas the experimentally obtained interaction parameters, particularly that associated with the third virial coefficient, exhibit a significant departure from ideality, leading us to conclude that further enhancements to the simulation model, such as the inclusion of excess salt, the allowance for size asymmetric electrolytes, or the use of a distance-dependent solvent dielectricity model, may be required. Molecular simulations also reveal that the condensation of divalent counterions onto the polyelectrolyte network backbone occurs preferentially over that of monovalent counterions.

Radiological properties of MAGIC normoxic polymer gel dosimetry

NASA Astrophysics Data System (ADS)

Aljamal, M.; Zakaria, A.; Shamsuddin, S.

2013-04-01

For a polymer gel dosimeter to be of use in radiation dosimetry, it should display water-equivalent radiological properties. In this study, the radiological properties of the MAGIC (Methacrylic and Ascorbic acid in Gelatin Initiated by Copper) normoxic polymer gels were investigated. The mass density (ρ) was determined based on Archimedes' principle. The weight fraction of elemental composition and the effective atomic number (Zeff) were calculated. The electron density was also measured with 90° scattering angle at room temperature. The linear attenuation coefficient (μ) of unirradiated gel, irradiated gel, and water were determined using Am-241 based on narrow beam geometry. Monte Carlo simulation was used to calculate the depth doses response of MAGIC gel and water for 6MV photon beam. The weight fractions of elements composition of MAGIC gel were close to that for water. The mass density was found to be 1027 ± 2 kg m-3, which is also very close to mass density of muscle tissue (1030 kg m-3) and 2.7% higher than that of water. The electron density (ρe) and atomic number (Zeff) were found to be 3.43 × 1029 e m-3 and 7.105, respectively. The electron density measured was 2.6% greater than that for water. The atomic number was very close to that for water. The prepared MAGIC gel was found to be water equivalent based on the study of element composition, mass density, electron density and atomic number. The linear attenuation coefficient of unirradiated gel was very close to that of water. The μ of irradiated gel was found to be linear with dose 2-40 Gy. The depth dose response for MAGIC gel from a 6 MV photon beam had a percentage dose difference to water of less than 1%. Therefore it satisfies the criteria to be a good polymer gel dosimeter for radiotherapy.

Poly(ethylene glycol)-Mediated Collagen Gel Mechanics Regulates Cellular Phenotypes in a Microchanneled Matrix.

PubMed

Rich, Max H; Lee, Min Kyung; Ballance, William C; Boppart, Marni; Kong, Hyunjoon

2017-08-14

For the past few decades, efforts have been extensively made to reproduce tissue of interests for various uses including fundamental bioscience studies, clinical treatments, and even soft robotic systems. In these studies, cells are often cultured in micropores introduced in a provisional matrix despite that bulk rigidity may negatively affect cellular differentiation involved in tissue formation. To this end, we hypothesized that suspending cells within a soft fibrous matrix that is encapsulated within the microchannels of a provisional matrix would allow us to mediate effects of the matrix rigidity on cells and, in turn, to increase the cell differentiation level. We examined this hypothesis by filling microchannels interpenetrating alginate matrices with collagen gels of controlled elastic moduli (i.e., 125 to 1 Pa). Myoblasts used as a model predifferentiated cell were suspended within the collagen gels. The elastic modulus of the collagen gels was decreased through the addition of poly(ethylene glycol) during the gel preparation. Myoblasts loaded in the collagen gel exhibited a higher myogenic differentiation level than those adhered to the collagen-coated microchannel wall. Furthermore, the collagen gel softened by poly(ethylene glycol) further increased the volume of the multinucleated myofibers. The role of collagen gel softness on cell differentiation became more significant when the bulk elastic modulus of the alginate matrix was tuned to be close to that of muscle tissue (i.e., 11 kPa). We believe that the results of this study would be useful to understanding phenotypic activities of a wide array of cells involved in tissue development and regeneration.

Mitomycin C dissolved in a reversible thermosetting gel: target tissue concentrations in the rabbit eye

PubMed Central

Ichien, K.; Yamamoto, T.; Kitazawa, Y.; Oguri, A.; Ando, H.; Kondo, Y.

1997-01-01

AIMS—To determine whether a new, reversible thermosetting gel enhances mitomycin C transfer to target ocular tissues in the rabbit eye.
METHODS—A 0.1 ml solution of mitomycin C containing 0.22 µg, 2.9 µg, or 28 µg of the agent dissolved in a reversible thermosetting gel consisting of methylcellulose, citric acid, and polyethylene glycol was injected subconjunctivally in 30 New Zealand albino rabbits. Scleral and conjunctival tissues were excised at 0.5, 1, 2, 4, or 24 hours after the injection and mitomycin C concentrations in these tissues were determined by high performance liquid chromatography. The concentration over time was approximated to a single exponential curve, and initial mitomycin C concentrations, time constants, and half life values were determined. Finally, the areas under the curves (AUCs) between 0.5 and 24 hours were calculated.
RESULTS—The mitomycin C concentrations in the target tissues were dose dependent and decreased rapidly over 24 hours. Both the initial mitomycin C concentrations as well as AUCs in these eyes treated with mitomycin C, dissolved in a reversible thermosetting gel, were higher than those in eyes treated similarly in a previous study in which the gel was not used.
CONCLUSION—Applied subconjunctivally in the rabbit eye, mitomycin C dissolved in the reversible thermosetting gel enhanced transfer of the agent to the sclera and the conjunctiva.

 PMID:9135413

Digital micromirror device projection printing system for meniscus tissue engineering.

PubMed

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

2013-07-01

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

Multiscale Computer Simulation of Failure in Aerogels

NASA Technical Reports Server (NTRS)

Good, Brian S.

2008-01-01

Aerogels have been of interest to the aerospace community primarily for their thermal properties, notably their low thermal conductivities. While such gels are typically fragile, recent advances in the application of conformal polymer layers to these gels has made them potentially useful as lightweight structural materials as well. We have previously performed computer simulations of aerogel thermal conductivity and tensile and compressive failure, with results that are in qualitative, and sometimes quantitative, agreement with experiment. However, recent experiments in our laboratory suggest that gels having similar densities may exhibit substantially different properties. In this work, we extend our original diffusion limited cluster aggregation (DLCA) model for gel structure to incorporate additional variation in DLCA simulation parameters, with the aim of producing DLCA clusters of similar densities that nevertheless have different fractal dimension and secondary particle coordination. We perform particle statics simulations of gel strain on these clusters, and consider the effects of differing DLCA simulation conditions, and the resultant differences in fractal dimension and coordination, on gel strain properties.

Crosslinkable hydrogels derived from cartilage, meniscus, and tendon tissue.

PubMed

Visser, Jetze; Levett, Peter A; te Moller, Nikae C R; Besems, Jeremy; Boere, Kristel W M; van Rijen, Mattie H P; de Grauw, Janny C; Dhert, Wouter J A; van Weeren, P René; Malda, Jos

2015-04-01

Decellularized tissues have proven to be versatile matrices for the engineering of tissues and organs. These matrices usually consist of collagens, matrix-specific proteins, and a set of largely undefined growth factors and signaling molecules. Although several decellularized tissues have found their way to clinical applications, their use in the engineering of cartilage tissue has only been explored to a limited extent. We set out to generate hydrogels from several tissue-derived matrices, as hydrogels are the current preferred cell carriers for cartilage repair. Equine cartilage, meniscus, and tendon tissue was harvested, decellularized, enzymatically digested, and functionalized with methacrylamide groups. After photo-cross-linking, these tissue digests were mechanically characterized. Next, gelatin methacrylamide (GelMA) hydrogel was functionalized with these methacrylated tissue digests. Equine chondrocytes and mesenchymal stromal cells (MSCs) (both from three donors) were encapsulated and cultured in vitro up to 6 weeks. Gene expression (COL1A1, COL2A1, ACAN, MMP-3, MMP-13, and MMP-14), cartilage-specific matrix formation, and hydrogel stiffness were analyzed after culture. The cartilage, meniscus, and tendon digests were successfully photo-cross-linked into hydrogels. The addition of the tissue-derived matrices to GelMA affected chondrogenic differentiation of MSCs, although no consequent improvement was demonstrated. For chondrocytes, the tissue-derived matrix gels performed worse compared to GelMA alone. This work demonstrates for the first time that native tissues can be processed into crosslinkable hydrogels for the engineering of tissues. Moreover, the differentiation of encapsulated cells can be influenced in these stable, decellularized matrix hydrogels.

Mathematical model of microbicidal flow dynamics and optimization of rheological properties for intra-vaginal drug delivery: Role of tissue mechanics and fluid rheology.

PubMed

Anwar, Md Rajib; Camarda, Kyle V; Kieweg, Sarah L

2015-06-25

Topically applied microbicide gels can provide a self-administered and effective strategy to prevent sexually transmitted infections (STIs). We have investigated the interplay between vaginal tissue elasticity and the yield-stress of non-Newtonian fluids during microbicide deployment. We have developed a mathematical model of tissue deformation driven spreading of microbicidal gels based on thin film lubrication approximation and demonstrated the effect of tissue elasticity and fluid yield-stress on the spreading dynamics. Our results show that both elasticity of tissue and yield-stress rheology of gel are strong determinants of the coating behavior. An optimization framework has been demonstrated which leverages the flow dynamics of yield-stress fluid during deployment to maximize retention while reaching target coating length for a given tissue elasticity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simultaneous confocal fluorescence microscopy and optical coherence tomography for drug distribution and tissue integrity assessment

NASA Astrophysics Data System (ADS)

Rinehart, Matthew T.; LaCroix, Jeffrey; Henderson, Marcus; Katz, David; Wax, Adam

2011-03-01

The effectiveness of microbicidal gels, topical products developed to prevent infection by sexually transmitted diseases including HIV/AIDS, is governed by extent of gel coverage, pharmacokinetics of active pharmaceutical ingredients (APIs), and integrity of vaginal epithelium. While biopsies provide localized information about drug delivery and tissue structure, in vivo measurements are preferable in providing objective data on API and gel coating distribution as well as tissue integrity. We are developing a system combining confocal fluorescence microscopy with optical coherence tomography (OCT) to simultaneously measure local concentrations and diffusion coefficients of APIs during transport from microbicidal gels into tissue, while assessing tissue integrity. The confocal module acquires 2-D images of fluorescent APIs multiple times per second allowing analysis of lateral diffusion kinetics. The custom Fourier domain OCT module has a maximum a-scan rate of 54 kHz and provides depth-resolved tissue integrity information coregistered with the confocal fluorescence measurements. The combined system is validated by imaging phantoms with a surrogate fluorophore. Time-resolved API concentration measured at fixed depths is analyzed for diffusion kinetics. This multimodal system will eventually be implemented in vivo for objective evaluation of microbicide product performance.

Proteomic analysis of zebrafish embryos exposed to simulated-microgravity

NASA Astrophysics Data System (ADS)

Hang, Xiaoming; Ma, Wenwen; Wang, Wei; Liu, Cong; Sun, Yeqing

Microgravity can induce a serial of physiological and pathological changes in human body, such as cardiovascular functional disorder, bone loss, muscular atrophy and impaired immune system function, etc. In this research, we focus on the influence of microgravity to vertebrate embryo development. As a powerful model for studying vertebrate development, zebrafish embryos at 8 hpf (hour past fertilization) and 24 hpf were placed into a NASA developed bioreac-tor (RCCS) to simulate microgravity for 64 and 48 hours, respectively. The same number of control embryos from the same parents were placed in a tissue culture dish at the same temper-ature of 28° C. Each experiment was repeated 3 times and analyzed by two-dimensional (2-D) gel electrophoresis. Image analysis of silver stained 2-D gels revealed that 64 from total 292 protein spots showed quantitative and qualitative variations that were significantly (P<0.05) and reproducibly different between simulate-microgravity treatment and the stationary control samples. 4 protein spots with significant expression alteration (P<0.01) were excised from 2-D gels and analyzed by MALDI-TOF/TOF mass spectra primarily. Of these proteins, 3 down-regulated proteins were identified as bectin 2, centrosomal protein of 135kDa and tropomyosin 4, while the up-regulated protein was identified as creatine kinase muscle B. Other protein spots showed significant expression alteration will be identified successively and the corresponding genes expression will also be measured by Q-PCR method at different development stages. The data presented in this study illustrate that zebrafish embryo can be significantly induced by microgravity on the expression of proteins involved in bone and muscle formation. Key Words: Danio rerio; Simulated-microgravity; Proteomics

Osteochondral Biopsy Analysis Demonstrates That BST-CarGel Treatment Improves Structural and Cellular Characteristics of Cartilage Repair Tissue Compared With Microfracture

PubMed Central

Méthot, Stéphane; Changoor, Adele; Tran-Khanh, Nicolas; Hoemann, Caroline D.; Stanish, William D.; Restrepo, Alberto; Shive, Matthew S.; Buschmann, Michael D.

2016-01-01

Objective The efficacy and safety of BST-CarGel, a chitosan-based medical device for cartilage repair, was compared with microfracture alone at 1 year during a multicenter randomized controlled trial (RCT) in the knee. The quality of repair tissue of osteochondral biopsies collected from a subset of patients was compared using blinded histological assessments. Methods The international RCT evaluated repair tissue quantity and quality by 3-dimensional quantitative magnetic resonance imaging as co-primary endpoints at 12 months. At an average of 13 months posttreatment, 21/41 BST-CarGel and 17/39 microfracture patients underwent elective second look arthroscopies as a tertiary endpoint, during which ICRS (International Cartilage Repair Society) macroscopic scoring was carried out, and osteochondral biopsies were collected. Stained histological sections were evaluated by blinded readers using ICRS I and II histological scoring systems. Collagen organization was evaluated using a polarized light microscopy score. Results BST-CarGel treatment resulted in significantly better ICRS macroscopic scores (P = 0.0002) compared with microfracture alone, indicating better filling, integration, and tissue appearance. Histologically, BST-CarGel resulted in a significant improvement of structural parameters—Surface Architecture (P = 0.007) and Surface/Superficial Assessment (P = 0.042)—as well as cellular parameters—Cell Viability (P = 0.006) and Cell Distribution (P = 0.032). No histological parameters were significantly better for the microfracture group. BST-CarGel treatment also resulted in a more organized repair tissue with collagen stratification more similar to native hyaline cartilage, as measured by polarized light microscopy scoring (P = 0.0003). Conclusion Multiple and independent analyses in this biopsy substudy demonstrated that BST-CarGel treatment results in improved structural and cellular characteristics of repair tissue at 1 year posttreatment compared with microfracture alone, supporting previously reported results by quantitative magnetic resonance imaging. PMID:26958314

Microwave Therapy for Bone Tumors

NASA Astrophysics Data System (ADS)

Takakuda, Kazuo; Inaoka, Shuken; Saito, Hirokazu; Hassan, Moinuddin; Koyama, Yoshikazu; Kuroda, Hiroshi; Kanaya, Tomohiro; Kosaka, Toshifumi; Tanaka, Shigeo; Miyairi, Hiroo; Shinomiya, Kenichi

In vivo microwave treatments for bone tumor are designed, which enable us to conserve the activity and functionality of the matrix of living tissues. This treatment is composed of two steps. In the first step, the tumor was coagulated by the application of microwaves emitted from the antenna inserted into the tumor tissue, and then removed. In the second step, the surrounding tissue suspected to be invaded with transformed cells was covered with hydro gels and heated similarly. The tissue itself was heated by the conduction from the gels. The tissue temperature should be kept at 60°C for 30 minutes. This treatment should kill the whole cells within the tissues, but the mechanical strength and the biochemical activity of the matrix should be left intact. The matrix preserves the mechanical functions and ensures the maximum regeneration ability of the tissue. In this study, various hydro gels were examined and the most promising one was selected. Animal experiments were carried out and successful heating verified the applicability of the treatment.

Flow visualization of a rocket injector spray using gelled propellant simulants

NASA Technical Reports Server (NTRS)

Green, James M.; Rapp, Douglas C.; Roncace, James

1991-01-01

A study was conducted at NASA-Lewis to compare the atomization characteristics of gelled and nongelled propellant simulants. A gelled propellant simulant composed of water, sodium hydroxide, and an acrylic acid polymer resin (as the gelling agent) was used to simulate the viscosity of an aluminum/PR-1 metallized fuel gel. Water was used as a comparison fluid to isolate the rheological effects of the water-gel and to simulate nongelled RP-1. The water-gel was injected through the central orifice of a triplet injector element and the central post of a coaxial injector element. Nitrogen gas flowed through the outer orifices of the triplet injector element and through the annulus of the coaxial injector element and atomized the gelled and nongelled liquids. Photographs of the water-gel spray patterns at different operating conditions were compared with images obtained using water and nitrogen. A laser light was used for illumination of the sprays. The results of the testing showed that the water sprays produced a finer and more uniform atomization than the water-gel sprays. Rheological analysis of the water-gel showed poor atomization caused by high viscosity of water-gel delaying the transition to turbulence.

Therapeutic potential of gel-based injectables for vocal fold regeneration

PubMed Central

Bartlett, Rebecca S.; Thibeault, Susan L.; Prestwich, Glenn D.

2012-01-01

Vocal folds are anatomically and biomechanically unique, thus complicating the design and implementation of tissue engineering strategies for repair and regeneration. Integration of an enhanced understanding of tissue biomechanics, wound healing dynamics and innovative gel-based therapeutics has generated enthusiasm for the notion that an efficacious treatment for vocal fold scarring could be clinically attainable within several years. Fibroblast phenotype and gene expression are mediated by the three-dimensional mechanical and chemical microenvironment at an injury site. Thus, therapeutic approaches need to coordinate spatial and temporal aspects of the wound healing response in an injured vocal tissue to achieve an optimal clinical outcome. Successful gel-based injectables for vocal fold scarring will require a keen understanding of how the native inflammatory response sets into motion the later extracellular matrix remodeling, which in turn will determine the ultimate biomechanical properties of the tissue. We present an overview of the challenges associated with this translation as well as the proposed gel-based injectable solutions. PMID:22456756

Dynamic impact indentation of hydrated biological tissues and tissue surrogate gels

NASA Astrophysics Data System (ADS)

Ilke Kalcioglu, Z.; Qu, Meng; Strawhecker, Kenneth E.; Shazly, Tarek; Edelman, Elazer; VanLandingham, Mark R.; Smith, James F.; Van Vliet, Krystyn J.

2011-03-01

For both materials engineering research and applied biomedicine, a growing need exists to quantify mechanical behaviour of tissues under defined hydration and loading conditions. In particular, characterisation under dynamic contact-loading conditions can enable quantitative predictions of deformation due to high rate 'impact' events typical of industrial accidents and ballistic insults. The impact indentation responses were examined of both hydrated tissues and candidate tissue surrogate materials. The goals of this work were to determine the mechanical response of fully hydrated soft tissues under defined dynamic loading conditions, and to identify design principles by which synthetic, air-stable polymers could mimic those responses. Soft tissues from two organs (liver and heart), a commercially available tissue surrogate gel (Perma-Gel™) and three styrenic block copolymer gels were investigated. Impact indentation enabled quantification of resistance to penetration and energy dissipative constants under the rates and energy densities of interest for tissue surrogate applications. These analyses indicated that the energy dissipation capacity under dynamic impact increased with increasing diblock concentration in the styrenic gels. Under the impact rates employed (2 mm/s to 20 mm/s, corresponding to approximate strain energy densities from 0.4 kJ/m3 to 20 kJ/m3), the energy dissipation capacities of fully hydrated soft tissues were ultimately well matched by a 50/50 triblock/diblock composition that is stable in ambient environments. More generally, the methodologies detailed here facilitate further optimisation of impact energy dissipation capacity of polymer-based tissue surrogate materials, either in air or in fluids.

Structure Analysis of Jungle-Gym-Type Gels by Brownian Dynamics Simulation

NASA Astrophysics Data System (ADS)

Ohta, Noriyoshi; Ono, Kohki; Takasu, Masako; Furukawa, Hidemitsu

2008-02-01

We investigated the structure and the formation process of two kinds of gels by Brownian dynamics simulation. The effect of flexibility of main chain oligomer was studied. From our results, hard gel with rigid main chain forms more homogeneous network structure than soft gel with flexible main chain. In soft gel, many small loops are formed, and clusters tend to shrink. This heterogeneous network structure may be caused by microgels. In the low density case, soft gel shows more heterogeneity than the high density case.

Study of kinetic desorption rate constant in fish muscle and agarose gel model using solid phase microextraction coupled with liquid chromatography with tandem mass spectrometry.

PubMed

Togunde, Oluranti Paul; Oakes, Ken; Servos, Mark; Pawliszyn, Janusz

2012-09-12

This study aims to use solid phase microextraction (SPME), a simple tool to investigate diffusion rate (time) constant of selected pharmaceuticals in gel and fish muscle by comparing desorption rate of diffusion of the drugs in both agarose gel prepared with phosphate-buffered saline (PBS; pH 7.4) and fish muscle. The gel concentration (agarose gel model) that could be used to simulate tissue matrix (fish muscle) for free diffusion of drugs under in vitro and in vivo conditions was determined to model mass transfer phenomena between fibre polymer coating and environmental matrix such that partition coefficients and desorption time constant (diffusion coefficient) can be determined. SPME procedure involves preloading the extraction phase (fibre) with the standards from spiked PBS for 1h via direct extraction. Subsequently, the preloaded fibre is introduced to the sample such fish or agarose gel for specified time ranging from 0.5 to 60 h. Then, fibre is removed at specified time and desorbed in 100 μL of desorption solution (acetonitrile: water 1:1) for 90 min under agitation speed of 1000 rpm. The samples extract were immediately injected to the instrument and analysed using liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). The limit of detection of the method in gel and fish muscle was 0.01-0.07 ng mL(-1) and 0.07-0.34 ng g(-1), respectively, while the limit quantification was 0.10-0.20 ng mL(-1) in gel samples and 0.40-0.97 ng g(-1) in fish sample. The reproducibility of the method was good (5-15% RSD). The results suggest that kinetics of desorption of the compounds in fish tissue and different viscosity of gel can be determined using desorption time constant. In this study, desorption time constant which is directly related to desorption rate (diffusion kinetics) of selected drugs from the fibre to the gel matrix is faster as the viscosity of the gel matrix reduces from 2% (w/v) to 0.8% (w/v). As the concentration of gel reduces, viscosity of the gel will be reduced therefore allowing faster diffusion which invariably affect desorption time constant. Also, desorption time constant of model drugs in the fish muscle and 0.8-0.9% (w/v) gel model are similar based on free diffusion of studied compounds. In addition, in vitro and in vivo desorption time constant comparison shows that desorption time constant in an in vivo system (live fish muscle) is generally higher than an in vitro system (dead fish muscle) except for sertraline and nordiazepam. This study demonstrates SPME as a simple investigative tool to understand kinetics of desorption in an in vivo system with a goal to measure desorption rate of pharmaceuticals in fish. Copyright © 2011 Elsevier B.V. All rights reserved.

Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor

NASA Technical Reports Server (NTRS)

Margolis, L. B.; Fitzgerald, W.; Glushakova, S.; Hatfill, S.; Amichay, N.; Baibakov, B.; Zimmerberg, J.

1997-01-01

The pathogenesis of HIV infection involves a complex interplay between both the infected and noninfected cells of human lymphoid tissue, the release of free viral particles, the de novo infection of cells, and the recirculatory trafficking of peripheral blood lymphocytes. To develop an in vitro model for studying these various aspects of HIV pathogenesis we have utilized blocks of surgically excised human tonsils and a rotating wall vessel (RWV) cell culture system. Here we show that (1) fragments of the surgically excised human lymphoid tissue remain viable and retain their gross cytoarchitecture for at least 3 weeks when cultured in the RWV system; (2) such lymphoid tissue gradually shows a loss of both T and B cells to the surrounding growth medium; however, this cellular migration is reversible as demonstrated by repopulation of the tissue by labeled cells from the growth medium; (3) this cellular migration may be partially or completely inhibited by embedding the blocks of lymphoid tissue in either a collagen or agarose gel matrix; these embedded tissue blocks retain most of the basic elements of a normal lymphoid cytoarchitecture; and (4) both embedded and nonembedded RWV-cultured blocks of human lymphoid tissue are capable of productive infection by HIV-1 of at least three various strains of different tropism and phenotype, as shown by an increase in both p24 antigen levels and free virus in the culture medium, and by the demonstration of HIV-1 RNA-positive cells inside the tissue identified by in situ hybridization. It is therefore reasonable to suggest that gel-embedded and nonembedded blocks of human lymphoid tissue, cocultured with a suspension of tonsillar lymphocytes in an RWV culture system, constitute a useful model for simulating normal lymphocyte recirculatory traffic and provide a new tool for testing the various aspects of HIV pathogenesis.

Evaluation of a Thermoprotective Gel for Hydrodissection During Percutaneous Microwave Ablation: In Vivo Results

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

Moreland, Anna J., E-mail: ajmoreland@gmail.com; Lubner, Meghan G., E-mail: mlubner@uwhealth.org; Ziemlewicz, Timothy J., E-mail: tziemlewicz@uwhealth.org

2015-06-15

PurposeTo evaluate whether thermoreversible poloxamer 407 15.4 % in water (P407) can protect non-target tissues adjacent to microwave (MW) ablation zones in a porcine model.Materials and MethodsMW ablation antennas were placed percutaneously into peripheral liver, spleen, or kidney (target tissues) under US and CT guidance in five swine such that the expected ablation zones would extend into adjacent diaphragm, body wall, or bowel (non-target tissues). For experimental ablations, P407 (a hydrogel that transitions from liquid at room temperature to semi-solid at body temperature) was injected into the potential space between target and non-target tissues, and the presence of a gel barriermore » was verified on CT. No barrier was used for controls. MW ablation was performed at 65 W for 5 min. Thermal damage to target and non-target tissues was evaluated at dissection.ResultsAntennas were placed 7 ± 3 mm from the organ surface for both control and gel-protected ablations (p = 0.95). The volume of gel deployed was 49 ± 27 mL, resulting in a barrier thickness of 0.8 ± 0.5 cm. Ablations extended into non-target tissues in 12/14 control ablations (mean surface area = 3.8 cm{sup 2}) but only 4/14 gel-protected ablations (mean surface area = 0.2 cm{sup 2}; p = 0.0005). The gel barrier remained stable at the injection site throughout power delivery.ConclusionWhen used as a hydrodissection material, P407 protected non-targeted tissues and was successfully maintained at the injection site for the duration of power application. Continued investigations to aid clinical translation appear warranted.« less

SU-E-T-243: MonteCarlo Simulation Study of Polymer and Radiochromic Gel for Three-Dimensional Proton Dose Distribution

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

Park, M; Jung, H; Kim, G

2014-06-01

Purpose: To estimate the three dimensional dose distributions in a polymer gel and a radiochromic gel by comparing with the virtual water phantom exposed to proton beams by applying Monte Carlo simulation. Methods: The polymer gel dosimeter is the compositeness material of gelatin, methacrylic acid, hydroquinone, tetrakis, and distilled water. The radiochromic gel is PRESAGE product. The densities of polymer and radiochromic gel were 1.040 and 1.0005 g/cm3, respectively. The shape of water phantom was a hexahedron with the size of 13 × 13 × 15 cm3. The proton beam energies of 72 and 116 MeV were used in themore » simulation. Proton beam was directed to the top of the phantom with Z-axis and the shape of beam was quadrangle with 10 × 10 cm2 dimension. The Percent depth dose and the dose distribution were evaluated for estimating the dose distribution of proton particle in two gel dosimeters, and compared with the virtual water phantom. Results: The Bragg-peak for proton particles in two gel dosimeters was similar to the virtual water phantom. Bragg-peak regions of polymer gel, radiochromic gel, and virtual water phantom were represented in the identical region (4.3 cm) for 72 MeV proton beam. For 116 MeV proton beam, the Bragg-peak regions of polymer gel, radiochromic gel, and virtual water phantom were represented in 9.9, 9.9 and 9.7 cm, respectively. The dose distribution of proton particles in polymer gel, radiochromic gel, and virtual water phantom was approximately identical in the case of 72 and 116 MeV energies. The errors for the simulation were under 10%. Conclusion: This work indicates the evaluation of three dimensional dose distributions by exposing proton particles to polymer and radiochromic gel dosimeter by comparing with the water phantom. The polymer gel and the radiochromic gel dosimeter show similar dose distributions for the proton beams.« less

Study on the Protective Effect of a New Manganese Superoxide Dismutase on the Microvilli of Rabbit Eyes Exposed to UV Radiation.

PubMed

Grumetto, Lucia; Del Prete, Antonio; Ortosecco, Giovanni; Barbato, Francesco; Del Prete, Salvatore; Borrelli, Antonella; Schiattarella, Antonella; Mancini, Roberto; Mancini, Aldo

2015-01-01

We present a study on the protective effects against UV radiation of a gel formulation containing a new recombinant form of manganese superoxide dismutase on the conjunctiva and corneal epithelia of rabbit eyes. The integrity of the microvilli of both ocular tissues has been considered as an indicator of the health of the tissues. Samples, collected by impression cytology technique, were added of 80 µL of a gel formulation containing superoxide dismutase (2.0 µg/mL) and irradiated with UV rays for 30 minutes and were evaluated with scanning electron microscopy. Wilcoxon test was used to verify the possible occurrence of statistically significant differences between damage for treated and nontreated tissues. Application of gel produces a significant reduction of damage by UV irradiation of ocular epithelia; both epithelia present a significant reduction of damaged microvilli number if treated with the superoxide dismutase gel formulation: the p values (differences between damage found for treated and nontreated both ocular tissues) for conjunctiva and cornea samples were p ≪ 0.01 and p ≪ 0.0001, respectively, at confidence level of 95%. The administration of this gel formulation before UV exposure plays a considerable protective role in ocular tissues of rabbit eye with a significant reduction of the damage.

Development of a Searchable Database of Cryoablation Simulations for Use in Treatment Planning

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

Boas, F. Edward, E-mail: boasf@mskcc.org; Srimathveeravalli, Govindarajan, E-mail: srimaths@mskcc.org; Durack, Jeremy C., E-mail: durackj@mskcc.org

PurposeTo create and validate a planning tool for multiple-probe cryoablation, using simulations of ice ball size and shape for various ablation probe configurations, ablation times, and types of tissue ablated.Materials and MethodsIce ball size and shape was simulated using the Pennes bioheat equation. Five thousand six hundred and seventy different cryoablation procedures were simulated, using 1–6 cryoablation probes and 1–2 cm spacing between probes. The resulting ice ball was measured along three perpendicular axes and recorded in a database. Simulated ice ball sizes were compared to gel experiments (26 measurements) and clinical cryoablation cases (42 measurements). The clinical cryoablation measurements weremore » obtained from a HIPAA-compliant retrospective review of kidney and liver cryoablation procedures between January 2015 and February 2016. Finally, we created a web-based cryoablation planning tool, which uses the cryoablation simulation database to look up the probe spacing and ablation time that produces the desired ice ball shape and dimensions.ResultsAverage absolute error between the simulated and experimentally measured ice balls was 1 mm in gel experiments and 4 mm in clinical cryoablation cases. The simulations accurately predicted the degree of synergy in multiple-probe ablations. The cryoablation simulation database covers a wide range of ice ball sizes and shapes up to 9.8 cm.ConclusionCryoablation simulations accurately predict the ice ball size in multiple-probe ablations. The cryoablation database can be used to plan ablation procedures: given the desired ice ball size and shape, it will find the number and type of probes, probe configuration and spacing, and ablation time required.« less

Bioactive and biocompatible pieces of HA/sol-gel glass mixtures obtained by the gel-casting method.

PubMed

Padilla, S; Sánchez-Salcedo, S; Vallet-Regí, M

2005-10-01

Hydroxyapatite (HA)/glass mixtures have shown a faster bioactive behaviour than HA itself. On the other hand, the gel-casting method is a simple and reproducible colloidal method to produce ceramic pieces with complex shapes. In this work, pieces of HA/glass mixtures were prepared by the gel-casting method. A study for obtaining concentrated slurries of these mixtures is reported; the bioactivity and biocompatibility of the obtained pieces have been studied also. The influence of pH, dispersant concentration, the content and milling of glass, and the way to prepare the suspensions were investigated. The lowest viscosity and better rheological properties were achieved with the lowest glass content, when the glass was added after the dispersion of the HA powder and when the glass was not milled after calcination. Fluid suspensions with a high solid content (50 vol.%) could be prepared and well-shaped pieces were obtained from these slurries. These pieces showed in vitro bioactive behavior in simulated body fluid; additionally, the proliferation and spreading assays with osteoblastic cells (HOS) showed that the pieces are biocompatible. The results obtained indicate that the gel-casting of HA/glass mixtures produces bioactive and biocompatible pieces with the required shapes. Therefore, these materials could be good candidates for clinical applications and scaffolds for tissue engineering. (c) 2005 Wiley Periodicals, Inc.

Dose distributions in phantoms irradiated in thermal columns of two different nuclear reactors.

PubMed

Gambarini, G; Agosteo, S; Altieri, S; Bortolussi, S; Carrara, M; Gay, S; Nava, E; Petrovich, C; Rosi, G; Valente, M

2007-01-01

In-phantom dosimetry studies have been carried out at the thermal columns of a thermal- and a fast-nuclear reactor for investigating: (a) the spatial distribution of the gamma dose and the thermal neutron fluence and (b) the accuracy at which the boron concentration should be estimated in an explanted organ of a boron neutron capture therapy patient. The phantom was a cylinder (11 cm in diameter and 12 cm in height) of tissue-equivalent gel. Dose images were acquired with gel dosemeters across the axial section of the phantom. The thermal neutron fluence rate was measured with activation foils in a few positions of this phantom. Dose and fluence rate profiles were also calculated with Monte Carlo simulations. The trend of these profiles do not show significant differences for the thermal columns considered in this work.

Absorbable Gels for Modulated Bioavailability of Vaccines. Phase I

DTIC Science & Technology

1996-11-01

most of these devices were designed for repairing soft tissues , interest in using such transient devices, with or without biologically active components...potential applications of the in-situ-forming implants, and the more recent gel-formers, have been described to entail their use for tissue regeneration and...In Situ-Forming Biodegradable Polymeric Implants for Tissue Regeneration . Polym. Prepr., 35(2), 437 (1994). Edelman, R. et al, Immunization of

Biomineralization of Fucoidan-Peptide Blends and Their Potential Applications in Bone Tissue Regeneration

PubMed Central

Pajovich, Harrison T.; Banerjee, Ipsita A.

2017-01-01

Fucoidan (Fuc), a natural polysaccharide derived from brown seaweed algae, and gelatin (Gel) were conjugated to form a template for preparation of biomimetic scaffolds for potential applications in bone tissue regeneration. To the Fuc–Gel we then incorporated the peptide sequence MTNYDEAAMAIASLN (MTN) derived from the E-F hand domain, known for its calcium binding properties. To mimic the components of the extracellular matrix of bone tissue, the Fuc–Gel–MTN assemblies were incubated in simulated body fluid (SBF) to induce biomineralization, resulting in the formation of β-tricalcium phosphate, and hydroxyapatite (HAp). The formed Fuc–Gel–MTN–beta–TCP/HAP scaffolds were found to display an average Young’s Modulus value of 0.32 GPa (n = 5) with an average surface roughness of 91 nm. Rheological studies show that the biomineralized scaffold exhibited higher storage and loss modulus compared to the composites formed before biomineralization. Thermal phase changes were studied through DSC and TGA analysis. XRD and EDS analyses indicated a biphasic mixture of β-tricalcium phosphate and hydroxyapatite and the composition of the scaffold. The scaffold promoted cell proliferation, differentiation and displayed actin stress fibers indicating the formation of cell-scaffold matrices in the presence of MT3C3-E1 mouse preosteoblasts. Osteogenesis and mineralization were found to increase with Fuc–Gel–MTN–beta–TCP/HAP scaffolds. Thus, we have developed a novel scaffold for possible applications in bone tissue engineering. PMID:29036882

Hybrid Hydroxyapatite Nanoparticle Colloidal Gels are Injectable Fillers for Bone Tissue Engineering

PubMed Central

Gu, Zhen; Jamal, Syed; Detamore, Michael S.

2013-01-01

Injectable bone fillers have emerged as an alternative to the invasive surgery often required to treat bone defects. Current bone fillers may benefit from improvements in dynamic properties such as shear thinning during injection and recovery of material stiffness after placement. Negatively charged inorganic hydroxyapatite (HAp) nanoparticles (NPs) were assembled with positively charged organic poly(d,l-lactic-co-glycolic acid) (PLGA) NPs to create a cohesive colloidal gel. This material is held together by electrostatic forces that may be disrupted by shear to facilitate extrusion, molding, or injection. Scanning electron micrographs of the dried colloidal gels showed a well-organized, three-dimensional porous structure. Rheology tests revealed that certain colloidal gels could recover after being sheared. Human umbilical cord mesenchymal stem cells were also highly viable when seeded on the colloidal gels. HAp/PLGA NP colloidal gels offer an attractive scheme for injectable filling and regeneration of bone tissue. PMID:23815275

Synthesis and Characterization of a Hydrogel with Controllable Electroosmosis: A Potential Brain Tissue Surrogate for Electrokinetic Transport

PubMed Central

Faraji, Amir H.; Cui, Jonathan J.; Guy, Yifat; Li, Ling; Weber, Stephen G.

2011-01-01

Electroosmosis is the bulk fluid flow initiated by application of an electric field to an electrolyte solution in contact with immobile objects with a non-zero ζ-potential such as the surface of a porous medium. Electroosmosis may be used to assist analytical separations. Several gel-based systems with varying electroosmotic mobilities have been made in this context. A method was recently developed to determine the ζ-potential of organotypic hippocampal slice cultures (OHSC) as a representative model for normal brain tissue. The ζ-potential of the tissue is significant. However, determining the role of the ζ-potential in solute transport in tissue in an electric field is difficult because the tissue's ζ-potential cannot be altered. We hypothesized that mass transport properties, namely the ζ-potential and tortuosity, could be modulated by controlling the composition of a set of hydrogels. Thus, poly(acrylamide-co-acrylic acid) gels were prepared with three compositions (by monomer weight percent): acrylamide/acrylic acid 100/0, 90/10, and 75/25. The ζ-potentials of these gels at pH 7.4 are distinctly different, and in fact vary approximately linearly with the weight percent of acrylic acid. We discovered that the 25% acrylic acid gel is a respectable model for brain tissue, as its ζ-potential is comparable to the OHSC. This series of gels permits the experimental determination of the importance of electrokinetic properties in a particular experiment or protocol. Additionally, tortuosities were measured electrokinetically and by evaluating diffusion coefficients. Hydrogels with well-defined ζ-potential and tortuosity may find utility in biomaterials, analytical separations, and as a surrogate model for OHSC and living biological tissues. PMID:21905710

Injectable alginate/hydroxyapatite gel scaffold combined with gelatin microspheres for drug delivery and bone tissue engineering.

PubMed

Yan, Jingxuan; Miao, Yuting; Tan, Huaping; Zhou, Tianle; Ling, Zhonghua; Chen, Yong; Xing, Xiaodong; Hu, Xiaohong

2016-06-01

Injectable and biodegradable alginate-based composite gel scaffolds doubly integrated with hydroxyapatite (HAp) and gelatin microspheres (GMs) were cross-linked via in situ release of calcium cations. As triggers of calcium cations, CaCO3 and glucono-D-lactone (GDL) were fixed as a mass ratio of 1:1 to control pH value ranging from 6.8 to 7.2 during gelation. Synchronously, tetracycline hydrochloride (TH) was encapsulated into GMs to enhance bioactivity of composite gel scaffolds. The effects of HAp and GMs on characteristics of gel scaffolds, including pH value, gelation time, mechanical properties, swelling ratio, degradation behavior and drug release, were investigated. The results showed that HAp and GMs successfully improved mechanical properties of gel scaffolds at strain from 0.1 to 0.5, which stabilized the gel network and decreased weight loss, as well as swelling ratio and gelation time. TH could be released from this composite gel scaffold into the local microenvironment in a controlled fashion by the organic/inorganic hybrid of hydrogel network. Our results demonstrate that the HAp and GMs doubly integrated alginate-based gel scaffolds, especially the one with 6% (w/v) HAp and 5% (w/v) GMs, have suitable physical performance and bioactive properties, thus provide a potential opportunity to be used for bone tissue engineering. The potential application of this gel scaffold in bone tissue engineering was confirmed by encapsulation behavior of osteoblasts. In combination with TH, the gel scaffold exhibited beneficial effects on osteoblast activity, which suggested a promising future for local treatment of pathologies involving bone loss. Copyright © 2016 Elsevier B.V. All rights reserved.

Feasibility of silica-hybridized collagen hydrogels as three-dimensional cell matrices for hard tissue engineering.

PubMed

Yu, Hye-Sun; Lee, Eun-Jung; Seo, Seog-Jin; Knowles, Jonathan C; Kim, Hae-Won

2015-09-01

Exploiting hydrogels for the cultivation of stem cells, aiming to provide them with physico-chemical cues suitable for osteogenesis, is a critical demand for bone engineering. Here, we developed hybrid compositions of collagen and silica into hydrogels via a simple sol-gel process. The physico-chemical and mechanical properties, degradation behavior, and bone-bioactivity were characterized in-depth; furthermore, the in vitro mesenchymal stem cell growth and osteogenic differentiation behaviors within the 3D hybrid gel matrices were communicated for the first time. The hydrolyzed and condensed silica phase enabled chemical links with the collagen fibrils to form networked hybrid gels. The hybrid gels showed improved chemical stability and greater resistance to enzymatic degradation. The in vitro apatite-forming ability was enhanced by the hybrid composition. The viscoelastic mechanical properties of the hybrid gels were significantly improved in terms of the deformation resistance to an applied load and the modulus values under a dynamic oscillation. Mesenchymal stem cells adhered well to the hybrid networks and proliferated actively with substantial cytoskeletal extensions within the gel matrices. Of note, the hybrid gels substantially reduced the cell-mediated gel contraction behaviors, possibly due to the stiffer networks and higher resistance to cell-mediated degradation. Furthermore, the osteogenic differentiation of cells, including the expression of bone-associated genes and protein, was significantly upregulated within the hybrid gel matrices. Together with the physico-chemical and mechanical properties, the cellular behaviors observed within 3D gel matrices, being different from the previous approaches reported on 2D substrates, provide new information on the feasibility and usefulness of the silica-collagen system for stem cell culture and tissue engineering of hard tissues. © The Author(s) 2015.

Histological analysis of effects of 24% EDTA gel for nonsurgical treatment of periodontal tissues.

PubMed

de Vasconcellos, Luana Marotta Reis; Ricardo, Lucilene Hernandes; Balducci, Ivan; de Vasconcellos, Luis Gustavo Oliveira; Carvalho, Yasmin Rodarte

2006-12-01

The aim of this study was to investigate, by means of histological and histomorphometric analysis, the effects of 24% ethylenediaminetetraacetic acid (EDTA) gel in periodontal tissue when used in combination with conventional periodontal treatment. Periodontitis was induced in the 2nd upper left permanent molars of 45 male Wistar rats by means of ligature. After 5 weeks, this was removed and debridement was performed. The animals were then randomly divided into 3 groups; group 1: mechanical treatment, group 2: mechanical treatment and EDTA gel application for 2 min, and group 3: mechanical treatment and placebo gel application for 2 min. After the treatment, rinsing was done with 0.9% saline solution for 1 min in all cases, followed by root notching in the deepest part of the pocket. After 4, 10, and 28 days the animals were sacrificed. The averages obtained were evaluated by means of test two-way analysis of variance (ANOVA) and Tukey statistical tests (P < 0.05). The results showed that with respect to the type of treatment employed, there were no statistically significant differences in the vitality of the periodontal tissue. It was concluded that 24% EDTA gel did not interfere with periodontal tissue repair when used in combination with conventional periodontal treatment.

Evaluation of synovium-derived mesenchymal stem cells and 3D printed nanocomposite scaffolds for tissue engineering

NASA Astrophysics Data System (ADS)

Pan, Jian-Feng; Li, Shuo; Guo, Chang-An; Xu, Du-Liang; Zhang, Feng; Yan, Zuo-Qin; Mo, Xiu-Mei

2015-08-01

Stem cells and scaffolds play a very important role in tissue engineering. Here, we isolated synovium-derived mesenchymal stem cells (SMSCs) from synovial membrane tissue and characterized stem-cell properties. Gelatin nanoparticles (NP) were prepared using a two-step desolvation method and then pre-mixed into different host matrix (silk fibroin (SF), gelatin (Gel), or SF-Gel mixture) to generate various 3D printed nanocomposite scaffolds (NP/SF, NP/SF-Gel, NP/Gel-1, and NP/Gel-2). The microstructure was examined by scanning electron microscopy. Biocompatibility assessment was performed through CCK-8 assay by coculturing with SMSCs at 1, 3, 7 and 14 days. According to the results, SMSCs are similar to other MSCs in their surface epitope expression, which are negative for CD45 and positive for CD44, CD90, and CD105. After incubation in lineage-specific medium, SMSCs could differentiate into chondrocytes, osteocytes and adipocytes. 3D printed nanocomposite scaffolds exhibited a good biocompatibility in the process of coculturing with SMSCs and had no negative effect on cell behavior. The study provides a strategy to obtain SMSCs and fabricate 3D printed nanocomposite scaffolds, the combination of which could be used for practical applications in tissue engineering.

SU-F-T-159: Monte Carlo Simulation Studies of Three-Dimensional Dose Distribution for Polymer Gel Dosimeter and Radiochromic Gel Dosimeter in a Proton Beam

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

Park, M; Kim, G; Jung, H

Purpose: The purpose of this simulation study is to evaluate the proton detectability of gel dosimeters, and estimate the three-dimensional dose distribution of protons in the radiochromic gel and polymer gel dosimeter compared with the dose distribution in water. Methods: The commercial composition ratios of normoxic polymer gel and LCV micelle radiochromic gel were included in this simulation study. The densities of polymer and radiochromic gel were 1.024 and 1.005 g/cm3, respectively. The 50, 80 and 140 MeV proton beam energies were selected. The dose distributions of protons in the polymer and radiochromic gel were simulated using Monte Carlo radiationmore » transport code (MCNPX 2.7.0, Los Alamos Laboratory). The water equivalent depth profiles and the dose distributions of two gel dosimeters were compared for the water. Results: In case of irradiating 50, 80 and 140 MeV proton beam to water phantom, the reference Bragg-peak depths are represented at 2.22, 5.18 and 13.98 cm, respectively. The difference in the water equivalent depth is represented to about 0.17 and 0.37 cm in the radiochromic gel and polymer gel dosimeter, respectively. The proton absorbed doses in the radiochromic gel dosimeter are calculated to 2.41, 3.92 and 6.90 Gy with increment of incident proton energies. In the polymer gel dosimeter, the absorbed doses are calculated to 2.37, 3.85 and 6.78 Gy with increment of incident proton energies. The relative absorbed dose in radiochromic gel (about 0.47 %) is similar to that of water than the relative absorbed dose of polymer gel (about 2.26 %). In evaluating the proton dose distribution, we found that the dose distribution of both gel dosimeters matched that of water in most cases. Conclusion: As the dosimetry device, the radiochromic gel dosimeter has the potential particle detectability and is feasible to use for quality assurance of proton beam therapy beam.« less

Disintegration kinetics of food gels during gastric digestion and its role on gastric emptying: an in vitro analysis.

PubMed

Guo, Qing; Ye, Aiqian; Lad, Mita; Ferrua, Maria; Dalgleish, Douglas; Singh, Harjinder

2015-03-01

The understanding of the disintegration and gastric emptying of foods in the stomach is important for designing functional foods. In this study, a dynamic stomach model (human gastric simulator, HGS) was employed to investigate the disintegration and subsequent emptying of two differently structured whey protein emulsion gels (soft and hard gels).The gels were mechanically ground into fragments to reproduce the particle size distribution of an in vivo gel bolus. The simulated gel bolus was prepared by mixing gel fragments and artificial saliva, and exposed to 5 hours of simulated gastric digestion in the presence and absence of pepsin. Results showed that regardless of pepsin, the soft gel always disintegrated faster than the hard gel. The presence of pepsin significantly accelerated the disintegration of both gels. In particular, it enhanced abrasion of the soft gel into fine particles (<0.425 mm) after 180 min of processing. The emptying of the gels was influenced by the combined effects of the original particle size of the gel boluses and their disintegration kinetics in the HGS. In the presence or absence of pepsin, the larger particles of the soft gel emptied slower than the hard one during the first 120 min of process. However, in the presence of pepsin, the soft gel emptied faster than the hard one after 120 min because of a higher level of disintegration. These findings highlight the role of food structure, bolus properties and biochemical effects on the disintegration and gastric emptying patterns of gels during gastric digestion.

Nanoparticle solutions as adhesives for gels and biological tissues

NASA Astrophysics Data System (ADS)

Rose, Séverine; Prevoteau, Alexandre; Elzière, Paul; Hourdet, Dominique; Marcellan, Alba; Leibler, Ludwik

2014-01-01

Adhesives are made of polymers because, unlike other materials, polymers ensure good contact between surfaces by covering asperities, and retard the fracture of adhesive joints by dissipating energy under stress. But using polymers to `glue' together polymer gels is difficult, requiring chemical reactions, heating, pH changes, ultraviolet irradiation or an electric field. Here we show that strong, rapid adhesion between two hydrogels can be achieved at room temperature by spreading a droplet of a nanoparticle solution on one gel's surface and then bringing the other gel into contact with it. The method relies on the nanoparticles' ability to adsorb onto polymer gels and to act as connectors between polymer chains, and on the ability of polymer chains to reorganize and dissipate energy under stress when adsorbed onto nanoparticles. We demonstrate this approach by pressing together pieces of hydrogels, for approximately 30 seconds, that have the same or different chemical properties or rigidities, using various solutions of silica nanoparticles, to achieve a strong bond. Furthermore, we show that carbon nanotubes and cellulose nanocrystals that do not bond hydrogels together become adhesive when their surface chemistry is modified. To illustrate the promise of the method for biological tissues, we also glued together two cut pieces of calf's liver using a solution of silica nanoparticles. As a rapid, simple and efficient way to assemble gels or tissues, this method is desirable for many emerging technological and medical applications such as microfluidics, actuation, tissue engineering and surgery.

Cardiac Ventricular HIFU: Convergence of Experiment and Theory in the Canine Model

NASA Astrophysics Data System (ADS)

Muratore, Robert; Abe, Yukio; Homma, Shunichi; Bernardi, Richard; Kalisz, Andrew; Feleppa, Ernest J.

2007-05-01

OBJECTIVE: HIFU is a promising technique for treating cardiac ventricular diseases such as sustained ventricular tachycardia. Ablations can potentially destroy arrhythmogenic foci and block reentrant circuits. Towards this end, we have learned to control HIFU lesions in the canine model in vivo. METHODS: Experiment — Thoracotomies were performed on anesthetized dogs, following IACUC guidelines. In this open-chest configuration, a polyethylene water-filled bag was coupled to the myocardium with degassed ultrasound gel. The transducer was lowered into the water. Ventricular locations were targeted and insonified with multiple 200-ms HIFU bursts of 60-W acoustic power; the bursts were triggered with the electrocardiogram QRS complex. The therapeutic transducer was a 35-mm focal length, 33-mm diameter PZT annular array, excited at 5.25 MHz. Its -3dB focal region dimensions were 2.5 mm axially and 0.3 mm transversely. A confocal diagnostic transducer was used for aiming and for recording backscattered radiofrequency ultrasound data. Theory — A comprehensive acoustic model has been developed. Individual modules numerically simulate physical processes such as ultrasound beam propagation, energy transfer, and heat flow within tissue. One set of modules simulates HIFU ablation in moving tissue. Tissue motion was obtained from digitized B-mode videos of transverse cross sections of a beating canine heart. Epicardial and endocardial surface positions were extracted from the video frames. Additional simulations of static tissue compared linear and nonlinear propagation models. RESULTS: Significant agreement between simulated and measured lesion sizes and between linear and nonlinear propagation models was demonstrated.

Dose of radiation enhancement, using silver nanoparticles in a human tissue equivalent gel dosimeter.

PubMed

Hassan, Muhammad; Waheed, Muhammad Mohsin; Anjum, Muhammad Naeem

2016-01-01

To quantify the radiation dose enhancement in a human tissue-equivalent polymer gel impregnated with silver nanoparticles. The case-control study was conducted at the Bahawalpur Institute of Nuclear Medicine and Oncology, Bahawalpur, Pakistan, in January 2014. Silver nanoparticles used in this study were prepared by wet chemical method. Polymer gel was prepared by known quantity of gelatine, methacrylic acid, ascorbic acid, copper sulphate pentahydrate, hydroquinone and water. Different concentrations of silver nanoparticles were added to the gel during its cooling process. The gel was cooled in six plastic vials of 50ml each. Two vials were used as a control sample while four vials were impregnated with silver nanoparticles. After 22 hours, the vials were irradiated with gamma rays by aCobalt-60 unit. Radiation enhancement was assessed by taking magnetic resonance images of the vials. The images were analysed using Image J software. The dose enhancement factor was 24.17% and 40.49% for 5Gy and 10Gy dose respectively. The dose enhancement factor for the gel impregnated with 0.10mM silver nanoparticles was 32.88% and 51.98% for 5Gy and 10Gy dose respectively. The impregnation of a tissue-equivalent gel with silver nanoparticles resulted in dose enhancement and this effect was magnified up to a certain level with the increase in concentration of silver nanoparticles.

Heating characteristics of the TRIPAS hyperthermia system for deep seated malignancy.

PubMed

Surowiec, A; Bicher, H I

1995-01-01

A deep heating hyperthermia device TRIPAS (a triapplicator system) consisting of three independent, dielectrically loaded horn applicators operating in phase at 300 MHz was investigated. The heating characteristics produced by this hyperthermia system were analyzed by means of thermochromic liquid-crystal cards and a modified CDRH (Center for Devices and Regulatory Health) elliptical phantom. Both homogenous and inhomogeneous phantoms were used, simulating high and low permittivity tissues (muscle and lung). These equivalent tissues were made of polyacrylamide gel. The semiquantitative heating pattern analysis showed a central heating of 1/3 of maximum heating at a depth of 10 cm in both homogenous (muscle) and heterogenous (muscle/fat) phantoms. Also more uniform temperature/SAR distributions were generated in muscle equivalent material than those in lung.

Self-Assembling Nanoclay Diffusion Gels for Bioactive Osteogenic Microenvironments.

PubMed

Shi, Pujiang; Kim, Yang-Hee; Mousa, Mohamed; Sanchez, Roxanna Ramnarine; Oreffo, Richard O C; Dawson, Jonathan I

2018-06-17

Laponite nanoparticles have attracted attention in the tissue engineering field for their protein interactions, gel-forming properties, and, more recently, osteogenic bioactivity. Despite growing interest in the osteogenic properties of Laponite, the application of Laponite colloidal gels to host the osteogenic differentiation of responsive stem cell populations remains unexplored. Here, the potential to harness the gel-forming properties of Laponite to generate injectable bioactive microenvironments for osteogenesis is demonstrated. A diffusion/dialysis gelation method allows the rapid formation of stable transparent gels from injectable, thixotropic Laponite suspensions in physiological fluids. Upon contact with buffered saline or blood serum, nanoporous gel networks exhibiting, respectively, fivefold and tenfold increases in gel stiffness are formed due to the reorganization of nanoparticle interactions. Laponite diffusion gels are explored as osteogenic microenvironments for skeletal stem cell containing populations. Laponite films support cell adhesion, proliferation, and differentiation of human bone marrow stromal cells in 2D. Laponite gel encapsulation significantly enhances osteogenic protein expression compared with 3D pellet culture controls. In both 2D and 3D conditions, cell associated mineralization is strongly enhanced. This study demonstrates that Laponite diffusion gels offer considerable potential as biologically active and clinically relevant bone tissue engineering scaffolds. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sol gel-derived hydroxyapatite films over porous calcium polyphosphate substrates for improved tissue engineering of osteochondral-like constructs.

PubMed

Lee, Whitaik David; Gawri, Rahul; Pilliar, Robert M; Stanford, William L; Kandel, Rita A

2017-10-15

Integration of in vitro-formed cartilage on a suitable substrate to form tissue-engineered implants for osteochondral defect repair is a considerable challenge. In healthy cartilage, a zone of calcified cartilage (ZCC) acts as an intermediary for mechanical force transfer from soft to hard tissue, as well as an effective interlocking structure to better resist interfacial shear forces. We have developed biphasic constructs that consist of scaffold-free cartilage tissue grown in vitro on, and interdigitated with, porous calcium polyphosphate (CPP) substrates. However, as CPP degrades, it releases inorganic polyphosphates (polyP) that can inhibit local mineralization, thereby preventing the formation of a ZCC at the interface. Thus, we hypothesize that coating CPP substrate with a layer of hydroxyapatite (HA) might prevent or limit this polyP release. To investigate this we tested both inorganic or organic sol-gel processing methods, asa barrier coating on CPP substrate to inhibit polyP release. Both types of coating supported the formation of ZCC in direct contact with the substrate, however the ZCC appeared more continuous in the tissue formed on the organic HA sol gel coated CPP. Tissues formed on coated substrates accumulated comparable quantities of extracellular matrix and mineral, but tissues formed on organic sol-gel (OSG)-coated substrates accumulated less polyP than tissues formed on inorganic sol-gel (ISG)-coated substrates. Constructs formed with OSG-coated CPP substrates had greater interfacial shear strength than those formed with ISG-coated and non-coated substrates. These results suggest that the OSG coating method can modify the location and distribution of ZCC and can be used to improve the mechanical integrity of tissue-engineered constructs formed on porous CPP substrates. Articular cartilage interfaces with bone through a zone of calcified cartilage. This study describes a method to generate an "osteochondral-like" implant that mimics this organization using isolated deep zone cartilage cells and a sol-gel hydroxyapatite coated bone substitute material composed of calcium polyphosphate (CPP). Developing a layer of calcified cartilage at the interface should contribute to enhancing the success of this "osteochondral-like" construct following implantation to repair cartilage defects. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Fibrin gel as a scaffold for photoreceptor cells differentiation from conjunctiva mesenchymal stem cells in retina tissue engineering.

PubMed

Soleimannejad, Mostafa; Ebrahimi-Barough, Somayeh; Soleimani, Masoud; Nadri, Samad; Tavangar, Seyed Mohammad; Roohipoor, Ramak; Yazdankhah, Meysam; Bayat, Neda; Riazi-Esfahani, Mohammad; Ai, Jafar

2018-06-01

Stem cell-based therapies are attraction approaches for regenerative medicine for treating retinal diseases. One of the limitations in cell therapy is cell death following post-injection whit preventing functional integration with retinal tissue. Fibrin gel, a bio-polymeric material with excellent biocompatibility, provides numerous advantages as a tissue engineering scaffold and a stem cell carrier. Therefore, current research is focusing on developing fibrin hydrogel scaffolds to protect stem cells during delivery and to stimulate endogenous regeneration through interactions of transplanted stem cells and retinal tissue. In this study fibrin gel was used as hydrogel scaffold for immobilization of cells. The structural characteristics of fibrin gel scaffold were examined with SEM. Rheological properties of fibrin gel were measured by rheometer and biodegradation rate of fibrin were assayed for 2 weeks. After isolation of stem cells CJMSCs, the cells were differentiated into photoreceptor-like cells by exposing with taurin for 14 days in tissue culture plate (TCP group) and fibrin hydrogel (3 D group). The attachment of cells was analyzed with SEM and MTT. The expression of rhodopsin, PKC, CRX, recoverin, peripherin, nestin and RPE65 as photoreceptor-like cell markers was evaluated by immunocytochemistry and quantitative real-time PCR (RT-PCR) in TCP and 3 D groups. The results of SEM analysis showed CJMSCs were well attached in fibrin gels and there were good integrity between cells and scaffold. The elastic modulus and constant degradation of the gel contributes to the growth and proliferation of cells. There was no toxicity effect of fibrin hydrogel on cells and the viability of cultured cells was higher in 3 D fibrin gels in comparison with TCP groups. After 2 weeks, the expression of rhodopsin, PKC, CRX, peripherin, recoverin, nestin and RPE65 as special markers of photoreceptor cells were detected by Real time PCR and immunofluorescence that these expressions in 3 D groups were higher than TCP groups. In conclusion, our findings showed that application of readily available sources of adult stem cells like human conjunctiva stem cells encapsulated in fibrin gel could be interesting strategy to enhance photoreceptor progenitor cell numbers for repair and regeneration of retina disease such as photoreceptor injury.

Radiation dose enhancement of gold nanoparticle on different polymer gel dosimeters

NASA Astrophysics Data System (ADS)

Jabaseelan Samuel, E. James; Srinivasan, K.; Poopathi, V.

2017-05-01

In this work, we evaluated the dose enhancement produced by gold nanoparticle on ten different polymer gel dosimeters with a concentration of 7mgAu /g over a wide photon energy range of 15KeV to 20MeV and the results were compared with Soft tissue ICRU-44 produced. Our result showed that maximum DEF was observed at 40KeV, while it was almost negligible at higher energy range. Dose enhancement produced by AuNP on the gel dosimeter medium was varied compared to the reference ICRU-44 tissue, it was ± <1% for PAGAT, NIPAM, nPAG and ± <5% for PABIG, VIPAR, HEAG, BANG1, nMAG & ± <10% for MAGIC, ABAGIC gel dosimeters. Hence, we conclude that choosing the proper gel dosimeter is essential in dose enhancement study.

Effects of a herbal gel containing carvacrol and chalcones on alveolar bone resorption in rats on experimental periodontitis.

PubMed

Botelho, Marco Antonio; Rao, Vietla Satyanarayana; Montenegro, Danusa; Bandeira, Mary Anne Menezes; Fonseca, Said Gonçalves Cruz; Nogueira, Nadia Accioly Pinto; Ribeiro, Ronaldo Albuquerque; Brito, Gerly Anne Castro

2008-04-01

Carvacrol and dimeric chalcones are the respective bioactive components of Lippia sidoides and Myracrodruon urundeuva, popular medicinal plants of Northeastern Brazil with proven antimicrobial and antiinflammatory properties. Periodontal disease is associated with inflammation and microbiological proliferation, thus the study aimed to investigate the effect of a topical gel based on carvacrol and chalcones in the experimental periodontal disease (EPD) in rats. Animals were treated with carvacrol and/or chalcones gel, immediately after EPD induction, three times a day for 11 days. Appropriate controls were included in the study. Animals were weighed daily. They were killed on day 11, the mandibles dissected and alveolar bone loss was measured. The periodontium were examined at histopathology and the neutrophil influx into the gingiva was assayed using myeloperoxidase activity. The bacterial flora were assessed through culture of the gingival tissue. Alveolar bone loss was significantly (p < 0.05) inhibited by combined carvacrol and chalcones gel, compared with the vehicle and non-treated groups. The treatment with the combined gel reduced tissue lesion at histopathology, decreased myeloperoxidase activity in gingival tissue and inhibited the growth of oral microorganisms as well as the weight loss. Carvacrol and chalcones combination gel has a beneficial effect upon EPD in this model. (c) 2008 John Wiley & Sons, Ltd.

Photocrosslinkable Gelatin/Tropoelastin Hydrogel Adhesives for Peripheral Nerve Repair.

PubMed

Soucy, Jonathan R; Shirzaei Sani, Ehsan; Portillo Lara, Roberto; Diaz, David; Dias, Felipe; Weiss, Anthony S; Koppes, Abigail N; Koppes, Ryan A; Annabi, Nasim

2018-05-09

Suturing peripheral nerve transections is the predominant therapeutic strategy for nerve repair. However, the use of sutures leads to scar tissue formation, hinders nerve regeneration, and prevents functional recovery. Fibrin-based adhesives have been widely used for nerve reconstruction, but their limited adhesive and mechanical strength and inability to promote nerve regeneration hamper their utility as a stand-alone intervention. To overcome these challenges, we engineered composite hydrogels that are neurosupportive and possess strong tissue adhesion. These composites were synthesized by photocrosslinking two naturally derived polymers, gelatin-methacryloyl (GelMA) and methacryloyl-substituted tropoelastin (MeTro). The engineered materials exhibited tunable mechanical properties by varying the GelMA/MeTro ratio. In addition, GelMA/MeTro hydrogels exhibited 15-fold higher adhesive strength to nerve tissue ex vivo compared to fibrin control. Furthermore, the composites were shown to support Schwann cell (SC) viability and proliferation, as well as neurite extension and glial cell participation in vitro, which are essential cellular components for nerve regeneration. Finally, subcutaneously implanted GelMA/MeTro hydrogels exhibited slower degradation in vivo compared with pure GelMA, indicating its potential to support the growth of slowly regenerating nerves. Thus, GelMA/MeTro composites may be used as clinically relevant biomaterials to regenerate nerves and reduce the need for microsurgical suturing during nerve reconstruction.

Characterization of partially hydrolyzed OCP crystals deposited in a gelatin matrix as a scaffold for bone tissue engineering

NASA Astrophysics Data System (ADS)

Ezoe, Yushi; Anada, Takahisa; Yamazaki, Hajime; Handa, Takuto; Kobayashi, Kazuhito; Takahashi, Tetsu; Suzuki, Osamu

2015-03-01

The present study was designed to investigate how hydrolysis of octacalcium phosphate (OCP) into hydroxyapatite is affected by the presence of gelatin (Gel) molecules and how osteoblastic cells respond to the resultant OCP hydrolyzate/Gel composites as the hydrolysis advances. OCP was prepared from a solution containing calcium and phosphate ions and Gel molecules, having a composition to produce a 40 wt% OCP as a final co-precipitate as the OCP/Gel. The precipitate was further incubated up to 40 h to advance the hydrolysis of OCP. These precipitates were processed to mold OCP/Gel sponges through lyophilization and dehydrothermal treatment. Chemical analysis, X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, and selected area electron diffraction revealed that the hydrolysis of OCP/Gel composite in hot water advanced in a time-dependent manner and faster than hydrolysis of OCP alone. The effect of Gel on the OCP hydrolysis was further examined in the presence of distinct concentrations of Gel molecules in hot water, showing that the Gel enhanced the hydrolysis as the concentration increased. Proliferation and differentiation of mouse bone marrow stromal ST-2 cells on the hydrolyzed OCP/Gel composites were compatible with Gel sponge alone after 21 days of culture, suggesting that these composites could be a candidate as a scaffold in bone tissue engineering.

Reduction of Brochothrix thermosphacta on beef surfaces following immobilization of nisin in calcium alginate gels.

PubMed

Cutter, C N; Siragusa, G R

1996-07-01

Lean and adipose beef carcass tissues inoculated with Brochothrix thermosphacta (BT) (approx. 4.50 log10 cfu cm-2) were left untreated (U) or treated with 100 micrograms ml-1 nisin (N), calcium alginate (A) or 100 micrograms ml-1 nisin immobilized in a calcium alginate gel (AN). Tissue samples were refrigerated after treatments and bacterial populations and nisin activity were determined at 0, 1, 2 and 7 d. U, A and N treatments of lean and adipose tissues did not suppress bacterial growth ( > 6 log10 cfu cm-2 by day 7) while treatments of lean and adipose tissues with AN suppressed bacteria ( > 2.42 log10 cfu cm-2 by day 7). Bacteriocin titres from both tissues were higher in AN vs N samples after the 7 d incubation. This study demonstrates that immobilization of nisin in a gel may be a more effective delivery system of a bacteriocin to the carcass surface than direct application.

An additive manufacturing-based PCL-alginate-chondrocyte bioprinted scaffold for cartilage tissue engineering.

PubMed

Kundu, Joydip; Shim, Jin-Hyung; Jang, Jinah; Kim, Sung-Won; Cho, Dong-Woo

2015-11-01

Regenerative medicine is targeted to improve, restore or replace damaged tissues or organs using a combination of cells, materials and growth factors. Both tissue engineering and developmental biology currently deal with the process of tissue self-assembly and extracellular matrix (ECM) deposition. In this investigation, additive manufacturing (AM) with a multihead deposition system (MHDS) was used to fabricate three-dimensional (3D) cell-printed scaffolds using layer-by-layer (LBL) deposition of polycaprolactone (PCL) and chondrocyte cell-encapsulated alginate hydrogel. Appropriate cell dispensing conditions and optimum alginate concentrations for maintaining cell viability were determined. In vitro cell-based biochemical assays were performed to determine glycosaminoglycans (GAGs), DNA and total collagen contents from different PCL-alginate gel constructs. PCL-alginate gels containing transforming growth factor-β (TGFβ) showed higher ECM formation. The 3D cell-printed scaffolds of PCL-alginate gel were implanted in the dorsal subcutaneous spaces of female nude mice. Histochemical [Alcian blue and haematoxylin and eosin (H&E) staining] and immunohistochemical (type II collagen) analyses of the retrieved implants after 4 weeks revealed enhanced cartilage tissue and type II collagen fibril formation in the PCL-alginate gel (+TGFβ) hybrid scaffold. In conclusion, we present an innovative cell-printed scaffold for cartilage regeneration fabricated by an advanced bioprinting technology. Copyright © 2013 John Wiley & Sons, Ltd.

Initial experiments with gel-water: towards MRI-linac dosimetry and imaging.

PubMed

Alnaghy, Sarah J; Gargett, Maegan; Liney, Gary; Petasecca, Marco; Begg, Jarrad; Espinoza, Anthony; Newall, Matthew K; Duncan, Mitchell; Holloway, Lois; Lerch, Michael L F; Lazea, Mircea; Rosenfeld, Anatoly B; Metcalfe, Peter

2016-12-01

Tracking the position of a moving radiation detector in time and space during data acquisition can replicate 4D image-guided radiotherapy (4DIGRT). Magnetic resonance imaging (MRI)-linacs need MRI-visible detectors to achieve this, however, imaging solid phantoms is an issue. Hence, gel-water, a material that provides signal for MRI-visibility, and which will in future work, replace solid water for an MRI-linac 4DIGRT quality assurance tool, is discussed. MR and CT images of gel-water were acquired for visualisation and electron density verification. Characterisation of gel-water at 0 T was compared to Gammex-RMI solid water, using MagicPlate-512 (M512) and RMI Attix chamber; this included percentage depth dose, tissue-phantom ratio (TPR 20/10 ), tissue-maximum ratio (TMR), profiles, output factors, and a gamma analysis to investigate field penumbral differences. MR images of a non-powered detector in gel-water demonstrated detector visualisation. The CT-determined gel-water electron density agreed with the calculated value of 1.01. Gel-water depth dose data demonstrated a maximum deviation of 0.7% from solid water for M512 and 2.4% for the Attix chamber, and by 2.1% for TPR 20/10 and 1.0% for TMR. FWHM and output factor differences between materials were ≤0.3 and ≤1.4%. M512 data passed gamma analysis with 100% within 2%, 2 mm tolerance for multileaf collimator defined fields. Gel-water was shown to be tissue-equivalent for dosimetry and a feasible option to replace solid water.

Gels prepared from egg yolk and its fractions for tissue engineering.

PubMed

Rodil, Andrea; Laca, Amanda; Paredes, Benjamín; Rendueles, Manuel; Meana, Álvaro; Díaz, Mario

2016-11-01

New biomaterials prepared from egg yolk and its main fractions (plasma and granules) have been developed for use in tissue engineering. Protein gels obtained via transglutaminase cross-linking were characterized by rheometry, texturometry and scanning electron microscopy. All the gels exhibited suitable physical and mechanical characteristics for use as potential biomaterials in skin regeneration. Specifically, results showed that these materials presented a compact, uniform structure, with granular gel being found to be the most resistant as well as the most elastic material. Accordingly, these gels were subsequently evaluated as scaffolds for murine fibroblast growth. The best results were obtained with granule gels. Not only adhesion and cell growth were detected when using these gels, but also continuous coatings of cells growing on their surface. These findings can be attributed to the higher protein content of this fraction and to the particular structure of its proteins. Thus, granules have proved to be an interesting potential raw material for scaffold development. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1577-1583, 2016. © 2016 American Institute of Chemical Engineers.

A nanoparticulate injectable hydrogel as a tissue engineering scaffold for multiple growth factor delivery for bone regeneration.

PubMed

Dyondi, Deepti; Webster, Thomas J; Banerjee, Rinti

2013-01-01

Gellan xanthan gels have been shown to be excellent carriers for growth factors and as matrices for several tissue engineering applications. Gellan xanthan gels along with chitosan nanoparticles of 297 ± 61 nm diameter, basic fibroblast growth factor (bFGF), and bone morphogenetic protein 7 (BMP7) were employed in a dual growth factor delivery system to promote the differentiation of human fetal osteoblasts. An injectable system with ionic and temperature gelation was optimized and characterized. The nanoparticle loaded gels showed significantly improved cell proliferation and differentiation due to the sustained release of growth factors. A differentiation marker study was conducted, analyzed, and compared to understand the effect of single vs dual growth factors and free vs encapsulated growth factors. Dual growth factor loaded gels showed a higher alkaline phosphatase and calcium deposition compared to single growth factor loaded gels. The results suggest that encapsulation and stabilization of growth factors within nanoparticles and gels are promising for bone regeneration. Gellan xanthan gels also showed antibacterial effects against Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis, the common pathogens in implant failure.

A Supramolecular Gel Approach to Minimize the Neural Cell Damage during Cryopreservation Process.

PubMed

Zeng, Jie; Yin, Yixia; Zhang, Li; Hu, Wanghui; Zhang, Chaocan; Chen, Wanyu

2016-03-01

The storage method for living cells is one of the major challenges in cell-based applications. Here, a novel supramolecular gel cryopreservation system (BDTC gel system) is introduced, which can observably increase the neural cell viability during cryopreservation process because this system can (1) confine the ice crystal growth in the porous of BDTC gel system, (2) decrease the amount of ice crystallization and cryopreservation system's freezing point, and (3) reduce the change rates of cell volumes and osmotic shock. In addition, thermoreversible BDTC supramolecular gel is easy to be removed after thawing so it does not hinder the adherence, growth, and proliferation of cells. The results of functionality assessments indicate that BDTC gel system can minimize the neural cell damage during cryopreservation process. This method will be potentially applied in cryopreservation of other cell types, tissues, or organs and will benefit cell therapy, tissue engineering, and organs transplantation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design, fabrication and characterization of oxidized alginate-gelatin hydrogels for muscle tissue engineering applications.

PubMed

Baniasadi, Hossein; Mashayekhan, Shohreh; Fadaoddini, Samira; Haghirsharifzamini, Yasamin

2016-07-01

In this study, we reported the preparation of self cross-linked oxidized alginate-gelatin hydrogels for muscle tissue engineering. The effect of oxidation degree (OD) and oxidized alginate/gelatin (OA/GEL) weight ratio were examined and the results showed that in the constant OA/GEL weight ratio, both cross-linking density and Young's modulus enhanced by increasing OD due to increment of aldehyde groups. Furthermore, the degradation rate was increased with increasing OD probably due to decrement in alginate molecular weight during oxidation reaction facilitated degradation of alginate chains. MTT cytotoxicity assays performed on Wharton's Jelly-derived umbilical cord mesenchymal stem cells cultured on hydrogels with OD of 30% showed that the highest rate of cell proliferation belong to hydrogel with OA/GEL weight ratio of 30/70. Overall, it can be concluded from all obtained results that the prepared hydrogel with OA/GEL weight ratio and OD of 30/70 and 30%, respectively, could be proper candidate for use in muscle tissue engineering. © The Author(s) 2016.

Preparation and Characterization of Cellulose Gels from Corn Cobs

USDA-ARS?s Scientific Manuscript database

Aqueous cellulose gels were prepared by extraction of ground corn cobs with hot aqueous sodium hydroxide/sodium hypochlorite and shearing. Initial shearing in a blender broke up cob tissue structure into individual cells and resulted in a gel. Subsequent shearing in a high pressure homogenizer incre...

Preparation and characterization of cellulose gels from corn cobs

USDA-ARS?s Scientific Manuscript database

Aqueous cellulose gels were prepared by extraction of ground corn cobs with hot aqueous sodium hydroxide/sodium hypochlorite and shearing. Initial shearing in a blender broke up cob tissue structure into individual cells and resulted in a gel. Subsequent shearing in a high pressure homogenizer incre...

Oxygen diffusion and consumption in extracellular matrix gels: implications for designing three-dimensional cultures.

PubMed

Colom, Adai; Galgoczy, Roland; Almendros, Isaac; Xaubet, Antonio; Farré, Ramon; Alcaraz, Jordi

2014-08-01

Three-dimensional (3D) cultures are increasingly used as tissue surrogates to study many physiopathological processes. However, to what extent current 3D culture protocols provide physiologic oxygen tension conditions remains ill defined. To address this limitation, oxygen tension was measured in a panel of acellular or cellularized extracellular matrix (ECM) gels with A549 cells, and analyzed in terms of oxygen diffusion and consumption. Gels included reconstituted basement membrane, fibrin and collagen. Oxygen diffusivity in acellular gels was up to 40% smaller than that of water, and the lower values were observed in the denser gels. In 3D cultures, physiologic oxygen tension was achieved after 2 days in dense (≥3 mg/mL) but not sparse gels, revealing that the latter gels are not suitable tissue surrogates in terms of oxygen distribution. In dense gels, we observed a dominant effect of ECM composition over density in oxygen consumption. All diffusion and consumption data were used in a simple model to estimate ranges for gel thickness, seeding density and time-window that may support physiologic oxygen tension. Thus, we identified critical variables for oxygen tension in ECM gels, and introduced a model to assess initial values of these variables, which may short-cut the optimization step of 3D culture studies. © 2013 Wiley Periodicals, Inc.

Dynamic analysis of a needle insertion for soft materials: Arbitrary Lagrangian-Eulerian-based three-dimensional finite element analysis.

PubMed

Yamaguchi, Satoshi; Tsutsui, Kihei; Satake, Koji; Morikawa, Shigehiro; Shirai, Yoshiaki; Tanaka, Hiromi T

2014-10-01

Our goal was to develop a three-dimensional finite element model that enables dynamic analysis of needle insertion for soft materials. To demonstrate large deformation and fracture, we used the arbitrary Lagrangian-Eulerian (ALE) method for fluid analysis. We performed ALE-based finite element analysis for 3% agar gel and three types of copper needle with bevel tips. To evaluate simulation results, we compared the needle deflection and insertion force with corresponding experimental results acquired with a uniaxial manipulator. We studied the shear stress distribution of agar gel on various time scales. For 30°, 45°, and 60°, differences in deflections of each needle between both sets of results were 2.424, 2.981, and 3.737mm, respectively. For the insertion force, there was no significant difference for mismatching area error (p<0.05) between simulation and experimental results. Our results have the potential to be a stepping stone to develop pre-operative surgical planning to estimate an optimal needle insertion path for MR image-guided microwave coagulation therapy and for analyzing large deformation and fracture in biological tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

Scaffold architecture and fibrin gels promote meniscal cell proliferation

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

Pawelec, K. M., E-mail: pawelec.km@gmail.com, E-mail: jw626@cam.ac.uk; Best, S. M.; Cameron, R. E.

2015-01-01

Stability of the knee relies on the meniscus, a complex connective tissue with poor healing ability. Current meniscal tissue engineering is inadequate, as the signals for increasing meniscal cell proliferation have not been established. In this study, collagen scaffold structure, isotropic or aligned, and fibrin gel addition were tested. Metabolic activity was promoted by fibrin addition. Cellular proliferation, however, was significantly increased by both aligned architectures and fibrin addition. None of the constructs impaired collagen type I production or triggered adverse inflammatory responses. It was demonstrated that both fibrin gel addition and optimized scaffold architecture effectively promote meniscal cell proliferation.

Rheological Properties of Cross-Linked Hyaluronan–Gelatin Hydrogels for Tissue Engineering

PubMed Central

Vanderhooft, Janssen L.; Alcoutlabi, Mataz; Magda, Jules J.; Prestwich, Glenn D.

2009-01-01

Hydrogels that mimic the natural extracellular matrix (ECM) are used in three-dimensional cell culture, cell therapy, and tissue engineering. A semi-synthetic ECM based on cross-linked hyaluronana offers experimental control of both composition and gel stiffness. The mechanical properties of the ECM in part determine the ultimate cell phenotype. We now describe a rheological study of synthetic ECM hydrogels with storage shear moduli that span three orders of magnitude, from 11 to 3 500 Pa, a range important for engineering of soft tissues. The concentration of the chemically modified HA and the cross-linking density were the main determinants of gel stiffness. Increase in the ratio of thiol-modified gelatin reduced gel stiffness by diluting the effective concentration of the HA component. PMID:18839402

Poster - Thur Eve - 69: Electron beam dosimetry in heterogeneous phantoms using the MAGIC normoxic polymer gel.

PubMed

Nedaie, H A; Ghahraman, A R; Bolouri, B; Arbabi, A

2012-07-01

Recently, radiation sensitive polymer gels are being used as a reliable dosimetry method for three-dimensional (3D) verification of radiation doses in clinical use. Some properties of gel dosimeters have made them useful in verifying complex situations in electron therapy. The aim of this study was to experimentally evaluate the influence of tissue inhomogeneities on electron beam dose distributions by use of polymer gel dosimetry. Another purpose was to evaluate the appropriateness of polymer gels for electron beam dosimetry applications. A cylindrical phantom filled with MAGIC polymer gel with a polyacrilic wall (ρ = 1.18 g.cm -3 ) was placed in a Perspex water-filled tank exactly underneath the bone inhomogeneity region .Then, the slab phantom was irradiated with a dose of 5Gy of 8MeV electrons to measure the dose distribution beyond the heterogeneity region. Afterwards, another cylindrical gel phantom similar to the above was used and irradiated with the same dose of 15 MeV electrons to measure the dose distribution beyond the same heterogeneity region. The same mentioned setup was repeated for measurement of the dose distribution beneath the air heterogeneity and homogenous phantom. The results of gel dosimetry under bone inhomogeneity have shown a reduction in dose. This is related to the high mass stopping and mass scattering powers of bone tissue. In addition, dose enhancement is seen laterally near the bone-tissue interface, due to increased side scattering of electrons. Hot and cold scatter lobes under heterogeneity regions are other effects that can be seen. The results of gel dosimetry under the air inhomogeneity have shown an increase in dose. This is related to the low mass stopping and mass scattering powers of the air cavity. When a high energy beam passes through a low-density medium or an air cavity, electronic equilibrium is lost along the central axis of the beam .The dose rebuild up is a consequence of this electronic disequilibrium. An overall good agreement was found between measurements with gel and with a diode detector for the single beam experiment. Electron dose distributions are significantly altered in the presence of tissue inhomogeneities such as bone and air cavities which are related to mass stopping and mass scattering powers of heterogeneous materials. © 2012 American Association of Physicists in Medicine.

SU-D-213-06: Dosimetry of Modulated Electron Radiation Therapy Using Fricke Gel Dosimeter

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

Gawad, M Abdel; Elgohary, M; Hassaan, M

Purpose: Modulated electron radiation therapy (MERT) has been proposed as an effective modality for treatment of superficial targets. MERT utilizes multiple beams of different energies which are intensity modulated to deliver optimized dose distribution. Energy independent dosimeters are thus needed for quantitative evaluations of MERT dose distributions and measurements of absolute doses delivered to patients. Thus in the current work we study the feasibility of Fricke gel dosimeters in MERT dosimetry. Methods: Batches of radiation sensitive Fricke gel is fabricated and poured into polymethyl methacrylate cuvettes. The samples were irradiated in solid water phantom and a thick layer of bolusmore » was used as a buildup. A spectrophotometer system was used for measuring the color changes (the absorbance) before and after irradiation and then we calculate net absorbance. We constructed calibration curves to relate the measured absorbance in terms of absorbed dose for all available electron energies. Dosimetric measurements were performed for mixed electron beam delivery and we also performed measurement for segmented field delivery with the dosimeter placed at the junction of two adjacent electron beams of different energies. Dose measured by our gel dosimetry is compared to that calculation from our precise treatment planning system. We also initiated a Monte Carlo study to evaluate the water equivalence of our dosimeters. MCBEAM and MCSIM codes were used for treatment head simulation and phantom dose calculation. PDDs and profiles were calculated for electron beams incident on a phantom designed with 1cm slab of Fricke gel. Results: The calibration curves showed no observed energy dependence with all studied electron beam energies. Good agreement was obtained between dose calculated and that obtained by gel dosimetry. Monte Carlo results illustrated the tissue equivalency of our Gel dosimeters. Conclusion: Fricke Gel dosimeters represent a good option for the dosimetric quality assurance prior to MERT application.« less

Hyaluronic acid doped-poly(3,4-ethylenedioxythiophene)/chitosan/gelatin (PEDOT-HA/Cs/Gel) porous conductive scaffold for nerve regeneration.

PubMed

Wang, Shuping; Guan, Shui; Zhu, Zhibo; Li, Wenfang; Liu, Tianqing; Ma, Xuehu

2017-02-01

Conducting polymer, as a "smart" biomaterial, has been increasingly used to construct tissue engineered scaffold for nerve tissue regeneration. In this study, a novel porous conductive scaffold was prepared by incorporating conductive hyaluronic acid (HA) doped-poly(3,4-ethylenedioxythiophene) (PEDOT-HA) nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. The physicochemical characteristics of Cs/Gel scaffold with 0-10wt% PEDOT-HA were analyzed and the results indicated that the incorporation of PEDOT-HA into scaffold increased the electrical and mechanical properties while decreasing the porosity and water absorption. Moreover, in vitro biodegradation of scaffold displayed a declining trend with the PEDOT-HA content increased. About the biocompatibility of conductive scaffold, neuron-like rat phaeochromocytoma (PC12) cells were cultured in scaffold to evaluate cell adhesion and growth. 8% PEDOT-HA/Cs/Gel scaffold had a higher cell adhesive efficiency and cell viability than the other conductive scaffolds. Furthermore, cells in the scaffold with 8wt% PEDOT-HA expressed higher synapse growth gene of GAP43 and SYP compared with Cs/Gel control group. These results suggest that 8%PEDOT-HA/Cs/Gel scaffold is an attractive cell culture conductive substrate which could support cell adhesion, survival, proliferation, and synapse growth for the application in nerve tissue regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of a Proposed Biodegradable 188Re Source for Brachytherapy Application

PubMed Central

Khorshidi, Abdollah; Ahmadinejad, Marjan; Hamed Hosseini, S.

2015-01-01

Abstract This study aimed to evaluate dosimetric characteristics based on Monte Carlo (MC) simulations for a proposed beta emitter bioglass 188Re seed for internal radiotherapy applications. The bioactive glass seed has been developed using the sol-gel technique. The simulations were performed for the seed using MC radiation transport code to investigate the dosimetric factors recommended by the AAPM Task Group 60 (TG-60). Dose distributions due to the beta and photon radiation were predicted at different radial distances surrounding the source. The dose rate in water at the reference point was calculated to be 7.43 ± 0.5 cGy/h/μCi. The dosimetric factors consisting of the reference point dose rate, D(r0,θ0), the radial dose function, g(r), the 2-dimensional anisotropy function, F(r,θ), the 1-dimensional anisotropy function, φan(r), and the R90 quantity were estimated and compared with several available beta-emitting sources. The element 188Re incorporated in bioactive glasses produced by the sol-gel technique provides a suitable solution for producing new materials for seed implants applied to brachytherapy applications in prostate and liver cancers treatment. Dose distribution of 188Re seed was greater isotropic than other commercially attainable encapsulated seeds, since it has no end weld to attenuate radiation. The beta radiation-emitting 188Re source provides high doses of local radiation to the tumor tissue and the short range of the beta particles limit damage to the adjacent normal tissue. PMID:26181543

RMP-02/MTN-006: A Phase 1 Rectal Safety, Acceptability, Pharmacokinetic, and Pharmacodynamic Study of Tenofovir 1% Gel Compared with Oral Tenofovir Disoproxil Fumarate

PubMed Central

Cranston, Ross D.; Kashuba, Angela; Hendrix, Craig W.; Bumpus, Namandjé N.; Richardson-Harman, Nicola; Elliott, Julie; Janocko, Laura; Khanukhova, Elena; Dennis, Robert; Cumberland, William G.; Ju, Chuan; Carballo-Diéguez, Alex; Mauck, Christine; McGowan, Ian

2012-01-01

Abstract This study was designed to assess the safety, acceptability, pharmacokinetic (PK), and pharmacodynamic (PD) responses to rectal administration of tenofovir (TFV) 1% vaginally formulated gel and oral tenofovir disoproxil fumarate (TDF). This study was designed as a phase 1, randomized, two-site (United States), double-blind, placebo-controlled study of sexually abstinent men and women. Eighteen participants received a single 300-mg exposure of oral TDF and were then randomized 2:1 to receive a single and then seven daily exposures of rectal TFV or hydroxyethyl cellulose (HEC) placebo gel. Safety endpoints included clinical adverse events (AEs) and mucosal safety parameters. Blood and colonic biopsies were collected for PK analyses and ex vivo HIV-1 challenge. No serious AEs were reported. However, AEs were significantly increased with 7-day TFV gel use, most prominently with gastrointestinal AEs (p=0.002). Only 25% of participants liked the TFV gel. Likelihood of use “if somewhat protective” was ∼75% in both groups. Indices of mucosal damage showed minimal changes. Tissue TFV diphosphate (TFV-DP) Cmax 30 min after single rectal exposure was 6–10 times greater than single oral exposure; tissue TFV-DP was 5.7 times greater following 7-day versus single rectal exposure. In vivo exposure correlated with significant ex vivo tissue infectibility suppression [single-rectal: p=0.12, analysis of covariance (ANCOVA) p=0.006; 7-day rectal: p=0.02, ANCOVA p=0.005]. Tissue PK–PD was significantly correlated (p=0.002). We conclude that rectal dosing with TFV 1% gel resulted in greater TFV-DP tissue detection than oral dosing with reduced ex vivo biopsy infectibility, enabling PK–PD correlations. On the basis of increased gastrointestinal AEs, rectally applied, vaginally formulated TFV was not entirely safe or acceptable, suggesting the need for alternative rectal-specific formulations. PMID:22943559

Topical Application of a Bioadhesive Black Raspberry Gel Modulates Gene Expression and Reduces Cyclooxygenase 2 Protein in Human Premalignant Oral Lesions

PubMed Central

Mallery, Susan R.; Zwick, Jared C.; Pei, Ping; Tong, Meng; Larsen, Peter E.; Shumway, Brian S.; Lu, Bo; Fields, Henry W.; Mumper, Russell J.; Stoner, Gary D.

2010-01-01

Reduced expression of proapoptotic and terminal differentiation genes in conjunction with increased levels of the proinflammatory and angiogenesis-inducing enzymes, cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS), correlate with malignant transformation of oral intraepithelial neoplasia (IEN). Accordingly, this study investigated the effects of a 10% (w/w) freeze-dried black raspberry gel on oral IEN histopathology, gene expression profiles, intraepithelial COX-2 and iNOS proteins, and microvascular densities. Our laboratories have shown that freeze-dried black raspberries possess antioxidant properties and also induce keratinocyte apoptosis and terminal differentiation. Oral IEN tissues were hemisected to provide samples for pretreatment diagnoses and establish baseline biochemical and molecular variables. Treatment of the remaining lesional tissue (0.5 g gel applied four times daily for 6 weeks) began 1 week after the initial biopsy. RNA was isolated from snap-frozen IEN lesions for microarray analyses, followed by quantitative reverse transcription-PCR validation. Additional epithelial gene-specific quantitative reverse transcription-PCR analyses facilitated the assessment of target tissue treatment effects. Surface epithelial COX-2 and iNOS protein levels and microvascular densities were determined by image analysis quantified immunohistochemistry. Topical berry gel application uniformly suppressed genes associated with RNA processing, growth factor recycling, and inhibition of apoptosis. Although the majority of participants showed posttreatment decreases in epithelial iNOS and COX-2 proteins, only COX-2 reductions were statistically significant. These data show that berry gel application modulated oral IEN gene expression profiles, ultimately reducing epithelial COX-2 protein. In a patient subset, berry gel application also reduced vascular densities in the superficial connective tissues and induced genes associated with keratinocyte terminal differentiation. PMID:18559542

Macrophages influence a competition of contact guidance and chemotaxis for fibroblast alignment in a fibrin gel coculture assay.

PubMed

Bromberek, B A; Enever, P A J; Shreiber, D I; Caldwell, M D; Tranquillo, R T

2002-05-01

Rat dermal fibroblasts were dispersed initially in the outer shell of a fibrin gel sphere, while the inner core either was devoid of cells or contained peritoneal exudate cells (primarily macrophages), thereby mimicking the inflammatory phase of wound healing. The fibroblasts compacted floating fibrin microspheres over time. In the absence of macrophages, the initial distribution of fibroblasts (only in the shell) induced circumferential alignment of fibrin fibrils via compaction of the shell relative to the core. The aligned fibrils created a contact guidance field, which was manifested by strong circumferential alignment of the fibroblasts. However, in the presence of macrophages, the fibroblasts exhibited more radial alignment despite the simultaneous contact guidance field in the circumferential direction associated with compaction. This was attributed to a chemotactic gradient emanating from the core due to a putative factor(s) released by the macrophages. The presence of a radial chemotactic stimulus was supported by the finding of even greater radial alignment when fibrin microspheres were embedded in an agarose-fibrin gel that abolished compaction and consequently the contact guidance field. Our assay permits the simulation of tissue morphogenetic processes that involve cell guidance phenomena and tractional restructuring of the extracellular matrix.

Sol gel derived hydroxyapatite coatings on titanium and its alloy Ti6Al4V

NASA Astrophysics Data System (ADS)

Stoch, A.; Jastrzebski, W.; Długoń, E.; Lejda, W.; Trybalska, B.; Stoch, G. J.; Adamczyk, A.

2005-06-01

Titanium has been used for many medical and dental applications; however, its joining to a living bone is not satisfactorily good or the implant integration with bone tissue takes several months.The aim of this work is to produce hydroxyapatite (HAP) coatings on titanium and its alloy for facilitating and shortening the processes towards osseointegration. HAP coatings were obtained by sol-gel method with sol solutions prepared from calcium nitrate tetrahydrate and triammonium phosphate trihydrate as the calcium and phosphorous sources. Two types of gelatine were added to the sol: agar-agar or animals gelatine. Both were found to enhance the formation and stability of amorphous HAP using soluble salts as the sources of calcium and phosphate. HAP coatings were deposited from HAP-GEL sol using dip-withdrawal technique, then the plates were dried and annealed at temperatures 460-750 °C. FTIR spectroscopy and XRD analysis were used to study the phase composition of phosphate coatings. Morphology and chemical analysis of HAP layers was performed using a scanning electron microscope equipped with an energy dispersive X-ray analyser (SEM+EDX). The biological activity of sol-gel phosphate coatings was observed during thermostatic held in simulated body fluid (SBF). It was found that chemical composition and structure of HAP coatings depends on pH and final thermal treatment of the layer.

Oxygen consumption in T-47D cells immobilized in alginate.

PubMed

Larsen, B E; Sandvik, J A; Karlsen, J; Pettersen, E O; Melvik, J E

2013-08-01

Encapsulation or entrapment of cells is increasingly being used in a wide variety of scientific studies for tissue engineering and development of novel medical devices. The effect on cell metabolism of such systems is, in general, not well characterized. In this work, a simple system for monitoring respiration of cells embedded in 3-D alginate cultures was characterized. T-47D cells were cultured in alginate gels. Oxygen concentration curves were recorded within cell-gel constructs using two different sensor systems, and cell viability and metabolic state were characterized using confocal microscopy and commercially available stains. At sufficient depth within constructs, recorded oxygen concentration curves were not significantly influenced by influx of oxygen through cell-gel layers and oxygen consumption rate could be calculated simply by dividing oxygen loss in the system per time, by the number of cells. This conclusion was supported by a 3-D numeric simulation. For the T-47D cells, the oxygen consumption rate was found to be 61 ± 6 fmol/cell/h, 3-4 times less than has previously been found for these cells, when grown exponentially in monolayer culture. The experimental set-up presented here may be varied in multiple ways by changing the cell-gel construct 3-D microenvironment, easily allowing investigation of a variety of factors on cell respiration. © 2013 John Wiley & Sons Ltd.

Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels

PubMed Central

Yue, Kan; Santiago, Grissel Trujillo-de; Alvarez, Mario Moisés; Tamayol, Ali; Annabi, Nasim; Khademhosseini, Ali

2015-01-01

Gelatin methacryloyl (GelMA) hydrogels have been widely used for various biomedical applications due to their suitable biological properties and tunable physical characteristics. Three dimensional (3D) GelMA hydrogels closely resemble some essential properties of native extracellular matrix (ECM) due to the presence of cell-attaching and matrix metalloproteinase responsive peptide motifs, which allow cells to proliferate and spread in GelMA-based scaffolds. GelMA is also versatile from a processing perspective. It crosslinks when exposed to light irradiation to form hydrogels with tunable mechanical properties which mimic the native ECM. It can also be microfabricated using different methodologies including micromolding, photomasking, bioprinting, self-assembly, and microfluidic techniques to generate constructs with controlled architectures. Hybrid hydrogel systems can also be formed by mixing GelMA with nanoparticles such as carbon nanotubes and graphene oxide, and other polymers to form networks with desired combined properties and characteristics for specific biological applications. Recent research has demonstrated the proficiency of GelMA-based hydrogels in a wide range of applications including engineering of bone, cartilage, cardiac, and vascular tissues, among others. Other applications of GelMA hydrogels, besides tissue engineering, include fundamental single-single cell research, cell signaling, drug and gene delivery, and bio-sensing. PMID:26414409

Quantitative Analysis of Microbicide Concentrations in Fluids, Gels and Tissues Using Confocal Raman Spectroscopy

PubMed Central

Chuchuen, Oranat; Henderson, Marcus H.; Sykes, Craig; Kim, Min Sung; Kashuba, Angela D. M.; Katz, David F.

2013-01-01

Topical vaginal anti-HIV microbicides are an important focus in female-based strategies to prevent the sexual transmission of HIV. Understanding microbicide pharmacokinetics is essential to development, characterization and implementation of efficacious microbicide drug delivery formulations. Current methods to measure drug concentrations in tissue (e.g., LC-MS/MS, liquid chromatography coupled with tandem mass spectrometry) are highly sensitive, but destructive and complex. This project explored the use of confocal Raman spectroscopy to detect microbicide drugs and to measure their local concentrations in fluids, drug delivery gels, and tissues. We evaluated three candidate microbicide drugs: tenofovir, Dapivirine and IQP-0528. Measurements were performed in freshly excised porcine buccal tissue specimens, gel vehicles and fluids using two Horiba Raman microscopes, one of which is confocal. Characteristic spectral peak calibrations for each drug were obtained using serial dilutions in the three matrices. These specific Raman bands demonstrated strong linear concentration dependences in the matrices and were characterized with respect to their unique vibrational signatures. At least one specific Raman feature was identified for each drug as a marker band for detection in tissue. Sensitivity of detection was evaluated in the three matrices. A specific peak was also identified for tenofovir diphosphate, the anti-HIV bioactive product of tenofovir after phosphorylation in host cells. Z-scans of drug concentrations vs. depth in excised tissue specimens, incubated under layers of tenofovir solution in a Transwell assay, showed decreasing concentration with depth from the surface into the tissue. Time-dependent concentration profiles were obtained from tissue samples incubated in the Transwell assay, for times ranging 30 minutes - 6 hours. Calibrations and measurements from tissue permeation studies for tenofovir showed good correlation with gold standard LC-MS/MS data. These results demonstrate that confocal Raman spectroscopy holds promise as a tool for practical, minimally invasive, label-free measurement of microbicide drug concentrations in fluids, gels and tissues. PMID:24386455

Tissue Viscoelasticity Imaging Using Vibration and Ultrasound Coupler Gel

NASA Astrophysics Data System (ADS)

Yamakawa, Makoto; Shiina, Tsuyoshi

2012-07-01

In tissue diagnosis, both elasticity and viscosity are important indexes. Therefore, we propose a method for evaluating tissue viscoelasticity by applying vibration that is usually performed in elastography and using an ultrasound coupler gel with known viscoelasticity. In this method, we use three viscoelasticity parameters based on the coupler strain and tissue strain: the strain ratio as an elasticity parameter, and the phase difference and the normalized hysteresis loop area as viscosity parameters. In the agar phantom experiment, using these viscoelasticity parameters, we were able to estimate the viscoelasticity distribution of the phantom. In particular, the strain ratio and the phase difference were robust to strain estimation error.

Biocompatible tissue scaffold compliance promotes salivary gland morphogenesis and differentiation.

PubMed

Peters, Sarah B; Naim, Nyla; Nelson, Deirdre A; Mosier, Aaron P; Cady, Nathaniel C; Larsen, Melinda

2014-06-01

Substrate compliance is reported to alter cell phenotype, but little is known about the effects of compliance on cell development within the context of a complex tissue. In this study, we used 0.48 and 19.66 kPa polyacrylamide gels to test the effects of the substrate modulus on submandibular salivary gland development in culture and found a significant decrease in branching morphogenesis in explants grown on the stiff 19.66 kPa gels relative to those grown on the more physiologically compliant 0.48 kPa gels. While proliferation and apoptosis were not affected by the substrate modulus, tissue architecture and epithelial acinar cell differentiation were profoundly perturbed by aberrant, high stiffness. The glands cultured on 0.48 kPa gels were similar to developing glands in morphology and expression of the differentiation markers smooth muscle alpha-actin (SM α-actin) in developing myoepithelial cells and aquaporin 5 (AQP5) in proacinar cells. At 19.66 kPa, however, tissue morphology and the expression and distribution of SM α-actin and AQP5 were disrupted. Significantly, aberrant gland development at 19.66 kPa could be rescued by both mechanical and chemical stimuli. Transfer of glands from 19.66 to 0.48 kPa gels resulted in substantial recovery of acinar structure and differentiation, and addition of exogenous transforming growth factor beta 1 at 19.66 kPa resulted in a partial rescue of morphology and differentiation within the proacinar buds. These results indicate that environmental compliance is critical for organogenesis, and suggest that both mechanical and chemical stimuli can be exploited to promote organ development in the contexts of tissue engineering and organ regeneration.

Biocompatible Tissue Scaffold Compliance Promotes Salivary Gland Morphogenesis and Differentiation

PubMed Central

Peters, Sarah B.; Naim, Nyla; Nelson, Deirdre A.; Mosier, Aaron P.; Cady, Nathaniel C.

2014-01-01

Substrate compliance is reported to alter cell phenotype, but little is known about the effects of compliance on cell development within the context of a complex tissue. In this study, we used 0.48 and 19.66 kPa polyacrylamide gels to test the effects of the substrate modulus on submandibular salivary gland development in culture and found a significant decrease in branching morphogenesis in explants grown on the stiff 19.66 kPa gels relative to those grown on the more physiologically compliant 0.48 kPa gels. While proliferation and apoptosis were not affected by the substrate modulus, tissue architecture and epithelial acinar cell differentiation were profoundly perturbed by aberrant, high stiffness. The glands cultured on 0.48 kPa gels were similar to developing glands in morphology and expression of the differentiation markers smooth muscle alpha-actin (SM α-actin) in developing myoepithelial cells and aquaporin 5 (AQP5) in proacinar cells. At 19.66 kPa, however, tissue morphology and the expression and distribution of SM α-actin and AQP5 were disrupted. Significantly, aberrant gland development at 19.66 kPa could be rescued by both mechanical and chemical stimuli. Transfer of glands from 19.66 to 0.48 kPa gels resulted in substantial recovery of acinar structure and differentiation, and addition of exogenous transforming growth factor beta 1 at 19.66 kPa resulted in a partial rescue of morphology and differentiation within the proacinar buds. These results indicate that environmental compliance is critical for organogenesis, and suggest that both mechanical and chemical stimuli can be exploited to promote organ development in the contexts of tissue engineering and organ regeneration. PMID:24410370

The cassava (Manihot esculenta Crantz) root proteome: protein identification and differential expression.

PubMed

Sheffield, Jeanne; Taylor, Nigel; Fauquet, Claude; Chen, Sixue

2006-03-01

Using high-resolution 2-DE, we resolved proteins extracted from fibrous and tuberous root tissues of 3-month-old cassava plants. Gel image analysis revealed an average of 1467 electrophoretically resolved spots on the fibrous gels and 1595 spots on the tuberous gels in pH 3-10 range. Protein spots from both sets of gels were digested with trypsin. The digests were subjected to nanoelectrospray quadrupole TOF tandem mass analysis. Currently, we have obtained 299 protein identifications for 292 gel spots corresponding to 237 proteins. The proteins span various functional categories from energy, primary and secondary metabolism, disease and defense, destination and storage, transport, signal transduction, protein synthesis, cell structure, and transcription to cell growth and division. Gel image analysis has shown unique, as well as up- and down-regulated proteins, present in the tuberous and the fibrous tissues. Quantitative and qualitative analysis of the cassava root proteome is an important step towards further characterization of differentially expressed proteins and the elucidation of the mechanisms underlying the development and biological functions of the two types of roots.

Experimental and theoretical investigation of intratumoral nanoparticle distribution to enhance magnetic nanoparticle hyperthermia

NASA Astrophysics Data System (ADS)

Attaluri, Anilchandra

Magnetic nanoparticles have gained prominence in recent years for use in clinical applications such as imaging, drug delivery, and hyperthermia. Magnetic nanoparticle hyperthermia is a minimally invasive and effective approach for confined heating in tumors with little collateral damage. One of the major problems in the field of magnetic nanoparticle hyperthermia is irregular heat distribution in tumors which caused repeatable heat distribution quite impossible. This causes under dosage in tumor area and overheating in normal tissue. In this study, we develop a unified approach to understand magnetic nanoparticle distribution and temperature elevations in gel and tumors. A microCT imaging system is first used to visualize and quantify nanoparticle distribution in both tumors and tissue equivalent phantom gels. The microCT based nanoparticle concentration is related to specific absorption rate (SAR) of the nanoparticles and is confirmed by heat distribution experiments in tissue equivalent phantom gels. An optimal infusion protocol is identified to generate controllable and repeatable nanoparticle distribution in tumors. In vivo animal experiments are performed to measure intratumoral temperature elevations in PC3 xenograft tumors implanted in mice during magnetic nanoparticle hyperthermia. The effect of nanofluid injection parameters on the resulted temperature distribution is studied. It shows that the tumor temperatures can be elevated above 50°C using very small amounts of ferrofluid with a relatively low magnetic field. Slower ferrofluid infusion rates result in smaller nanoparticle distribution volumes in the tumors, however, it gives the much required controllability and repeatability when compared to the higher infusion rates. More nanoparticles occupy a smaller volume in the vicinity of the injection site with slower infusion rates, causing higher temperature elevations in the tumors. Based on the microCT imaging analyses of nanoparticles in tumors, a mass transport model is developed to simulate nanoparticle convection and diffusion in tumors, heat-induced tumor structural changes, as well as nanoparticle re-distribution during nanoparticle hyperthermia procedures. The modeled thermal damage induced nanoparticle redistribution predicts a 20% increase in the radius of the spherical tissue region containing nanoparticles. The developed model has demonstrated the feasibility of enhancing nanoparticle dispersion from injection sites using targeted thermal damage.

[Effects of aloe gel on doxorubicin-induced extravasation injury in rats].

PubMed

Liu, Xue-Hua; Xia, Hong; Zhou, Xiu-Tian; Luo, Wen; Zhou, Jian-Guo; Dong, Lin

2009-04-01

Aloe has preventive effects on some chemotherapy-induced extravasation injuries. This study was to investigate the effect and mechanism of aloe gel on doxorubicin-induced extravasation injury. Sprague-Dawley (SD) rats were used to establish the extravasation injury model induced by doxorubicin. Thirty SD rats were randomly divided into three groups: control group, aloe gel group (1 g/L) and 50% magnesium sulfate group. The area of extravasation was measured and the degree of injury was observed. The injured tissues were resected from two randomly selected rats in each group on the 1st, 4th, 7th, 11th, and 18th day after treatments. Pathological morphology of the resected tissues was observed under an optical microscope after hematoxylin and eosin (HE) staining. The exosmosis skin and subcutaneous tissues of rats were resected five days after treatments. Then the wounds were interruptedly sutured. When sutures were removed on the 7th day after operation, the condition of primary wound healing and the healing time were recorded. Expressions of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in the exosmosis skin and subcutaneous tissues were detected by immunohistochemistry. The area and the degree of extravasation injury were smaller and less severe in the aloe gel and magnesium sulfate groups than in the control group (P<0.01). The rates of primary wound healing were significantly higher in the aloe gel (60.0%) and magnesium sulfate (66.7%) groups than in the control group (20.0%); while the healing time was significantly shorter in the aloe gel (9.6+/-1.64 d) and magnesium sulfate (9.33+/-1.40 d) groups than in the control group (12.13+/-2.06 d) (both P<0.01). Moreover, the expression levels of VEGF and EGFR were higher in the aloe gel group than in the control group. The preventive and therapeutic effects of aloe gel on doxorubicin-induced extravasation injury are satisfactory, which may be in relation to the up-regulation of VEGF and EGFR.

Automatic and quantitative measurement of collagen gel contraction using model-guided segmentation

NASA Astrophysics Data System (ADS)

Chen, Hsin-Chen; Yang, Tai-Hua; Thoreson, Andrew R.; Zhao, Chunfeng; Amadio, Peter C.; Sun, Yung-Nien; Su, Fong-Chin; An, Kai-Nan

2013-08-01

Quantitative measurement of collagen gel contraction plays a critical role in the field of tissue engineering because it provides spatial-temporal assessment (e.g., changes of gel area and diameter during the contraction process) reflecting the cell behavior and tissue material properties. So far the assessment of collagen gels relies on manual segmentation, which is time-consuming and suffers from serious intra- and inter-observer variability. In this study, we propose an automatic method combining various image processing techniques to resolve these problems. The proposed method first detects the maximal feasible contraction range of circular references (e.g., culture dish) and avoids the interference of irrelevant objects in the given image. Then, a three-step color conversion strategy is applied to normalize and enhance the contrast between the gel and background. We subsequently introduce a deformable circular model which utilizes regional intensity contrast and circular shape constraint to locate the gel boundary. An adaptive weighting scheme was employed to coordinate the model behavior, so that the proposed system can overcome variations of gel boundary appearances at different contraction stages. Two measurements of collagen gels (i.e., area and diameter) can readily be obtained based on the segmentation results. Experimental results, including 120 gel images for accuracy validation, showed high agreement between the proposed method and manual segmentation with an average dice similarity coefficient larger than 0.95. The results also demonstrated obvious improvement in gel contours obtained by the proposed method over two popular, generic segmentation methods.

Platelet-rich plasma combined with agarose as a bioactive scaffold to enhance cartilage repair: an in vitro study.

PubMed

Yin, Zhaowei; Yang, Xiaofei; Jiang, Yiqiu; Xing, Linzi; Xu, Yang; Lu, Yiming; Ding, Peng; Ma, Junxin; Xu, Yan; Gui, Jianchao

2014-03-01

The purpose of this study was to determine whether the platelet-rich plasma-agarose gel scaffold could be a bioactive scaffold capable of growth factors release for cartilage repair. Porcine chondrocytes were seeded in agarose gel and platelet-rich plasma-agarose gel. During the 28-days culture, microstructure of hydrogels and morphologies of chondrocytes seeded in the hydrogels were observed using scanning electron microscope; viability of chondrocytes in gels was examined by live/dead assay; qualitative and quantitative analysis of glycosaminoglycan, collagen and DNA were assessed by histological, immunohistochemical staining and biochemical assay; gene expression was measured by real-time polymerase chain reaction. In vitro cartilage ring models were used to evaluate the integration of the scaffolds, and the integration strength was analyzed by mechanical push-out tests. Scanning electron microscope revealed both scaffolds had highly uniform porous structure. Live/dead scaffolds showed 100% cells alive in both groups. After 28-days culture, glycosaminoglycan, collagen, DNA content and chondrocyte-related genes expression in platelet-rich plasma-agarose gel were significantly higher than pure agarose gel. Integration strength in platelet-rich plasma-agarose gel was also higher compared to pure agarose gel. Platelet-rich plasma showed a positive effect on chondrocytes proliferation, differentiation and integration between native cartilage and engineered tissue when combined with agarose gel. Our findings suggest that platelet-rich plasma-agarose gel scaffold is a promising bioactive scaffold for future cartilage tissue engineering and future clinical works.

Mathematical Modeling of Uniaxial Mechanical Properties of Collagen Gel Scaffolds for Vascular Tissue Engineering

PubMed Central

Irastorza, Ramiro M.; Drouin, Bernard; Blangino, Eugenia; Mantovani, Diego

2015-01-01

Small diameter tissue-engineered arteries improve their mechanical and functional properties when they are mechanically stimulated. Applying a suitable stress and/or strain with or without a cycle to the scaffolds and cells during the culturing process resides in our ability to generate a suitable mechanical model. Collagen gel is one of the most used scaffolds in vascular tissue engineering, mainly because it is the principal constituent of the extracellular matrix for vascular cells in human. The mechanical modeling of such a material is not a trivial task, mainly for its viscoelastic nature. Computational and experimental methods for developing a suitable model for collagen gels are of primary importance for the field. In this research, we focused on mechanical properties of collagen gels under unconfined compression. First, mechanical viscoelastic models are discussed and framed in the control system theory. Second, models are fitted using system identification. Several models are evaluated and two nonlinear models are proposed: Mooney-Rivlin inspired and Hammerstein models. The results suggest that Mooney-Rivlin and Hammerstein models succeed in describing the mechanical behavior of collagen gels for cyclic tests on scaffolds (with best fitting parameters 58.3% and 75.8%, resp.). When Akaike criterion is used, the best is the Mooney-Rivlin inspired model. PMID:25834840

Mathematical modeling of uniaxial mechanical properties of collagen gel scaffolds for vascular tissue engineering.

PubMed

Irastorza, Ramiro M; Drouin, Bernard; Blangino, Eugenia; Mantovani, Diego

2015-01-01

Small diameter tissue-engineered arteries improve their mechanical and functional properties when they are mechanically stimulated. Applying a suitable stress and/or strain with or without a cycle to the scaffolds and cells during the culturing process resides in our ability to generate a suitable mechanical model. Collagen gel is one of the most used scaffolds in vascular tissue engineering, mainly because it is the principal constituent of the extracellular matrix for vascular cells in human. The mechanical modeling of such a material is not a trivial task, mainly for its viscoelastic nature. Computational and experimental methods for developing a suitable model for collagen gels are of primary importance for the field. In this research, we focused on mechanical properties of collagen gels under unconfined compression. First, mechanical viscoelastic models are discussed and framed in the control system theory. Second, models are fitted using system identification. Several models are evaluated and two nonlinear models are proposed: Mooney-Rivlin inspired and Hammerstein models. The results suggest that Mooney-Rivlin and Hammerstein models succeed in describing the mechanical behavior of collagen gels for cyclic tests on scaffolds (with best fitting parameters 58.3% and 75.8%, resp.). When Akaike criterion is used, the best is the Mooney-Rivlin inspired model.

Improving Joint Function Using Photochemical Hydrogels for Articular Surface Repair

DTIC Science & Technology

2017-02-01

dilution groups , tdeg increased with increasing concentration of EDC/NHS. Mechanical testing Values for storage modulus in spontaneous control gels (25.86...red) in 48-well nontreated tissue culture plates. As a positive control , a subset group of gels without tethered growth factor was exposed to 0.3 nM...in a cartilage ring and capped with fibrin and collagen gel. A control group consisted of chondrocytes encapsulated in fibrin gel. Constructs were

Orientation of chain molecules in ionotropic gels: a Brownian dynamics model

NASA Astrophysics Data System (ADS)

Woelki, Stefan; Kohler, Hans-Helmut

2003-09-01

As is known from birefringence measurements, polysaccharide molecules of ionotropic gels are preferentially orientated normal to the direction of gel growth. In this paper the orientation effect is investigated by means of an off-lattice Brownian dynamics model simulating the gel formation process. The model describes the integration of a single coarse grained phantom chain into the growing gel. The equations of motion of the chain are derived. The computer simulations show that, during the process of integration, the chain is contracting normal to the direction of gel growth. A scaling relation is obtained for the degree of contraction as a function of the length parameters of the chain, the velocity of the gel formation front and the rate constant of the crosslinking reaction. It is shown that the scaling relation, if applied to the example of ionotropic copper alginate gel, leads to reasonable predictions of the time course of the degree of contraction of the alginate chains.

Ultraflexible organic amplifier with biocompatible gel electrodes.

PubMed

Sekitani, Tsuyoshi; Yokota, Tomoyuki; Kuribara, Kazunori; Kaltenbrunner, Martin; Fukushima, Takanori; Inoue, Yusuke; Sekino, Masaki; Isoyama, Takashi; Abe, Yusuke; Onodera, Hiroshi; Someya, Takao

2016-04-29

In vivo electronic monitoring systems are promising technology to obtain biosignals with high spatiotemporal resolution and sensitivity. Here we demonstrate the fabrication of a biocompatible highly conductive gel composite comprising multi-walled carbon nanotube-dispersed sheet with an aqueous hydrogel. This gel composite exhibits admittance of 100 mS cm(-2) and maintains high admittance even in a low-frequency range. On implantation into a living hypodermal tissue for 4 weeks, it showed a small foreign-body reaction compared with widely used metal electrodes. Capitalizing on the multi-functional gel composite, we fabricated an ultrathin and mechanically flexible organic active matrix amplifier on a 1.2-μm-thick polyethylene-naphthalate film to amplify (amplification factor: ∼200) weak biosignals. The composite was integrated to the amplifier to realize a direct lead epicardial electrocardiography that is easily spread over an uneven heart tissue.

In situ delivery of thermosensitive gel-mediated 5-fluorouracil microemulsion for the treatment of colorectal cancer

PubMed Central

Wang, Lu-Lu; Huang, Shuai; Guo, Hui-Hui; Han, Yan-Xing; Zheng, Wen-Sheng; Jiang, Jian-Dong

2016-01-01

In situ administration of 5-fluorouracil (5FU) “thermosensitive” gel effectively reduced systemic side effects in treating colon rectal cancer; however, the penetration efficacy of the formulation was considerably low due to the poor lipid solubility of 5FU. The aim of this study was to develop thermosensitive gel-mediated 5FU water-in-oil microemulsion (TG-5FU-ME) for improving the infiltration of 5FU. An in vitro release test showed that TG-5FU-ME sustained the drug’s release up to 10 hours. TG-5FU-ME exhibited good stability, and the microemulsion entrapped did not show any change in morphology and 5FU content during the 4-month storage. Transportation test in the Caco-2 cell monolayer showed that TG-5FU-ME had a permeability 6.3 times higher than that of 5FU thermosensitive gel, and the intracellular uptake of 5FU increased by 5.4-fold compared to that of 5FU thermosensitive gel. In vivo tissue distribution analysis exhibited that the TG-5FU-ME group had drug levels in rectal tissue and mesenteric lymph nodes, which were significantly higher than those of 5FU thermosensitive gel group, with very low blood levels of 5FU in both groups. Furthermore, TG-5FU-ME was not associated with detectable morphological damage to the rectal tissue. Conclusively, TG-5FU-ME might be an efficient rectal delivery system to treat colorectal cancer. PMID:27660416

Thickness sensing of hMSCs on collagen gel directs stem cell fate

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

Leong, Wen Shing; Tay, Chor Yong; Yu, Haiyang

Research highlights: {yields} hMSCs appeared to sense thin collagen gel (130 {mu}m) with higher effective modulus as compared to thick gel (1440 {mu}m). {yields} Control of collagen gel thickness can modulate cellular behavior, even stem cell fate (neuronal vs. Quiescent). {yields} Distinct cellular behavior of hMSCs on thin and thick collagen gel suggests long range interaction of hMSCs with collagen gel. -- Abstract: Mechanically compliant substrate provides crucial biomechanical cues for multipotent stem cells to regulate cellular fates such as differentiation, proliferation and maintenance of their phenotype. Effective modulus of which cells sense is not only determined by intrinsic mechanicalmore » properties of the substrate, but also the thickness of substrate. From our study, it was found that interference from underlying rigid support at hundreds of microns away could induce significant cellular response. Human mesenchymal stem cells (hMSCs) were cultured on compliant biological gel, collagen type I, of different thickness but identical ECM composition and local stiffness. The cells sensed the thin gel (130 {mu}m) as having a higher effective modulus than the thick gel (1440 {mu}m) and this was reflected in their changes in morphology, actin fibers structure, proliferation and tissue specific gene expression. Commitment into neuronal lineage was observed on the thin gel only. Conversely, the thick gel (1440 {mu}m) was found to act like a substrate with lower effective modulus that inhibited actin fiber polymerization. Stem cells on the thick substrate did not express tissue specific genes and remained at their quiescent state. This study highlighted the need to consider not only the local modulus but also the thickness of biopolymer gel coating during modulation of cellular responses.« less

Pharmacokinetic modeling of a gel-delivered dapivirine microbicide in humans.

PubMed

Halwes, Michael E; Steinbach-Rankins, Jill M; Frieboes, Hermann B

2016-10-10

Although a number of drugs have been developed for the treatment and prevention of human immunodeficiency virus (HIV) infection, it has proven difficult to optimize the drug and dosage parameters. The vaginal tissue, comprised of epithelial, stromal and blood compartments presents a complex system which challenges evaluation of drug kinetics solely through empirical effort. To provide insight into the underlying processes, mathematical modeling and computational simulation have been applied to the study of retroviral microbicide pharmacokinetics. Building upon previous pioneering work that modeled the delivery of Tenofovir (TFV) via topical delivery to the vaginal environment, here we computationally evaluate the performance of the retroviral inhibitor dapivirine released from a microbicide gel. We adapt the TFV model to simulate the multicompartmental diffusion and uptake of dapivirine into the blood plasma and vaginal compartments. The results show that dapivirine is expected to accumulate at the interface between the gel and epithelium compartments due to its hydrophobic characteristics. Hydrophobicity also results in decreased diffusivity, which may impact distribution by up to 2 orders of magnitude compared to TFV. Maximum concentrations of dapivirine in the epithelium, stroma, and blood were 9.9e7, 2.45e6, and 119pg/mL, respectively. This suggests that greater initial doses or longer time frames are required to obtain higher drug concentrations in the epithelium. These observations may have important ramifications if a specific time frame is required for efficacy, or if a minimum/maximum concentration is needed in the mucus, epithelium, or stroma based on combined efficacy and safety data. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of formalin-fixed paraffin-embedded tissues in the proteomic analysis of parathyroid glands

PubMed Central

2011-01-01

Background Proteomic research in the field of parathyroid tissues is limited by the very small dimension of the glands and by the low incidence of cancer lesions (1%). Formalin-fixed paraffin-embedded (FFPE) tissue specimens are a potentially valuable resource for discovering protein cancer biomarkers. In this study we have verified the applicability of a heat induced protein extraction from FFPE parathyroid adenoma tissues followed by a gel-based or gel-free proteomic approach in order to achieve protein separation and identification. Results The best results for high quality MS spectra and parameters, were obtained by using a gel-free approach, and up to 163 unique proteins were identified. Similar results were obtained by applying both SDS-out and SDS-out + TCA/Acetone techniques during the gel-free method. Western blot analysis carried out with specific antibodies suggested that the antigenicity was not always preserved, while specific immunoreactions were detected for calmodulin, B box and SPRY domain-containing protein (BSPRY), peroxiredoxin 6 (PRDX 6) and parvalbumin. Conclusions In spite of some limitations mainly due to the extensive formalin-induced covalent cross-linking, our results essentially suggest the applicability of a proteomic approach to FFPE parathyroid specimens. From our point of view, FFPE extracts might be an alternative source, especially in the validation phase of protein biomarkers when a large cohort of samples is required and the low availability of frozen tissues might be constraining. PMID:21651755

A spectrophotometer-based diffusivity assay reveals that diffusion hindrance of small molecules in extracellular matrix gels used in 3D cultures is dominated by viscous effects.

PubMed

Galgoczy, Roland; Pastor, Isabel; Colom, Adai; Giménez, Alicia; Mas, Francesc; Alcaraz, Jordi

2014-08-01

The design of 3D culture studies remains challenging due to the limited understanding of extracellular matrix (ECM)-dependent hindered diffusion and the lack of simple diffusivity assays. To address these limitations, we set up a cost-effective diffusivity assay based on a Transwell plate and the spectrophotometer of a Microplate Reader, which are readily accessible to cell biology groups. The spectrophotometer-based assay was used to assess the apparent diffusivity D of FITC-dextrans with molecular weight (4-70kDa) spanning the physiological range of signaling factors in a panel of acellular ECM gels including Matrigel, fibrin and type I collagen. Despite their technical differences, D data exhibited ∼15% relative difference with respect to FRAP measurements. Our results revealed that diffusion hindrance of small particles is controlled by the enhanced viscosity of the ECM gel in conformance with the Stokes-Einstein equation rather than by geometrical factors. Moreover, we provided a strong rationale that the enhanced ECM viscosity is largely contributed to by unassembled ECM macromolecules. We also reported that gels with the lowest D exhibited diffusion hindrance closest to the large physiologic hindrance of brain tissue, which has a typical pore size much smaller than ECM gels. Conversely, sparse gels (≤1mg/ml), which are extensively used in 3D cultures, failed to reproduce the hindered diffusion of tissues, thereby supporting that dense (but not sparse) ECM gels are suitable tissue surrogates in terms of macromolecular transport. Finally, the consequences of reduced diffusivity in terms of optimizing the design of 3D culture experiments were addressed in detail. Copyright © 2014 Elsevier B.V. All rights reserved.

Dextran and gelatin based photocrosslinkable tissue adhesive.

PubMed

Wang, Tao; Nie, Jun; Yang, Dongzhi

2012-11-06

A two-component tissue adhesive based on biocompatible and bio-degradable polymers (oxidized urethane dextran (Dex-U-AD) and gelatin) was prepared and photocrosslinked under the ultraviolet (UV) irradiation. The adhesive could adhere to surface of gelatin, which simulated the human tissue steadily. The structures of above Dex-U-AD were characterized by FTIR, (1)H NMR spectroscopy and XRD. The adhesion property of result products was evaluated by lap-shear test. The maximum adhesion strength could reach to 4.16±0.72 MPa which was significantly higher than that of fibrin glue. The photopolymerization process of Dex-U-AD/gelatin was monitored by real time infrared spectroscopy (RTIR). It took less than 5 min to complete the curing process. The cytotoxicity of Dex-U-AD/gelatin also was evaluated which indicated that Dex-U-AD/gelatin gels were nontoxic to L929 cell. The relationship between all the above-mentioned properties and degree of oxidization of Dex-U-AD was assessed. The obtained products have the potential to serve as tissue adhesive in the future. Copyright © 2012 Elsevier Ltd. All rights reserved.

MAGIC-f Gel in Nuclear Medicine Dosimetry: study in an external beam of Iodine-131

NASA Astrophysics Data System (ADS)

Schwarcke, M.; Marques, T.; Garrido, C.; Nicolucci, P.; Baffa, O.

2010-11-01

MAGIC-f gel applicability in Nuclear Medicine dosimetry was investigated by exposure to a 131I source. Calibration was made to provide known absorbed doses in different positions around the source. The absorbed dose in gel was compared with a Monte Carlo Simulation using PENELOPE code and a thermoluminescent dosimetry (TLD). Using MRI analysis for the gel a R2-dose sensitivity of 0.23 s-1Gy-1was obtained. The agreement between dose-distance curves obtained with Monte Carlo simulation and TLD was better than 97% and for MAGIC-f and TLD was better than 98%. The results show the potential of polymer gel for application in nuclear medicine where three dimensional dose distribution is demanded.

Indocyanine-green-loaded microballoons for biliary imaging in cholecystectomy

NASA Astrophysics Data System (ADS)

Mitra, Kinshuk; Melvin, James; Chang, Shufang; Park, Kyoungjin; Yilmaz, Alper; Melvin, Scott; Xu, Ronald X.

2012-11-01

We encapsulate indocyanine green (ICG) in poly[(D,L-lactide-co-glycolide)-co-PEG] diblock (PLGA-PEG) microballoons for real-time fluorescence and hyperspectral imaging of biliary anatomy. ICG-loaded microballoons show superior fluorescence characteristics and slower degradation in comparison with pure ICG. The use of ICG-loaded microballoons in biliary imaging is demonstrated in both biliary-simulating phantoms and an ex vivo tissue model. The biliary-simulating phantoms are prepared by embedding ICG-loaded microballoons in agar gel and imaged by a fluorescence imaging module in a Da Vinci surgical robot. The ex vivo model consists of liver, gallbladder, common bile duct, and part of the duodenum freshly dissected from a domestic swine. After ICG-loaded microballoons are injected into the gallbladder, the biliary structure is imaged by both hyperspectral and fluorescence imaging modalities. Advanced spectral analysis and image processing algorithms are developed to classify the tissue types and identify the biliary anatomy. While fluorescence imaging provides dynamic information of movement and flow in the surgical region of interest, data from hyperspectral imaging allow for rapid identification of the bile duct and safe exclusion of any contaminant fluorescence from tissue not part of the biliary anatomy. Our experiments demonstrate the technical feasibility of using ICG-loaded microballoons for biliary imaging in cholecystectomy.

Multiscale Computer Simulation of Tensile and Compressive Strain in Polymer- Coated Silica Aerogels

NASA Technical Reports Server (NTRS)

Good, Brian

2009-01-01

While the low thermal conductivities of silica aerogels have made them of interest to the aerospace community as lightweight thermal insulation, the application of conformal polymer coatings to these gels increases their strength significantly, making them potentially useful as structural materials as well. In this work we perform multiscale computer simulations to investigate the tensile and compressive strain behavior of silica and polymer-coated silica aerogels. Aerogels are made up of clusters of interconnected particles of amorphous silica of less than bulk density. We simulate gel nanostructure using a Diffusion Limited Cluster Aggregation (DLCA) procedure, which produces aggregates that exhibit fractal dimensions similar to those observed in real aerogels. We have previously found that model gels obtained via DLCA exhibited stress-strain curves characteristic of the experimentally observed brittle failure. However, the strain energetics near the expected point of failure were not consistent with such failure. This shortcoming may be due to the fact that the DLCA process produces model gels that are lacking in closed-loop substructures, compared with real gels. Our model gels therefore contain an excess of dangling strands, which tend to unravel under tensile strain, producing non-brittle failure. To address this problem, we have incorporated a modification to the DLCA algorithm that specifically produces closed loops in the model gels. We obtain the strain energetics of interparticle connections via atomistic molecular statics, and abstract the collective energy of the atomic bonds into a Morse potential scaled to describe gel particle interactions. Polymer coatings are similarly described. We apply repeated small uniaxial strains to DLCA clusters, and allow relaxation of the center eighty percent of the cluster between strains. The simulations produce energetics and stress-strain curves for looped and nonlooped clusters, for a variety of densities and interaction parameters.

Tretinoin Photostability

PubMed Central

Rosso, James Del; Harper, Julie; Pillai, Radhakrishnan; Moore, Robert

2013-01-01

Background: Various formulations of tretinoin have been reported to be unstable after exposure to artificial light or sunlight. The observation that tretinoin is photolabile in the presence of light led to the recommendation that tretinoin be applied in the evening in order to avoid photodegradation, which could potentially reduce efficacy. More recently, the development of innovative vehicle formulations has led, in some cases, to a marked decrease in the photodegradation of tretinoin. Objective: To compare the photostability of a micronized aqueous-based formulation of tretinoin gel 0.05% with tretinoin gel 0.025% following exposure to fluorescent and simulated solar light conditions in vitro. Methods: Micronized tretinoin gel 0.05% and tretinoin gel 0.025% were exposed to fluorescent light over eight hours or simulated solar light up to 600mJ/cm2 (equivalent to 30 minimal erythemal dose). Product samples were prepared and analyzed for tretinoin concentration using high-performance liquid chromatography. Additional duplicate samples were similarly prepared and analyzed after 2, 4, 6, and 8 hours. Results: There was an 11-percent degradation of tretinoin 0.05% formulated as the micronized gel compared to an 86-percent degradation of tretinoin 0.025% formulated as the conventional gel following eight hours of exposure to fluorescent light in vitro. The degradation of tretinoin 0.025% in the conventional gel was greater than 83 percent within two hours. In the second light exposure study, in vitro exposure to simulated solar light provided a gradual dose-response effect with tretinoin 0.05% formulated as the micronized tretinoin gel. The photodegradation of tretinoin 0.025% in the conventional gel was more immediate and of substantial magnitude (>85%) after exposures at all minimal erythemal dose levels. Conclusion: Tretinoin 0.05% formulated as a micronized gel 0.05% showed minimal degradation when exposed to fluorescent light over eight hours. This same formulation exhibited a clear dose-response degradation pattern when exposed to simulated solar light. In contrast, tretinoin 0.025% formulated in a conventional gel exhibited marked photodegradation within the first two hours when exposed to both light conditions in vitro. This information adds to the body of evidence that supports the observation that certain vehicle formulations may reduce the potential for photodegradation of tretinoin. PMID:23441237

Ultraflexible organic amplifier with biocompatible gel electrodes

PubMed Central

Sekitani, Tsuyoshi; Yokota, Tomoyuki; Kuribara, Kazunori; Kaltenbrunner, Martin; Fukushima, Takanori; Inoue, Yusuke; Sekino, Masaki; Isoyama, Takashi; Abe, Yusuke; Onodera, Hiroshi; Someya, Takao

2016-01-01

In vivo electronic monitoring systems are promising technology to obtain biosignals with high spatiotemporal resolution and sensitivity. Here we demonstrate the fabrication of a biocompatible highly conductive gel composite comprising multi-walled carbon nanotube-dispersed sheet with an aqueous hydrogel. This gel composite exhibits admittance of 100 mS cm−2 and maintains high admittance even in a low-frequency range. On implantation into a living hypodermal tissue for 4 weeks, it showed a small foreign-body reaction compared with widely used metal electrodes. Capitalizing on the multi-functional gel composite, we fabricated an ultrathin and mechanically flexible organic active matrix amplifier on a 1.2-μm-thick polyethylene-naphthalate film to amplify (amplification factor: ∼200) weak biosignals. The composite was integrated to the amplifier to realize a direct lead epicardial electrocardiography that is easily spread over an uneven heart tissue. PMID:27125910

Elastic deformation and failure in protein filament bundles: Atomistic simulations and coarse-grained modeling.

PubMed

Hammond, Nathan A; Kamm, Roger D

2008-07-01

The synthetic peptide RAD16-II has shown promise in tissue engineering and drug delivery. It has been studied as a vehicle for cell delivery and controlled release of IGF-1 to repair infarcted cardiac tissue, and as a scaffold to promote capillary formation for an in vitro model of angiogenesis. The structure of RAD16-II is hierarchical, with monomers forming long beta-sheets that pair together to form filaments; filaments form bundles approximately 30-60 nm in diameter; branching networks of filament bundles form macroscopic gels. We investigate the mechanics of shearing between the two beta-sheets constituting one filament, and between cohered filaments of RAD16-II. This shear loading is found in filament bundle bending or in tensile loading of fibers composed of partial-length filaments. Molecular dynamics simulations show that time to failure is a stochastic function of applied shear stress, and that for a given loading time behavior is elastic for sufficiently small shear loads. We propose a coarse-grained model based on Langevin dynamics that matches molecular dynamics results and facilities extending simulations in space and time. The model treats a filament as an elastic string of particles, each having potential energy that is a periodic function of its position relative to the neighboring filament. With insight from these simulations, we discuss strategies for strengthening RAD16-II and similar materials.

Functional properties of protein from frozen mantle and fin of jumbo squid Dosidicus gigas in function of pH and ionic strength.

PubMed

Rocha-Estrada, J G; Córdova-Murueta, J H; García-Carreño, F L

2010-10-01

Functional properties of protein from mantle and fin of the jumbo squid Dosidicus gigas were explained based on microscopic muscle fiber and protein fractions profiles as observed in SDS-PAGE. Fin has higher content of connective tissue and complex fiber arrangement, and we observed higher hardness of fin gels as expected. Myosin heavy chain (MHC) was found in sarcoplasmic, myofibril and soluble-in-alkali fractions of mantle and only in sarcoplasmic and soluble-in-alkali fractions of fin. An additive effect of salt concentration and pH affected the solubility and foaming properties. Fin and mantle proteins yielded similar results in solubility tests, but significant differences occurred for specific pH and concentrations of salt. Foaming capacity was proportional to solubility; foam stability was also affected by pH and salt concentration. Hardness and fracture strength of fin gels were significantly higher than mantle gels; gels from proteins of both tissues reached the highest level in the folding test. Structural and molecular properties, such as MHC and paramyosin solubility, arrangement of muscle fibers and the content of connective tissue were useful to explain the differences observed in these protein properties. High-strength gels can be formed from squid mantle or fin muscle. Fin displayed similar or better properties than mantle in all tests.

Acoustic transients in pulsed holmium laser ablation: effects of pulse duration

NASA Astrophysics Data System (ADS)

Asshauer, Thomas; Delacretaz, Guy P.; Jansen, E. Duco; Welch, Ashley J.; Frenz, Martin

1995-01-01

The goal of this work was to study the influence of pulse duration on acoustic transient generation in holmium laser ablation. For this, the generation and collapse of cavitation bubbles induced by Q-switched and free-running laser pulses delivered under water were investigated. Polyacrylamide gel of 84% water content served as a model for soft tissue. This gel is a more realistic tissue phantom than water because it mimics not only the optical properties but also the mechanical properties of tissue. The dynamics of bubble formation inside the clear gel were observed by 1 ns time resolved flash videography. A polyvinylidenefluoride (PVDF) needle probe transducer measured absolute values of pressure amplitudes. Pressure wave generation by cavitation bubble collapse was observed in all phantoms used. Maximum pressures of more than 180 bars at 1 mm from the collapse center were observed in water and high water-contents gels with a pulse energy of 200 mJ and a 400 micrometers fiber. A strong dependency of the bubble collapse pressure on the pulse duration for constant pulse energy was observed in gel as well as in water. For pulse durations longer than 400 microsecond(s) a 90% reduction of pressure amplitudes relative to 100 microsecond(s) pulses was found. This suggests that optimization of pulse duration offers a degree of freedom allowing us to minimize the risk of acoustical damage in medical applications like arthroscopy and angioplasty.

A functionalizable reverse thermal gel based on a polyurethane/PEG block copolymer

PubMed Central

Park, Daewon; Wu, Wei; Wang, Yadong

2010-01-01

Injectable reverse thermal gels have great potentials as biomaterials for tissue engineering and drug delivery. However, most existing gels lack functional groups that can be modified with biomolecules that can guide cell/material interactions. We created an amine-functionalized ABA block copolymer, poly(ethylene glycol)-poly(serinol hexamethylene urethane), or ESHU. This reverse thermal gel consists of a hydrophobic block (B): poly(serinol hexamethylene urethane) and a hydrophilic block (A): poly(ethylene glycol). The polymer was characterized by GPC, FTIR and 1H FTNMR. Rheological study demonstrated that ESHU solution in phosphate-buffered saline initiated phase transition at 32°C and reached maximum elastic modulus at 37°C. The in vitro degradation tests performed in PBS and cholesterol esterase solutions revealed that the polymer was hydrolyzable and the presence of cholesterol esterase greatly accelerated the hydrolysis. The in vitro cytotoxicity tests carried out using baboon smooth muscle cells demonstrated that ESHU had good cytocompatibility with cell viability indistinguishable from tissue culture treated polystyrene. Subcutaneous implantation in rats revealed well tolerated accurate inflammatory response with moderate ED-1 positive macrophages in the early stages, which largely resolved 4 weeks post-implantation. We functionalized ESHU with a hexapeptide, Ile-Lys-Val-Ala-Val-Ser (IKVAVS), which gelled rapidly at body temperature. We expect this new platform of functionalizable reverse thermal gels to provide versatile biomaterials in tissue engineering and regenerative medicine. PMID:20937526

Comparison between Monte Carlo simulation and measurement with a 3D polymer gel dosimeter for dose distributions in biological samples

NASA Astrophysics Data System (ADS)

Furuta, T.; Maeyama, T.; Ishikawa, K. L.; Fukunishi, N.; Fukasaku, K.; Takagi, S.; Noda, S.; Himeno, R.; Hayashi, S.

2015-08-01

In this research, we used a 135 MeV/nucleon carbon-ion beam to irradiate a biological sample composed of fresh chicken meat and bones, which was placed in front of a PAGAT gel dosimeter, and compared the measured and simulated transverse-relaxation-rate (R2) distributions in the gel dosimeter. We experimentally measured the three-dimensional R2 distribution, which records the dose induced by particles penetrating the sample, by using magnetic resonance imaging. The obtained R2 distribution reflected the heterogeneity of the biological sample. We also conducted Monte Carlo simulations using the PHITS code by reconstructing the elemental composition of the biological sample from its computed tomography images while taking into account the dependence of the gel response on the linear energy transfer. The simulation reproduced the experimental distal edge structure of the R2 distribution with an accuracy under about 2 mm, which is approximately the same as the voxel size currently used in treatment planning.

Comparison between Monte Carlo simulation and measurement with a 3D polymer gel dosimeter for dose distributions in biological samples.

PubMed

Furuta, T; Maeyama, T; Ishikawa, K L; Fukunishi, N; Fukasaku, K; Takagi, S; Noda, S; Himeno, R; Hayashi, S

2015-08-21

In this research, we used a 135 MeV/nucleon carbon-ion beam to irradiate a biological sample composed of fresh chicken meat and bones, which was placed in front of a PAGAT gel dosimeter, and compared the measured and simulated transverse-relaxation-rate (R2) distributions in the gel dosimeter. We experimentally measured the three-dimensional R2 distribution, which records the dose induced by particles penetrating the sample, by using magnetic resonance imaging. The obtained R2 distribution reflected the heterogeneity of the biological sample. We also conducted Monte Carlo simulations using the PHITS code by reconstructing the elemental composition of the biological sample from its computed tomography images while taking into account the dependence of the gel response on the linear energy transfer. The simulation reproduced the experimental distal edge structure of the R2 distribution with an accuracy under about 2 mm, which is approximately the same as the voxel size currently used in treatment planning.

Development of a new mini-invasive tumour hyperthermia probe using high-temperature water vapour.

PubMed

Yu, Tian-Hua; Zhou, Yi-Xin; Liu, Jing

2004-01-01

A new mini-invasive hyperthermia probe using high-temperature water vapour for deep regional tumour treatment was developed in this paper. The vacuum insulation mechanism was incorporated into the probe to avoid heating damage to the normal tissues around the edge of the insertion path. To better understand the heat transfer behaviour in living tissues due to operation of the probe, theoretical models based on the Pennes' equation were established and two closed form analytical solutions under constant flux or temperature heating at the tip of probe were obtained. Parametric studies were performed to investigate the influence of various parameters on the temperature response of tissues heated by the probe. Further, several simulating experiments on the actual heating performance of the probe fabricated in this paper were conducted on the in vitro biological materials (fresh pork) and phantom gel. It was demonstrated that the probe can cause a high enough temperature over the treatment area to thermally destroy the tumour tissue in due time, while the temperature over the surrounding healthy tissues can be kept below a safe threshold value. This mini-invasive heating probe may have significant applications in future clinical tumour hyperthermia.

Photocurable surgical tissue adhesive glues composed of photoreactive gelatin and poly(ethylene glycol) diacrylate.

PubMed

Nakayama, Y; Matsuda, T

1999-01-01

This article presents a novel photochemically driven surgical tissue adhesive technology using photoreactive gelatins and a water-soluble difunctional macromer (poly(ethylene glycol) diacrylate: PEGDA).The gelatins were partially derivatized with photoreactive groups, such as ultraviolet light (UV)-reactive benzophenone and visible light-reactive xanthene dye (e.g., fluorescein sodium salt, eosin Y, and rose bengal). A series of the prepared photocurable tissue adhesive glues, consisting of the photoreactive gelatin, PEGDA, and a saline solution with or without ascorbic acid as a reducing agent, were viscous solutions under warming, and their effectiveness was evaluated as hemostasis- and anastomosis-aid in cardiovascular surgery. Regardless of the type of photoreactive groups, the irradiation of the photocurable tissue adhesive glues by UV or visible light within 1 min produced water-swollen gels, which had a high adhesive strength to wet collagen film. These were due to the synergistic action of photoreactive group-initiated photo-cross-linking and photograft polymerization. An increase in the irradiation time resulted in increased gel yield and reduced water swellability. A decrease in the molecular weight of PEGDA and an increase in concentration of both gelatin and PEGDA resulted in reduced water swellability and increased tensile and burst strengths of the resultant gels. In rats whose livers were injured with a trephine in laparotomy, the bleeding spots were coated with the photocurable adhesive glue and irradiated through an optical fiber. The coated solution was immediately converted to a swollen gel. The gel was tightly adhered to the liver tissue presumably by interpenetration, and concomitantly hemostasis was completed. The anastomosis treatment with the photocurable glue in the canine abdominal or thoracic aortas incised with a knife resulted in little bleeding under pulsatile flow after declamping. Histological examination showed that the glues photocured on rat liver surfaces were gradually degraded with time in vivo with infiltration of inflammatory cells and connective tissues without necrotic sign in surrounding tissue. In addition, in the laparoscopic surgery, percutaneous delivery of the glue and its in situ photogelation on rat liver surfaces were demonstrated using a specially designed fiberscope. These results indicate that the photocurable glues developed here may serve as a biodegradable tissue adhesive glue usable in cardiovascular surgery and endoscopic surgery. Copyright 1999 John Wiley & Sons, Inc.

Development of sol-gel bioactive glass for hard tissue regeneration

NASA Astrophysics Data System (ADS)

Noor, Siti Noor Fazliah Mohd; Zain, Nurul Shazwani Mohd; Wei, Poh Yong; Azizan, Nur Syazana; Mohamad, Hasmaliza

2016-12-01

The regeneration of hard tissues requires various contributing factors such as cells, scaffolds and growth factors. Bioactive glasses are known for its properties to stimulate hard tissue regeneration. In this study, sol-gel bioactive glasses (BG) were prepared and characterized. Sol-gel BG powders having particle size less than 25 µm were incubated with cell culture medium for 4 hours at 37°C on continuous rolling, and then the medium was filtered using 0.22 µm syringe filters. Prior to use, the SGBG-conditioned media were supplemented with 10% (v/v) fetal bovine serum and 1% (v/v) antibiotic-antimycotic, and were allowed to equilibrate overnight inside a CO2 incubator. The human dental pulp stem cells (DPSC) were incubated with the BG-conditioned media and their viability and proliferation were assessed at day 1, 2, 4 and 7 using Alamar Blue and MTT assays. The results showed that BG at various powders to liquid ratio concentrations promoted DPSC growth. The BG have potential to be used for hard tissue regeneration especially in the field of regenerative dentistry.

Structure of chitosan gels mineralized by sorption

NASA Astrophysics Data System (ADS)

Modrzejewska, Z.; Skwarczyńska, A.; Douglas, T. E. L.; Biniaś, D.; Maniukiewicz, W.; Sielski, J.

2015-10-01

The paper presents the structural studies of mineralized chitosan hydrogels. Hydrogels produced by using sodium beta-glycerophosphate (Na-β-GP) as a neutralizing agent. Mineralization was performed method "post loading", which consisted in sorption to the gels structure Ca ions. In order to obtain - in the structure of gels - compounds similar to the hydroxyapatites present naturally in bone tissue, gels after sorption were modified in: pH 7 buffer and sodium hydrogen phosphate. In order to determine the structural properties of the gels, the following methods were used: infrared spectroscopy with Fourier transformation, FTIR, X-ray diffractometry, XRD, scanning electron microscopy, SEM.

Fabrication and characterization of polymer gel for MRI phantom with embedded lesion particles

NASA Astrophysics Data System (ADS)

In, Eunji; Naguib, Hani E.; Haider, Masoom

2012-04-01

Magnetic Resonance Imaging (MRI) is a medical imaging technique used in radiology to visualize the detailed internal structure and body soft tissues in complete 3D image. MRI performs best when optimal imaging parameters such as contrast, signal to noise ratio (SNR), spatial resolution and total scan time are utilized. However, due to a variety of imaging parameters that differ with the manufacturer, a calibration medium that allows the control of these parameters is necessary. Therefore, a phantom that behaves similar to human soft tissue is developed to replace a real human. Polymer gel is novel material that has great potential in the medical imaging. Since very few have focused on examining the behavior of polymer lesions, the motivation of this study is to develop a polymer gel phantom, especially for liver, with embedded lesions. Both the phantom and lesions should be capable of reflecting T1 and T2 relaxation values through various characterization processes. In this paper, phantom and lesion particles were fabricated with carrageenan as a gelling agent by physical aggregation. Agar was used as supplementary gelling agent and T2 modifier and Gd-DTPA as T1 modifier. The polymer gel samples were fabricated by varying the concentrations of the gelling agent, and T1 and T2 modifiers. The lesion particles were obtained by extracting molten polymer gel solution in chilled oil bath to obtain spherical shape. The polymer gel properties including density, elastic modulus, dielectric constant and optical properties were measured to compare with human tissue values for long period of time.

Topical ketoprofen TDS patch versus diclofenac gel: efficacy and tolerability in benign sport related soft‐tissue injuries

PubMed Central

Esparza, Francisco; Cobián, César; Jiménez, José Fernando; García‐Cota, Juan José; Sánchez, Carlos; SETRADE, Antonio Maestro and the working group for the acute pain study of

2007-01-01

Objective To compare the ketoprofen TDS patch with diclofenac gel in the treatment of traumatic acute pain in benign sport‐related soft‐tissue injuries. Design 7–14 treatment days, prospective, randomised, open study. Patients Outpatients aged 18–70 years diagnosed for painful benign sport‐related soft‐tissue injury (sprains, strains and contusions within the prior 48 h), randomised to either ketoprofen patch 100 mg once daily (n = 114) or diclofenac gel 2–4 g three times daily (n = 109). Intervention 7–14 days of topical non‐steroidal anti‐inflammatory drugs treatment to assess the pain intensity changes (daily activities and spontaneous at rest) in a daily diary (100‐mm Visual Analogue Scale (VAS)). Main outcome measurement Pain intensity (VAS). Results The ketoprofen patch was not inferior to diclofenac gel in reducing the baseline pain during daily activities (difference of –1.17 mm in favour of ketoprofen patch, 95% CI (–5.86 to 3.52), reducing to the baseline VAS 79%. Ketoprofen patch presented also a higher cure rate (64%) than diclofenac gel (46%) at day 7 (p = 0.004). Patient opinions about the treatment comfort (pharmaceutical shape, application and dosage) were also statistically higher for the ketoprofen patch (>80% of the patients rated as good or excellent the patch removal and skin adherence). Conclusion Ketoprofen patches are effective and safe pain relievers for the treatment of sports injury pain with advantages compared with diclofenac gel. PMID:17138642

Bioactive Molecules Release and Cellular Responses of Alginate-Tricalcium Phosphate Particles Hybrid Gel

PubMed Central

Bang, Sumi; Zhang, Shengmin

2017-01-01

In this article, a hybrid gel has been developed using sodium alginate (Alg) and α-tricalcium phosphate (α-TCP) particles through ionic crosslinking process for the application in bone tissue engineering. The effects of pH and composition of the gel on osteoblast cells (MC3T3) response and bioactive molecules release have been evaluated. At first, a slurry of Alg and α-TCP has been prepared using an ultrasonicator for the homogeneous distribution of α-TCP particles in the Alg network and to achieve adequate interfacial interaction between them. After that, CaCl2 solution has been added to the slurry so that ionic crosslinked gel (Alg-α-TCP) is formed. The developed hybrid gel has been physico-chemically characterized using Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and a swelling study. The SEM analysis depicted the presence of α-TCP micro-particles on the surface of the hybrid gel, while cross-section images signified that the α-TCP particles are fully embedded in the porous gel network. Different % swelling ratio at pH 4, 7 and 7.4 confirmed the pH responsiveness of the Alg-α-TCP gel. The hybrid gel having lower % α-TCP particles showed higher % swelling at pH 7.4. The hybrid gel demonstrated a faster release rate of bovine serum albumin (BSA), tetracycline (TCN) and dimethyloxalylglycine (DMOG) at pH 7.4 and for the grade having lower % α-TCP particles. The MC3T3 cells are viable inside the hybrid gel, while the rate of cell proliferation is higher at pH 7.4 compared to pH 7. The in vitro cytotoxicity analysis using thiazolyl blue tetrazolium bromide (MTT), bromodeoxyuridine (BrdU) and neutral red assays ascertained that the hybrid gel is non-toxic for MC3T3 cells. The experimental results implied that the non-toxic and biocompatible Alg-α-TCP hybrid gel could be used as scaffold in bone tissue engineering. PMID:29135939

Monitoring sinew contraction during formation of tissue-engineered fibrin-based ligament constructs.

PubMed

Paxton, Jennifer Z; Wudebwe, Uchena N G; Wang, Anqi; Woods, Daniel; Grover, Liam M

2012-08-01

The ability to study the gross morphological changes occurring during tissue formation is vital to producing tissue-engineered structures of clinically relevant dimensions in vitro. Here, we have used nondestructive methods of digital imaging and optical coherence tomography to monitor the early-stage formation and subsequent maturation of fibrin-based tissue-engineered ligament constructs. In addition, the effect of supplementation with essential promoters of collagen synthesis, ascorbic acid (AA) and proline (P), has been assessed. Contraction of the cell-seeded fibrin gel occurs unevenly within the first 5 days of culture around two fixed anchor points before forming a longitudinal ligament-like construct. AA+P supplementation accelerates gel contraction in the maturation phase of development, producing ligament-like constructs with a higher collagen content and distinct morphology to that of unsupplemented constructs. These studies highlight the importance of being able to control the methods of tissue formation and maturation in vitro to enable the production of tissue-engineered constructs with suitable replacement tissue characteristics for repair of clinical soft-tissue injuries.

Laser-Induced Focused Ultrasound for Cavitation Treatment: Toward High-Precision Invisible Sonic Scalpel.

PubMed

Lee, Taehwa; Luo, Wei; Li, Qiaochu; Demirci, Hakan; Guo, L Jay

2017-10-01

Beyond the implementation of the photoacoustic effect to photoacoustic imaging and laser ultrasonics, this study demonstrates a novel application of the photoacoustic effect for high-precision cavitation treatment of tissue using laser-induced focused ultrasound. The focused ultrasound is generated by pulsed optical excitation of an efficient photoacoustic film coated on a concave surface, and its amplitude is high enough to produce controllable microcavitation within the focal region (lateral focus <100 µm). Such microcavitation is used to cut or ablate soft tissue in a highly precise manner. This work demonstrates precise cutting of tissue-mimicking gels as well as accurate ablation of gels and animal eye tissues. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

2D-DIGE proteomic analysis of mesenchymal stem cell cultured on the elasticity-tunable hydrogels.

PubMed

Kuboki, Thasaneeya; Kantawong, Fahsai; Burchmore, Richard; Dalby, Matthew J; Kidoaki, Satoru

2012-01-01

The present study focuses on mechanotransduction in mesenchymal stem cells (MSCs) in response to matrix elasticity. By using photocurable gelatinous gels with tunable stiffness, proteomic profiles of MSCs cultured on tissue culture plastic, soft (3 kPa) and stiff (52 kPa) matrices were deciphered using 2-dimensional differential in-gel analysis (2D-DIGE). The DIGE data, tied to immunofluorescence, indicated abundance and organization changes in the cytoskeletonal proteins as well as differential regulation of important signaling-related proteins, stress-responsing proteins and also proteins involved in collagen synthesis. The major CSK proteins including actin, tubulin and vimentin of the cells cultured on the gels were remarkably changed their expressions. Significant down-regulation of α-tubulin and β-actin can be observed on gel samples in comparison to the rigid tissue culture plates. The expression abundance of vimentin appeared to be highest in the MSCs cultured on hard gels. These results suggested that the substrate stiffness significantly affects expression balances in cytoskeletal proteins of MSCs with some implications to cellular tensegrity.

Gelatin methacrylamide hydrogel with graphene nanoplatelets for neural cell-laden 3D bioprinting.

PubMed

Wei Zhu; Harris, Brent T; Zhang, Lijie Grace

2016-08-01

Nervous system is extremely complex which leads to rare regrowth of nerves once injury or disease occurs. Advanced 3D bioprinting strategy, which could simultaneously deposit biocompatible materials, cells and supporting components in a layer-by-layer manner, may be a promising solution to address neural damages. Here we presented a printable nano-bioink composed of gelatin methacrylamide (GelMA), neural stem cells, and bioactive graphene nanoplatelets to target nerve tissue regeneration in the assist of stereolithography based 3D bioprinting technique. We found the resultant GelMA hydrogel has a higher compressive modulus with an increase of GelMA concentration. The porous GelMA hydrogel can provide a biocompatible microenvironment for the survival and growth of neural stem cells. The cells encapsulated in the hydrogel presented good cell viability at the low GelMA concentration. Printed neural construct exhibited well-defined architecture and homogenous cell distribution. In addition, neural stem cells showed neuron differentiation and neurites elongation within the printed construct after two weeks of culture. These findings indicate the 3D bioprinted neural construct has great potential for neural tissue regeneration.

Characterization of UC781-Tenofovir Combination Gel Products for HIV-1 Infection Prevention in an Ex Vivo Ectocervical Model

PubMed Central

Cost, Marilyn; Dezzutti, Charlene S.; Clark, Meredith R.; Friend, David R.; Akil, Ayman

2012-01-01

HIV continues to be a problem worldwide. Topical vaginal microbicides represent one option being evaluated to stop the spread of HIV. With drug candidates that have a specific action against HIV now being studied, it is important that, when appropriate and based on the mechanism of action, the drug permeates the tissue so that it can be delivered to specific targets which reside there. Novel formulations of the nucleotide reverse transcriptase inhibitor tenofovir (TFV) and the nonnucleoside reverse transcriptase inhibitor UC781 have been developed and evaluated here. Gels with three distinct rheological properties were prepared. The three gels released both UC781 and TFV under in vitro conditions at concentrations equal to or above the reported 50% effective concentrations (EC50s). The drug concentrations in ectocervical tissues were well in excess of the reported EC50s. The gels maintain ectocervical viability and prevent infection of ectocervical explants after a HIV-1 challenge. This study successfully demonstrates the feasibility of using this novel combination of antiretroviral agents in an aqueous gel as an HIV infection preventative. PMID:22430977

Strain-enhanced stress relaxation impacts nonlinear elasticity in collagen gels

PubMed Central

Nam, Sungmin; Hu, Kenneth H.; Chaudhuri, Ovijit

2016-01-01

The extracellular matrix (ECM) is a complex assembly of structural proteins that provides physical support and biochemical signaling to cells in tissues. The mechanical properties of the ECM have been found to play a key role in regulating cell behaviors such as differentiation and malignancy. Gels formed from ECM protein biopolymers such as collagen or fibrin are commonly used for 3D cell culture models of tissue. One of the most striking features of these gels is that they exhibit nonlinear elasticity, undergoing strain stiffening. However, these gels are also viscoelastic and exhibit stress relaxation, with the resistance of the gel to a deformation relaxing over time. Recent studies have suggested that cells sense and respond to both nonlinear elasticity and viscoelasticity of ECM, yet little is known about the connection between nonlinear elasticity and viscoelasticity. Here, we report that, as strain is increased, not only do biopolymer gels stiffen but they also exhibit faster stress relaxation, reducing the timescale over which elastic energy is dissipated. This effect is not universal to all biological gels and is mediated through weak cross-links. Mechanistically, computational modeling and atomic force microscopy (AFM) indicate that strain-enhanced stress relaxation of collagen gels arises from force-dependent unbinding of weak bonds between collagen fibers. The broader effect of strain-enhanced stress relaxation is to rapidly diminish strain stiffening over time. These results reveal the interplay between nonlinear elasticity and viscoelasticity in collagen gels, and highlight the complexity of the ECM mechanics that are likely sensed through cellular mechanotransduction. PMID:27140623

Bioactivity of gel-glass powders in the CaO-SiO2 system: a comparison with ternary (CaO-P2O5-SiO2) and quaternary glasses (SiO2-CaO-P2O5-Na2O).

PubMed

Saravanapavan, Priya; Jones, Julian R; Pryce, Russell S; Hench, Larry L

2003-07-01

Bioactive glasses react chemically with body fluids in a manner that is compatible with the repair processes of the tissues. This results in the formation of an interfacial bond between the glasses and living tissue. Bioactive glasses also stimulate bone-cell proliferation. This behavior is dependent on the chemical composition as well as the surface texture of the glasses. It has been recently reported that gel-derived monolith specimens in the binary SiO2 - CaO are bioactive over a similar molar range of SiO2 content as the previously studied ternary CaO-P2O5-SiO2 system. In this report, the preparation and bioactivity of the binary gel-glass powder with 70 mol % SiO2 is discussed and its bioactivity is compared with the melt-derived 45S5 (quaternary) Bioglass and sol-gel-derived 58S (ternary) bioactive gel-glass compositions. Dissolution kinetic parameters K(1) and K(2) were also computed based on the silicon release for all glass powders. It was shown that the simple two-component SiO2-CaO gel-glass powder is bioactive with comparable dissolution rates as the clinically used melt-derived 45S5 Bioglass powder and extensively studied sol-gel-derived 58S gel-glass powder. Copyright 2003 Wiley Periodicals, Inc.

Injectable thermosensitive chitosan/β-glycerophosphate/collagen hydrogel maintains the plasticity of skeletal muscle satellite cells and supports their in vivo viability.

PubMed

Ding, Ke; Yang, Zhong; Zhang, Yu-Long; Xu, Jian-Zhong

2013-09-01

A cell carrier plays an important role in the maintenance, growth and engraftment of specific cells aimed for defined therapeutic uses in many tissue engineering strategies. A suitable microenvironment for the cells allows for the maximum efficacy of the hybrid device. We have prepared an injectable thermosensitive chitosan/β-glycerophosphate/collagen (C/GP/Co) gel and investigated its potential application as a support for the culture of skeletal muscle satellite cells (SMSCs). A cell viability assay was used to evaluate the in vitro cytocompatibility of the gel. Cell growth was assessed by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) and histological analysis. The influence of the C/GP/Co gel on the plasticity of SMSCs seeded at the surface of the gel was assessed by induction of the myogenic, osteogenic and adipogenic differentiation. C/GP/Co gel provided the appropriate environment for the culture of SMSCs in vitro. In addition, the C/GP/Co gel supported SMSC plasticity. In vivo testing of the SMSC-seeded gel was investigated by subcutaneous injection into the dorsum of nude mice. Cell viability was assessed both by in vivo imaging and histological examination of the explants. In conclusion, C/GP/Co hydrogel is a cytocompatible carrier for the in vivo delivery of SMSCs and supportive for SMSC plasticity. Thus, this gel has potential applications in tissue engineering and regenerative medicine. © 2013 International Federation for Cell Biology.

A cumulative shear mechanism for tissue damage initiation in shock-wave lithotripsy.

PubMed

Freund, Jonathan B; Colonius, Tim; Evan, Andrew P

2007-09-01

Evidence suggests that inertial cavitation plays an important role in the renal injury incurred during shock-wave lithotripsy. However, it is unclear how tissue damage is initiated, and significant injury typically occurs only after a sufficient dose of shock waves. Although it has been suggested that shock-induced shearing might initiate injury, estimates indicate that individual shocks do not produce sufficient shear to do so. In this paper, we hypothesize that the cumulative shear of the many shocks is damaging. This mechanism depends on whether there is sufficient time between shocks for tissue to relax to its unstrained state. We investigate the mechanism with a physics-based simulation model, wherein the basement membranes that define the tubules and vessels in the inner medulla are represented as elastic shells surrounded by viscous fluid. Material properties are estimated from in-vitro tests of renal basement membranes and documented mechanical properties of cells and extracellular gels. Estimates for the net shear deformation from a typical lithotripter shock (approximately 0.1%) are found from a separate dynamic shock simulation. The results suggest that the larger interstitial volume (approximately 40%) near the papilla tip gives the tissue there a relaxation time comparable to clinical shock delivery rates (approximately 1 Hz), thus allowing shear to accumulate. Away from the papilla tip, where the interstitial volume is smaller (approximately 20%), the model tissue relaxes completely before the next shock would be delivered. Implications of the model are that slower delivery rates and broader focal zones should both decrease injury, consistent with some recent observations.

Low-frequency dielectric spectroscopy as a tool for studying the compatibility between pharmaceutical gels and mucous tissue.

PubMed

Hägerström, Helene; Edsman, Katarina; Strømme, Maria

2003-09-01

This interdisciplinary work demonstrates how low-frequency dielectric spectroscopy, a technique that is frequently used within physics, can be used to assess the possibilities of intimate surface contact between a polymer gel and mucous tissue, which is generally considered to be the first step in the mucoadhesion process. The dielectric responses of five different gels, of freshly excised porcine nasal mucosa and of systems made by combining the two were measured. All spectra were modeled by a Randles electric circuit containing a diffusion element, a barrier resistance in parallel with a capacitance, and a high-frequency resistance. The results were used to create a measure of the compatibility between the gel and the mucus, which we have named the compatibility factor. Thus, the compatibility factor provides us with a measure of the ease with which a charged species passes the interface between a gel and the mucus layer. The compatibility factor is calculated from the high frequency (kHz region) response of the gel, of the mucosa, and of the combined system. The two highest compatibility factors in this study were obtained for gels based on crosslinked poly(acrylic acid) and chitosan, which was in agreement with the results from mucoadhesion measurements that were performed using a tensile strength method. Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association

Injectable biocompatible and biodegradable pH-responsive hollow particle gels containing poly(acrylic acid): the effect of copolymer composition on gel properties.

PubMed

Halacheva, Silvia S; Adlam, Daman J; Hendow, Eseelle K; Freemont, Tony J; Hoyland, Judith; Saunders, Brian R

2014-05-12

The potential of various pH-responsive alkyl (meth)acrylate ester- and (meth)acrylic acid-based copolymers, including poly(methyl methacrylate-co-acrylic acid) (PMMA-AA) and poly(n-butyl acrylate-co-methacrylic acid) (PBA-MAA), to form pH-sensitive biocompatible and biodegradable hollow particle gel scaffolds for use in non-load-bearing soft tissue regeneration have been explored. The optimal copolymer design criteria for preparation of these materials have been established. Physical gels which are both pH- and redox-sensitive were formed only from PMMA-AA copolymers. MMA is the optimal hydrophobic monomer, whereas the use of various COOH-containing monomers, e.g., MAA and AA, will always induce a pH-triggered physical gelation. The PMMA-AA gels were prepared at physiological pH range from concentrated dispersions of swollen, hollow, polymer-based particles cross-linked with either cystamine (CYS) or 3,3'-dithiodipropionic acid dihydrazide (DTP). A linear relationship between particle swelling ratios, gel elasticity, and ductility was observed. The PMMA-AA gels with lower AA contents feature lower swelling ratios, mechanical strengths, and ductilities. Increasing the swelling ratio (e.g., through increasing AA content) decreased the intraparticle elasticity; however, intershell contact and gel elasticity were found to increase. The mechanical properties and performance of the gels were tuneable upon varying the copolymers' compositions and the structure of the cross-linker. Compared to PMMA-AA/CYS, the PMMA-AA/DTP gels were more elastic and ductile. The biodegradability and cytotoxicity of the new hollow particle gels were tested for the first time and related to their composition, mechanical properties, and morphology. The new PMMA-AA/CYS and PMMA-AA/DTP gels have shown good biocompatibility, biodegradability, strength, and interconnected porosity and therefore have good potential as a tissue repair agent.

Magneto-acousto-electrical Measurement Based Electrical Conductivity Reconstruction for Tissues.

PubMed

Zhou, Yan; Ma, Qingyu; Guo, Gepu; Tu, Juan; Zhang, Dong

2018-05-01

Based on the interaction of ultrasonic excitation and magnetoelectrical induction, magneto-acousto-electrical (MAE) technology was demonstrated to have the capability of differentiating conductivity variations along the acoustic transmission. By applying the characteristics of the MAE voltage, a simplified algorithm of MAE measurement based conductivity reconstruction was developed. With the analyses of acoustic vibration, ultrasound propagation, Hall effect, and magnetoelectrical induction, theoretical and experimental studies of MAE measurement and conductivity reconstruction were performed. The formula of MAE voltage was derived and simplified for the transducer with strong directivity. MAE voltage was simulated for a three-layer gel phantom and the conductivity distribution was reconstructed using the modified Wiener inverse filter and Hilbert transform, which was also verified by experimental measurements. The experimental results are basically consistent with the simulations, and demonstrate that the wave packets of MAE voltage are generated at tissue interfaces with the amplitudes and vibration polarities representing the values and directions of conductivity variations. With the proposed algorithm, the amplitude and polarity of conductivity gradient can be restored and the conductivity distribution can also be reconstructed accurately. The favorable results demonstrate the feasibility of accurate conductivity reconstruction with improved spatial resolution using MAE measurement for tissues with conductivity variations, especially suitable for nondispersive tissues with abrupt conductivity changes. This study demonstrates that the MAE measurement based conductivity reconstruction algorithm can be applied as a new strategy for nondestructive real-time monitoring of conductivity variations in biomedical engineering.

3D-printed soft-tissue physical models of renal malignancies for individualized surgical simulation: a feasibility study.

PubMed

Maddox, Michael M; Feibus, Allison; Liu, James; Wang, Julie; Thomas, Raju; Silberstein, Jonathan L

2018-03-01

To construct patient-specific physical three-dimensional (3D) models of renal units with materials that approximates the properties of renal tissue to allow pre-operative and robotic training surgical simulation, 3D physical kidney models were created (3DSystems, Rock Hill, SC) using computerized tomography to segment structures of interest (parenchyma, vasculature, collection system, and tumor). Images were converted to a 3D surface mesh file for fabrication using a multi-jet 3D printer. A novel construction technique was employed to approximate normal renal tissue texture, printers selectively deposited photopolymer material forming the outer shell of the kidney, and subsequently, an agarose gel solution was injected into the inner cavity recreating the spongier renal parenchyma. We constructed seven models of renal units with suspected malignancies. Partial nephrectomy and renorrhaphy were performed on each of the replicas. Subsequently all patients successfully underwent robotic partial nephrectomy. Average tumor diameter was 4.4 cm, warm ischemia time was 25 min, RENAL nephrometry score was 7.4, and surgical margins were negative. A comparison was made between the seven cases and the Tulane Urology prospectively maintained robotic partial nephrectomy database. Patients with surgical models had larger tumors, higher nephrometry score, longer warm ischemic time, fewer positive surgical margins, shorter hospitalization, and fewer post-operative complications; however, the only significant finding was lower estimated blood loss (186 cc vs 236; p = 0.01). In this feasibility study, pre-operative resectable physical 3D models can be constructed and used as patient-specific surgical simulation tools; further study will need to demonstrate if this results in improvement of surgical outcomes and robotic simulation education.

Continuum-level modelling of cellular adhesion and matrix production in aggregates.

PubMed

Geris, Liesbet; Ashbourn, Joanna M A; Clarke, Tim

2011-05-01

Key regulators in tissue-engineering processes such as cell culture and cellular organisation are the cell-cell and cell-matrix interactions. As mathematical models are increasingly applied to investigate biological phenomena in the biomedical field, it is important, for some applications, that these models incorporate an adequate description of cell adhesion. This study describes the development of a continuum model that represents a cell-in-gel culture system used in bone-tissue engineering, namely that of a cell aggregate embedded in a hydrogel. Cell adhesion is modelled through the use of non-local (integral) terms in the partial differential equations. The simulation results demonstrate that the effects of cell-cell and cell-matrix adhesion are particularly important for the survival and growth of the cell population and the production of extracellular matrix by the cells, concurring with experimental observations in the literature.

Cation-containing lipid membranes – experiment and md simulations

DOE PAGES

Kučerka, Norbert; Dushanov, Ermuhammas; Kholmurodov, Kholmirzo T.; ...

2017-11-27

Here, using small angle neutron diffraction and molecular dynamics simulations we studied the interactions between calcium (Ca 2+) or zinc (Zn 2+) cations, and oriented gel phase dipalmitoyl-phosphatidylcholine (DPPC) bilayers. For both cations studied at ~1:7 divalent metal ion to lipid molar ratio (Me2+:DPPC), bilayer thickness increased. Simulation results helped reveal subtle differences in the effects of the two cations on gel phase membranes.

Computer Simulation of Fracture in Aerogels

NASA Technical Reports Server (NTRS)

Good, Brian S.

2006-01-01

Aerogels are of interest to the aerospace community primarily for their thermal properties, notably their low thermal conductivities. While the gels are typically fragile, recent advances in the application of conformal polymer layers to these gels has made them potentially useful as lightweight structural materials as well. In this work, we investigate the strength and fracture behavior of silica aerogels using a molecular statics-based computer simulation technique. The gels' structure is simulated via a Diffusion Limited Cluster Aggregation (DLCA) algorithm, which produces fractal structures representing experimentally observed aggregates of so-called secondary particles, themselves composed of amorphous silica primary particles an order of magnitude smaller. We have performed multi-length-scale simulations of fracture in silica aerogels, in which the interaction b e e n two secondary particles is assumed to be described by a Morse pair potential parameterized such that the potential range is much smaller than the secondary particle size. These Morse parameters are obtained by atomistic simulation of models of the experimentally-observed amorphous silica "bridges," with the fracture behavior of these bridges modeled via molecular statics using a Morse/Coulomb potential for silica. We consider the energetics of the fracture, and compare qualitative features of low-and high-density gel fracture.

Detection of ultraviolet radiation using tissue equivalent radiochromic gel materials

NASA Astrophysics Data System (ADS)

Bero, M. A.; Abukassem, I.

2009-05-01

Ferrous Xylenol-orange Gelatin gel (FXG) is known to be sensitive to ionising radiation such as γ and X-rays. The effect of ionising radiation is to produce an increase in the absorption over a wide region of the visible spectrum, which is proportional to the absorbed dose. This study demonstrates that FXG gel is sensitive to ultraviolet radiation and therefore it could functions as UV detector. Short exposure to UV radiation produces linear increase in absorption measured at 550nm, however high doses of UV cause the ion indicator colour to fad away in a manner proportional to the incident UV energy. Light absorbance increase at the rate of 1.1% per minute of irradiation was monitored. The exposure level at which the detector has linear response is comparable to the natural summer UV radiation. Evaluating the UV ability to pass through tissue equivalent gel materials shows that most of the UV gets absorbed in the first 5mm of the gel materials, which demonstrate the damaging effects of this radiation type on human skin and eyes. It was concluded that FXG gel dosimeter has the potential to offer a simple, passive ultraviolet radiation detector with sensitivity suitable to measure and visualises the natural sunlight UV exposure directly by watching the materials colour changes.

An effective placental cotyledons proteins extraction method for 2D gel electrophoresis.

PubMed

Tan, Niu J; Daim, Leona D J; Jamil, Amilia A M; Mohtarrudin, Norhafizah; Thilakavathy, Karuppiah

2017-03-01

Effective protein extraction is essential especially in producing a well-resolved proteome on 2D gels. A well-resolved placental cotyledon proteome, with good reproducibility, have allowed researchers to study the proteins underlying the physiology and pathophysiology of pregnancy. The aim of this study is to determine the best protein extraction protocol for the extraction of protein from placental cotyledons tissues for a two-dimensional gel electrophoresis (2D-GE). Based on widely used protein extraction strategies, 12 different extraction methodologies were carefully selected, which included one chemical extraction, two mechanical extraction coupled protein precipitations, and nine chemical extraction coupled protein precipitations. Extracted proteins were resolved in a one-dimensional gel electrophoresis and 2D-GE; then, it was compared with set criteria: extraction efficacy, protein resolution, reproducibility, and recovery efficiency. Our results revealed that a better profile was obtained by chemical extraction in comparison to mechanical extraction. We further compared chemical extraction coupled protein precipitation methodologies, where the DNase/lithium chloride-dense sucrose homogenization coupled dichloromethane-methanol precipitation (DNase/LiCl-DSH-D/MPE) method showed good protein extraction efficiency. This, however, was carried out with the best protein resolution and proteome reproducibility on 2D-gels. DNase/LiCl-DSH-D/MPE was efficient in the extraction of proteins from placental cotyledons tissues. In addition, this methodology could hypothetically allow the protein extraction of any tissue that contains highly abundant lipid and glycogen. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Heat transfer within hydrodissection fluids: An analysis of thermal conduction and convection using liquid and gel materials.

PubMed

Johnson, Alexander; Brace, Christopher

2015-01-01

Interventional oncology procedures such as thermal ablation are becoming widely used for many tumours in the liver, kidney and lung. Thermal ablation refers to the focal destruction of tissue by generating cytotoxic temperatures in the treatment zone. Hydrodissection - separating tissues with fluids - protects healthy tissues adjacent to the ablation treatment zone to improve procedural safety, and facilitate more aggressive power application or applicator placement. However, fluids such as normal saline and 5% dextrose in water (D5W) can migrate into the peritoneum, reducing their protective efficacy. As an alternative, a thermo-gelable poloxamer 407 (P407) solution has been recently developed to facilitate hydrodissection procedures. We hypothesise that the P407 gel material does not provide convective heat dissipation from the ablation site, and therefore may alter the heat transfer dynamics compared to liquid materials during hydrodissection-assisted thermal ablation. The purpose of this study was to investigate the heat dissipation mechanics within D5W, liquid P407 and gel P407 hydrodissection barriers. Overall it was shown that the gel P407 dissipated heat primarily through conduction, whereas the liquid P407 and D5W dissipated heat through convection. Furthermore, the rate of temperature change within the gel P407 was greater than liquid P407 and D5W. Testing to evaluate the in vivo efficacy of the fluids with different modes of heat dissipation seems warranted for further study.

Improved quality of cartilage repair by bone marrow mesenchymal stem cells for treatment of an osteochondral defect in a cynomolgus macaque model

PubMed Central

Araki, Susumu; Imai, Shinji; Ishigaki, Hirohito; Mimura, Tomohiro; Nishizawa, Kazuya; Ueba, Hiroaki; Kumagai, Kousuke; Kubo, Mitsuhiko; Mori, Kanji; Ogasawara, Kazumasa; Matsusue, Yoshitaka

2015-01-01

Background and purpose Integration of repaired cartilage with surrounding native cartilage is a major challenge for successful tissue-engineering strategies of cartilage repair. We investigated whether incorporation of mesenchymal stem cells (MSCs) into the collagen scaffold improves integration and repair of cartilage defects in a cynomolgus macaque model. Methods Cynomolgus macaque bone marrow-derived MSCs were isolated and incorporated into type-I collagen gel. Full-thickness osteochondral defects (3 mm in diameter, 5 mm in depth) were created in the patellar groove of 36 knees of 18 macaques and were either left untreated (null group, n = 12), had collagen gel alone inserted (gel group, n = 12), or had collagen gel incorporating MSCs inserted (MSC group, n = 12). After 6, 12, and 24 weeks, the cartilage integration and tissue response were evaluated macroscopically and histologically (4 null, 4 gel, and 4 MSC knees at each time point). Results The gel group showed most cartilage-rich reparative tissue covering the defect, owing to formation of excessive cartilage extruding though the insufficient subchondral bone. Despite the fact that a lower amount of new cartilage was produced, the MSC group had better-quality cartilage with regular surface, seamless integration with neighboring naïve cartilage, and reconstruction of trabecular subchondral bone. Interpretation Even with intensive investigation, MSC-based cell therapy has not yet been established in experimental cartilage repair. Our model using cynomolgus macaques had optimized conditions, and the method using MSCs is superior to other experimental settings, allowing the possibility that the procedure might be introduced to future clinical practice. PMID:25175660

Pharmacokinetic assessment of dapivirine vaginal microbicide gel in healthy, HIV-negative women.

PubMed

Nel, Annalene M; Coplan, Paul; Smythe, Shanique C; McCord, Karen; Mitchnick, Mark; Kaptur, Paulina E; Romano, Joseph

2010-11-01

To assess the pharmacokinetics of dapivirine in plasma and dapivirine concentrations in cervicovaginal fluids (CVF) and cervicovaginal tissues following vaginal administration of dapivirine microbicide gel in healthy, HIV-negative women for 10 days. A randomized, double-blind, phase I study was conducted at a single research center in South Africa. A total of 18 women used dapivirine gel (0.001%, 0.005%, or 0.02%) once daily on Days 1 and 10 and twice daily on Days 2-9. Pharmacokinetics of dapivirine were assessed in plasma on Days 1 and 10. Dapivirine concentrations were measured in CVF on Days 1 and 10 and in cervicovaginal tissues on Day 10. Safety was evaluated through laboratory tests (hematology, clinical chemistry, and urinalysis), physical examinations, and assessment of adverse events. Plasma concentrations of dapivirine increased over time with gel dose and were greater on Day 10 (C(max) 31 to 471 pg/ml) than Day 1 (C(max) 23 to 80 pg/ml). T(max) was 10-12 h on Day 1, and 9 h on Day 10. Concentrations in CVF generally increased with dose but were highly variable among participants. Mean peak values ranged from 4.6-8.3 × 10(6) pg/ml on Day 1 and from 2.3-20.7 × 10(6) pg/ml on Day 10 across dose groups. Dapivirine was detectable in all tissue biopsies on Day 10 at concentrations of 1.0-356 × 10(3) pg/mg. Dapivirine was widely distributed throughout the lower genital tract with low systemic absorption when administered in a vaginal gel formulation for 10 consecutive days. The gel was safe and well tolerated.

Development of a conjunctival tissue substitute on the basis of plastic compressed collagen.

PubMed

Drechsler, C C; Kunze, A; Kureshi, A; Grobe, G; Reichl, S; Geerling, G; Daniels, J T; Schrader, S

2017-03-01

Ocular surface disorders, such as pterygium, cicatricial pemphigoid and external disruptions, can cause severe inflammation, scarring, fornix shortening as well as ankyloblepharon. Current treatments do not resolve these conditions sufficiently. The aim of this study was to evaluate clinical applicability and suitability of plastic compressed collagen to serve as a substrate for the expansion of human conjunctival epithelial cells in order to develop an epithelialized conjunctival substitute for fornix reconstruction. Human conjunctival epithelial cells were expanded on plastic compressed collagen gels. Epithelial cell characteristics were evaluated by haematoxylin and eosin staining, electron microscopy and cytokeratin expression. The expression of putative epithelial progenitor cell markers p63α, ABCG2 and CK15 was assessed by immunostaining. The proliferative capacity and clonal growth of the cells was evaluated before (P0) and after expansion (P1) on the plastic compressed collagen gels by colony forming efficiency assay. The potential clinical applicability of this gel substitutes was evaluated by assessment of their biomechanical properties as well as their surgical handling. Human conjunctival epithelial cells cultured on plastic and plastic compressed collagen gels formed a confluent cell layer and expressed CK19. The cells showed expression of the putative epithelial progenitor cell markers p63α, ABCG2 and CK15 and sustained colony forming ability. The compressed collagen gels showed a high ultimate tensile strength and elasticity and the surgical handling of gels was comparable to amniotic membrane. An epithelialized conjunctival tissue construct on the basis of compressed collagen might therefore be a promising alternative bioartificial tissue substitute for conjunctival reconstruction. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

MAGIC polymer gel for dosimetric verification in boron neutron capture therapy

PubMed Central

Heikkinen, Sami; Kotiluoto, Petri; Serén, Tom; Seppälä, Tiina; Auterinen, Iiro; Savolainen, Sauli

2007-01-01

Radiation‐sensitive polymer gels are among the most promising three‐dimensional dose verification tools developed to date. We tested the normoxic polymer gel dosimeter known by the acronym MAGIC (methacrylic and ascorbic acid in gelatin initiated by copper) to evaluate its use in boron neutron capture therapy (BNCT) dosimetry. We irradiated a large cylindrical gel phantom (diameter: 10 cm; length: 20 cm) in the epithermal neutron beam of the Finnish BNCT facility at the FiR 1 nuclear reactor. Neutron irradiation was simulated with a Monte Carlo radiation transport code MCNP. To compare dose–response, gel samples from the same production batch were also irradiated with 6 MV photons from a medical linear accelerator. Irradiated gel phantoms then underwent magnetic resonance imaging to determine their R2 relaxation rate maps. The measured and normalized dose distribution in the epithermal neutron beam was compared with the dose distribution calculated by computer simulation. The results support the feasibility of using MAGIC gel in BNCT dosimetry. PACS numbers: 87.53.Qc, 87.53.Wz, 87.66.Ff PMID:17592463

Shear wave propagation in anisotropic soft tissues and gels

PubMed Central

Namani, Ravi; Bayly, Philip V.

2013-01-01

The propagation of shear waves in soft tissue can be visualized by magnetic resonance elastography (MRE) [1] to characterize tissue mechanical properties. Dynamic deformation of brain tissue arising from shear wave propagation may underlie the pathology of blast-induced traumatic brain injury. White matter in the brain, like other biological materials, exhibits a transversely isotropic structure, due to the arrangement of parallel fibers. Appropriate mathematical models and well-characterized experimental systems are needed to understand wave propagation in these structures. In this paper we review the theory behind waves in anisotropic, soft materials, including small-amplitude waves superimposed on finite deformation of a nonlinear hyperelastic material. Some predictions of this theory are confirmed in experimental studies of a soft material with controlled anisotropy: magnetically-aligned fibrin gel. PMID:19963987

Effect of Young's modulus on bubble formation and pressure waves during pulsed holmium ablation of tissue phantoms

NASA Astrophysics Data System (ADS)

Jansen, E. Duco; Asshauer, Thomas; Frenz, Martin; Delacretaz, Guy P.; Motamedi, Massoud; Welch, Ashley J.

1995-05-01

Mechanical injury during pulsed laser ablation of tissue is caused by rapid bubble expansions and collapse or by laser-induced pressure waves. In this study the effect of material elasticity on the ablation process has been investigated. Polyacrylamide tissue phantoms with various water concentrations (75-95%) were made. The Young's moduli of the gels were determined by measuring the stress-strain relationship. An optical fiber (200 or 400 micrometers ) was translated into the clear gel and one pulse of holmium:YAG laser radiation was given. The laser was operated in either the Q-switched mode (tau) p equals 500 ns, Qp equals 14 +/- 1 mJ, 200 micrometers fiber, Ho equals 446 mJ/mm2) or the free-running mode ((tau) p equals 100 microsecond(s) , Qp equals 200 +/- 5 mJ, 400 micrometers fiber, Ho equals 1592 mJ/mm2). Bubble formation inside the gels was recorded using a fast flash photography setup while simultaneously recording pressures with a PVDP needle hydrophone (40 ns risetime) positioned in the gel, approximately 2 mm away from the fibertip. A thermo-elastic expansion wave was measured only during Q-switched pulse delivery. The amplitude of this wave (approximately equals 40 bar at 1 mm from the fiber) did not vary significantly in any of the phantoms investigated. Rapid bubble formation and collapse was observed inside the clear gels. Upon bubble collapse, a pressure transient was emitted; the amplitude of this transient depended strongly on bubble size and geometry. It was found that (1) the bubble was almost spherical for the Q-switched pulse and became more elongated for the free-running pulse, and (2) the maximum bubble size and thus the collapse amplitude decreased with an increase in Young's modulus (from 68 +/- 11 bar at 1 mm in 95% water gel to 25 +/- 10 bar at 1 mm in 75% water gel).

Fibrin-based tissue engineering: comparison of different methods of autologous fibrinogen isolation.

PubMed

Dietrich, Maren; Heselhaus, Johanna; Wozniak, Justyna; Weinandy, Stefan; Mela, Petra; Tschoeke, Beate; Schmitz-Rode, Thomas; Jockenhoevel, Stefan

2013-03-01

This study is focussed on the optimal method of autologous fibrinogen isolation with regard to the yield and the use as a scaffold material. This is particularly relevant for pediatric patients with strictly limited volumes of blood. The following isolation methods were evaluated: cryoprecipitation, ethanol (EtOH) precipitation, ammonium sulfate [(NH(4))(2)SO(4))] precipitation, ammonium sulfate precipitation combined with cryoprecipitation, and polyethylene glycol precipitation combined with cryoprecipitation. Fibrinogen yields were quantified spectrophotometrically and by electrophoretic analyses. To test the influence of the different isolation methods on the microstructure of the fibrin gels, scanning electron microscopy (SEM) was used and the mechanical strength of the cell-free and cell-seeded fibrin gels was tested by burst strength measurements. Cytotoxicity assays were performed to analyze the effect of various fibrinogen isolation methods on proliferation, apoptosis, and necrosis. Tissue development and cell migration were analyzed in all samples using immunohistochemical techniques. The synthesis of collagen as an extracellular matrix component by human umbilical cord artery smooth muscle cells in fibrin gels was measured using hydroxyproline assay. Compared to cryoprecipitation, all other considered methods were superior in quantitative analyses, with maximum fibrinogen yields of ∼80% of total plasma fibrinogen concentration using ethanol precipitation. SEM imaging demonstrated minor differences in the gel microstructure. Ethanol-precipitated fibrin gels exhibited the best mechanical properties. None of the isolation methods had a cytotoxic effect on the cells. Collagen production was similar in all gels except those from ammonium sulfate precipitation. Histological analysis showed good cell compatibility for ethanol-precipitated gels. The results of the present study demonstrated that ethanol precipitation is a simple and effective method for isolation of fibrinogen and a suitable alternative to cryoprecipitation. This technique allows minimization of the necessary blood volume for fibrinogen isolation, particularly important for pediatric applications, and also has no negative influence on microstructure, mechanical properties, cell proliferation, or tissue development.

Dosimetry of gamma chamber blood irradiator using PAGAT gel dosimeter and Monte Carlo simulations

PubMed Central

Mohammadyari, Parvin; Zehtabian, Mehdi; Sina, Sedigheh; Tavasoli, Ali Reza

2014-01-01

Currently, the use of blood irradiation for inactivating pathogenic microbes in infected blood products and preventing graft‐versus‐host disease (GVHD) in immune suppressed patients is greater than ever before. In these systems, dose distribution and uniformity are two important concepts that should be checked. In this study, dosimetry of the gamma chamber blood irradiator model Gammacell 3000 Elan was performed by several dosimeter methods including thermoluminescence dosimeters (TLD), PAGAT gel dosimetry, and Monte Carlo simulations using MCNP4C code. The gel dosimeter was put inside a glass phantom and the TL dosimeters were placed on its surface, and the phantom was then irradiated for 5 min and 27 sec. The dose values at each point inside the vials were obtained from the magnetic resonance imaging of the phantom. For Monte Carlo simulations, all components of the irradiator were simulated and the dose values in a fine cubical lattice were calculated using tally F6. This study shows that PAGAT gel dosimetry results are in close agreement with the results of TL dosimetry, Monte Carlo simulations, and the results given by the vendor, and the percentage difference between the different methods is less than 4% at different points inside the phantom. According to the results obtained in this study, PAGAT gel dosimetry is a reliable method for dosimetry of the blood irradiator. The major advantage of this kind of dosimetry is that it is capable of 3D dose calculation. PACS number: 87.53.Bn PMID:24423829

Improvement of the light-tissue coupling for better outcome of phototherapies

NASA Astrophysics Data System (ADS)

da Silva, Dilleys Ferreira; Vollet Filho, José Dirceu; Fortunato, Thereza Cury; Moriyama, Lilian Tan; Grecco, Clovis; Pratavieira, Sebastião.; Kurachi, Cristina; Bagnato, Vanderlei Salvador

2018-02-01

Phototherapies have been increasingly used in several applications such as the control of pain and inflammatory processes, photodynamic therapy, and even aesthetics uses. After many decades, the dosimetry for those techniques remains challenging. One of the key issues is the lack of homogeneity obtained for tissue illumination, which may limit adequate treatment. Especially concerning lesions, the surface tissue is usually irregular, and the light does not couple to the tissue efficiently to promote an effective treatment. A series of experiments have been performed using optical phantoms, in which coupling was improved by introducing a gel with a low concentration of scattering agents between the fiber and the phantom as an attempt to improve the homogeneity of light distribution within the phantoms. The effects promoted by roughness on phantom tissue surfaces are considerably attenuated when the coupling gel was introduced, resulting in a more uniform illumination pattern that may be used to promote better phototherapy treatments outcome.

A simple protocol for protein extraction of recalcitrant fruit tissues suitable for 2-DE and MS analysis.

PubMed

Song, Jun; Braun, Gordon; Bevis, Eric; Doncaster, Kristen

2006-08-01

Fruit tissues are considered recalcitrant plant tissue for proteomic analysis. Three phenol-free protein extraction procedures for 2-DE were compared and evaluated on apple fruit proteins. Incorporation of hot SDS buffer, extraction with TCA/acetone precipitation was found to be the most effective protocol. The results from SDS-PAGE and 2-DE analysis showed high quality proteins. More than 500 apple polypeptides were separated on a small scale 2-DE gel. The successful protocol was further tested on banana fruit, in which 504 and 386 proteins were detected in peel and flesh tissues, respectively. To demonstrate the quality of the extracted proteins, several protein spots from apple and banana peels were cut from 2-DE gels, analyzed by MS and have been tentatively identified. The protocol described in this study is a simple procedure which could be routinely used in proteomic studies of many types of recalcitrant fruit tissues.

Water-Hydrogel Binding Affinity Modulates Freeze-Drying-Induced Micropore Architecture and Skeletal Myotube Formation.

PubMed

Rich, Max H; Lee, Min Kyung; Marshall, Nicholas; Clay, Nicholas; Chen, Jinrong; Mahmassani, Ziad; Boppart, Marni; Kong, Hyunjoon

2015-08-10

Freeze-dried hydrogels are increasingly used to create 3D interconnected micropores that facilitate biomolecular and cellular transports. However, freeze-drying is often plagued by variance in micropore architecture based on polymer choice. We hypothesized that water-polymer binding affinity plays a significant role in sizes and numbers of micropores formed through freeze-drying, influencing cell-derived tissue quality. Poly(ethylene glycol)diacrylate (PEGDA) hydrogels with alginate methacrylate (AM) were used due to AM's higher binding affinity for water than PEGDA. PEGDA-AM hydrogels with larger AM concentrations resulted in larger sizes and numbers of micropores than pure PEGDA hydrogels, attributed to the increased mass of water binding to the PEGDA-AM gel. Skeletal myoblasts loaded in microporous PEGDA-AM hydrogels were active to produce 3D muscle-like tissue, while those loaded in pure PEGDA gels were localized on the gel surface. We propose that this study will be broadly useful in designing and improving the performance of various microporous gels.

Kinetics and mechanism of release from glyceryl monostearate-based implants: evaluation of release in a gel simulating in vivo implantation.

PubMed

Allababidi, S; Shah, J C

1998-06-01

The overall objective of the study was to design an implantable delivery system based on glyceryl monostearate (GMS) for the site-specific delivery of antibiotics for the prevention of surgical wound infection. To design the implant, a release method had to be developed that simulate the in vivo implantation conditions to be able to predict the release characteristics from the implants when they are actually used in vivo. Also, identifying the release kinetics and mechanism and evaluating the factors that influence the release of drugs from the GMS-based matrix were necessary to allow further design of implants that could yield a desired release rate. The release of cefazolin was monitored from GMS matrixes implanted into agar gel, simulating subcutaneous tissues with respect to viscosity and water content. The gel method resulted in observation of spatial and temporal concentration profiles in the immediate vicinity of the implants, indicating the benefits of local drug delivery; however, there was no significant difference between the cumulative release profiles by the gel method or the vial release method. The release of cefazolin from the GMS-based matrix with the vial method followed Higuchi's square root of time kinetics. The release rate was found to be directly proportional to cefazolin load (A) and the surface area (SA) of the matrix as expressed by the following equation: = 0.24ASA. On the basis of this equation, one can design a variety of GMS matrixes that would result in a desired release rate or release duration. This also indicated that cefazolin release followed the release kinetics of a freely soluble drug from an insoluble matrix and hence it is a diffusion-controlled process. The effect of drug solubility on the release kinetics was determined by comparing the release kinetics of the poorly water soluble ciprofloxacin (0.16 mg/mL) to that of the highly water soluble cefazolin (325 mg/mL). The release duration of ciprofloxacin (80 h) was longer than that of cefazolin (25 h) from identical GMS matrixes. Although ciprofloxacin release was initially controlled by the matrix, agitation accelerated disintegration of the matrix and release due to its poor solubility, and ciprofloxacin release appeared to be a dissolution-controlled process following zero-order release kinetics.

Improved properties of bone and cartilage tissue from 3D inkjet-bioprinted human mesenchymal stem cells by simultaneous deposition and photocrosslinking in PEG-GelMA.

PubMed

Gao, Guifang; Schilling, Arndt F; Hubbell, Karen; Yonezawa, Tomo; Truong, Danh; Hong, Yi; Dai, Guohao; Cui, Xiaofeng

2015-11-01

Bioprinting of bone and cartilage suffers from low mechanical properties. Here we have developed a unique inkjet bioprinting approach of creating mechanically strong bone and cartilage tissue constructs using poly(ethylene glycol) dimethacrylate, gelatin methacrylate, and human MSCs. The printed hMSCs were evenly distributed in the polymerized PEG-GelMA scaffold during layer-by-layer assembly. The procedure showed a good biocompatibility with >80% of the cells surviving the printing process and the resulting constructs provided strong mechanical support to the embedded cells. The printed mesenchymal stem cells showed an excellent osteogenic and chondrogenic differentiation capacity. Both osteogenic and chondrogenic differentiation as determined by specific gene and protein expression analysis (RUNX2, SP7, DLX5, ALPL, Col1A1, IBSP, BGLAP, SPP1, Col10A1, MMP13, SOX9, Col2A1, ACAN) was improved by PEG-GelMA in comparison to PEG alone. These observations were consistent with the histological evaluation. Inkjet bioprinted-hMSCs in simultaneously photocrosslinked PEG-GelMA hydrogel scaffolds demonstrated an improvement of mechanical properties and osteogenic and chondrogenic differentiation, suggesting its promising potential for usage in bone and cartilage tissue engineering.

Polyelectrolyte gels as bending actuators: modeling and numerical simulation

NASA Astrophysics Data System (ADS)

Wallmersperger, Thomas; Keller, Karsten; Attaran, Abdolhamid

2013-04-01

Polyelectrolyte gels are ionic electroactivematerials. They have the ability to react as both, sensors and actuators. As actuators they can be used e.g. as artificial muscles or drug delivery control; as sensors they may be used for measuring e.g. pressure, pH or other ion concentrations in the solution. In this research both, anionic and cationic polyelectrolyte gels placed in aqueous solution with mobile anions and cations are investigated. Due to external stimuli the polyelectrolyte gels can swell or shrink enormously by the uptake or delivery of solvent. In the present research a coupled multi-field problem within a continuum mechanics framework is proposed. The modeling approach introduces a set of equations governing multiple fields of the problem, including the chemical field of the ionic species, the electrical field and the mechanical field. The numerical simulation is performed by using the Finite Element Method. Within the study some test cases will be carried out to validate our model. In the works by Gülch et al., the application of combined anionic-cationic gels as grippers was shown. In the present research for an applied electric field, the change of the concentrations and the electric potential in the complete polymer is simulated by the given formulation. These changes lead to variations in the osmotic pressure resulting in a bending of different polyelectrolyte gels. In the present research it is shown that our model is capable of describing the bending behavior of anionic or cationic gels towards the different electrodes (cathode or anode).

Matrix-associated implantation of predifferentiated mesenchymal stem cells versus articular chondrocytes: in vivo results of cartilage repair after 1 year.

PubMed

Marquass, Bastian; Schulz, Ronny; Hepp, Pierre; Zscharnack, Matthias; Aigner, Thomas; Schmidt, Stefanie; Stein, Frank; Richter, Robert; Osterhoff, Georg; Aust, Gabriele; Josten, Christoph; Bader, Augustinus

2011-07-01

The use of predifferentiated mesenchymal stem cells (MSC) leads to better histological results compared with undifferentiated MSC in sheep. This raises the need for a longer term follow-up study and comparison with a clinically established method. We hypothesized that chondrogenic in vitro predifferentiation of autologous MSC embedded in a collagen I hydrogel leads to better structural repair of a chronic osteochondral defect in an ovine stifle joint after 1 year. We further hypothesized that resulting histological results would be comparable with those of chondrocyte-seeded matrix-associated autologous chondrocyte transplantation (MACT). Controlled laboratory study. Predifferentiation period of ovine MSC within collagen gel in vitro was defined by assessment of several cellular and molecular biological parameters. For the animal study, 2 osteochondral lesions (7-mm diameter) were created at the medial femoral condyles of the hind legs in 9 sheep. Implantation of MSC gels was performed 6 weeks after defect creation. Thirty-six defects were divided into 4 treatment groups: (1) chondrogenically predifferentiated MSC gels (pre-MSC gels), (2) undifferentiated MSC gels (un-MSC gels), (3) MACT gels, and (4) untreated controls (UC). Histological, immunohistochemical, and radiological evaluations followed after 12 months. After 12 months in vivo, pre-MSC gels showed significantly better histological outcome compared with un-MSC gels and UC. Compared with MACT gels, the overall scores were higher for O'Driscoll and International Cartilage Repair Society (ICRS). The repair tissue of the pre-MSC group showed immunohistochemical detection of interzonal collagen type II staining. Radiological evaluation supported superior bonding of pre-MSC gels to perilesional native cartilage. Compared with previous work by our group, no degradation of the repair tissue between 6 and 12 months in vivo, particularly in pre-MSC gels, was observed. Repair of chronic osteochondral defects with collagen hydrogels composed of chondrogenically predifferentiated MSC shows no signs of degradation after 1 year in vivo. In addition, pre-MSC gels lead to partially superior histological results compared with articular chondrocytes. The results suggest an encouraging method for future treatment of focal osteochondral defects without donor site morbidity by harvesting articular chondrocytes.

Effect of Gold Nanoparticles on Prostate Dose Distribution under Ir-192 Internal and 18 MV External Radiotherapy Procedures Using Gel Dosimetry and Monte Carlo Method.

PubMed

Khosravi, H; Hashemi, B; Mahdavi, S R; Hejazi, P

2015-03-01

Gel polymers are considered as new dosimeters for determining radiotherapy dose distribution in three dimensions. The ability of a new formulation of MAGIC-f polymer gel was assessed by experimental measurement and Monte Carlo (MC) method for studying the effect of gold nanoparticles (GNPs) in prostate dose distributions under the internal Ir-192 and external 18MV radiotherapy practices. A Plexiglas phantom was made representing human pelvis. The GNP shaving 15 nm in diameter and 0.1 mM concentration were synthesized using chemical reduction method. Then, a new formulation of MAGIC-f gel was synthesized. The fabricated gel was poured in the tubes located at the prostate (with and without the GNPs) and bladder locations of the phantom. The phantom was irradiated to an Ir-192 source and 18 MV beam of a Varian linac separately based on common radiotherapy procedures used for prostate cancer. After 24 hours, the irradiated gels were read using a Siemens 1.5 Tesla MRI scanner. The absolute doses at the reference points and isodose curves resulted from the experimental measurement of the gels and MC simulations following the internal and external radiotherapy practices were compared. The mean absorbed doses measured with the gel in the presence of the GNPs in prostate were 15% and 8 % higher than the corresponding values without the GNPs under the internal and external radiation therapies, respectively. MC simulations also indicated a dose increase of 14 % and 7 % due to presence of the GNPs, for the same experimental internal and external radiotherapy practices, respectively. There was a good agreement between the dose enhancement factors (DEFs) estimated with MC simulations and experiment gel measurements due to the GNPs. The results indicated that the polymer gel dosimetry method as developed and used in this study, can be recommended as a reliable method for investigating the DEF of GNPs in internal and external radiotherapy practices.

A Multi-Compartment, Single and Multiple Dose Pharmacokinetic Study of the Vaginal Candidate Microbicide 1% Tenofovir Gel

PubMed Central

Schwartz, Jill L.; Rountree, Wes; Kashuba, Angela D. M.; Brache, Vivian; Creinin, Mitchell D.; Poindexter, Alfred; Kearney, Brian P.

2011-01-01

Background Tenofovir (TFV) gel is being evaluated as a microbicide with pericoital and daily regimens. To inhibit viral replication locally, an adequate concentration in the genital tract is critical. Methods and Findings Forty-nine participants entered a two-phase study: single-dose (SD) and multi-dose (MD), were randomized to collection of genital tract samples (endocervical cells [ECC], cervicovaginal aspirate and vaginal biopsies) at one of seven time points [0.5, 1, 2, 4, 6, 8, or 24 hr(s)] post-dose following SD exposure of 4 mL 1% TFV gel and received a single dose. Forty-seven were randomized to once (QD) or twice daily (BID) dosing for 2 weeks and to collection of genital tract samples at 4, 8 or 24 hrs after the final dose, but two discontinued prior to gel application. Blood was collected during both phases at the seven times post-dose. TFV exposure was low in blood plasma for SD and MD; median Cmax was 4.0 and 3.4 ng/mL, respectively (C≤29 ng/mL). TFV concentrations were high in aspirates and tissue after SD and MD, ranging from 1.2×104 to 9.9×106 ng/mL and 2.1×102 to 1.4×106 ng/mL, respectively, and did not noticeably differ between proximal and distal tissue. TFV diphosphate (TFV-DP), the intracellular active metabolite, was high in ECC, ranging from 7.1×103 to 8.8×106 ng/mL. TFV-DP was detectable in approximately 40% of the tissue samples, ranging from 1.8×102 to 3.5×104 ng/mL. AUC for tissue TFV-DP was two logs higher after MD compared to SD, with no noticeable differences when comparing QD and BID. Conclusions Single-dose and multiple-dose TFV gel exposure resulted in high genital tract concentrations for at least 24 hours post-dose with minimal systemic absorption. These results support further study of TFV gel for HIV prevention. Trial registration ClinicalTrials.gov NCT00561496 PMID:22039430

Doxorubicin-loaded Zein in situ gel for interstitial chemotherapy.

PubMed

Cao, Xiaoying; Geng, Jianning; Su, Suwen; Zhang, Linan; Xu, Qian; Zhang, Li; Xie, Yinghua; Wu, Shaomei; Sun, Yongjun; Gao, Zibin

2012-01-01

A novel drug delivery system of doxorubicin (DOX)-loaded Zein in situ gel for interstitial chemotherapy was investigated in this study. The possible mechanisms of drug release were described according to morphological analysis by optical microscopy and scanning electronic microscope (SEM). In vitro and in vivo anti-tumor activity studies showed that DOX-loaded Zein in situ gel was superior to DOX solution. Local pharmacokinetics in tumor tissue was studied by quantitative analysis with confocal laser scanning microscopy (CLSM) combined with microdialysis technology. A pharmacokinetics mathematical model of DOX-loaded Zein in situ gel in tumors was then built.

Use of magnetic micro-cantilevers to study the dynamics of 3D engineered smooth muscle constructs

NASA Astrophysics Data System (ADS)

Liu, Alan; Zhao, Ruogang; Copeland, Craig; Chen, Christopher; Reich, Daniel

2013-03-01

The normal and pathological response of arterial tissue to mechanical stimulus sheds important light on such conditions as atherosclerosis and hypertension. While most previous methods of determining the biomechanical properties of arteries have relied on excised tissue, we have devised a system that enables the growth and in situ application of forces to arrays of stable suspended microtissues consisting of arterial smooth muscle cells (SMCs). Briefly, this magnetic microtissue tester system consists of arrays of pairs of elastomeric magnetically actuated micro-cantilevers between which SMC-infused 3D collagen gels self-assemble and remodel into aligned microtissue constructs. These devices allow us to simultaneously apply force and track stress-strain relationships of multiple microtissues per substrate. We have studied the dilatory capacity and subsequent response of the tissues and find that the resulting stress-strain curves show viscoelastic behavior as well as a linear dynamic recovery. These results provide a foundation for elucidating the mechanical behavior of this novel model system as well as further experiments that simulate pathological conditions. Supported in part by NIH grant HL090747.

Laser-generated ultrasound for high-precision cutting of tissue-mimicking gels (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lee, Taehwa; Luo, Wei; Li, Qiaochu; Guo, L. Jay

2017-03-01

Laser-generated focused ultrasound has shown great promise in precisely treating cells and tissues by producing controlled micro-cavitation within the acoustic focal volume (<100 um). However, the previous demonstration used cells and tissues cultured on glass substrates. The glass substrates were found to be critical to cavitation, because ultrasound amplitude doubles due to the reflection from the substrate, thus allowing for reaching pressure amplitude to cavitation threshold. In other words, without the sound reflecting substrate, pressure amplitude may not be strong enough to create cavitation, thus limiting its application to only cultured biomaterials on the rigid substrates. By using laser-generated focused ultrasound without relying on sound-reflecting substrates, we demonstrate free-field cavitation in water and its application to high-precision cutting of tissue-mimicking gels. In the absence of a rigid boundary, strong pressure for cavitation was enabled by recently optimized photoacoustic lens with increased focal gain (>30 MPa, negative pressure amplitude). By moving cavitation spots along pre-defined paths through a motorized stage, tissue-mimicking gels of different elastic moduli were cut into different shapes (rectangle, triangle, and circle), leaving behind the same shape of holes, whose sizes are less than 1 mm. The cut line width is estimated to be less than 50 um (corresponding to localized cavitation region), allowing for accurate cutting. This novel approach could open new possibility for in-vivo treatment of diseased tissues in a high-precision manner (i.e., high-precision invisible sonic scalpel).

Cell-laden hydrogel/titanium microhybrids: Site-specific cell delivery to metallic implants for improved integration.

PubMed

Koenig, Geraldine; Ozcelik, Hayriye; Haesler, Lisa; Cihova, Martina; Ciftci, Sait; Dupret-Bories, Agnes; Debry, Christian; Stelzle, Martin; Lavalle, Philippe; Vrana, Nihal Engin

2016-03-01

Porous titanium implants are widely used in dental, orthopaedic and otorhinolaryngology fields to improve implant integration to host tissue. A possible step further to improve the integration with the host is the incorporation of autologous cells in porous titanium structures via cell-laden hydrogels. Fast gelling hydrogels have advantageous properties for in situ applications such as localisation of specific cells and growth factors at a target area without dispersion. The ability to control the cell types in different regions of an implant is important in applications where the target tissue (i) has structural heterogeneity (multiple cell types with a defined spatial configuration with respect to each other); (ii) has physical property gradients essential for its function (such as in the case of osteochondral tissue transition). Due to their near immediate gelation, such gels can also be used for site-specific modification of porous titanium structures, particularly for implants which would face different tissues at different locations. Herein, we describe a step by step design of a model system: the model cell-laden gel-containing porous titanium implants in the form of titanium microbead/hydrogel (maleimide-dextran or maleimide-PVA based) microhybrids. These systems enable the determination of the effect of titanium presence on gel properties and encapsulated cell behaviour as a miniaturized version of full-scale implants, providing a system compatible with conventional analysis methods. We used a fibroblast/vascular endothelial cell co-cultures as our model system and by utilising single microbeads we have quantified the effect of gel microenvironment (degradability, presence of RGD peptides within gel formulation) on cell behaviour and the effect of the titanium presence on cell behaviour and gel formation. Titanium presence slightly changed gel properties without hindering gel formation or affecting cell viability. Cells showed a preference to move towards the titanium beads and fibroblast proliferation was significantly higher in hybrids compared to gel only controls. The MMP (Matrix Metalloproteinase)-sensitive hydrogels induced sprouting by cells in co-culture configuration which was quantified by fluorescence microscopy, confocal microscopy and qRT-PCR (Quantitative Reverse transcription polymerase chain reaction). When the microhybrid up-scaled to 3D thick structures, cellular localisation in specific areas of the 3D titanium structures was achieved, without decreasing overall cell proliferation compared to titanium only scaffolds. Microhybrids of titanium and hydrogels are useful models for deciding the necessary modifications of metallic implants and they can be used as a modelling system for the study of tissue/titanium implant interactions. This article demonstrates a method to apply cell-laden hydrogels to porous titanium implants and a model of titanium/hydrogel interaction at micro-level using titanium microbeads. The feasibility of site-specific modification of titanium implants with cell-laden microgels has been demonstrated. Use of titanium microbeads in combination with hydrogels with conventional analysis techniques as described in the article can facilitate the characterisation of surface modification of titanium in a relevant model system. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A highly adhesive and naturally derived sealant.

PubMed

Assmann, Alexander; Vegh, Andrea; Ghasemi-Rad, Mohammad; Bagherifard, Sara; Cheng, George; Sani, Ehsan Shirzaei; Ruiz-Esparza, Guillermo U; Noshadi, Iman; Lassaletta, Antonio D; Gangadharan, Sidhu; Tamayol, Ali; Khademhosseini, Ali; Annabi, Nasim

2017-09-01

Conventional surgical techniques to seal and repair defects in highly stressed elastic tissues are insufficient. Therefore, this study aimed to engineer an inexpensive, highly adhesive, biocompatible, and biodegradable sealant based on a modified and naturally derived biopolymer, gelatin methacryloyl (GelMA). We tuned the degree of gelatin modification, prepolymer concentration, photoinitiator concentration, and crosslinking conditions to optimize the physical properties and adhesion of the photocrosslinked GelMA sealants. Following ASTM standard tests that target wound closure strength, shear resistance, and burst pressure, GelMA sealant was shown to exhibit adhesive properties that were superior to clinically used fibrin- and poly(ethylene glycol)-based glues. Chronic in vivo experiments in small as well as translational large animal models proved GelMA to effectively seal large lung leakages without the need for sutures or staples, presenting improved performance as compared to fibrin glue, poly(ethylene glycol) glue and sutures only. Furthermore, high biocompatibility of GelMA sealant was observed, as evidenced by a low inflammatory host response and fast in vivo degradation while allowing for adequate wound healing at the same time. Combining these results with the low costs, ease of synthesis and application of the material, GelMA sealant is envisioned to be commercialized not only as a sealant to stop air leakages, but also as a biocompatible and biodegradable hydrogel to support lung tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Soft Tissue Augmentation with Autologous Platelet Gel and β-TCP: A Histologic and Histometric Study in Mice

PubMed Central

Ceccarelli, Maurizio; Marchetti, Massimiliano; Piattelli, Adriano; Mortellaro, Carmen

2016-01-01

Background. Facial aging is a dynamic process involving both soft tissue and bony structures. Skin atrophy, with loss of tone, elasticity, and distribution of facial fat, coupled with gravity and muscle activity, leads to wrinkling and folds. Purpose. The aim of the study was to evaluate microporous tricalcium phosphate (β-TCP) and autologous platelet gel (APG) mix in mice for oral and maxillofacial soft tissue augmentation. The hypothesis was that β-TCP added with APG was able to increase the biostimulating effect on fibroblasts and quicken resorption. Materials and Methods. Ten female, 6–8-week-old black-haired mice were selected. β-TCP/APG gel was injected into one cheek; the other was used as control. The animals were sacrificed at 8 weeks and histologically evaluated. Results. The new fibroblast was intensively stained with acid fuchsin and presented in contact with β-TCP. At higher magnification, actively secreting fibroblasts were observed at the periphery of β-TCP with a well differentiated fibroblast cell line and blood vessels. Acid fuchsin stained cutaneous structures in pink: no epidermal/dermal alterations or pathological inflammatory infiltrates were detected. The margins of β-TCP granules were clear and not diffused near tissues. Conclusion. APG with β-TCP preserves skin morphology, without immune response, with an excellent tolerability and is a promising scaffold for cells and biomaterial for soft tissue augmentation. PMID:27478828

Soft Tissue Augmentation with Autologous Platelet Gel and β-TCP: A Histologic and Histometric Study in Mice.

PubMed

Scarano, Antonio; Ceccarelli, Maurizio; Marchetti, Massimiliano; Piattelli, Adriano; Mortellaro, Carmen

2016-01-01

Background. Facial aging is a dynamic process involving both soft tissue and bony structures. Skin atrophy, with loss of tone, elasticity, and distribution of facial fat, coupled with gravity and muscle activity, leads to wrinkling and folds. Purpose. The aim of the study was to evaluate microporous tricalcium phosphate (β-TCP) and autologous platelet gel (APG) mix in mice for oral and maxillofacial soft tissue augmentation. The hypothesis was that β-TCP added with APG was able to increase the biostimulating effect on fibroblasts and quicken resorption. Materials and Methods. Ten female, 6-8-week-old black-haired mice were selected. β-TCP/APG gel was injected into one cheek; the other was used as control. The animals were sacrificed at 8 weeks and histologically evaluated. Results. The new fibroblast was intensively stained with acid fuchsin and presented in contact with β-TCP. At higher magnification, actively secreting fibroblasts were observed at the periphery of β-TCP with a well differentiated fibroblast cell line and blood vessels. Acid fuchsin stained cutaneous structures in pink: no epidermal/dermal alterations or pathological inflammatory infiltrates were detected. The margins of β-TCP granules were clear and not diffused near tissues. Conclusion. APG with β-TCP preserves skin morphology, without immune response, with an excellent tolerability and is a promising scaffold for cells and biomaterial for soft tissue augmentation.

Generation of strip-format fibrin-based engineered heart tissue (EHT).

PubMed

Schaaf, Sebastian; Eder, Alexandra; Vollert, Ingra; Stöhr, Andrea; Hansen, Arne; Eschenhagen, Thomas

2014-01-01

This protocol describes a method for casting fibrin-based engineered heart tissue (EHT) in standard 24-well culture dishes. In principle, a hydrogel tissue engineering method requires cardiomyocytes, a liquid matrix that forms a gel, a casting mold, and a device that keeps the developing tissue in place. This protocol refers to neonatal rat heart cells as the cell source; the matrix of choice is fibrin, and the tissues are generated in rectangular agarose-casting molds (12 × 3 × 3 mm) prepared in standard 24-well cell culture dishes, in which a pair of flexible silicone posts is suspended from above. A master mix of freshly isolated cells, medium, fibrinogen, and thrombin is pipetted into the casting mold and, over a period of 2 h, polymerizes and forms a fibrin cell block around two silicone posts. Silicone racks holding four pairs of silicone posts each are used to transfer the fresh fibrin cell blocks into new 24-well dishes with culture medium. Without further handling, the cells start to remodel the fibrin gel, form contacts with each other, elongate, and condense the gel to approximately ¼ of the initial volume. Spontaneous and rhythmic contractions start after 1 week. EHTs are viable and relatively stable for several weeks in this format and can be subjected to repeated measurements of contractile function and final morphological and molecular analyses.

Laser-Raman microprobe identification of inclusions in capsules associated with silicone gel breast implants.

PubMed

Centeno, J A; Mullick, F G; Panos, R G; Miller, F W; Valenzuela-Espinoza, A

1999-07-01

Raman spectroscopy (the analysis of scattered photons after excitation with a monochromatic light source) provides a nondestructive method for identifying organic and inorganic materials on the basis of the molecule's characteristic spectrum of vibrational frequencies. Although the technique has been predominantly applied in sciences other than pathology, the recent advent of high-quality microscope optics coupled to optical Raman spectrometers (a variation known as a Raman microprobe) rendered this technique amenable to applications in human pathology. In the Raman microprobe, a laser beam is focused on a spot approximately 1 microm in diameter on the surface of the sample, e.g., tissue, and the scattered light is collected and analyzed. In this investigation, we used the Raman microprobe for the identification of foreign materials in breast implant capsular tissues. The characteristic silicone group frequencies associated with the silicon-oxygen stretch, the silicone-carbon stretch, the silicon-methyl and the methyl carbon-hydrogen stretch frequencies were used to identify polydimethylsiloxane and to define chemical differences among the various other implant-related inclusions. All of the inclusions were positively identified in a series of 44 capsules from silicone gel-filled implants: polydimethylsiloxane was found in 44 of 44 capsules surrounding silicone gel-filled implants; polyurethane was seen in 4 of 4 capsules around polyurethane foam-coated gel-filled implants; 4 of 4 capsules enveloping Dacron patch gel-filled implants revealed Dacron; and talc was identified in 8 of these 44 capsules. Raman microspectroscopy provides a rapid, accurate, and sensitive method for identifying inclusions associated with silicone and other implant materials in tissue.

Effects of cross-linked high-molecular-weight hyaluronic acid on epidural fibrosis: experimental study.

PubMed

Isık, Semra; Taşkapılıoğlu, M Özgür; Atalay, Fatma Oz; Dogan, Seref

2015-01-01

Epidural fibrosis is nonphysiological scar formation, usually at the site of neurosurgical access into the spinal canal, in the intimate vicinity of and around the origin of the radicular sheath. The formation of dense fibrous tissue causes lumbar and radicular pain. In addition to radicular symptoms, the formation of scar tissue may cause problems during reoperation. The authors aimed to investigate the effects of cross-linked high-molecular-weight hyaluronic acid (HA), an HA derivative known as HA gel, on the prevention of epidural fibrosis by using histopathological and biochemical parameters. Fifty-six adult female Sprague-Dawley rats were evaluated. The rats were divided into 4 groups. Rats in the sham group (n = 14) underwent laminectomy and discectomy and received no treatment; rats in the control group (n = 14) underwent laminectomy and discectomy and received 0.9% NaCl treatment in the surgical area; rats in the HA group (n = 14) received HA treatment at the surgical area after laminectomy and discectomy; and rats in the HA gel group (n = 14) underwent laminectomy and discectomy in addition to receiving treatment with cross-linked high-molecular-weight HA in the surgical area. All rats were decapitated after 4 weeks, and the specimens were evaluated histopathologically and biochemically. The results were statistically compared using the Mann-Whitney U-test. Compared with the sham and control groups, the HA and HA gel groups showed significantly lower fibroblast cell density and tissue hydroxyproline concentrations (p < 0.05). There was statistically significant lower dural adhesion and foreign-body reaction between the control and HA gel groups (p < 0.05). Granulation tissue and epidural fibrosis were significantly lower in the HA and HA gel groups compared with the sham group (p < 0.05). There were no significant differences in any histopathological parameters or biochemical values between Groups 3 and 4 (p > 0.05). Cross-linked high-molecular-weight HA had positive effects on the prevention of epidural fibrosis and the reduction of fibrotic tissue density. The efficacy of this agent should also be verified in further experimental and clinical studies.

Injectable barriers for waste isolation

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

Persoff, P.; Finsterle, S.; Moridis, G.J.

In this paper the authors report laboratory work and numerical simulation done in support of development and demonstration of injectable barriers formed from either of two fluids: colloidal silica or polysiloxane. Two principal problems addressed here are control of gel time and control of plume emplacement in the vadose zone. Gel time must be controlled so that the viscosity of the barrier fluid remains low long enough to inject the barrier, but increases soon enough to gel the barrier in place. During injection, the viscosity must be low enough to avoid high injection pressures which could uplift or fracture themore » formation. To test the grout gel time in the soil, the injection pressure was monitored as grouts were injected into sandpacks. When grout is injected into the vadose zone, it slumps under the influence of gravity, and redistributes due to capillary forces as it gels. The authors have developed a new module for the reservoir simulator TOUGH2 to model grout injection into the vadose zone, taking into account the increase of liquid viscosity as a function of gel concentration and time. They have also developed a model to calculate soil properties after complete solidification of the grout. The numerical model has been used to design and analyze laboratory experiments and field pilot tests. The authors present the results of computer simulations of grout injection, redistribution, and solidification.« less

Mesenchymal Stromal Cells form Vascular Tubes when Placed in Fibrin Sealant and Accelerate Wound Healing in Vivo

PubMed Central

Mendez, Julio J.; Ghaedi, Mahboobe; Sivarapatna, Amogh; Dimitrievska, Sashka; Shao, Zhen; Osuji, Chinedum; Steinbacher, Derek M.; Leffell, David J.; Niklason, Laura E.

2014-01-01

Non-healing, chronic wounds are a growing public health problem and may stem from insufficient angiogenesis in affected sites. Here, we have developed a fibrin formulation that allows adipose-derived mesenchymal stromal cells (ADSCs) to form tubular structures in vitro. The tubular structures express markers of endothelium, including CD31 and VE-Cadherin, as well as the pericyte marker NG2. The ability for the MSCs to form tubular structures within the fibrin gels was directly dependent on the stoichiometric ratios of thrombin and fibrinogen and the resulting gel concentration, as well as on the presence of bFGF. Fibrin gel formulations that varied in stiffness were tested. ADSCs that are embedded in a stiff fibrin formulation express VE-cadherin and CD31 as shown by PCR, FACS and immunostaining. Confocal imaging analysis demonstrated that tubular structures formed, containing visible lumens, in the stiff fibrin gels in vitro. There was also a difference in the amounts of bFGF secreted by ADSCs grown in the stiffer gels as compared to softer gels. Additionally, hAT-MSCs gave rise to perfusable vessels that were VE-cadherin positive after subcutaneous injection into mice, whereas the softer fibrin formulation containing ADSCs did not. The application of ADSCs delivered in the stiff fibrin gels allowed for the wounds to heal more quickly, as assessed by wound size, amount of granulation tissue and collagen content. Interestingly, following 5 days of healing, the ADSCs remained within the fibrin gel and did not integrate into the granulation tissue of healing wounds in vivo. These data show that ADSCs are able to form tubular structures within fibrin gels, and may also contribute to faster wound healing, as compared with no treatment or to wounds treated with fibrin gels devoid of ADSCs. PMID:25433608

Rifampicin exacerbates isoniazid-induced toxicity in human but not in rat hepatocytes in tissue-like cultures

PubMed Central

Shen, C; Meng, Q; Zhang, G; Hu, W

2007-01-01

Background and purpose: Rifampicin has been extensively reported to exacerbate the hepatotoxicity of isoniazid in patients with tuberculosis. However, this was controversially claimed by previous reports using rat models. This study evaluated the effect of rifampicin on isoniazid-induced hepatocyte toxicity by using human and rat hepatocytes in tissue-like culture. Experimental approach: Hepatocytes in tissue-like gel entrapment were used to examine isoniazid toxicity, as shown by cell viability, intracellular glutathione content and albumin secretion. For demonstration of the differential effects of rifampicin on human and rat hepatocytes, induction by rifampicin of cytochrome P450 (CYP) 2E1, a major enzyme associated with isoniazid hepatotoxicity, was detected by 4-nitrocatechol formation and RT-PCR analysis. Key results: Rifampicin (12 μM) enhanced isoniazid-induced toxicity in human hepatocytes but not in rat hepatocytes. Enhanced CYP 2E1 enzymic activity and mRNA expression were similarly detected in human hepatocytes but not in rat hepatocytes. Both rat and human hepatocytes in gel entrapment were more sensitive to isoniazid treatment compared with the corresponding hepatocytes in a monolayer culture. Conclusions and implications: The difference in induction of CYP 2E1 by rifampicin between rat and human hepatocytes accounted for the difference in exacerbation of isoniazid hepatocyte toxicity by rifampicin, with more significant toxicity in gel entrapment than in monolayer cultures. Thus, human hepatocytes in tissue-like cultures (gel entrapment) could be an effective model for hepatotoxicity research in vitro, closer to the in vivo situation. PMID:18071298

Two-Step Self-Assembly of Liposome-Multidomain Peptide Nanofiber Hydrogel for Time-Controlled Release

PubMed Central

2015-01-01

Progress in self-assembly and supramolecular chemistry has been directed toward obtaining macromolecular assemblies with higher degrees of complexity, simulating the highly structured environment in natural systems. One approach to this type of complexity are multistep, multicomponent, self-assembling systems that allow approaches comparable to traditional multistep synthetic organic chemistry; however, only a few examples of this approach have appeared in the literature. Our previous work demonstrated nanofibrous mimics of the extracellular matrix. Here we demonstrate the ability to create a unique hydrogel, developed by stepwise self-assembly of multidomain peptide fibers and liposomes. The two-component system allows for controlled release of bioactive factors at multiple time points. The individual components of the self-assembled gel and the composite hydrogel were characterized by TEM, SEM, and rheometry, demonstrating that peptide nanofibers and lipid vesicles both retain their structural integrity in the composite gel. The rheological robustness of the hydrogel is shown to be largely unaffected by the presence of liposomes. Release studies from the composite gels loaded with different growth factors EGF, MCP-1, and PlGF-1 showed delay and prolongation of release by liposomes entrapped in the hydrogel compared to more rapid release from the hydrogel alone. This bimodal release system may have utility in systems where timed cascades of biological signals may be valuable, such as in tissue regeneration. PMID:25308335

Avidin self-associates with boric acid gel suspensions: an affinity boron carrier that might be developed for boron neutron-capture therapy.

PubMed

Bench, Bennie J; Johnson, Rebecca; Hamilton, Craig; Gooch, Joey; Wright, John R

2004-02-15

It has been shown in preliminary studies that the antibacterial protein avidin self-associates with the boric acid gel polymer, and avidin-coated gel particles in the micrometer and submicrometer size ranges are of interest for boron neutron-capture therapy (BNCT), which is neutron-induced fission of boron-10 to produce intense alpha radiation for tumor destruction. The gel particles carry large amounts of boron-10 and are theoretically able effect a meaningful tissue dosing through BNCT. A gross precipitation of gel particles occurs within 46 min of mixing when the avidin/colloid ratio is about 0.34 g avidin/g colloid. This is a minimum time if gel and avidin concentrations are in the low microgram/milliliter range, but at higher proportions of avidin the time delay to precipitation increases significantly; i.e., the colloid surface becomes blocked, inhibiting lattice formation. The avidin-coated gel particles eventually cross-link, forming a solid matrix and precipitating on a timescale measured on the order of an hour. At shorter exposure times rapid agglutination-like reactions were observed with biotinylated bovine albumin, suggesting that two-stage pretargeting of specific tissues should be possible with biotinylated antitumor antibodies. However, for BNCT to be practical, avidin's interaction with the gel needs to be strengthened, and all aryl-B(OH)(2) groups on the particle surfaces must be blocked, or else the particles will interact strongly and nonspecifically with each other and with the carbohydrate groups present on most cell surfaces. Glyceric acid delays the precipitation of the particle suspensions while most simple and complex carbohydrates accelerate it.

Durable protection from vaginal simian-human immunodeficiency virus infection in macaques by tenofovir gel and its relationship to drug levels in tissue.

PubMed

Dobard, Charles; Sharma, Sunita; Martin, Amy; Pau, Chou-Pong; Holder, Angela; Kuklenyik, Zsuzsanna; Lipscomb, Jonathan; Hanson, Debra L; Smith, James; Novembre, Francis J; García-Lerma, J Gerardo; Heneine, Walid

2012-01-01

A vaginal gel containing 1% tenofovir (TFV) was found to be safe and effective in reducing HIV infection in women when used pericoitally. Because of the long intracellular half-life of TFV and high drug exposure in vaginal tissues, we hypothesized that a vaginal gel containing TFV may provide long-lasting protection. Here, we performed delayed-challenge experiments and showed that vaginal 1% TFV gel protected 4/6 macaques against vaginal simian-human immunodeficiency virus (SHIV) exposures occurring 3 days after gel application, demonstrating long-lasting protection. Despite continued gel dosing postinfection, neither breakthrough infection had evidence of drug resistance by ultrasensitive testing of SHIV in plasma and vaginal lavage. Analysis of the active intracellular tenofovir diphosphate (TFV-DP) in vaginal lymphocytes collected 4 h to 3 days after gel dosing persistently showed high TFV-DP levels (median, 1,810 fmol/10(6) cells) between 4 and 24 h that exceed the 95% inhibitory concentration (IC(95)), reflecting rapid accumulation and long persistence. In contrast to those in peripheral blood mononuclear cells (PBMCs) following oral dosing, TFV-DP levels in vaginal lymphocytes decreased approximately 7-fold by 3 days, exhibiting a much higher rate of decay. We observed a strong correlation between intracellular TFV-DP in vaginal lymphocytes, in vitro antiviral activity, and in vivo protection, suggesting that TFV-DP above the in vitro IC(95) in vaginal lymphocytes is a good predictor of high efficacy. Data from this model reveal an extended window of protection by TFV gel that supports coitus-independent use. The identification of protective TFV-DP concentrations in vaginal lymphocytes may facilitate the evaluation of improved delivery methods of topical TFV and inform clinical studies.

Structural evolution of Colloidal Gels under Flow

NASA Astrophysics Data System (ADS)

Boromand, Arman; Maia, Joao; Jamali, Safa

Colloidal suspensions are ubiquitous in different industrial applications ranging from cosmetic and food industries to soft robotics and aerospace. Owing to the fact that mechanical properties of colloidal gels are controlled by its microstructure and network topology, we trace the particles in the networks formed under different attraction potentials and try to find a universal behavior in yielding of colloidal gels. Many authors have implemented different simulation techniques such as molecular dynamics (MD) and Brownian dynamics (BD) to capture better picture during phase separation and yielding mechanism in colloidal system with short-ranged attractive force. However, BD neglects multi-body hydrodynamic interactions (HI) which are believed to be responsible for the second yielding of colloidal gels. We envision using dissipative particle dynamics (DPD) with modified depletion potential and hydrodynamic interactions, as a coarse-grain model, can provide a robust simulation package to address the gel formation process and yielding in short ranged-attractive colloidal systems. The behavior of colloidal gels with different attraction potentials under flow is examined and structural fingerprints of yielding in these systems will be discussed.

The selectivity of protein-imprinted gels and its relation to protein properties: A computer simulation study.

PubMed

Yankelov, Rami; Yungerman, Irena; Srebnik, Simcha

2017-07-01

Polymer-based protein recognition systems have enormous potential within clinical and diagnostic fields due to their reusability, biocompatibility, ease of manufacturing, and potential specificity. Imprinted polymer matrices have been extensively studied and applied as a simple technique for creating artificial polymer-based recognition gels for a target molecule. Although this technique has been proven effective when targeting small molecules (such as drugs), imprinting of proteins have so far resulted in materials with limited selectivity due to the large molecular size of the protein and aqueous environment. Using coarse-grained molecular simulation, we investigate the relation between protein makeup, polymer properties, and the selectivity of imprinted gels. Nonspecific binding that results in poor selectivity is shown to be strongly dependent on surface chemistry of the template and competitor proteins as well as on polymer chemistry. Residence time distributions of proteins diffusing within the gels provide a transparent picture of the relation between polymer constitution, protein properties, and the nonspecific interactions with the imprinted gel. The pronounced effect of protein surface chemistry on imprinted gel specificity is demonstrated. Copyright © 2017 John Wiley & Sons, Ltd.

Development and testing of an optoacoustic imaging system for monitoring and guiding prostate cancer therapies

NASA Astrophysics Data System (ADS)

Spirou, Gloria M.; Vitkin, I. Alex; Wilson, B. C.; Whelan, William M.; Henrichs, Paul M.; Mehta, Ketan; Miller, Tom; Yee, Andrew; Meador, James; Oraevsky, Alexander A.

2004-07-01

Laser Optoacoustic Imaging System (LOIS) combines high tissue contrast based on the optical properties of tissue and high spatial resolution based on ultrawide-band ultrasonic detection. Patients undergoing thermal or photodynamic therapy of prostate cancer may benefit from capability of LOIS to detect and monitor treatment-induced changes in tissue optical properties and blood flow. The performance of a prototype LOIS was evaluated via 2D optoacoustic images of dye-colored objects of various shapes, small tubes with blood simulating veins and arteries, and thermally coagulated portions of chicken breasts imbedded tissue-mimicking gelatin phantoms. The optoacoustic image contrast was proportional to the ratio of the absorption coefficient between the embedded objects and the surrounding gel. The contrast of the venous blood relative to the background exceeded 250%, and the contrast of the thermally coagulated portions of flesh relative to the untreated tissue ranged between -100% to +200%, dependent on the optical wavelength. We used a 32-element optoacoustic transducer array and a novel design of low-noise preamplifiers and wide-band amplifiers to perform these studies. The system was optimized for imaging at a depth of ~50 mm. The system spatial resolution was better than 1-mm. The advantages and limitations of various signal-processing methods were investigated. LOIS demonstrates clinical potential for non- or minimally-invasive monitoring of treatment-induced tissue changes.

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

NASA Astrophysics Data System (ADS)

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

2013-03-01

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

Image guided constitutive modeling of the silicone brain phantom

NASA Astrophysics Data System (ADS)

Puzrin, Alexander; Skrinjar, Oskar; Ozan, Cem; Kim, Sihyun; Mukundan, Srinivasan

2005-04-01

The goal of this work is to develop reliable constitutive models of the mechanical behavior of the in-vivo human brain tissue for applications in neurosurgery. We propose to define the mechanical properties of the brain tissue in-vivo, by taking the global MR or CT images of a brain response to ventriculostomy - the relief of the elevated intracranial pressure. 3D image analysis translates these images into displacement fields, which by using inverse analysis allow for the constitutive models of the brain tissue to be developed. We term this approach Image Guided Constitutive Modeling (IGCM). The presented paper demonstrates performance of the IGCM in the controlled environment: on the silicone brain phantoms closely simulating the in-vivo brain geometry, mechanical properties and boundary conditions. The phantom of the left hemisphere of human brain was cast using silicon gel. An inflatable rubber membrane was placed inside the phantom to model the lateral ventricle. The experiments were carried out in a specially designed setup in a CT scanner with submillimeter isotropic voxels. The non-communicative hydrocephalus and ventriculostomy were simulated by consequently inflating and deflating the internal rubber membrane. The obtained images were analyzed to derive displacement fields, meshed, and incorporated into ABAQUS. The subsequent Inverse Finite Element Analysis (based on Levenberg-Marquardt algorithm) allowed for optimization of the parameters of the Mooney-Rivlin non-linear elastic model for the phantom material. The calculated mechanical properties were consistent with those obtained from the element tests, providing justification for the future application of the IGCM to in-vivo brain tissue.

Designing injectable beta-hairpin peptide hydrogels for cartilage tissue engineering application

NASA Astrophysics Data System (ADS)

Sinthuvanich, Chomdao

In this work, it was demonstrated that peptide-based gels having different electrostatic network character but similar mechanical properties can be designed by modulating the primary sequence of the peptides used for self-assembly. As a result, HLT2 and HET1 peptides, having formal charge states of +5 per monomer, were designed using MAX8, a peptide with a charge state of +7 per monomer, as a template. Using gels prepared from all three peptides (MAX8, HLT2, and HET1), it was shown that the electropositive character of the network influences chondrocyte behavior. Specifically, the less electropositive gel (HLT2) is able to maintain chondrocyte viability and phenotype. In contrast, chondrocytes encapsulated in the more positively charged gel (MAX8) are more prone to dedifferentiation, resulting in tissue constructs with inferior mechanical properties. Gels prepared from peptides having the same net charge but differing only in their primary sequences (HLT2 and HET1) were also shown to influence cell behavior, but only during the early period of culturing. If constructs derived from these two different peptide gels are allowed to culture for extended times, their mechanical properties become similar. This suggests that the amino acid composition and sequence of the peptides used to make the gels also influences cell behavior, but perhaps not to the extent that network electrostatics plays. Supplementation of bioactive factors in the culturing media, as opposed to being encapsulated directly in the network, was shown to adversely affect the cellular response resulting in tissue constructs where extracellular matrix (ECM) components are non-uniformly distributed. When bioactive factors were encapsulated and co-delivered with cells, positive results were observed, particularly when cells were co-encapsulated with the growth factor, TGF-β1. The effect of TGF-β1 on cellular response and the mechanical properties of the tissue-engineered constructs is largely governed by the ability of the growth factor to be retained within the hydrogels and made available to the cells, which in turn, dictate the quality of the engineered tissue. Rational peptide design was also employed to generate negatively charged peptides capable of folding and self-assembling under physiological conditions to afford electronegative gel. Initial designs resulted in peptides that undergo gelation in response to a change in environmental pH and temperature. Modification of these initially designed peptides led to the design of VE3 and VEQ1, two negatively charged peptides that can be used to directly encapsulate chondrocytes providing gel-cell constructs with homogeneous cellular distribution. Finally, the positively charged peptide gel (HET1) and negatively charged peptide gel (VE3) were compared to investigate the influence of vastly different network electrostatics on the response of encapsulated primary chondrocytes. In these gels, a majority of cells were able to retain their chondrocyte phenotype within the scaffold regardless of which gel was used for encapsulation and delivery. However, the positively charge hydrogel is better at supporting cell proliferation and ECM accumulation. On the other hand, the cells encapsulated in the negatively charged hydrogel were less proliferative and the negatively charged hydrogel had a limited ability to retain ECM produced by the cells. In contrast, when culturing in the presence of TGF-β1, constructs derived from the negatively charged gel showed greater compressive moduli than those derived from the positively charged hydrogel. This difference is largely due to the amount of TGF-β1 made available to the encapsulated cells as a function of time, which was found to be governed by the electrostatic character of the hydrogel network. This work indicates that network electrostatics influence the response of encapsulated chondrocytes, retention of secreted ECM, and the diffusion of bioactive factors necessary for the generation of engineered cartilage. During the course of these studies, I have a serendipitous discovery that a derivative of one of the material forming β-hairpin peptides displays anticancer activity. Chapter 8 describes this peptide, SVS-1, and its mechanism of action. (Abstract shortened by UMI.).

Effects of a Pseudophysiological Environment on the Elastic and Viscoelastic Properties of Collagen Gels

PubMed Central

Meghezi, Sébastien; Couet, Frédéric; Chevallier, Pascale; Mantovani, Diego

2012-01-01

Vascular tissue engineering focuses on the replacement of diseased small-diameter blood vessels with a diameter less than 6 mm for which adequate substitutes still do not exist. One approach to vascular tissue engineering is to culture vascular cells on a scaffold in a bioreactor. The bioreactor establishes pseudophysiological conditions for culture (medium culture, 37°C, mechanical stimulation). Collagen gels are widely used as scaffolds for tissue regeneration due to their biological properties; however, they exhibit low mechanical properties. Mechanical characterization of these scaffolds requires establishing the conditions of testing in regard to the conditions set in the bioreactor. The effects of different parameters used during mechanical testing on the collagen gels were evaluated in terms of mechanical and viscoelastic properties. Thus, a factorial experiment was adopted, and three relevant factors were considered: temperature (23°C or 37°C), hydration (aqueous saline solution or air), and mechanical preconditioning (with or without). Statistical analyses showed significant effects of these factors on the mechanical properties which were assessed by tensile tests as well as stress relaxation tests. The last tests provide a more consistent understanding of the gels' viscoelastic properties. Therefore, performing mechanical analyses on hydrogels requires setting an adequate environment in terms of temperature and aqueous saline solution as well as choosing the adequate test. PMID:22844285

The mechanism of plasma-assisted penetration of NO2- in model tissues

NASA Astrophysics Data System (ADS)

He, Tongtong; Liu, Dingxin; Liu, Zhijie; Liu, Zhichao; Li, Qiaosong; Rong, Mingzhe; Kong, Michael G.

2017-11-01

Cold atmospheric plasmas are reportedly capable of enhancing the percutaneous absorption of drugs, which is a development direction of plasma medicine. This motivated us to study how the enhancement effect was realized. In this letter, gelatin gel films were used as surrogates of human tissues, NaNO2 was used as a representative of small-molecule drugs, and cross-field and linear-field plasma jets were used for the purpose of enhancing the penetration of NaNO2 through the gelatin gel films. The permeability of gelatin gel films was quantified by measuring the NO2- concentration in water which was covered by those films. It was found that the gas flow and electric field of cold plasmas played a crucial role in the permeability enhancement of the model tissues, but the effect of gas flow was mainly confined in the surface layer, while the effect of the electric field was holistic. Those effects might be attributed to the localized squeezing of particles by gas flow and the weakening of the ion-dipole interaction by the AC electric field. The enhancement effect decreases with the increasing mass fraction of gelatin because the macromolecules of gelatin could significantly hinder the penetration of small molecules in the model tissues.

Bioprinted Osteogenic and Vasculogenic Patterns for Engineering 3D Bone Tissue.

PubMed

Byambaa, Batzaya; Annabi, Nasim; Yue, Kan; Trujillo-de Santiago, Grissel; Alvarez, Mario Moisés; Jia, Weitao; Kazemzadeh-Narbat, Mehdi; Shin, Su Ryon; Tamayol, Ali; Khademhosseini, Ali

2017-08-01

Fabricating 3D large-scale bone tissue constructs with functional vasculature has been a particular challenge in engineering tissues suitable for repairing large bone defects. To address this challenge, an extrusion-based direct-writing bioprinting strategy is utilized to fabricate microstructured bone-like tissue constructs containing a perfusable vascular lumen. The bioprinted constructs are used as biomimetic in vitro matrices to co-culture human umbilical vein endothelial cells and bone marrow derived human mesenchymal stem cells in a naturally derived hydrogel. To form the perfusable blood vessel inside the bioprinted construct, a central cylinder with 5% gelatin methacryloyl (GelMA) hydrogel at low methacryloyl substitution (GelMA LOW ) was printed. We also develop cell-laden cylinder elements made of GelMA hydrogel loaded with silicate nanoplatelets to induce osteogenesis, and synthesized hydrogel formulations with chemically conjugated vascular endothelial growth factor to promote vascular spreading. It was found that the engineered construct is able to support cell survival and proliferation during maturation in vitro. Additionally, the whole construct demonstrates high structural stability during the in vitro culture for 21 days. This method enables the local control of physical and chemical microniches and the establishment of gradients in the bioprinted constructs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Injectable thermosensitive chitosan/glycerophosphate-based hydrogels for tissue engineering and drug delivery applications: a review.

PubMed

Tahrir, Farzaneh G; Ganji, Fariba; Ahooyi, Taha M

2015-01-01

Recently, great attention has been paid to in situ gel-forming chitosan/glycerophosphate (CS/Gp) formulation due to its high biocompatibility with incorporated cells and medical agents, biodegradability and sharp thermosensitive gelation. CS/Gp is in liquid state at room temperature and after minimally invasive administration into the desired tissue, it forms a solid-like gel as a response to temperature increase. The overview of various recently patented strategies on injectable delivery systems indicates the significance of this formulation in biomedical applications. This thermosensitive hydrogel has a great potential as scaffold material in tissue engineering, due to its good biocompatibility, minimal immune reaction, high antibacterial nature, good adhesion to cells and the ability to be molded in various geometries. Moreover, CS/Gp hydrogel has been utilized as a smart drug delivery system to increase patient compliance by maintaining the drug level in the therapeutic window for a long time while avoiding the need for frequent injections of the therapeutic agent. This review paper highlights the recent patents and investigations on different formulations of CS/Gp hydrogels as tissue engineering scaffolds and carriers for therapeutic agents. Additionally, the dominant mechanism of sol-gel transition in those systems as well as their physicochemical properties and biocompatibility are discussed in detail.

Bioprinting 3D cell-laden hydrogel microarray for screening human periodontal ligament stem cell response to extracellular matrix.

PubMed

Ma, Yufei; Ji, Yuan; Huang, Guoyou; Ling, Kai; Zhang, Xiaohui; Xu, Feng

2015-12-22

Periodontitis is an inflammatory disease negatively affecting up to 15% of adults worldwide. Periodontal ligament stem cells (PDLSCs) hold great promises for periodontal tissue regeneration, where it is necessary to find proper extracellular matrix (ECM) materials (e.g., composition, concentration). In this study, we proposed a bioprinting-based approach to generate nano-liter sized three-dimensional (3D) cell-laden hydrogel array with gradient of ECM components, through controlling the volume ratio of two hydrogels, such as gelatin methacrylate (GelMA) and poly(ethylene glycol) (PEG) dimethacrylate. The resulting cell-laden array with a gradient of GelMA/PEG composition was used to screen human PDLSC response to ECM. The behavior (e.g., cell viability, spreading) of human PDLSCs in GelMA/PEG array were found to be depended on the volume ratios of GelMA/PEG, with cell viability and spreading area decreased along with increasing the ratio of PEG. The developed approach would be useful for screening cell-biomaterial interaction in 3D and promoting regeneration of functional tissue.

Formation of composite polyacrylamide and silicone substrates for independent control of stiffness and strain.

PubMed

Simmons, Chelsey S; Ribeiro, Alexandre J S; Pruitt, Beth L

2013-02-21

Cells that line major tissues in the body such as blood vessels, lungs and gastrointestinal tract experience deformation from mechanical strain with our heartbeat, breathing, and other daily activities. Tissues also remodel in both development and disease, changing their mechanical properties. Taken together, cells can experience vastly different mechanical cues resulting from the combination of these interdependent stimuli. To date, most studies of cellular mechanotransduction have been limited to assays in which variations in substrate stiffness and strain were not combined. Here, we address this technological gap by implementing a method that can simultaneously tune both substrate stiffness and mechanical strain. Substrate stiffness is controlled with different monomer and crosslinker ratios during polyacrylamide gel polymerization, and strain is transferred from the underlying silicone platform when stretched. We demonstrate this platform with polyacrylamide gels with elastic moduli at 6 kPa and 20 kPa in combination with two different silicone formulations. The gels remain attached with up to 50% applied strains. To validate strain transfer through the gels into cells, we employ particle-tracking methods and observe strain transmission via cell morphological changes.

Formation of composite polyacrylamide and silicone substrates for independent control of stiffness and strain

PubMed Central

Simmons, Chelsey S.; Ribeiro, Alexandre J. S.; Pruitt, Beth L.

2013-01-01

Cells that line major tissues in the body such as blood vessels, lungs and gastrointestinal tract experience deformation from mechanical strain with our heartbeat, breathing, and other daily activities. Tissues also remodel in both development and disease, changing their mechanical properties. Taken together, cells can experience vastly different mechanical cues resulting from the combination of these interdependent stimuli. To date, most studies of cellular mechanotransduction have been limited to assays in which variations in substrate stiffness and strain were not combined. Here, we address this technological gap by implementing a method that can simultaneously tune both substrate stiffness and mechanical strain. Substrate stiffness is controlled with different monomer and crosslinker ratios during polyacrylamide gel polymerization, and strain is transferred from the underlying silicone platform when stretched. We demonstrate this platform with polyacrylamide gels with elastic moduli at 6 kPa and 20 kPa in combination with two different silicone formulations. The gels remain attached with up to 50% applied strains. To validate strain transfer through the gels into cells, we employ particle-tracking methods and observe strain transmission via cell morphological changes. PMID:23287818

Tissue Cells Feel and Respond to the Stiffness of Their Substrate

NASA Astrophysics Data System (ADS)

Discher, Dennis E.; Janmey, Paul; Wang, Yu-li

2005-11-01

Normal tissue cells are generally not viable when suspended in a fluid and are therefore said to be anchorage dependent. Such cells must adhere to a solid, but a solid can be as rigid as glass or softer than a baby's skin. The behavior of some cells on soft materials is characteristic of important phenotypes; for example, cell growth on soft agar gels is used to identify cancer cells. However, an understanding of how tissue cells-including fibroblasts, myocytes, neurons, and other cell types-sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels (or to other cells) with which elasticity can be tuned to approximate that of tissues. Key roles in molecular pathways are played by adhesion complexes and the actin-myosin cytoskeleton, whose contractile forces are transmitted through transcellular structures. The feedback of local matrix stiffness on cell state likely has important implications for development, differentiation, disease, and regeneration.

Simultaneous Separation of Acidic and Basic Isoperoxidases in Wounded Potato Tissue by Acrylamide Gel Electrophoresis 1

PubMed Central

Borchert, Rolf; Decedue, Charles J.

1978-01-01

Preparation and use of a newly developed pH 4.3 horizontal thin layer acrylamide gel which permits the simultaneous separation of acidic and basic isoperoxidases in up to 30 samples is described. Use of cytochrome c, horseradish peroxidase, and a purified potato isoperoxidase as internal standards for a range in isoelectric points of peroxidases from pH 3 to 11 is introduced to facilitate comparison of results obtained with different materials and different methods. Distribution of tissue-specific isoperoxidases in different cell layers of wounded potato (Solanum tuberosum L.) tissue is shown and their purification described. Evidence for the in vitro degradation of basic potato isoperoxidases resulting in more acidic forms similar to isoperoxidases occurring in wounded potato tissue is presented. The significance of this observation for the postulated differential function of different isoperoxidases is discussed. ImagesFig. 1-3 PMID:16660608

[Silicone in autoimmune diseases and cancer].

PubMed

Elejabeitia, J

1999-01-01

In 1992 the Food and Drug Administration (FDA) announced the restriction of silicone gel-filled breast implants until research protocol studies evaluate the relationship of silicone to connective tissue diseases, and the association of the silicone implants with breast carcinoma. Since them comprehensive epidemiologic studies have concluded that there is no connection between breast implants and the known connective tissue diseases or between the implants and breast carcinoma. During the same year, The American College of Rheumatology said that it have not been demonstrated the relationship between silicone gel breast implants and any systemic disease. Although this, the FDA restriction continues.

Perfusion directed 3D mineral formation within cell-laden hydrogels.

PubMed

Sawyer, Stephen William; Shridhar, Shivkumar Vishnempet; Zhang, Kairui; Albrecht, Lucas; Filip, Alex; Horton, Jason; Soman, Pranav

2018-06-08

Despite the promise of stem cell engineering and the new advances in bioprinting technologies, one of the major challenges in the manufacturing of large scale bone tissue scaffolds is the inability to perfuse nutrients throughout thick constructs. Here, we report a scalable method to create thick, perfusable bone constructs using a combination of cell-laden hydrogels and a 3D printed sacrificial polymer. Osteoblast-like Saos-2 cells were encapsulated within a gelatin methacrylate (GelMA) hydrogel and 3D printed polyvinyl alcohol (PVA) pipes were used to create perfusable channels. A custom-built bioreactor was used to perfuse osteogenic media directly through the channels in order to induce mineral deposition which was subsequently quantified via microCT. Histological staining was used to verify mineral deposition around the perfused channels, while COMSOL modeling was used to simulate oxygen diffusion between adjacent channels. This information was used to design a scaled-up construct containing a 3D array of perfusable channels within cell-laden GelMA. Progressive matrix mineralization was observed by cells surrounding perfused channels as opposed to random mineral deposition in static constructs. MicroCT confirmed that there was a direct relationship between channel mineralization within perfused constructs and time within the bioreactor. Furthermore, the scalable method presented in this work serves as a model on how large-scale bone tissue replacement constructs could be made using commonly available 3D printers, sacrificial materials, and hydrogels. © 2018 IOP Publishing Ltd.

Source Determination of Red Gel Pen Inks using Raman Spectroscopy and Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy combined with Pearson's Product Moment Correlation Coefficients and Principal Component Analysis.

PubMed

Mohamad Asri, Muhammad Naeim; Mat Desa, Wan Nur Syuhaila; Ismail, Dzulkiflee

2018-01-01

The potential combination of two nondestructive techniques, that is, Raman spectroscopy (RS) and attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectroscopy with Pearson's product moment correlation (PPMC) coefficient (r) and principal component analysis (PCA) to determine the actual source of red gel pen ink used to write a simulated threatening note, was examined. Eighteen (18) red gel pens purchased from Japan and Malaysia from November to December 2014 where one of the pens was used to write a simulated threatening note were analyzed using RS and ATR-FTIR spectroscopy, respectively. The spectra of all the red gel pen inks including the ink deposited on the simulated threatening note gathered from the RS and ATR-FTIR analyses were subjected to PPMC coefficient (r) calculation and principal component analysis (PCA). The coefficients r = 0.9985 and r = 0.9912 for pairwise combination of RS and ATR-FTIR spectra respectively and similarities in terms of PC1 and PC2 scores of one of the inks to the ink deposited on the simulated threatening note substantiated the feasibility of combining RS and ATR-FTIR spectroscopy with PPMC coefficient (r) and PCA for successful source determination of red gel pen inks. The development of pigment spectral library had allowed the ink deposited on the threatening note to be identified as XSL Poppy Red (CI Pigment Red 112). © 2017 American Academy of Forensic Sciences.

Foldable and Cytocompatible Sol-gel TiO2 Photonics

NASA Astrophysics Data System (ADS)

Li, Lan; Zhang, Ping; Wang, Wei-Ming; Lin, Hongtao; Zerdoum, Aidan B.; Geiger, Sarah J.; Liu, Yangchen; Xiao, Nicholas; Zou, Yi; Ogbuu, Okechukwu; Du, Qingyang; Jia, Xinqiao; Li, Jingjing; Hu, Juejun

2015-09-01

Integrated photonics provides a miniaturized and potentially implantable platform to manipulate and enhance the interactions between light and biological molecules or tissues in in-vitro and in-vivo settings, and is thus being increasingly adopted in a wide cross-section of biomedical applications ranging from disease diagnosis to optogenetic neuromodulation. However, the mechanical rigidity of substrates traditionally used for photonic integration is fundamentally incompatible with soft biological tissues. Cytotoxicity of materials and chemicals used in photonic device processing imposes another constraint towards these biophotonic applications. Here we present thin film TiO2 as a viable material for biocompatible and flexible integrated photonics. Amorphous TiO2 films were deposited using a low temperature (<250 °C) sol-gel process fully compatible with monolithic integration on plastic substrates. High-index-contrast flexible optical waveguides and resonators were fabricated using the sol-gel TiO2 material, and resonator quality factors up to 20,000 were measured. Following a multi-neutral-axis mechanical design, these devices exhibit remarkable mechanical flexibility, and can sustain repeated folding without compromising their optical performance. Finally, we validated the low cytotoxicity of the sol-gel TiO2 devices through in-vitro cell culture tests. These results demonstrate the potential of sol-gel TiO2 as a promising material platform for novel biophotonic devices.

Variations in chondrogenesis of human bone marrow-derived mesenchymal stem cells in fibrin/alginate blended hydrogels

PubMed Central

Ma, Kun; Titan, Ashley L.; Stafford, Melissa; Zheng, Chun hua; Levenston, Marc E.

2012-01-01

Fibrin and alginate hydrogels have been widely used to support chondrogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs) for articular cartilage and fibrocartilage tissue engineering, with distinct advantages and disadvantages to each material. Attempting to produce a gel scaffold exhibiting beneficial characteristics of both materials, we fabricated fibrin/alginate blended hydrogels at various blend ratios and evaluated the gel morphology, mechanical properties and their support for BM-MSC chondrogenesis. Results show that when the fibrin/alginate ratio decreased, the fibrin architecture transitioned from uniform to interconnected fibrous and finally to disconnected islands against an alginate background, with opposing trends in the alginate architecture. Fibrin maintained gel extensibility and promoted cell proliferation, while alginate improved the gel biostability and better supported glycosaminoglycan and collagen II production and chondrogenic gene expression. Blended gels had physical and biological characteristics intermediate between fibrin and alginate. Of the blends examined, FA 40:8 (40 mg/mL fibrinogen blended with 8 mg/mL alginate) was found to be the most appropriate group for future studies on tension-driven BM-MSC fibrochondrogenesis. As BM-MSC differentiation appeared to vary between fibrin and alginate regions of blended scaffolds, this study also highlighted the potential to develop spatially heterogeneous tissues through manipulating the heterogeneity of scaffold composition. PMID:22750738

Foldable and Cytocompatible Sol-gel TiO2 Photonics

PubMed Central

Li, Lan; Zhang, Ping; Wang, Wei-Ming; Lin, Hongtao; Zerdoum, Aidan B.; Geiger, Sarah J.; Liu, Yangchen; Xiao, Nicholas; Zou, Yi; Ogbuu, Okechukwu; Du, Qingyang; Jia, Xinqiao; Li, Jingjing; Hu, Juejun

2015-01-01

Integrated photonics provides a miniaturized and potentially implantable platform to manipulate and enhance the interactions between light and biological molecules or tissues in in-vitro and in-vivo settings, and is thus being increasingly adopted in a wide cross-section of biomedical applications ranging from disease diagnosis to optogenetic neuromodulation. However, the mechanical rigidity of substrates traditionally used for photonic integration is fundamentally incompatible with soft biological tissues. Cytotoxicity of materials and chemicals used in photonic device processing imposes another constraint towards these biophotonic applications. Here we present thin film TiO2 as a viable material for biocompatible and flexible integrated photonics. Amorphous TiO2 films were deposited using a low temperature (<250 °C) sol-gel process fully compatible with monolithic integration on plastic substrates. High-index-contrast flexible optical waveguides and resonators were fabricated using the sol-gel TiO2 material, and resonator quality factors up to 20,000 were measured. Following a multi-neutral-axis mechanical design, these devices exhibit remarkable mechanical flexibility, and can sustain repeated folding without compromising their optical performance. Finally, we validated the low cytotoxicity of the sol-gel TiO2 devices through in-vitro cell culture tests. These results demonstrate the potential of sol-gel TiO2 as a promising material platform for novel biophotonic devices. PMID:26344823

Foldable and Cytocompatible Sol-gel TiO2 Photonics.

PubMed

Li, Lan; Zhang, Ping; Wang, Wei-Ming; Lin, Hongtao; Zerdoum, Aidan B; Geiger, Sarah J; Liu, Yangchen; Xiao, Nicholas; Zou, Yi; Ogbuu, Okechukwu; Du, Qingyang; Jia, Xinqiao; Li, Jingjing; Hu, Juejun

2015-09-07

Integrated photonics provides a miniaturized and potentially implantable platform to manipulate and enhance the interactions between light and biological molecules or tissues in in-vitro and in-vivo settings, and is thus being increasingly adopted in a wide cross-section of biomedical applications ranging from disease diagnosis to optogenetic neuromodulation. However, the mechanical rigidity of substrates traditionally used for photonic integration is fundamentally incompatible with soft biological tissues. Cytotoxicity of materials and chemicals used in photonic device processing imposes another constraint towards these biophotonic applications. Here we present thin film TiO2 as a viable material for biocompatible and flexible integrated photonics. Amorphous TiO2 films were deposited using a low temperature (<250 °C) sol-gel process fully compatible with monolithic integration on plastic substrates. High-index-contrast flexible optical waveguides and resonators were fabricated using the sol-gel TiO2 material, and resonator quality factors up to 20,000 were measured. Following a multi-neutral-axis mechanical design, these devices exhibit remarkable mechanical flexibility, and can sustain repeated folding without compromising their optical performance. Finally, we validated the low cytotoxicity of the sol-gel TiO2 devices through in-vitro cell culture tests. These results demonstrate the potential of sol-gel TiO2 as a promising material platform for novel biophotonic devices.

The characteristics of bacterial nanocellulose gel releasing silk sericin for facial treatment.

PubMed

Aramwit, Pornanong; Bang, Nipaporn

2014-12-09

Recently, naturally derived facial masks with beneficial biological properties have received increasing interest. In this study, silk sericin-releasing bacterial nanocellulose gel was developed to be applied as a bioactive mask for facial treatment. The silk sericin-releasing bacterial nanocellulose gel produced at a pH of 4.5 had an ultrafine and extremely pure fiber network structure. The mechanical properties and moisture absorption ability of the gel were improved, compared to those of the commercially available paper mask. Silk sericin could be control-released from the gel. A peel test with porcine skin showed that the gel was less adhesive than the commercially available paper mask, which would be removed from the face more easily without pain. The in vitro cytotoxicity test showed that the gel was not toxic to L929 mouse fibroblast and HaCaT human keratinocyte cells. Furthermore, when implanted subcutaneously and evaluated according to ISO10993-6 standard, the gel was not irritant to tissue. The silk sericin-releasing bacterial nanocellulose gel had appropriate physical and biological properties and safety for the facial treatment application.

Biocompatibility of a Sonicated Silk Gel for Cervical Injection During Pregnancy

PubMed Central

Critchfield, Agatha S.; Mccabe, Reid; Klebanov, Nikolai; Richey, Lauren; Socrate, Simona; Norwitz, Errol R.; Kaplan, David L.; House, Michael

2014-01-01

Objective: To evaluate the biocompatibility of silk gel for cervical injection. Study Design: Silk gel was injected into the cervix of pregnant rats on day 13 (n = 11) and harvested at day 17. Histology of silk gel was compared with suture controls. Also, human cervical fibroblasts were cultured on silk gel and tissue culture plastic (TCP) in vitro. Cell viability, proliferation, metabolic activity, gene expression (COL1A1, COL3A1, and COX2), and release of proinflammatory mediators (interleukin [IL] 6 and IL-8) were evaluated. Results: In vivo, a mild foreign body response was seen surrounding the silk gel and suture controls. In vitro, cervical fibroblasts were viable, metabolically active, and proliferating at 72 hours. Release of IL-6 and IL-8 was similar on silk gel and TCP. Collagen and COX2 gene expression was similar or slightly decreased compared with TCP. Conclusions: Silk gel was well tolerated in vivo and in vitro, which supports continuing efforts to develop silk gels as an alternative to cervical cerclage. PMID:24520079

Gel phase in hydrated calcium dipicolinate

NASA Astrophysics Data System (ADS)

Rajak, Pankaj; Mishra, Ankit; Sheng, Chunyang; Tiwari, Subodh; Krishnamoorthy, Aravind; Kalia, Rajiv K.; Nakano, Aiichiro; Vashishta, Priya

2017-11-01

The mineralization of dipicolinic acid (DPA) molecules in bacterial spore cores with Ca2+ ions to form Ca-DPA is critical to the wet-heat resistance of spores. This resistance to "wet-heat" also depends on the physical properties of water and DPA in the hydrated Ca-DPA-rich protoplasm. Using reactive molecular dynamics simulations, we have determined the phase diagram of hydrated Ca-DPA as a function of temperature and water concentration, which shows the existence of a gel phase along with distinct solid-gel and gel-liquid phase transitions. Simulations reveal monotonically decreasing solid-gel-liquid transition temperatures with increasing hydration, which explains the experimental trend of wet-heat resistance of bacterial spores. Our observation of different phases of water also reconciles previous conflicting experimental findings on the state of water in bacterial spores. Further comparison with an unmineralized hydrated DPA system allows us to quantify the importance of Ca mineralization in decreasing diffusivity and increasing the heat resistance of the spore.

Computer simulation of immobilized pH gradients at acidic and alkaline extremes - A quest for extended pH intervals

NASA Technical Reports Server (NTRS)

Mosher, Richard A.; Bier, Milan; Righetti, Pier Giorgio

1986-01-01

Computer simulations of the concentration profiles of simple biprotic ampholytes with Delta pKs 1, 2, and 3, on immobilized pH gradients (IPG) at extreme pH values (pH 3-4 and pH 10-11) show markedly skewed steady-state profiles with increasing kurtosis at higher Delta pK values. Across neutrality, all the peaks are symmetric irrespective of their Delta pK values, but they show very high contribution to the conductivity of the background gel and significant alteration of the local buffering capacity. The problems of skewness, due to the exponential conductivity profiles at low and high pHs, and of gel burning due to a strong electroosmotic flow generated by the net charges in the gel matrix, also at low and high pHs, are solved by incorporating in the IPG gel a strong viscosity gradient. This is generated by a gradient of linear polyacrylamide which is trapped in the gel by the polymerization process.

Lippia sidoides and Myracrodruon urundeuva gel prevents alveolar bone resorption in experimental periodontitis in rats.

PubMed

Botelho, M A; Rao, V S; Carvalho, C B M; Bezerra-Filho, J G; Fonseca, S G C; Vale, M L; Montenegro, D; Cunha, F; Ribeiro, R A; Brito, G A

2007-09-25

In Brazilian folk medicine, Lippia sidoides (Ls) and Myracrodruon urundeuva (Mu) have gained popularity and reputation as effective antimicrobial and anti-inflammatory agents. This work aimed to evaluate the effect of topical herbal gel from Ls 0.5% (v/w) and Mu 5% (w/w) in experimental periodontal disease (EPD) in rats. Wistar rats were subjected to ligature placement around the second upper left molars. Animals were treated topically with Ls and/or Mu-based gel, immediately after EPD induction and three times/day for 11 days until the rats were sacrificed (11th day). Saline-based gel was utilized as control for all experiments and doxycycline based gel 10% (w/w) was utilized as reference substance. Animals were weighed daily. Alveolar bone loss was measured as the difference (in millimeters) between the cusp tip and the alveolar bone. The periodontum and the surrounding gingivae were examined at histopathology, as well as the neutrophil influx into the gingivae was assayed using myeloperoxidase activity and cytokine production mainly tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels by ELISA method. The local bacterial flora was assessed through culture of the gingival tissue in standard aerobic and anaerobic media. Alveolar bone loss was significantly inhibited by Ls and Mu combined treatment compared to the saline control group. Ls and Mu combined treatment reduced tissue lesion at histopathology, with partial preservation of the periodontum, coupled to decreased myeloperoxidase activity as well as significantly inhibited TNF-alpha and IL-1beta production in gingival tissue compared to the saline control group. Ls and Mu combined treatment also prevented the growth of oral microorganisms and the weight loss. Ls and Mu combined based gel treatment preserved alveolar bone resorption and demonstrated anti-inflammatory and antibacterial activities in experimental periodontitis.

The mechanical properties and cytotoxicity of cell-laden double-network hydrogels based on photocrosslinkable gelatin and gellan gum biomacromolecules.

PubMed

Shin, Hyeongho; Olsen, Bradley D; Khademhosseini, Ali

2012-04-01

A major goal in the application of hydrogels for tissue engineering scaffolds, especially for load-bearing tissues such as cartilage, is to develop hydrogels with high mechanical strength. In this study, a double-network (DN) strategy was used to engineer strong hydrogels that can encapsulate cells. We improved upon previously studied double-network (DN) hydrogels by using a processing condition compatible with cell survival. The DN hydrogels were created by a two-step photocrosslinking using gellan gum methacrylate (GGMA) for the rigid and brittle first network, and gelatin methacrylamide (GelMA) for the soft and ductile second network. We controlled the degree of methacrylation of each polymer so that they obtain relevant mechanical properties as each network. The DN was formed by photocrosslinking the GGMA, diffusing GelMA into the first network, and photocrosslinking the GelMA to form the second network. The formation of the DN was examined by diffusion tests of the large GelMA molecules into the GGMA network, the resulting enhancement in the mechanical properties, and the difference in mechanical properties between GGMA/GelMA single networks (SN) and DNs. The resulting DN hydrogels exhibited the compressive failure stress of up to 6.9 MPa, which approaches the strength of cartilage. It was found that there is an optimal range of the crosslink density of the second network for high strength of DN hydrogels. DN hydrogels with a higher mass ratio of GelMA to GGMA exhibited higher strength, which shows promise in developing even stronger DN hydrogels in the future. Three dimensional (3D) encapsulation of NIH-3T3 fibroblasts and the following viability test showed the cell-compatibility of the DN formation process. Given the high strength and the ability to encapsulate cells, the DN hydrogels made from photocrosslinkable macromolecules could be useful for the regeneration of load-bearing tissues. Copyright © 2012 Elsevier Ltd. All rights reserved.

The mechanical properties and cytotoxicity of cell-laden double-network hydrogels based on photocrosslinkable gelatin and gellan gum biomacromolecules

PubMed Central

Shin, Hyeongho; Olsen, Bradley D.; Khademhosseini, Ali

2012-01-01

A major goal in the application of hydrogels for tissue engineering scaffolds, especially for load-bearing tissues such as cartilage, is to develop hydrogels with high mechanical strength. In this study, a double-network (DN) strategy was used to engineer strong hydrogels that can encapsulate cells. We improved upon previously studied double-network (DN) hydrogels by using a processing condition compatible with cell survival. The DN hydrogels were created by a two-step photocrosslinking using gellan gum methacrylate (GGMA) for the rigid and brittle first network, and gelatin methacrylamide (GelMA) for the soft and ductile second network. We controlled the degree of methacrylation of each polymer so that they obtain relevant mechanical properties as each network. The DN was formed by photocrosslinking the GGMA, diffusing GelMA into the first network, and photocrosslinking the GelMA to form the second network. The formation of the DN was examined by diffusion tests of the large GelMA molecules into the GGMA network, the resulting enhancement in the mechanical properties, and the difference in mechanical properties between GGMA/GelMA single networks (SN) and DNs. The resulting DN hydrogels exhibited the compressive failure stress of up to 6.9 MPa, which approaches the strength of cartilage. It was found that there is an optimal range of the crosslink density of the second network for high strength of DN hydrogels. DN hydrogels with a higher mass ratio of GelMA to GGMA exhibited higher strength, which shows promise in developing even stronger DN hydrogels in the future. Three dimensional (3D) encapsulation of NIH-3T3 fibroblasts and the following viability test showed the cell-compatibility of the DN formation process. Given the high strength and the ability to encapsulate cells, the DN hydrogels made from photocrosslinkable macromolecules could be useful for the regeneration of load-bearing tissues. PMID:22265786

Proteomic identification of processes and pathways characteristic of osmoregulatory tissues in spiny dogfish shark (Squalus acanthias).

PubMed

Lee, Jinoo; Valkova, Nelly; White, Mark P; Kültz, Dietmar

2006-09-01

We used dogfish shark (Squalus acanthias) as a model for proteome analysis of six different tissues to evaluate tissue-specific protein expression on a global scale and to deduce specific functions and the relatedness of multiple tissues from their proteomes. Proteomes of heart, brain, kidney, intestine, gill, and rectal gland were separated by two-dimensional gel electrophoresis (2DGE), gel images were matched using Delta 2D software and then evaluated for tissue-specific proteins. Sixty-one proteins (4%) were found to be in only a single type of tissue and 535 proteins (36%) were equally abundant in all six tissues. Relatedness between tissues was assessed based on tissue-specific expression patterns of all 1465 consistently resolved protein spots. This analysis revealed that tissues with osmoregulatory function (kidney, intestine, gill, rectal gland) were more similar in their overall proteomes than non-osmoregulatory tissues (heart, brain). Sixty-one proteins were identified by MALDI-TOF/TOF mass spectrometry and biological functions characteristic of osmoregulatory tissues were derived from gene ontology and molecular pathway analysis. Our data demonstrate that the molecular machinery for energy and urea metabolism and the Rho-GTPase/cytoskeleton pathway are enriched in osmoregulatory tissues of sharks. Our work provides a strong rationale for further study of the contribution of these mechanisms to the osmoregulation of marine sharks.

Synthesis and Fabrication of Collagen-Coated Ostholamide Electrospun Nanofiber Scaffold for Wound Healing.

PubMed

Kandhasamy, Subramani; Perumal, Sathiamurthi; Madhan, Balaraman; Umamaheswari, Narayanan; Banday, Javid Ahmad; Perumal, Paramasivan Thirumalai; Santhanakrishnan, Vichangal Pridiuldi

2017-03-15

A novel scaffold for effective wound healing treatment was developed utilizing natural product bearing collagen-based biocompatible electrospun nanofibers. Initially, ostholamide (OSA) was synthesized from osthole (a natural coumarin), characterized by 1 H, 13 C, DEPT-135 NMR, ESI-MS, and FT-IR spectroscopy analysis. OSA was incorporated into polyhydroxybutyrate (PHB) and gelatin (GEL), which serve as templates for electrospun nanofibers. The coating of OSA-PHB-GEL nanofibers with collagen resulted in PHB-GEL-OSA-COL nanofibrous scaffold which mimics extracellular matrix and serves as an effective biomaterial for tissue engineering applications, especially for wound healing. PHB-GEL-OSA-COL, along with PHB-GEL-OSA and collagen film (COLF), was characterized in vitro and in vivo to determine its efficacy. The developed PHB-GEL-OSA-COL nanofibers posed an impressive mechanical stability, an essential requirement for wound healing. The presence of OSA had contributed to antimicrobial efficacy. These scaffolds exhibited efficient antibacterial activity against common wound pathogens, Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). The zones of inhibition were observed to be 14 ± 22 and 10 ± 2 mm, respectively. It was observed that nanofibrous scaffold had the ability to release OSA in a controlled manner, and hence, OSA would be present at the site of application and exhibit bioactivity in a sustained manner. PHB-GEL-OSA-COL nanofiber was determined to be stable against enzymatic degradation, which is the most important parameter for promoting proliferation of cells contributing to repair and remodeling of tissues during wound healing applications. As hypothesized, PHB-GEL-OSA-COL was observed to imbibe excellent cytocompatibility, which was determined using NIH 3T3 fibroblast cell proliferation studies. PHB-GEL-OSA-COL exhibited excellent wound healing efficacy which was confirmed using full thickness excision wound model in Wistar rats. The rats treated with PHB-GEL-OSA-COL nanofibrous scaffold displayed enhanced healing when compared to untreated control. Both in vitro and in vivo analysis of PHB-GEL-OSA-COL presents a strong case of therapeutic biomaterial suiting wound repair and regeneration.

Estimation of the influence of radical effect in the proton beams using a combined approach with physical data and gel data

NASA Astrophysics Data System (ADS)

Haneda, K.

2016-04-01

The purpose of this study was to estimate an impact on radical effect in the proton beams using a combined approach with physical data and gel data. The study used two dosimeters: ionization chambers and polymer gel dosimeters. Polymer gel dosimeters have specific advantages when compared to other dosimeters. They can measure chemical reaction and they are at the same time a phantom that can map in three dimensions continuously and easily. First, a depth-dose curve for a 210 MeV proton beam measured using an ionization chamber and a gel dosimeter. Second, the spatial distribution of the physical dose was calculated by Monte Carlo code system PHITS: To verify of the accuracy of Monte Carlo calculation, and the calculation results were compared with experimental data of the ionization chamber. Last, to evaluate of the rate of the radical effect against the physical dose. The simulation results were compared with the measured depth-dose distribution and showed good agreement. The spatial distribution of a gel dose with threshold LET value of proton beam was calculated by the same simulation code. Then, the relative distribution of the radical effect was calculated from the physical dose and gel dose. The relative distribution of the radical effect was calculated at each depth as the quotient of relative dose obtained using physical and gel dose. The agreement between the relative distributions of the gel dosimeter and Radical effect was good at the proton beams.

Induction of spontaneous hyaline cartilage regeneration using a double-network gel: efficacy of a novel therapeutic strategy for an articular cartilage defect.

PubMed

Kitamura, Nobuto; Yasuda, Kazunori; Ogawa, Munehiro; Arakaki, Kazunobu; Kai, Shuken; Onodera, Shin; Kurokawa, Takayuki; Gong, Jian Ping

2011-06-01

A double-network (DN) gel, which was composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) and poly-(N,N'-dimetyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. To establish the efficacy of a therapeutic strategy for an articular cartilage defect using a DN gel. Controlled laboratory study. A 4.3-mm-diameter osteochondral defect was created in rabbit trochlea. A DN gel plug was implanted into the defect of the right knee so that a defect 2 mm in depth remained after surgery. An untreated defect of the left knee provided control data. The osteochondral defects created were examined by histological and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction (PCR) analysis at 4 and 12 weeks. Samples were quantitatively evaluated with 2 scoring systems reported by Wayne et al and O'Driscoll et al. The DN gel-implanted defect was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type 2 collagen. Quantitative evaluation using the grading scales revealed a significantly higher score in the DN gel-implanted defects compared with the untreated control at each period (P < .0001). The mean relative values of type 2 collagen mRNAs in the regenerated tissue were obviously higher in the DN gel-implanted defect than in the untreated control at each period. The mean surface roughness of the untreated control was significantly higher than the normal cartilage at 12 weeks (P = .0106), while there was no statistical difference between the DN gel-implanted and normal knees. This study using the mature rabbit femoral trochlea osteochondral defect model demonstrated that DN gel implantation is an effective treatment to induce cartilage regeneration in vivo without any cultured cells or mammalian-derived scaffolds. This study has prompted us to develop a potential innovative strategy to repair cartilage lesions in the field of joint surgery.

An In Vitro Investigation of Platelet-Rich Plasma-Gel as a Cell and Growth Factor Delivery Vehicle for Tissue Engineering

PubMed Central

Jalowiec, Jagoda M.; D'Este, Matteo; Bara, Jennifer Jane; Denom, Jessica; Menzel, Ursula; Alini, Mauro; Herrmann, Marietta

2016-01-01

Platelet-rich plasma (PRP) has been used for different applications in human and veterinary medicine. Many studies have shown promising therapeutic effects of PRP; however, there are still many controversies regarding its composition, properties, and clinical efficacy. The aim of this study was to evaluate the influence of different platelet concentrations on the rheological properties and growth factor (GF) release profile of PRP-gels. In addition, the viability of incorporated bone marrow-derived human mesenchymal stem cells (MSCs) was investigated. PRP (containing 1000 × 103, 2000 × 103, and 10,000 × 103 platelets/μL) was prepared from human platelet concentrates. Platelet activation and gelification were achieved by addition of human thrombin. Viscoelastic properties of PRP-gels were evaluated by rheological studies. The release of GFs and inflammatory proteins was measured using a membrane-based protein array and enzyme-linked immunosorbent assay. MSC viability and proliferation in PRP-gels were assessed over 7 days by cell viability staining. Cell proliferation was examined using DNA quantification. Regardless of the platelet content, all tested PRP-gels showed effective cross-linking. A positive correlation between protein release and the platelet concentration was observed at all time points. Among the detected proteins, the chemokine CCL5 was the most abundant. The greatest release appeared within the first 4 h after gelification. MSCs could be successfully cultured in PRP-gels over 7 days, with the highest cell viability and DNA content found in PRP-gels with 1000 × 103 platelets/μL. The results of this study suggest that PRP-gels represent a suitable carrier for both cell and GF delivery for tissue engineering. Notably, a platelet concentration of 1000 × 103 platelets/μL appeared to provide the most favorable environment for MSCs. Thus, the platelet concentration is an important consideration for the clinical application of PRP-gels. PMID:26467221

Crystalline-gel-molten phase transitions of water in calcium dipicolinate (Ca-DPA)

NASA Astrophysics Data System (ADS)

Tiwari, Subodh; Mishra, Ankit; Sheng, Chunyang; Rajak, Pankaj; Kalia, Rajiv; Nakano, Aiichiro; Vashishta, Priya

The heat resistance of bacterial spores directly correlates to the protoplast dehydration and presence of dipicolinic acid (DPA) and its associated metal salts at the core. Bacteria's structural integrity in moist heat conferred by high concentration of DPA and calcium DPA salts depends on the properties are additional water molecules and temperature. In our reactive MD simulations, we characterize different possible phases and the transport properties of water molecules. We observed solid-gel and gel-liquid phase transitions of the hydrated Ca-DPA system. These simulations reveal monotonically decreasing solid-gel-liquid transition temperatures with increasing cell hydration, reflecting the experimental trend of moist-heat resistance of bacterial spores. We also observed that the calcification of bacterial spores further increases the transition temperatures. This research is supported by DTRA Grant No. HDTRA1-14-1-0074.

Auto-Origami and Soft Programmable Transformers: Simulation Studies of Liquid Crystal Elastomers and Swelling Polymer Gels

NASA Astrophysics Data System (ADS)

Konya, Andrew; Santangelo, Christian; Selinger, Robin

2014-03-01

When the underlying microstructure of an actuatable material varies in space, simple sheets can transform into complex shapes. Using nonlinear finite element elastodynamic simulations, we explore the design space of two such materials: liquid crystal elastomers and swelling polymer gels. Liquid crystal elastomers (LCE) undergo shape transformations induced by stimuli such as heating/cooling or illumination; complex deformations may be programmed by ``blueprinting'' a non-uniform director field in the sample when the polymer is cross-linked. Similarly, swellable gels can undergo shape change when they are swollen anisotropically as programmed by recently developed halftone gel lithography techniques. For each of these materials we design and test programmable motifs which give rise to complex deformation trajectories including folded structures, soft swimmers, apertures that open and close, bas relief patterns, and other shape transformations inspired by art and nature. In order to accommodate the large computational needs required to model these materials, our 3-d nonlinear finite element elastodynamics simulation algorithm is implemented in CUDA, running on a single GPU-enabled workstation.

Platelet gel biotechnology applied to regenerative surgery of intrabony defects in patients with refractory generalized aggressive peridontitis. Case report.

PubMed

Mauro, S; Orlando, L; Panzoni, R; Orlando, P F

2003-01-01

Platelet gel biotechnology, a method which has all the components of "tissue engineering" techniques, potentiates the already known healing process of guided tissue regeneration procedures (GTR) by multiplying the number of molecules that activate the healing response and by grafting in the host site various cell types, among which stem cells. Here are reported cases of patients affected by refractory generalized aggressive periodontitis treated with the association GTR and platelet gel biotechnology to verify if the contribution of the gel would produce superior results than those obtained by surgery alone which had been previously applied to the same sites with negative results. Three patients in therapy from 4 to 11 years, already subjected to surgery (GTR) and antibiotic therapy, were reoperated with the adjunct of autologous platelet gel. At a distance of 15.2 months (range 11-17 months) the operated sites showed a reduction in probing pocket depth of 3.4 mm (range 2.8-4.8 mm) and a gain in clinical attachment level of 3.1 mm (range 3-3.5 mm). The association of platelet gel biotechnology with GTR in the surgical treatment of intrabony defects of refractory generalized aggressive periodontitis patients seems to produce results similar to those reported for patients with chronic adult periodontitis. The observations at 15.2 months indicate that there is a stability over time of the results in those sites where previous surgical therapy had shown relapse.

Two forms of alpha-amylase in mantle tissue of Mytilus galloprovincialis: purification and molecular properties of form II.

PubMed

Lombraña, M; Suárez, P; San Juan, F

2005-09-01

alpha-Amylase activity has been shown for the first time in a non-digestive tissue from Mytilus galloprovincialis. alpha-amylase from mussel mantle tissue has been purified by affinity chromatography on insoluble starch, followed by gel-filtration chromatography on Superdex-200. The chromatographic and electrophoretic behaviour of M. galloprovincialis alpha-amylase and stability characteristics suggest two forms of this enzyme: one form forming stable aggregates (form I) and a monomeric form (form II) that is more abundant, active and unstable. Both forms show an inverse quantitative variation. Purified form II was highly unstable and the molecular mass was estimated to be 66 kDa by sodium dodecyl sulphate (SDS)-gel electrophoresis. Maximum activity was noted at pH 6.5 and 35 degrees C.

Hydrogels for efficient light delivery in optogenetic applications

NASA Astrophysics Data System (ADS)

Johannsmeier, S.; Torres, M. L.; Ripken, T.; Heinemann, D.; Heisterkamp, A.

2018-02-01

Light-based therapies have been established for various indications, such as skin conditions, cancer or neonatal jaundice. Advances in the field of optogenetics open up new horizons for light-tissue interactions with an organism-wide impact. Excitable tissues, such as nerve and muscle tissues, can be controlled by light after the introduction of light-sensitive ion channels. Since these organs are generally not easily accessible to illumination in vivo, there is an increasing need for effective biocompatible waveguides for light delivery. These devices not only have to guide and distribute the light as desired with minimal losses, they should also mimic the mechanical properties of the surrounding tissue to ensure compatibility. In this project, we are tuning the properties of hydrogels from poly(ethylene glycol) derivatives to achieve compatibility with muscle tissue as well as optimal light guiding and distribution for optogenetic applications at the heart. The excitation light is coupled into the hydrogel with a biocompatible fiber. Properties of the hydrogel are mainly tuned by monomer length and concentration. Total reflection can be achieved by embedding a fiber-like hydrogel with a high refractive index into a second, low refractive index gel. Different geometries and scattering microparticles are used for light distribution in a flat gel patch. Targeted cell attachment can be achieved by introducing a protein layer to the otherwise bioinert gel. After optimization, the hydrogel may be used to deliver light for the excitation of genetically altered cardiomyocytes for controlled contraction.

Fabrication and characterization of highly porous barium titanate based scaffold coated by Gel/HA nanocomposite with high piezoelectric coefficient for bone tissue engineering applications.

PubMed

Ehterami, Arian; Kazemi, Mansure; Nazari, Bahareh; Saraeian, Payam; Azami, Mahmoud

2018-03-01

It is well established that the piezoelectric effect plays an important physiological role in bone growth, remodeling and fracture healing. Barium titanate, as a well-known piezoelectric ceramic, is especially an attractive material as a scaffold for bone tissue engineering applications. In this regard, we tried to fabricate a highly porous barium titanate based scaffolds by foam replication method and polarize them by applying an external electric field. In order to enhance the mechanical and biological properties, polarized/non-polarized scaffolds were coated with gelatin and nanostructured HA and characterized for their morphologies, porosities, piezoelectric and mechanical properties. The results showed that the compressive strength and piezoelectric coefficient of porous scaffolds increased with the increase of sintering temperature. After being coated with Gel/HA nanocomposite, the interconnected porous structure and pore size of the scaffolds almost remain unchanged while the Gel/nHA-coated scaffolds exhibited enhanced compressive strength and elastic modulus compared with the uncoated samples. Also, the effect of polarizing and coating of optimal scaffolds on adhesion, viability, and proliferation of the MG63 osteoblast-like cell line was evaluated by scanning electron microscope (SEM) and MTT assay. The cell culture experiments revealed that developed scaffolds had good biocompatibility and cells were able to adhere, proliferate and migrate into pores of the scaffolds. Furthermore, cell density was significantly higher in the coated scaffolds at all tested time-points. These results indicated that highly porous barium titanate scaffolds coated with Gel/HA nanocomposite has great potential in tissue engineering applications for bone tissue repair and regeneration. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preparation, characterization, and biological properties of organic-inorganic nanocomposite coatings on titanium substrates prepared by sol-gel.

PubMed

Catauro, Michelina; Bollino, Flavia; Papale, Ferdinando

2014-02-01

When surface-reactive (bioactive) coatings are applied to medical implants by means of the sol-gel dip-coating technique, the biological proprieties of the surface of the implant can be locally modified to match the properties of the surrounding tissues to provide a firm fixation of the implant. The aim of this study has been to synthesize, via sol-gel, organoinorganic nanoporous materials and to dip-coat a substrate to use in dental applications. Different systems have been prepared consisting of an inorganic zirconium-based matrix, in which a biodegradable polymer, the poly-ε-caprolactone was incorporated in different percentages. The materials synthesized by the sol-gel process, before gelation, when they were still in sol phase, have been used to coat a titanium grade 4 (Ti-4) substrate to change its surface biological properties. Thin films have been obtained by means of the dip-coating technique. A microstructural analysis of the obtained coatings was performed using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy. The biological proprieties have been investigated by means of tests in vitro. The bone-bonding capability of the nanocomposite films has been evaluated by examining the appearance of apatite on their surface when plunged in a simulated body fluid (SBF) with ion concentrations nearly equal to those of human blood plasma. The examination of apatite formation on the nanocomposites, after immersion in SBF, has been carried out by SEM equipped with energy-dispersive X-ray spectroscopy. To evaluate cells-materials interaction, human osteosarcoma cell line (Saos-2) has been seeded on specimens and cell vitality evaluated by WST-8 assay. © 2013 Wiley Periodicals, Inc.

Catalytic control over supramolecular gel formation

NASA Astrophysics Data System (ADS)

Boekhoven, Job; Poolman, Jos M.; Maity, Chandan; Li, Feng; van der Mee, Lars; Minkenberg, Christophe B.; Mendes, Eduardo; van Esch, Jan H.; Eelkema, Rienk

2013-05-01

Low-molecular-weight gels show great potential for application in fields ranging from the petrochemical industry to healthcare and tissue engineering. These supramolecular gels are often metastable materials, which implies that their properties are, at least partially, kinetically controlled. Here we show how the mechanical properties and structure of these materials can be controlled directly by catalytic action. We show how in situ catalysis of the formation of gelator molecules can be used to accelerate the formation of supramolecular hydrogels, which drastically enhances their resulting mechanical properties. Using acid or nucleophilic aniline catalysis, it is possible to make supramolecular hydrogels with tunable gel-strength in a matter of minutes, under ambient conditions, starting from simple soluble building blocks. By changing the rate of formation of the gelator molecules using a catalyst, the overall rate of gelation and the resulting gel morphology are affected, which provides access to metastable gel states with improved mechanical strength and appearance despite an identical gelator composition.

Interplay between stiffness and degradation of architectured gelatin hydrogels leads to differential modulation of chondrogenesis in vitro and in vivo.

PubMed

Sarem, Melika; Arya, Neha; Heizmann, Miriam; Neffe, Axel T; Barbero, Andrea; Gebauer, Tim P; Martin, Ivan; Lendlein, Andreas; Shastri, V Prasad

2018-03-15

The limited capacity of cartilage to heal large lesions through endogenous mechanisms has led to extensive effort to develop materials to facilitate chondrogenesis. Although physical-chemical properties of biomaterials have been shown to impact in vitro chondrogenesis, whether these findings are translatable in vivo is subject of debate. Herein, architectured 3D hydrogel scaffolds (ArcGel) (produced by crosslinking gelatin with ethyl lysine diisocyanate (LDI)) were used as a model system to investigate the interplay between scaffold mechanical properties and degradation on matrix deposition by human articular chondrocytes (HAC) from healthy donors in vitro and in vivo. Using ArcGel scaffolds of different tensile and shear modulus, and degradation behavior; in this study, we compared the fate of ex vivo engineered ArcGels-chondrocytes constructs, i.e. the traditional tissue engineering approach, with thede novoformation of cartilaginous tissue in HAC laden ArcGels in an ectopic nude mouse model. While the softer and fast degrading ArcGel (LNCO3) was more efficient at promoting chondrogenic differentiation in vitro, upon ectopic implantation, the stiffer and slow degrading ArcGel (LNCO8) was superior in maintaining chondrogenic phenotype in HAC and retention of cartilaginous matrix. Furthermore, surprisingly the de novo formation of cartilage tissue was promoted only in LNCO8. Since HAC cultured for only three days in the LNCO8 environment showed upregulation of hypoxia-associated genes, this suggests a potential role for hypoxia in the observed in vivo outcomes. In summary, this study sheds light on how immediate environment (in vivo versus in vitro) can significantly impact the outcomes of cell-laden biomaterials. In this study, 3D architectured hydrogels (ArcGels) with different mechanical and biodegradation properties were investigated for their potential to promote formation of cartilaginous matrix by human articular chondrocytes in vitro and in vivo. Two paradigms were explored (i) ex vivo engineering followed by in vivo implantation in ectopic site of nude mice and (ii) short in vitro culture (3 days) followed by implantation to induce de novo cartilage formation. Softer and fast degrading ArcGel were better at promoting chondrogenesis in vitro, while stiffer and slow degrading ArcGel were strikingly superior in both maintaining chondrogenesis in vivo and inducing de novo formation of cartilage. Our findings highlight the importance of the interplay between scaffold mechanics and degradation in chondrogenesis. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

DIGE Analysis of Human Tissues.

PubMed

Gelfi, Cecilia; Capitanio, Daniele

2018-01-01

Two-dimensional difference gel electrophoresis (2-D DIGE) is an advanced and elegant gel electrophoretic analytical tool for comparative protein assessment. It is based on two-dimensional gel electrophoresis (2-DE) separation of fluorescently labeled protein extracts. The tagging procedures are designed to not interfere with the chemical properties of proteins with respect to their pI and electrophoretic mobility, once a proper labeling protocol is followed. The two-dye or three-dye systems can be adopted and their choice depends on specific applications. Furthermore, the use of an internal pooled standard makes 2-D DIGE a highly accurate quantitative method enabling multiple protein samples to be separated on the same two-dimensional gel. The image matching and cross-gel statistical analysis generates robust quantitative results making data validation by independent technologies successful.

Enhanced viability of corneal epithelial cells for efficient transport/storage using a structurally modified calcium alginate hydrogel.

PubMed

Wright, Bernice; Cave, Richard A; Cook, Joseph P; Khutoryanskiy, Vitaliy V; Mi, Shengli; Chen, Bo; Leyland, Martin; Connon, Che J

2012-05-01

Therapeutic limbal epithelial stem cells could be managed more efficiently if clinically validated batches were transported for 'on-demand' use. In this study, corneal epithelial cell viability in calcium alginate hydrogels was examined under cell culture, ambient and chilled conditions for up to 7 days. Cell viability improved as gel internal pore size increased, and was further enhanced with modification of the gel from a mass to a thin disc. Ambient storage conditions were optimal for supporting cell viability in gel discs. Cell viability in gel discs was significantly enhanced with increases in pore size mediated by hydroxyethyl cellulose. Our novel methodology of controlling alginate gel shape and pore size together provides a more practical and economical alternative to established corneal tissue/cell storage methods.

Measurement and Modeling of Acoustic Fields in a Gel Phantom at High Intensities

NASA Astrophysics Data System (ADS)

Canney, Michael S.; Bailey, Michael R.; Khokhlova, Vera A.; Crum, Lawrence A.

2006-05-01

The goal of this work was to compare measured and numerically predicted HIFU pressure waveforms in water and a tissue-mimicking phantom. Waveforms were measured at the focus of a 2-MHz HIFU transducer with a fiber optic hydrophone. The transducer was operated with acoustic powers ranging from 2W to 300W. A KZK-type equation was used for modeling the experimental conditions. Strongly asymmetric nonlinear waves with peak positive pressure up to 80 MPa and peak negative pressure up to 20 MPa were measured in water, while waves up to 50 MPa peak positive pressure and 15 MPa peak negative pressure were measured in tissue phantoms. The values of peak negative pressure corresponded well with numerical simulations and were significantly smaller than predicted by linear extrapolation from low-level measurements. The values of peak positive pressures differed only at high levels of excitation where bandwidth limitations of the hydrophone failed to fully capture the predicted sharp shock fronts.

MAGIC with formaldehyde applied to dosimetry of HDR brachytherapy source

NASA Astrophysics Data System (ADS)

Marques; T; Fernandes; J; Barbi; G; Nicolucci; P; Baffa; O

2009-05-01

The use of polymer gel dosimeters in brachytherapy can allow the determination of three-dimensional dose distributions in large volumes and with high spatial resolution if an adequate calibration process is performed. One of the major issues in these experiments is the polymer gel response dependence on dose rate when high dose rate sources are used and the doses in the vicinity of the sources are to be determinated. In this study, the response of a modified MAGIC polymer gel with formaldehyde around an Iridium-192 HDR brachytherapy source is presented. Experimental results obtained with this polymer gel were compared with ionization chamber measurements and with Monte Carlo simulation with PENELOPE. A maximum difference of 3.10% was found between gel dose measurements and Monte Carlo simulation at a radial distance of 18 mm from the source. The results obtained show that the gel's response is strongly influenced by dose rate and that a different calibration should be used for the vicinity of the source and for regions of lower dose rates. The results obtained in this study show that, provided the proper calibration is performed, MAGIC with formaldehyde can be successfully used to accurate determinate dose distributions form high dose rate brachytherapy sources.

Visualizing the Histotripsy Process: Bubble Cloud-Cancer Cell Interactions in a Tissue-Mimicking Environment.

PubMed

Vlaisavljevich, Eli; Maxwell, Adam; Mancia, Lauren; Johnsen, Eric; Cain, Charles; Xu, Zhen

2016-10-01

Histotripsy is a non-invasive ultrasonic ablation method that uses cavitation to mechanically fractionate tissue into acellular debris. With a sufficient number of pulses, histotripsy can completely fractionate tissue into a liquid-appearing homogenate with no cellular structures. The location, shape and size of lesion formation closely match those of the cavitation cloud. Previous work has led to the hypothesis that the rapid expansion and collapse of histotripsy bubbles fractionate tissue by inducing large stress and strain on the tissue structures immediately adjacent to the bubbles. In the work described here, the histotripsy bulk tissue fractionation process is visualized at the cellular level for the first time using a custom-built 2-MHz transducer incorporated into a microscope stage. A layer of breast cancer cells were cultured within an optically transparent fibrin-based gel phantom to mimic cells inside a 3-D extracellular matrix. To test the hypothesis, the cellular response to single and multiple histotripsy pulses was investigated using high-speed optical imaging. Bubbles were always generated in the extracellular space, and significant cell displacement/deformation was observed for cells directly adjacent to the bubble during both bubble expansion and collapse. The largest displacements were observed during collapse for cells immediately adjacent to the bubble, with cells moving more than 150-300 μm in less than 100 μs. Cells often underwent multiple large deformations (>150% strain) over multiple pulses, resulting in the bisection of cells multiple times before complete removal. To provide theoretical support to the experimental observations, a numerical simulation was conducted using a single-bubble model, which indicated that histotripsy exerts the largest strains and cell displacements in the regions immediately adjacent to the bubble. The experimental and simulation results support our hypothesis, which helps to explain the formation of the sharp lesions formed in histotripsy therapy localized to the regions directly exposed to the bubbles. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Three-Dimensional-Bioprinted Dopamine-Based Matrix for Promoting Neural Regeneration.

PubMed

Zhou, Xuan; Cui, Haitao; Nowicki, Margaret; Miao, Shida; Lee, Se-Jun; Masood, Fahed; Harris, Brent T; Zhang, Lijie Grace

2018-03-14

Central nerve repair and regeneration remain challenging problems worldwide, largely because of the extremely weak inherent regenerative capacity and accompanying fibrosis of native nerves. Inadequate solutions to the unmet needs for clinical therapeutics encourage the development of novel strategies to promote nerve regeneration. Recently, 3D bioprinting techniques, as one of a set of valuable tissue engineering technologies, have shown great promise toward fabricating complex and customizable artificial tissue scaffolds. Gelatin methacrylate (GelMA) possesses excellent biocompatible and biodegradable properties because it contains many arginine-glycine-aspartic acids (RGD) and matrix metalloproteinase sequences. Dopamine (DA), as an essential neurotransmitter, has proven effective in regulating neuronal development and enhancing neurite outgrowth. In this study, GelMA-DA neural scaffolds with hierarchical structures were 3D-fabricated using our custom-designed stereolithography-based printer. DA was functionalized on GelMA to synthesize a biocompatible printable ink (GelMA-DA) for improving neural differentiation. Additionally, neural stem cells (NSCs) were employed as the primary cell source for these scaffolds because of their ability to terminally differentiate into a variety of cell types including neurons, astrocytes, and oligodendrocytes. The resultant GelMA-DA scaffolds exhibited a highly porous and interconnected 3D environment, which is favorable for supporting NSC growth. Confocal microscopy analysis of neural differentiation demonstrated that a distinct neural network was formed on the GelMA-DA scaffolds. In particular, the most significant improvements were the enhanced neuron gene expression of TUJ1 and MAP2. Overall, our results demonstrated that 3D-printed customizable GelMA-DA scaffolds have a positive role in promoting neural differentiation, which is promising for advancing nerve repair and regeneration in the future.

Peri-tumor administration of 5-fluorouracil sol-gel using a hollow microneedle for treatment of gastric cancer.

PubMed

Jung, Yoon Suk; Koo, Dong-Hoe; Yang, Jeong-Yoon; Lee, Hee-Young; Park, Jung-Hwan; Park, Jung Ho

2018-11-01

The aim of this study was to investigate the effectiveness of treating gastric cancer by injecting a pluronic F-127 sol-gel formulation of 5-fluorouracil (5-FU) into normal tissue surrounding the tumor using a hollow microneedle. The MTS tetrazolium assay was performed to assess the cytotoxicity of 5-FU after application to gastric cancer cells at different concentrations for 1, 5 and 10 h. Gastric cancer cells were inoculated subcutaneously into 30 male nude mice (CrjBALB/c-nu/nu mice, male); the inoculated mouse were divided into three groups. One group received no treatment, whereas the two other groups received free 5-FU gel (40 mg/kg) and 5-FU gel (40 mg/kg) for 4 days, respectively. Mean tumor volume, apoptotic index (TUNEL) and proliferative index (Ki 67) were evaluated in all groups. Cell viability was 77.3% when 1.22 g of free 5-FU was administered, whereas cell viability was 37.4% and 43.5% when 0.122 g of free 5-FU was administered per hour for 10 h and 0.244 g of free 5-FU was administered for 5 h (p < .01). The 5-FU sol-gel induced apoptosis and significantly inhibited cell proliferation compared to the free 5-FU (p < .01). In addition, xenografted tumor growth was significantly suppressed by administration of the 5-FU sol-gel formulation to inoculated mice (p < .01), and 71% (5/7) of xenografted tumors disappeared after 4 weeks. In conclusion, peri-tumor injection of a 5-FU sol-gel formulation into normal tissue surrounding the tumor mass using a hollow microneedle is an effective method for treating gastric cancer.

Biocompatible Injectable Hydrogel with Potent Wound Healing and Antibacterial Properties.

PubMed

Hoque, Jiaul; Prakash, Relekar G; Paramanandham, Krishnamoorthy; Shome, Bibek R; Haldar, Jayanta

2017-04-03

Two component injectable hydrogels that cross-link in situ have been used as noninvasive wound-filling devices, i.e., sealants. These materials carry a variety of functions at the wound sites, such as sealing leaks, ceasing unwanted bleeding, binding tissues together, and assisting in wound healing processes. However, commonly used sealants typically lack antibacterial properties. Since bacterial infection at the wound site is very common, bioadhesive materials with intrinsic antibacterial properties are urgently required. Herein, we report a biocompatible injectable hydrogel with inherent bioadhesive, antibacterial, and hemostatic capabilities suitable for wound sealing applications. The hydrogels were developed in situ from an antibacterial polymer, N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC), and a bioadhesive polymer, polydextran aldehyde. The gels were shown to be active against both Gram-positive and Gram-negative bacteria, including drug-resistant ones such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and β-lactam-resistant Klebsiela pneumoniae. Mechanistic studies revealed that the gels killed bacteria upon contact by disrupting the membrane integrity of the pathogen. Importantly, the gels were shown to be efficacious in preventing sepsis in a cecum ligation and puncture (CLP) model in mice. While only 12.5% of animals survived in the case of mice with punctured cecam but with no gel on the punctured area (control), 62.5% mice survived when the adhesive gel was applied to the punctured area. Furthermore, the gels were also shown to be effective in facilitating wound healing in rats and ceasing bleeding from a damaged liver in mice. Notably, the gel showed negligible toxicity toward human red blood cells (only 2-3% hemolysis) and no inflammation to the surrounding tissue upon subcutaneous implantation in mice, thus proving it as a safe and effective antibacterial sealant.

Minimally invasive photopolymerization in intervertebral disc tissue cavities

NASA Astrophysics Data System (ADS)

Schmocker, Andreas M.; Khoushabi, Azadeh; Gantenbein-Ritter, Benjamin; Chan, Samantha; Bonél, Harald Marcel; Bourban, Pierre-Etienne; Mânson, Jan Anders; Schizas, Constantin; Pioletti, Dominique; Moser, Christophe

2014-03-01

Photopolymerized hydrogels are commonly used for a broad range of biomedical applications. As long as the polymer volume is accessible, gels can easily be hardened using light illumination. However, in clinics, especially for minimally invasive surgery, it becomes highly challenging to control photopolymerization. The ratios between polymerizationvolume and radiating-surface-area are several orders of magnitude higher than for ex-vivo settings. Also tissue scattering occurs and influences the reaction. We developed a Monte Carlo model for photopolymerization, which takes into account the solid/liquid phase changes, moving solid/liquid-boundaries and refraction on these boundaries as well as tissue scattering in arbitrarily designable tissue cavities. The model provides a tool to tailor both the light probe and the scattering/absorption properties of the photopolymer for applications such as medical implants or tissue replacements. Based on the simulations, we have previously shown that by adding scattering additives to the liquid monomer, the photopolymerized volume was considerably increased. In this study, we have used bovine intervertebral disc cavities, as a model for spinal degeneration, to study photopolymerization in-vitro. The cavity is created by enzyme digestion. Using a custom designed probe, hydrogels were injected and photopolymerized. Magnetic resonance imaging (MRI) and visual inspection tools were employed to investigate the successful photopolymerization outcomes. The results provide insights for the development of novel endoscopic light-scattering polymerization probes paving the way for a new generation of implantable hydrogels.

Penis invalidating cicatricial outcomes in an enlargement phalloplasty case with polyacrylamide gel (Formacryl).

PubMed

Parodi, P C; Dominici, M; Moro, U

2006-01-01

The present article reports the case of a patient subjected to polyacrylamide polymers-composed gel cutaneous infiltration in the penis for cosmetic purposes, resulting in severe invalidating outcomes. A significant tissue reaction to the subcutaneous injection of polyacrylamide gel for the penis enlargement purpose resulted in permanent and invalidating scars both on the esthetic and functional levels. Such a result must be simply taken into account both singly and in the light of the international literature to exclude this method as standard uro-andrologic activity.

Optimization of the first dimension for separation by two-dimensional gel electrophoresis of basic proteins from human brain tissue.

PubMed

Pennington, Kyla; McGregor, Emma; Beasley, Clare L; Everall, Ian; Cotter, David; Dunn, Michael J

2004-01-01

A major cause of poor resolution in the alkaline pH range of two-dimensional electrophoresis (2-DE) gels is unsatisfactory separation of basic proteins in the first dimension. We have compared methods for the separation of basic proteins in the isoelectric focusing dimension of human brain proteins. The combined use of anodic cup-loading and the hydroxyethyldisulphide containing solution (DeStreak) produced better resolution in both analytical and micropreparative protein loaded 2-DE gels than the other methods investigated.

A comparative in vitro study of the digestibility of heat- and high pressure-induced gels prepared from industrial milk whey proteins

NASA Astrophysics Data System (ADS)

He, Jin-Song; Mu, Tai-Hua; Wang, Juan

2013-06-01

We undertook this study to compare the digestibility of heat- and high pressure-induced gels produced from whey protein isolate (WPI). To simulate in vivo gastrointestinal digestion of WPI gels, a pepsin-trypsin digestion system was used. The in vitro protein digestibility of WPI gels induced by high pressure (400 MPa and 30 min; P-gel) and those induced by heat (80°C and 30 min; H-gel) was compared using a protein concentration of 0.14 g mL-1. The in vitro protein digestibility of P-gels was significantly greater than that of H-gels (p<0.05). The size-exclusion chromatography profiles of the hydrolysates showed that the P-gel generated more and smaller peptides than natural WPI and H-gels. Furthermore, Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed some soluble disulfide-mediated aggregation in the P-gel, while there was more insoluble aggregation in the H-gel than the P-gel. The P-gel was more sensitive to proteinase than the H-gel, which was related to the content of S-S bonds, and this in turn could be attributed to the differences in the gelation mechanism between the H-gel and P-gel.

Production of Composite Scaffold Containing Silk Fibroin, Chitosan, and Gelatin for 3D Cell Culture and Bone Tissue Regeneration.

PubMed

Li, Jianqing; Wang, Qiuke; Gu, Yebo; Zhu, Yu; Chen, Liang; Chen, Yunfeng

2017-11-08

BACKGROUND Bone tissue engineering, a powerful tool to treat bone defects, is highly dependent on use of scaffolds. Both silk fibroin (SF) and chitosan (Cs) are biocompatible and actively studied for reconstruction of tissue engineering. Gelatin (Gel) is also widely applied in the biomedical field due to its low antigenicity and physicochemical stability. MATERIAL AND METHODS In this study, 4 different types of scaffolds were constructed - SF, SF/Cs, SF/Gel, and SF/Cs/Gel - and we compared their physical and chemical properties as well as biological characterization of these scaffolds to determine the most suitable scaffold for use in bone regeneration. First, these scaffolds were produced via chemical cross-linking method and freeze-drying technique. Next, the characterization of internal structure was studied using scanning electron microscopy and the porosity was evaluated by liquid displacement method. Then, we compared physicochemical properties such as water absorption rate and degradation property. Finally, MC3T3-E1 cells were inoculated on the scaffolds to study the biocompatibility and osteogenesis of the three-dimensional (3D) scaffolds in vitro. RESULTS The composite scaffold formed by all 3 components was the best for use in bone regeneration. CONCLUSIONS We conclude that the best scaffold among the 4 studied for MC3T3-E1 cells is our SF/Cs/Gel scaffold, suggesting a new choice for bone regeneration that can be used to treat bone defects or fractures in clinical practice.

Separation and characterization of needle and xylem maritime pine proteins.

PubMed

Costa, P; Pionneau, C; Bauw, G; Dubos, C; Bahrmann, N; Kremer, A; Frigerio, J M; Plomion, C

1999-01-01

Two-dimensional gel electrophoresis (2-DE) and image analysis are currently used for proteome analysis in maritime pine (Pinus pinaster Ait.). This study presents a database of expressed proteins extracted from needles and xylem, two important tissues for growth and wood formation. Electrophoresis was carried out by isoelectric focusing (IEF) in the first dimension and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the second. Silver staining made it possible to detect an average of 900 and 600 spots on 2-DE gels from needles and xylem, respectively. A total of 28 xylem and 35 needle proteins were characterized by internal peptide microsequencing. Out of these 63 proteins, 57 (90%) could be identified based on amino acid similarity with known proteins, of which 24 (42%) have already been described in conifers. Overall comparison of both tissues indicated that 29% and 36% of the spots were specific to xylem and needles, respectively, while the other spots were of identical molecular weight and isoelectric point. The homology of spot location in 2-DE patterns was further validated by sequence analysis of proteins present in both tissues. A proteomic database of maritime pine is accessible on the internet (http://www.pierroton.inra.fr/genetics/2D/).

Human dermal and gingival fibroblasts in a three-dimensional culture: a comparative study on matrix remodeling.

PubMed

Chaussain Miller, C; Septier, D; Bonnefoix, M; Lecolle, S; Lebreton-Decoster, C; Coulomb, B; Pellat, B; Godeau, G

2002-03-01

Free-floating collagen lattice is considered a useful tool for assessing wound healing in vitro. This work compared extracellular matrix remodeling in collagen lattices populated by gingival or dermal fibroblasts. For 21 days we followed gel contraction and changes in cell number of collagen lattices seeded with l.5 x 10(5) fibroblasts of each tissue. We also used indirect immunodetection to study extracellular matrix components, metalloproteinases (MMPs), and their tissues inhibitors (TIMPs). In addition, the presence of MMPs and TIMPs in the culture media was analyzed by zymography and western blotting. No significant difference was found concerning gel contraction and changes in cell number. We observed the early expression of fibrillin I and collagen type III, apparently codistributed and at the end of the gel contraction their disappearance. Concomitantly we demonstrated the expression of MMPs and TIMPs, initially localized in cellular cytoplasm, then spreading in the extracellular compartment, and even found in the culture medium. This remodeling was more rapid and intense with gingival fibroblasts than dermal fibroblasts. In conclusion, gingival fibroblasts seem more efficient at remodeling the connective tissue than dermal fibroblasts and could lead to the better wound healing observed in vivo.

Poly(vinyl alcohol) gels as photoacoustic breast phantoms revisited.

PubMed

Xia, Wenfeng; Piras, Daniele; Heijblom, Michelle; Steenbergen, Wiendelt; van Leeuwen, Ton G; Manohar, Srirang

2011-07-01

A popular phantom in photoacoustic imaging is poly(vinyl alcohol) (PVA) hydrogel fabricated by freezing and thawing (F-T) aqueous solutions of PVA. The material possesses acoustic and optical properties similar to those of tissue. Earlier work characterized PVA gels in small test specimens where temperature distributions during F-T are relatively homogeneous. In this work, in breast-sized samples we observed substantial temperature differences between the shallow regions and the interior during the F-T procedure. We investigated whether spatial variations were also present in the acoustic and optical properties. The speed of sound, acoustic attenuation, and optical reduced scattering coefficients were measured on specimens sampled at various locations in a large phantom. In general, the properties matched values quoted for breast tissue. But while acoustic properties were relatively homogeneous, the reduced scattering was substantially different at the surface compared with the interior. We correlated these variations with gel microstructure inspected using scanning electron microscopy. Interestingly, the phantom's reduced scattering spatial distribution matches the optical properties of the standard two-layer breast model used in x ray dosimetry. We conclude that large PVA samples prepared using the standard recipe make excellent breast tissue phantoms.

Proteomic analysis of intestinal tissues from mice fed with Lentinula edodes-derived polysaccharides.

PubMed

Xu, Xiaofei; Yang, Jiguo; Ning, Zhengxiang; Zhang, Xuewu

2016-01-01

Lentinula edodes-derived polysaccharides are well known for their immunomodulation and antitumor activities. However, the mechanisms of action have not been fully elucidated. This study presents proteomic analysis of the colon and small intestine from mice fed with an immunostimulating heteropolysaccharide L2 from the fruit body of L. edodes. Two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-TOF MS/MS were employed to characterize the protein profiles. Twenty nine gel spots representing 20 proteins in colon tissues and 38 gel spots in small intestine tissues representing 23 proteins were identified as showing significant changes in abundance. These differential proteins in abundance are mainly involved in metabolism, binding, structural components, and response to stimulus. Protein-protein interaction network analysis demonstrated mapping of the 20 colon proteins to a 7-protein and a 3-protein sub-network, and mapping of the 23 small intestine proteins to a 9-protein and a 5-protein sub-network. All the 40 altered proteins were integrated into a unified network containing 25 proteins, suggesting the existence of a concerted mechanism, although acting on the colon and small intestine separately. These findings facilitate the understanding of the regulatory mechanism in response to L2 treatment.

Gelation of soybean protein and polysaccharides delays digestion.

PubMed

Hu, Bing; Chen, Qing; Cai, Qimeng; Fan, Yun; Wilde, Peter J; Rong, Zhen; Zeng, Xiaoxiong

2017-04-15

Xanthan gum and carrageenan, representing the medium and highly negatively charged polysaccharides, were heated respectively together with soybean protein isolate (SPI) at different biopolymer ratios. Upon mixing with simulated stomach juice (SSJ), the xanthan-SPI and carrageenan-SPI at biopolymer ratios higher than 0.01 leads to self-assembled gelation immediately. Stronger gel is formed under higher biopolymer ratios. Highly negatively charged carrageenan forms a stronger gel than that composed with xanthan gum. SDS-PAGE results show the digestibility of SPI is delayed after incorporation with the polysaccharides, which is enhanced with the increase of the biopolymer mass ratios. And the polysaccharide with higher negative charge has stronger potential in delaying the digestion of SPI. Furthermore, the microstructure of the xanthan-SPI and carrageenan-SPI gel before and after simulated stomach digestion was characterized by scanning electron microscope (SEM), which also confirms that the gel delays the digestion of soybean protein. Copyright © 2016 Elsevier Ltd. All rights reserved.

Photo-cross-linkable methacrylated gelatin and hydroxyapatite hybrid hydrogel for modularly engineering biomimetic osteon.

PubMed

Zuo, Yicong; Liu, Xiaolu; Wei, Dan; Sun, Jing; Xiao, Wenqian; Zhao, Huan; Guo, Likun; Wei, Qingrong; Fan, Hongsong; Zhang, Xingdong

2015-05-20

Modular tissue engineering holds great potential in regenerating natural complex tissues by engineering three-dimensional modular scaffolds with predefined geometry and biological characters. In modular tissue-like construction, a scaffold with an appropriate mechanical rigidity for assembling fabrication and high biocompatibility for cell survival is the key to the successful bioconstruction. In this work, a series of composite hydrogels (GH0, GH1, GH2, and GH3) based on a combination of methacrylated gelatin (GelMA) and hydroxyapatite (HA) was exploited to enhance hydrogel mechanical rigidity and promote cell functional expression for osteon biofabrication. These composite hydrogels presented a lower swelling ratio, higher mechanical moduli, and better biocompatibility when compared to the pure GelMA hydrogel. Furthermore, on the basis of the composite hydrogel and photolithograph technology, we successfully constructed an osteon-like concentric double-ring structure in which the inner ring encapsulating human umbilical vascular endothelial cells (HUVECs) was designed to imitate blood vessel tubule while the outer ring encapsulating human osteoblast-like cells (MG63s) acts as part of bone. During the coculture period, MG63s and HUVECs exhibited not only satisfying growth status but also the enhanced genic expression of osteogenesis-related and angiogenesis-related differentiations. These results demonstrate this GelMA-HA composite hydrogel system is promising for modular tissue engineering.

Structurally Caused Freezing Point Depression of Biological Tissues

PubMed Central

Bloch, Rene; Walters, D. H.; Kuhn, Werner

1963-01-01

When investigating the freezing behaviour (by thermal analysis) of the glycerol-extracted adductor muscle of Mytilus edulis it was observed that the temperature of ice formation in the muscular tissue was up to 1.5°C lower than the freezing point of the embedding liquid, a 0.25 N KCl solution with pH = 4.9 with which the tissue had been equilibrated prior to the freezing experiment. A smaller freezing point depression was observed if the pH values of the embedding 0.25 N KCl solution were above or below pH = 4.9. Reasoning from results obtained previously in analogous experiments with artificial gels, the anomalous freezing depression is explained by the impossibility of growing at the normal freezing temperature regular macroscopic crystals inside the gel, due to the presence of the gel network. The freezing temperature is here determined by the size of the microprisms penetrating the meshes of the network at the lowered freezing temperature. This process leads finally to an ice block of more or less regular structure in which the filaments are embedded. Prerequisite for this hindrance of ideal ice growth is a sufficient tensile strength of the filamental network. The existence of structurally caused freezing point depression in biological tissue is likely to invalidate many conclusions reported in the literature, in which hypertonicity was deduced from cryoscopic data. PMID:13971682

Self-Assembly of Molecular Threads into Reversible Gels

NASA Astrophysics Data System (ADS)

Sayar, Mehmet; Stupp, Samuel I.

2001-03-01

Reversible gels formed by low concentrations of molecular gelators that self-assemble into fibers with molecular width and extremely long length have been studied via Monte Carlo simulations. The gelators of interest have two kinds of interactions, one governs self-assembly into fibers and the other provides inter-fiber connectivity to drive the formation of a network. The off-lattice Monte Carlo simulation presented here is based on a point particle representation of gelators. In this model each particle can form only two strong bonds, that enable linear fiber formation, but a variable number of weak bonds which provide inter-fiber connectivity. The gel formation has been studied as a function of concentration of monomers, the strength of interactions, number of bonding sites per particle for weak interactions, and the stiffness of the fibers. The simulation results are compared with two experimental systems synthesized in our group in order to understand gelation mechanisms.

Preparation of a collagen/polymer hybrid gel designed for tissue membranes. Part I: controlling the polymer-collagen cross-linking process using an ethanol/water co-solvent.

PubMed

Nam, Kwangwoo; Kimura, Tsuyoshi; Funamoto, Seiichi; Kishida, Akio

2010-02-01

The drawback with collagen/2-methacryloyloxyethyl phosphorylcholine (MPC) polymer hybrid gels (collagen/phospholipid polymer hybrid gels) prepared in alkaline morpholinoethane sulfonic acid (MES) aqueous solution is that the cross-linking rate between the polymer and the collagen is low. To solve this problem, ethanol has been adopted as the reaction solvent, to prevent 1-ethyl-3-(3-dimethylaminopropyl)-1-carbodiimide hydrochloride (EDC) hydrolysis. Alterations in the ethanol mole concentration changed the cross-linking rate between the MPC polymer and the collagen gel. Prevention of EDC hydrolysis is clearly observed; protonation of carboxyl groups implies that the ratio of ethanol to water should be controlled. The polymer shows signs of penetration into the collagen gel layer, thus forming a totally homogeneous phase gel. This affects the mechanical strength of the collagen gel, making the gel much stiffer and brittle with an increase in the swelling ratio, as compared with that prepared in MES buffer. However, it is possible to obtain a collagen/phospholipid polymer hybrid gel with a high polymer portion and the cross-linking rate can be successfully controlled.

Green synthesis of silver nanoparticles aimed at improving theranostics

NASA Astrophysics Data System (ADS)

Vedelago, José; Gomez, Cesar G.; Valente, Mauro; Mattea, Facundo

2018-05-01

Nowadays, the combination of diagnosis and therapy, known as theranostics, is one of the keys for an optimal treatment for cancer diseases. Theranostics can be significantly improved by incorporating metallic nanoparticles that are specifically delivered and accumulated in cancerous tissue. In this context, precise knowledge about dosimetric effects in nanoparticle-infused tissues as well as the detection and processing of emerging radiation are extremely important issues. In the last years the first studies on theranostic nanomaterials in gel dosimetry have been presented but there is still a broad field of study to explore. Most of gel dosimetric materials are extremely sensible to modifications in their composition, the addition of enhancers, metallic or inorganic charges can alter their stability and dosimetric properties; therefore, thorough studies must be made before the incorporation of any type of modifier. In this work, the synthesis of metallic nanoparticles suitable for gel dosimetry for x-ray applications is presented. A green synthesis process of silver nanoparticles coated with porcine skin gelatin by thermal reduction of silver nitrate is presented. Nanoparticles were obtained and purified for their application in gel dosimetry. Also, nanoparticles size distribution, reaction yield and the preliminar application as theranostic agents were tested in Fricke gel dosimetry in the keV range. The obtained nanoparticles were successfully used in theranostic applications acting as fluorescent agents and dose enhancers in X-ray beam irradiation simultaneously.

Mapping Glycosaminoglycan–Hydroxyapatite Colloidal Gels as Potential Tissue Defect Fillers

PubMed Central

2015-01-01

Malleable biomaterials such as Herschel–Bulkley (H–B) fluids possess shear responsive rheological properties and are capable of self-assembly and viscoelastic recovery following mechanical disruption (e.g., surgical placement via injection or spreading). This study demonstrated that the addition of moderate molecular weight glycosaminoglycans (GAGs) such as chondroitin sulfate (CS) (Mw = 15–30 kDa) and hyaluronic acid (HA) (Mw = 20–41 kDa) can be used to modify several rheological properties including consistency index (K), flow-behavior index (n), and yield stress (τy) of submicrometer hydroxyapatite (HAP) (Davg ≤ 200 nm) colloidal gels. GAG–HAP colloidal mixtures exhibited substantial polymer–particle synergism, likely due to “bridging” flocculation, which led to a synergistic increase in consistency index (KGAG-HAP ≥ KGAG + KHAP) without compromising shear-thinning behavior (n < 1) of the gel. In addition, GAG–HAP colloids containing high concentrations of HAP (60–80% w/v) exhibited substantial yield stress (τy ≥ 100 Pa) and viscoelastic recovery properties (G′recovery ≥ 64%). While rheological differences were observed between CS–HAP and HA–HAP colloidal gels, both CS and HA represent feasible options for future studies involving bone defect filling. Overall, this study identified mixture regions where rheological properties in CS–HAP and HA–HAP colloidal gels aligned with desired properties to facilitate surgical placement in non-load-bearing tissue-filling applications such as calvarial defects. PMID:24606047

In vitro profiling of the vaginal permeation potential of anti-HIV microbicides and the influence of formulation excipients.

PubMed

Grammen, Carolien; Augustijns, Patrick; Brouwers, Joachim

2012-11-01

In the search for an effective anti-HIV microbicidal gel, limited drug penetration into the vaginal submucosa is a possible reason for failed protection against HIV transmission. To address this issue in early development, we here describe a simple in vitro strategy to predict the tissue permeation potential of vaginally applied drugs, based on solubility, permeability and flux assessment. We demonstrated this approach for four model microbicides (tenofovir, darunavir, saquinavir mesylate and dapivirine) and additionally examined the influence of formulation excipients on the permeation potential. When formulated in an aqueous-based HEC gel, high flux values across an HEC-1A cell layer were reached by tenofovir, as a result of its high aqueous solubility. In contrast, saquinavir and dapivirine fluxes remained low due to poor permeability and solubility, respectively. These low fluxes suggest limited in vivo tissue penetration, possibly leading to lack of efficacy. Dapivirine fluxes, however, could be enhanced up to 30-fold, by including formulation excipients such as polyethylene glycol 1000 (20%) or cyclodextrins (5%) in the HEC gels. Alternative formulations, i.e. emulsions or silicone elastomer gels, were less effective in flux enhancement compared to cyclodextrin-HEC gels. In conclusion, implementing the proposed solubility and permeability profiling in early microbicide development may contribute to the successful selection of promising microbicide candidates and appropriate formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

Novel enzymatically cross-linked hyaluronan hydrogels support the formation of 3D neuronal networks.

PubMed

Broguiere, Nicolas; Isenmann, Luca; Zenobi-Wong, Marcy

2016-08-01

Hyaluronan (HA) is an essential component of the central nervous system's extracellular matrix and its high molecular weight (MW) form has anti-inflammatory and anti-fibrotic properties relevant for regenerative medicine. Here, we introduce a new hydrogel based on high MW HA which is cross-linked using the transglutaminase (TG) activity of the activated blood coagulation factor XIII (FXIIIa). These HA-TG gels have significant advantages for neural tissue engineering compared to previous HA gels. Due to their chemical inertness in the absence of FXIIIa, the material can be stored long-term, is stable in solution, and shows no cytotoxicity. The gelation is completely cell-friendly due to the specificity of the enzyme and the gelation rate can be tuned from seconds to hours at physiological pH and independently of stiffness. The gels are injectable, and attach covalently to fibrinogen and fibrin, two common bioactive components in in vitro tissue engineering, as well as proteins present in vivo, allowing the gels to covalently bind to brain or spinal cord defects. These optimal chemical and bioactive properties of HA-TG gels enabled the formation of 3D neuronal cultures of unprecedented performance, showing fast neurite outgrowth, axonal and dendritic speciation, strong synaptic connectivity in 3D networks, and rapidly-occurring and long-lasting coordinated electrical activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fabrication of 3D-culture platform with sandwich architecture for preserving liver-specific functions of hepatocytes using 3D bioprinter.

PubMed

Arai, Kenichi; Yoshida, Toshiko; Okabe, Motonori; Goto, Mitsuaki; Mir, Tanveer Ahmad; Soko, Chika; Tsukamoto, Yoshinari; Akaike, Toshihiro; Nikaido, Toshio; Zhou, Kaixuan; Nakamura, Makoto

2017-06-01

The development of new three-dimensional (3D) cell culture system that maintains the physiologically relevant signals of hepatocytes is essential in drug discovery and tissue engineering research. Conventional two-dimensional (2D) culture yields cell growth, proliferation, and differentiation. However, gene expression and signaling profiles can be different from in vivo environment. Here, we report the fabrication of a 3D culture system using an artificial scaffold and our custom-made inkjet 3D bioprinter as a new strategy for studying liver-specific functions of hepatocytes. We built a 3D culture platform for hepatocytes-attachment and formation of cell monolayer by interacting the galactose chain of galactosylated alginate gel (GA-gel) with asialoglycoprotein receptor (ASGPR) of hepatocytes. The 3D geometrical arrangement of cells was controlled by using 3D bioprinter, and cell polarity was controlled with the galactosylated hydrogels. The fabricated GA-gel was able to successfully promote adhesion of hepatocytes. To observe liver-specific functions and to mimic hepatic cord, an additional parallel layer of hepatocytes was generated using two gel sheets. These results indicated that GA-gel biomimetic matrices can be used as a 3D culture system that could be effective for the engineering of liver tissues. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1583-1592, 2017. © 2017 Wiley Periodicals, Inc.

Synthesis of embryonic tendon-like tissue by human marrow stromal/mesenchymal stem cells requires a three-dimensional environment and transforming growth factor β3.

PubMed

Kapacee, Zoher; Yeung, Ching-Yan Chloé; Lu, Yinhui; Crabtree, David; Holmes, David F; Kadler, Karl E

2010-10-01

Tendon-like tissue generated from stem cells in vitro has the potential to replace tendons and ligaments lost through injury and disease. However, thus far, no information has been available on the mechanism of tendon formation in vitro and how to accelerate the process. We show here that human mesenchymal stem cells (MSCs) and bone marrow-derived mononuclear cells (BM-MNCs) can generate tendon-like tissue in 7days mediated by transforming growth factor (TGF) β3. MSCs cultured in fixed-length fibrin gels spontaneously synthesized narrow-diameter collagen fibrils and exhibited fibripositors (actin-rich, collagen fibril-containing plasma membrane protrusions) identical to those that occur in embryonic tendon. In contrast, BM-MNCs did not synthesize tendon-like tissue under these conditions. We performed real-time PCR analysis of MSCs and BM-MNCs. MSCs upregulated genes encoding type I collagen, TGFβ3, and Smad2 at the time of maximum contraction of the tendon-like tissue (7days). Western blot analysis showed phosphorylation of Smad2 at maximum contraction. The TGFβ inhibitor SB-431542, blocked the phosphorylation of Smad2 and stopped the formation of tendon-like tissue. Quantitative PCR showed that BM-MNCs expressed very low levels of TGFβ3 compared to MSCs. Therefore we added exogenous TGFβ3 protein to BM-MNCs in fibrin gels, which resulted in phosphorylation of Smad2, synthesis of collagen fibrils, the appearance of fibripositors at the plasma membrane, and the formation of tendon-like tissue. In conclusion, MSCs that self-generate TGFβ signaling or the addition of TGFβ3 protein to BM-MNCs in fixed-length fibrin gels spontaneously make embryonic tendon-like tissue in vitro within 7days. Copyright © 2010 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

The Influence of Arginine on the Response of Enamel Matrix Derivative (EMD) Proteins to Thermal Stress: Towards Improving the Stability of EMD-Based Products

PubMed Central

Bolisetty, Sreenath; Marascio, Matteo; Gemperli Graf, Anja; Garamszegi, Laszlo; Mezzenga, Raffaele; Fischer, Peter; Månson, Jan-Anders

2015-01-01

In a current procedure for periodontal tissue regeneration, enamel matrix derivative (EMD), which is the active component, is mixed with a propylene glycol alginate (PGA) gel carrier and applied directly to the periodontal defect. Exposure of EMD to physiological conditions then causes it to precipitate. However, environmental changes during manufacture and storage may result in modifications to the conformation of the EMD proteins, and eventually premature phase separation of the gel and a loss in therapeutic effectiveness. The present work relates to efforts to improve the stability of EMD-based formulations such as Emdogain™ through the incorporation of arginine, a well-known protein stabilizer, but one that to our knowledge has not so far been considered for this purpose. Representative EMD-buffer solutions with and without arginine were analyzed by 3D-dynamic light scattering, UV-Vis spectroscopy, transmission electron microscopy and Fourier transform infrared spectroscopy at different acidic pH and temperatures, T, in order to simulate the effect of pH variations and thermal stress during manufacture and storage. The results provided evidence that arginine may indeed stabilize EMD against irreversible aggregation with respect to variations in pH and T under these conditions. Moreover, stopped-flow transmittance measurements indicated arginine addition not to suppress precipitation of EMD from either the buffers or the PGA gel carrier when the pH was raised to 7, a fundamental requirement for dental applications. PMID:26670810

The Influence of Arginine on the Response of Enamel Matrix Derivative (EMD) Proteins to Thermal Stress: Towards Improving the Stability of EMD-Based Products.

PubMed

Apicella, Alessandra; Heunemann, Peggy; Bolisetty, Sreenath; Marascio, Matteo; Gemperli Graf, Anja; Garamszegi, Laszlo; Mezzenga, Raffaele; Fischer, Peter; Plummer, Christopher J; Månson, Jan-Anders

2015-01-01

In a current procedure for periodontal tissue regeneration, enamel matrix derivative (EMD), which is the active component, is mixed with a propylene glycol alginate (PGA) gel carrier and applied directly to the periodontal defect. Exposure of EMD to physiological conditions then causes it to precipitate. However, environmental changes during manufacture and storage may result in modifications to the conformation of the EMD proteins, and eventually premature phase separation of the gel and a loss in therapeutic effectiveness. The present work relates to efforts to improve the stability of EMD-based formulations such as Emdogain™ through the incorporation of arginine, a well-known protein stabilizer, but one that to our knowledge has not so far been considered for this purpose. Representative EMD-buffer solutions with and without arginine were analyzed by 3D-dynamic light scattering, UV-Vis spectroscopy, transmission electron microscopy and Fourier transform infrared spectroscopy at different acidic pH and temperatures, T, in order to simulate the effect of pH variations and thermal stress during manufacture and storage. The results provided evidence that arginine may indeed stabilize EMD against irreversible aggregation with respect to variations in pH and T under these conditions. Moreover, stopped-flow transmittance measurements indicated arginine addition not to suppress precipitation of EMD from either the buffers or the PGA gel carrier when the pH was raised to 7, a fundamental requirement for dental applications.

Metal-polysiloxane shields for radiation therapy of maxillo-facial tumors.

PubMed

Farahani, M; Eichmiller, F C; McLaughlin, W L

1991-01-01

In the treatment of some head and neck lesions with high-intensity radiation (teletherapy), an essential procedure is the application of an individually customized shielding appliance, which is designed, modeled, and formed into a working extra- or intraoral stent for the purpose of sparing healthy tissues. The present state of the art is slow and technique intensive, which can add to patient discomfort and inconvenience during molding and fabrication. A new formulation is described, which offers speed and ease of forming a moldable composite stent especially for intraoral use. Interleaved stacks of calibrated thin radiochromic film strips and soft-tissue-simulating plastic (polystyrene) layers gave a means of mapping one- or two-dimensional profiles of dose distributions adjacent to the high-density shielding materials using a spectrophotometer equipped with a gel scanner or a scanning laser-beam microdensitometer. Tests using collimated gamma-ray beams from a 60Co teletherapy unit were made in order to measure the dose distribution near interfaces of tissue-simulating polymer and the composite stent material with and without mixtures of metals (Ag-Cu and Sn-Sb). These results show that quickly formed composites made of a flexible resin with high concentrations of powdered spherical metal alloys provide effective custom-designed shielding, and, with a thin overlayer of the resin without metal, a diminished back-scattered radiation dose to normal tissues. An example of a successful formulation is a mixture of 90% by weight Ag-Cu alloy powder in a vinyl polysiloxane resin. This material is a moldable putty which, upon polymerization, forms a rigid elastomeric material, providing a half-value layer of approximately 2.5 to 2.8 cm for a gamma-ray beam from a 60Co source.

3D bioprinting mesenchymal stem cell-laden construct with core-shell nanospheres for cartilage tissue engineering

NASA Astrophysics Data System (ADS)

Zhu, Wei; Cui, Haitao; Boualam, Benchaa; Masood, Fahed; Flynn, Erin; Rao, Raj D.; Zhang, Zhi-Yong; Zhang, Lijie Grace

2018-05-01

Cartilage tissue is prone to degradation and has little capacity for self-healing due to its avascularity. Tissue engineering, which provides artificial scaffolds to repair injured tissues, is a novel and promising strategy for cartilage repair. 3D bioprinting offers even greater potential for repairing degenerative tissue by simultaneously integrating living cells, biomaterials, and biological cues to provide a customized scaffold. With regard to cell selection, mesenchymal stem cells (MSCs) hold great capacity for differentiating into a variety of cell types, including chondrocytes, and could therefore be utilized as a cartilage cell source in 3D bioprinting. In the present study, we utilize a tabletop stereolithography-based 3D bioprinter for a novel cell-laden cartilage tissue construct fabrication. Printable resin is composed of 10% gelatin methacrylate (GelMA) base, various concentrations of polyethylene glycol diacrylate (PEGDA), biocompatible photoinitiator, and transforming growth factor beta 1 (TGF-β1) embedded nanospheres fabricated via a core-shell electrospraying technique. We find that the addition of PEGDA into GelMA hydrogel greatly improves the printing resolution. Compressive testing shows that modulus of the bioprinted scaffolds proportionally increases with the concentrations of PEGDA, while swelling ratio decreases with the increase of PEGDA concentration. Confocal microscopy images illustrate that the cells and nanospheres are evenly distributed throughout the entire bioprinted construct. Cells grown on 5%/10% (PEGDA/GelMA) hydrogel present the highest cell viability and proliferation rate. The TGF-β1 embedded in nanospheres can keep a sustained release up to 21 d and improve chondrogenic differentiation of encapsulated MSCs. The cell-laden bioprinted cartilage constructs with TGF-β1-containing nanospheres is a promising strategy for cartilage regeneration.

A comparison of different bioinks for 3D bioprinting of fibrocartilage and hyaline cartilage.

PubMed

Daly, Andrew C; Critchley, Susan E; Rencsok, Emily M; Kelly, Daniel J

2016-10-07

Cartilage is a dense connective tissue with limited self-repair capabilities. Mesenchymal stem cell (MSC) laden hydrogels are commonly used for fibrocartilage and articular cartilage tissue engineering, however they typically lack the mechanical integrity for implantation into high load bearing environments. This has led to increased interested in 3D bioprinting of cell laden hydrogel bioinks reinforced with stiffer polymer fibres. The objective of this study was to compare a range of commonly used hydrogel bioinks (agarose, alginate, GelMA and BioINK™) for their printing properties and capacity to support the development of either hyaline cartilage or fibrocartilage in vitro. Each hydrogel was seeded with MSCs, cultured for 28 days in the presence of TGF-β3 and then analysed for markers indicative of differentiation towards either a fibrocartilaginous or hyaline cartilage-like phenotype. Alginate and agarose hydrogels best supported the development of hyaline-like cartilage, as evident by the development of a tissue staining predominantly for type II collagen. In contrast, GelMA and BioINK ™ (a PEGMA based hydrogel) supported the development of a more fibrocartilage-like tissue, as evident by the development of a tissue containing both type I and type II collagen. GelMA demonstrated superior printability, generating structures with greater fidelity, followed by the alginate and agarose bioinks. High levels of MSC viability were observed in all bioinks post-printing (∼80%). Finally we demonstrate that it is possible to engineer mechanically reinforced hydrogels with high cell viability by co-depositing a hydrogel bioink with polycaprolactone filaments, generating composites with bulk compressive moduli comparable to articular cartilage. This study demonstrates the importance of the choice of bioink when bioprinting different cartilaginous tissues for musculoskeletal applications.

3D bioprinting mesenchymal stem cell-laden construct with core-shell nanospheres for cartilage tissue engineering.

PubMed

Zhu, Wei; Cui, Haitao; Boualam, Benchaa; Masood, Fahed; Flynn, Erin; Rao, Raj D; Zhang, Zhi-Yong; Zhang, Lijie Grace

2018-05-04

Cartilage tissue is prone to degradation and has little capacity for self-healing due to its avascularity. Tissue engineering, which provides artificial scaffolds to repair injured tissues, is a novel and promising strategy for cartilage repair. 3D bioprinting offers even greater potential for repairing degenerative tissue by simultaneously integrating living cells, biomaterials, and biological cues to provide a customized scaffold. With regard to cell selection, mesenchymal stem cells (MSCs) hold great capacity for differentiating into a variety of cell types, including chondrocytes, and could therefore be utilized as a cartilage cell source in 3D bioprinting. In the present study, we utilize a tabletop stereolithography-based 3D bioprinter for a novel cell-laden cartilage tissue construct fabrication. Printable resin is composed of 10% gelatin methacrylate (GelMA) base, various concentrations of polyethylene glycol diacrylate (PEGDA), biocompatible photoinitiator, and transforming growth factor beta 1 (TGF-β1) embedded nanospheres fabricated via a core-shell electrospraying technique. We find that the addition of PEGDA into GelMA hydrogel greatly improves the printing resolution. Compressive testing shows that modulus of the bioprinted scaffolds proportionally increases with the concentrations of PEGDA, while swelling ratio decreases with the increase of PEGDA concentration. Confocal microscopy images illustrate that the cells and nanospheres are evenly distributed throughout the entire bioprinted construct. Cells grown on 5%/10% (PEGDA/GelMA) hydrogel present the highest cell viability and proliferation rate. The TGF-β1 embedded in nanospheres can keep a sustained release up to 21 d and improve chondrogenic differentiation of encapsulated MSCs. The cell-laden bioprinted cartilage constructs with TGF-β1-containing nanospheres is a promising strategy for cartilage regeneration.

Measurement of the Dynamic Shear Modulus of Mouse Brain Tissue In Vivo By Magnetic Resonance Elastography

PubMed Central

Atay, Stefan M.; Kroenke, Christopher D.; Sabet, Arash; Bayly, Philip V.

2008-01-01

In this study, the magnetic resonance elastography (MRE) technique was used to estimate the dynamic shear modulus of mouse brain tissue in vivo. The technique allows visualization and measurement of mechanical shear waves excited by lateral vibration of the skull. Quantitative measurements of displacement in three dimensions (3-D) during vibration at 1200 Hz were obtained by applying oscillatory magnetic field gradients at the same frequency during an MR imaging sequence. Contrast in the resulting phase images of the mouse brain is proportional to displacement. To obtain estimates of shear modulus, measured displacement fields were fitted to the shear wave equation. Validation of the procedure was performed on gel characterized by independent rheometry tests and on data from finite element simulations. Brain tissue is, in reality, viscoelastic and nonlinear. The current estimates of dynamic shear modulus are strictly relevant only to small oscillations at a specific frequency, but these estimates may be obtained at high frequencies (and thus high deformation rates), non-invasively throughout the brain. These data complement measurements of nonlinear viscoelastic properties obtained by others at slower rates, either ex vivo or invasively. PMID:18412500

Analysis of metal-binding proteins separated by non-denaturating gel electrophoresis using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS).

PubMed

Becker, J Susanne; Mounicou, Sandra; Zoriy, Miroslav V; Becker, J Sabine; Lobinski, Ryszard

2008-09-15

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) have become established as very efficient and sensitive biopolymer and elemental mass spectrometric techniques for studying metal-binding proteins (metalloproteins) in life sciences. Protein complexes present in rat tissues (liver and kidney) were separated in their native state in the first dimension by blue native gel electrophoresis (BN-PAGE). Essential and toxic metals, such as zinc, copper, iron, nickel, chromium, cadmium and lead, were detected by scanning the gel bands using quadrupole LA-ICP-MS with and without collision cell as a microanalytical technique. Several proteins were identified by using MALDI-TOF-MS together with a database search. For example, on one protein band cut from the BN-PAGE gel and digested with the enzyme trypsin, two different proteins - protein FAM44B and cathepsin B precursor - were identified. By combining biomolecular and elemental mass spectrometry, it was possible to characterize and identify selected metal-binding rat liver and kidney tissue proteins.

The application of silicon sol-gel technology to forensic blood substitute development: Mimicking aspects of whole human blood rheology.

PubMed

Stotesbury, Theresa; Illes, Mike; Wilson, Paul; Vreugdenhil, Andrew J

2017-01-01

Solution-gelation chemistry has promising applications in forensic synthetic blood substitute development. This research offers a silicon-based sol-gel approach to creating stable materials that share similar rheological properties to that of whole human blood samples. Room temperature, high water content, silicon sol-gels were created using the organosilane precursors 3-glycidoxypropyltrimethoxysilane and tetraethylorthosilicate along with various concentrations of filler and pigment. Shear-thinning non-Newtonian properties were observed within most formulations of the presented materials. The effects of colloidal concentration, temperature, age and filler addition on the viscosity of the sol-gels were investigated. SEM-EDS analysis was used to identify the behavior of the fillers within the film and support their inclusion for basic bloodstain pattern simulation. A final proposed candidate sol-gel was assessed using a previously reported passive drip simulation test on a hard, dry surface and passed. This works represents encouraging development in providing safe material alternatives to using whole human blood for forensic training and research. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Swimming micro-robot powered by stimuli-sensitive gel

NASA Astrophysics Data System (ADS)

Masoud, Hassan; Alexeev, Alexander

2012-11-01

Using three-dimensional computer simulations, we design a simple maneuverable micro-swimmer that can self-propel and navigate in highly viscous (low Reynolds-number) environments. Our simple swimmer consists of a cubic gel body which periodically changes volume in response to external stimuli, two rigid rectangular flaps attached to the opposite sides of the gel body, and a flexible steering flap at the front end of the swimmer. The stimuli-sensitive body undergoes periodic expansions (swelling) and contractions (deswelling) leading to a time-irreversible beating motion of the propulsive flaps that propel the micro-swimmer. Thus, the responsive gel body acts as an ``engine'' actuating the motion of the swimmer. We examine how the swimming speed depends on the gel and flap properties. We also probe how the swimmer trajectory can be changed using a responsive steering flap whose curvature is controlled by an external stimulus. We show that the turning occurs due to steering flap bending and periodic beating. Furthermore, our simulations reveal that the turning direction can be regulated by changing the intensity of external stimulus.

Mechano-responsive hydrogels crosslinked by reactive block copolymer micelles

NASA Astrophysics Data System (ADS)

Xiao, Longxi

Hydrogels are crosslinked polymeric networks that can swell in water without dissolution. Owing to their structural similarity to the native extracelluar matrices, hydrogels have been widely used in biomedical applications. Synthetic hydrogels have been designed to respond to various stimuli, but mechanical signals have not incorporated into hydrogel matrices. Because most tissues in the body are subjected to various types of mechanical forces, and cells within these tissues have sophisticated mechano-transduction machinery, this thesis is focused on developing hydrogel materials with built-in mechano-sensing mechanisms for use as tissue engineering scaffolds or drug release devices. Self-assembled block copolymer micelles (BCMs) with reactive handles were employed as the nanoscopic crosslinkers for the construction of covalently crosslinked networks. BCMs were assembled from amphiphilic diblock copolymers of poly(n-butyl acrylate) and poly(acrylic acid) partially modified with acrylate. Radical polymerization of acrylamide in the presence of micellar crosslinkers gave rise to elastomeric hydrogels whose mechanical properties can be tuned by varying the BCM composition and concentration. TEM imaging revealed that the covalently integrated BCMs underwent strain-dependent reversible deformation. A model hydrophobic drug, pyrene, loaded into the core of BCMs prior to the hydrogel formation, was dynamically released in response to externally applied mechanical forces, through force-induced reversible micelle deformation and the penetration of water molecules into the micelle core. The mechano-responsive hydrogel has been studied for tissue repair and regeneration purposes. Glycidyl methacrylate (GMA)-modified hyaluronic acid (HA) was photochemically crosslinked in the presence of dexamethasone (DEX)-loaded crosslinkable BCMs. The resultant HA gels (HAxBCM) contain covalently integrated micellar compartments with DEX being sequestered in the hydrophobic core. Compared to the traditional HA gels prepared by radical crosslinking of HAGMA, HAxBCM gels exhibited improved drug loading and release capacity. Moreover, compressive forces exerted on the gels were transmitted to the crosslinked BCMs, resulting in a force-modulated DEX release on demand. Micelle mobility in the crosslinked networks was analyzed by fluorescence correlation spectroscopy using nile red loaded BCMs. The anti-inflammatory activities of DEX-releasing HAxBCM gels were evaluated via the in vitro culture of lipopolysaccharide-activated macrophages.

The use of water-soluble mucoadhesive gels for the intravesical delivery of epirubicin to the bladder for the treatment of non-muscle-invasive bladder cancer.

PubMed

Chatta, Dani; Cottrell, Lewis; Burnett, Bruce; Laverty, Garry; McConville, Christopher

2015-10-01

To develop an epirubicin-loaded, water-soluble mucoadhesive gels that have the correct rheological properties to facilitate their delivery into the bladder via a catheter, while allowing for their spread across the bladder wall with limited expansion of the bladder and increasing the retention of epirubicin in the bladder and flushing with urine. Epirubicin-loaded hydroxyl ethyl cellulose (HEC) and hydroxy propyl methyl cellulose (HPMC) gels were manufactured and tested for their rheological properties. Their ability to be pushed through a catheter was also assessed as was their in-vitro drug release, spreading in a bladder and retention of epirubicin after flushing with simulated urine. Epirubicin drug release was viscosity-dependent. The 1 and 1.5% HEC gels and the 1, 1.5 and 2% HPMC gels had the correct viscosity to be administered through a model catheter and spread evenly across the bladder wall under the pressure of the detrusor muscle. The epirubicin-loaded gels had an increased retention time in the bladder when compared with a standard intravesical solution of epirubicin, even after successive flushes with simulated urine. The increased retention of epirubicin in the bladder by the HEC and HPMC gels warrant further investigation, using an in-vivo model, to assess their potential for use as treatment for non-muscle-invasive bladder cancer. © 2015 Royal Pharmaceutical Society.

Nano/macro porous bioactive glass scaffold

NASA Astrophysics Data System (ADS)

Wang, Shaojie

Bioactive glass (BG) and ceramics have been widely studied and developed as implants to replace hard tissues of the musculo-skeletal system, such as bones and teeth. Recently, instead of using bulk materials, which usually do not degrade rapidly enough and may remain in the human body for a long time, the idea of bioscaffold for tissue regeneration has generated much interest. An ideal bioscaffold is a porous material that would not only provide a three-dimensional structure for the regeneration of natural tissue, but also degrade gradually and, eventually be replaced by the natural tissue completely. Among various material choices the nano-macro dual porous BG appears as the most promising candidate for bioscaffold applications. Here macropores facilitate tissue growth while nanopores control degradation and enhance cell response. The surface area, which controls the degradation of scaffold can also be tuned by changing the nanopore size. However, fabrication of such 3D structure with desirable nano and macro pores has remained challenging. In this dissertation, sol-gel process combined with spinodal decomposition or polymer sponge replication method has been developed to fabricate the nano-macro porous BG scaffolds. Macropores up to 100microm are created by freezing polymer induced spinodal structure through sol-gel transition, while larger macropores (>200um) of predetermined size are obtained by the polymer sponge replication technique. The size of nanopores, which are inherent to the sol-gel method of glass fabrication, has been tailored using several approaches: Before gel point, small nanopores are generated using acid catalyst that leads to weakly-branched polymer-like network. On the other hand, larger nanopores are created with the base-catalyzed gel with highly-branched cluster-like structure. After the gel point, the nanostructure can be further modified by manipulating the sintering temperature and/or the ammonia concentration used in the solvent exchange process. Although both techniques lower the surface area of BG scaffolds, the temperature-dependent sintering process closes nanopores through densification, while the concentration-dependent solvent exchange process enlarges nanopores through Ostwald-ripening type coarsening. Therefore, nanopore size and surface area of BG scaffold are independently controlled using these methods. In vitro cell and in vivo animal tissue responses have been investigated to evaluate the performance of the nano-macro porous BG scaffold. The cells are found to migrate and penetrate deep into the 3D nano-macro porous structure, while exhibiting excellent adhesion to the bioscaffold surface. Importantly, the new tissue with both blood vessels and collagen fibers is formed deep inside the implanted scaffolds without obvious inflammatory reaction. Furthermore, our observations show biological benefits of the nanopores in the BG scaffold. In comparison to BG scaffold without nanopores, cells migrate and penetrate into nano-macro dual-porous BG scaffold faster and deeper mainly because of the increase of surface area. To study the effect of nanopore topography, we fabricated BG scaffolds with the same surface area but different nanopore sizes. It is found that the initial cell attachment is significantly enhanced on the BG scaffold with the same surface area but smaller nanopores size, indicating that the nanopore topography strongly influences the performance of BG scaffold. In conclusion, the present results demonstrate most clearly the usefulness of our nano-macro dual-porous BG as a novel and superior 3D bioscaffold for regenerative medicine and hard tissue engineering.

Injectable, degradable, electroactive nanocomposite hydrogels containing conductive polymer nanoparticles for biomedical applications

PubMed Central

Wang, Qinmei; Wang, Qiong; Teng, Wei

2016-01-01

Injectable electroactive hydrogels (eGels) are promising in regenerative medicine and drug delivery, however, it is still a challenge to obtain such hydrogels simultaneously possessing other properties including uniform structure, degradability, robustness, and biocompatibility. An emerging strategy to endow hydrogels with desirable properties is to incorporate functional nanoparticles in their network. Herein, we report the synthesis and characterization of an injectable hydrogel based on oxidized alginate (OA) crosslinking gelatin reinforced by electroactive tetraaniline-graft-OA nanoparticles (nEOAs), where nEOAs are expected to impart electroactivity besides reinforcement without significantly degrading the other properties of hydrogels. Assays of transmission electron microscopy, 1H nuclear magnetic resonance, and dynamic light scattering reveal that EOA can spontaneously and quickly self-assemble into robust nanoparticles in water, and this nanoparticle structure can be kept at pH 3~9. Measurement of the gel time by rheometer and the stir bar method confirms the formation of the eGels, and their gel time is dependent on the weight content of nEOAs. As expected, adding nEOAs to hydrogels does not cause the phase separation (scanning electron microscopy observation), but it improves mechanical strength up to ~8 kPa and conductivity up to ~10−6 S/cm in our studied range. Incubating eGels in phosphate-buffered saline leads to their further swelling with an increase of water content <6% and gradual degradation. When growing mesenchymal stem cells on eGels with nEOA content ≤14%, the growth curves and morphology of cells were found to be similar to that on tissue culture plastic; when implanting these eGels on a chick chorioallantoic membrane for 1 week, mild inflammation response appeared without any other structural changes, indicating their good in vitro and in vivo biocompatibility. With injectability, uniformity, degradability, electroactivity, relative robustness, and biocompatibility, these eGels may have a huge potential as scaffolds for tissue regeneration and matrix for stimuli responsive drug release. PMID:26792990

Novel layered double hydroxides-hydroxyapatite/gelatin bone tissue engineering scaffolds: Fabrication, characterization, and in vivo study.

PubMed

Fayyazbakhsh, Fateme; Solati-Hashjin, Mehran; Keshtkar, Abbas; Shokrgozar, Mohammad Ali; Dehghan, Mohammad Mehdi; Larijani, Bagher

2017-07-01

Developing porous biodegradable scaffolds through simple methods is one of the main approaches of bone tissue engineering (BTE). In this work, a novel BTE composite containing layered double hydroxides (LDH), hydroxyapatite (HA) and gelatin (GEL) was fabricated using co-precipitation and solvent-casting methods. Physiochemical characterizations showed that the chemical composition and microstructure of the scaffolds were similar to the natural spongy bone. Interconnected macropores ranging over 100 to 600μm were observed for both scaffolds while the porosity of 90±0.12% and 92.11±0.15%, as well as, Young's modulus of 19.8±0.41 and 12.5±0.35GPa were reported for LDH/GEL and LDH-HA/GEL scaffolds, respectively. The scaffolds were degraded in deionized water after a month. The SEM images revealed that between two scaffolds, the LDH-HA/GEL with needle-like secondary HA crystals showed better bioactivity. According to the alkaline phosphatase activity and Alizarin red staining results, LDH-HA/GEL scaffolds demonstrated better bone-specific activities comparing to LDH/Gel scaffold as well as control sample (P<0.05). The rabbit adipose stem cells (ASCs) were extracted and cultured, then seeded on the LDH-HA/GEL scaffolds after confluence. Three groups of six adult rabbits were prepared: the scaffold+ASCs group, the empty scaffold group and the control group. The critical defects were made on the left radius and the scaffolds with or without ASCs were implanted there while the control group was left without any treatment. All animals were sacrificed after 12weeks. Histomorphometric results showed that the regeneration of defects was accelerated by scaffold implantation but ASC-seeding significantly improved the quality of new bone formation (P<0.05). The results confirmed the good performance of LDH-HA/GEL scaffold to induce bone regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

SU-E-T-753: Three-Dimensional Dose Distributions of Incident Proton Particle in the Polymer Gel Dosimeter and the Radiochromic Gel Dosimeter: A Simulation Study with MCNP Code

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

Park, M; Kim, G; Ji, Y

Purpose: The purpose of this study is to estimate the three-dimensional dose distributions in the polymer and the radiochromic gel dosimeter, and to identify the detectability of both gel dosimeters by comparing with the water phantom in case of irradiating the proton particles. Methods: The normoxic polymer gel and the LCV micelle radiochromic gel were used in this study. The densities of polymer and the radiochromic gel dosimeter were 1.024 and 1.005 g/cm{sup 3}, respectively. The dose distributions of protons in the polymer and radiochromic gel were simulated using Monte Carlo radiation transport code (MCNPX, Los Alamos National Laboratory). Themore » shape of phantom irradiated by proton particles was a hexahedron with the dimension of 12.4 × 12.4 × 15.0 cm{sup 3}. The energies of proton beam were 50, 80, and 140 MeV energies were directed to top of the surface of phantom. The cross-sectional view of proton dose distribution in both gel dosimeters was estimated with the water phantom and evaluated by the gamma evaluation method. In addition, the absorbed dose(Gy) was also calculated for evaluating the proton detectability. Results: The evaluation results show that dose distributions in both gel dosimeters at intermediated section and Bragg-peak region are similar with that of the water phantom. At entrance section, however, inconsistencies of dose distribution are represented, compared with water. The relative absorbed doses in radiochromic and polymer gel dosimeter were represented to be 0.47 % and 2.26 % difference, respectively. These results show that the radiochromic gel dosimeter was better matched than the water phantom in the absorbed dose evaluation. Conclusion: The polymer and the radiochromic gel dosimeter show similar characteristics in dose distributions for the proton beams at intermediate section and Bragg-peak region. Moreover the calculated absorbed dose in both gel dosimeters represents similar tendency by comparing with that in water phantom.« less

Technical Note: Multipurpose CT, ultrasound, and MRI breast phantom for use in radiotherapy and minimally invasive interventions

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

Ruschin, Mark, E-mail: Mark.Ruschin@sunnybrook.ca; Chin, Lee; Ravi, Ananth

Purpose: To develop a multipurpose gel-based breast phantom consisting of a simulated tumor with realistic imaging properties in CT, ultrasound and MRI, or a postsurgical cavity on CT. Applications for the phantom include: deformable image registration (DIR) quality assurance (QA), autosegmentation validation, and localization testing and training for minimally invasive image-guided procedures such as those involving catheter or needle insertion. Methods: A thermoplastic mask of a typical breast patient lying supine was generated and then filled to make an array of phantoms. The background simulated breast tissue consisted of 32.4 g each of ballistic gelatin (BG) powder and Metamusil™ (MM)more » dissolved in 800 ml of water. Simulated tumors were added using the following recipe: 12 g of barium sulfate (1.4% v/v) plus 0.000 14 g copper sulfate plus 0.7 g of MM plus 7.2 g of BG all dissolved in 75 ml of water. The phantom was evaluated quantitatively in CT by comparing Hounsfield units (HUs) with actual breast tissue. For ultrasound and MRI, the phantoms were assessed based on subjective image quality and signal-difference to noise (SDNR) ratio, respectively. The stiffness of the phantom was evaluated based on ultrasound elastography measurements to yield an average Young’s modulus. In addition, subjective tactile assessment of phantom was performed under needle insertion. Results: The simulated breast tissue had a mean background value of 24 HU on CT imaging, which more closely resembles fibroglandular tissue (40 HU) as opposed to adipose (−100 HU). The tumor had a mean CT number of 45 HU, which yielded a qualitatively realistic image contrast relative to the background either as an intact tumor or postsurgical cavity. The tumor appeared qualitatively realistic on ultrasound images, exhibiting hypoechoic characteristics compared to background. On MRI, the tumor exhibited a SDNR of 3.7. The average Young’s modulus was computed to be 15.8 ± 0.7 kPa (1 SD). Conclusions: We have developed a process to efficiently and inexpensively produce multipurpose breast phantoms containing simulated tumors visible on CT, ultrasound, and MRI. The phantoms have been evaluated for image quality and elasticity and can serve as a medium for DIR QA, autosegmentation QA, and training for minimally invasive procedures.« less

An evaluation of 10 percent and 20 percent benzocaine gels in patients with acute toothaches: efficacy, tolerability and compliance with label dose administration directions.

PubMed

Hersh, Elliot V; Ciancio, Sebastian G; Kuperstein, Arthur S; Stoopler, Eric T; Moore, Paul A; Boynes, Sean G; Levine, Steven C; Casamassimo, Paul; Leyva, Rina; Mathew, Tanya; Shibly, Othman; Creighton, Paul; Jeffers, Gary E; Corby, Patricia M A; Turetzky, Stanley N; Papas, Athena; Wallen, Jillian; Idzik-Starr, Cynthia; Gordon, Sharon M

2013-05-01

The authors evaluated the efficacy and tolerability of 10 percent and 20 percent benzocaine gels compared with those of a vehicle (placebo) gel for the temporary relief of toothache pain. They also assessed the compliance with the label dose administration directions on the part of participants with toothache pain. Under double-masked conditions, 576 participants self-applied study gel to an open tooth cavity and surrounding oral tissues. Participants evaluated their pain intensity and pain relief for 120 minutes. The authors determined the amount of gel the participants applied. The responders' rates (the primary efficacy parameter), defined as the percentage of participants who had an improvement in pain intensity as exhibited by a pain score reduction of at least one unit on the dental pain scale from baseline for two consecutive assessments any time between the five- and 20-minute points, were 87.3 percent, 80.7 percent and 70.4 percent, respectively, for 20 percent benzocaine gel, 10 percent benzocaine gel and vehicle gel. Both benzocaine gels were significantly (P ≤ .05) better than vehicle gel; the 20 percent benzocaine gel also was significantly (P ≤ .05) better than the 10 percent benzocaine gel. The mean amount of gel applied was 235.6 milligrams, with 88.2 percent of participants applying 400 mg or less. Both 10 percent and 20 percent benzocaine gels were more efficacious than the vehicle gel, and the 20 percent benzocaine gel was more efficacious than the 10 percent benzocaine gel. All treatments were well tolerated by participants. Practical Implications. Patients can use 10 percent and 20 percent benzocaine gels to temporarily treat toothache pain safely.

An evaluation of 10 percent and 20 percent benzocaine gels in patients with acute toothaches

PubMed Central

Hersh, Elliot V.; Ciancio, Sebastian G.; Kuperstein, Arthur S.; Stoopler, Eric T.; Moore, Paul A.; Boynes, Sean G.; Levine, Steven C.; Casamassimo, Paul; Leyva, Rina; Mathew, Tanya; Shibly, Othman; Creighton, Paul; Jeffers, Gary E.; Corby, Patricia M.A.; Turetzky, Stanley N.; Papas, Athena; Wallen, Jillian; Idzik-Starr, Cynthia; Gordon, Sharon M.

2013-01-01

Background The authors evaluated the efficacy and tolerability of 10 percent and 20 percent benzocaine gels compared with those of a vehicle (placebo) gel for the temporary relief of toothache pain. They also assessed the compliance with the label dose administration directions on the part of participants with toothache pain. Methods Under double-masked conditions, 576 participants self-applied study gel to an open tooth cavity and surrounding oral tissues. Participants evaluated their pain intensity and pain relief for 120 minutes. The authors determined the amount of gel the participants applied. Results The responders’ rates (the primary efficacy parameter), defined as the percentage of participants who had an improvement in pain intensity as exhibited by a pain score reduction of at least one unit on the dental pain scale from baseline for two consecutive assessments any time between the five- and 20-minute points, were 87.3 percent, 80.7 percent and 70.4 percent, respectively, for 20 percent benzocaine gel, 10 percent benzocaine gel and vehicle gel. Both benzocaine gels were significantly (P ≤ .05) better than vehicle gel; the 20 percent benzocaine gel also was significantly (P ≤ .05) better than the 10 percent benzocaine gel. The mean amount of gel applied was 235.6 milligrams, with 88.2 percent of participants applying 400 mg or less. Conclusions Both 10 percent and 20 percent benzocaine gels were more efficacious than the vehicle gel, and the 20 percent benzocaine gel was more efficacious than the 10 percent benzocaine gel. All treatments were well tolerated by participants. Practical Implications Patients can use 10 percent and 20 percent benzocaine gels to temporarily treat toothache pain safely. PMID:23633700

Effects of microcurrent application alone or in combination with topical Hypericum perforatum L. and Arnica montana L. on surgically induced wound healing in Wistar rats.

PubMed

Castro, Fabiene C B; Magre, Amanda; Cherpinski, Ricardo; Zelante, Paulo M; Neves, Lia M G; Esquisatto, Marcelo A M; Mendonça, Fernanda A S; Santos, Gláucia M T

2012-07-01

This study evaluated the wound healing activity of microcurrent application alone or in combination with topical Hypericum perforatum L. and Arnica montana L. on skin surgical incision surgically induced on the back of Wistar rats. The animals were randomly divided into six groups: (1) no intervention (control group); (2) microcurrent application (10 μA/2 min); (3) topical application of gel containing H. perforatum; (4) topical application of H. perforatum gel and microcurrent (10 μA/2 min); (5) topical application of gel containing A. montana; (6) topical application of A. montana gel and microcurrent (10 μA/2 min). Tissue samples were obtained on the 2nd, 6th and 10th days after injury and submitted to structural and morphometric analysis. Differences in wound healing were observed between treatments when compared to the control group. Microcurrent application alone or combined with H. perforatum gel or A. montana gel exerted significant effects on wound healing in this experimental model in all of the study parameters (P<0.05) when compared to the control group with positive effects seen regarding newly formed tissue, number of newly formed blood vessels and percentage of mature collagen fibers. The morphometric data confirmed the structural findings. In conclusion, application of H. perforatum or A. montana was effective on experimental wound healing when compared to control, but significant differences in the parameters studied were only observed when these treatments were combined with microcurrent application. Copyright © 2012 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

FT-IR study of the polysaccharides isolated from the skin juice, gel juice, and flower of Aloe vera tissues affected by fertilizer treatment

PubMed Central

2012-01-01

Background This experiment was conducted to evaluate the effect of different amounts of fertilizers on the polysaccharides of Aloe vera plant. There were four different treatments, viz. T1 = 150% N, T2 = 150% P, T3 = 150% K, and T4 = 150% NPK (50% N + 50% P + 50% K) soil. Crude water-soluble polysaccharides were isolated from the gel juice, skin juice, and flowers of A. vera planted in these soils. Results Result indicates that skin juice contained 2.4 times the level of polysaccharides in gel juice from one plant, suggesting the potential industrial application of A. vera skin rather than discarding it. After anion-exchange chromatography, neutral polysaccharides accounted for 58.1% and 78.5% of the total recovered neutral and acidic polysaccharide preparations from the gel juice and skin juice, respectively, whereas the crude flower polysaccharides were largely composed of weakly acidic polysaccharides (84.2%). Sugar analysis of the polysaccharides after gel permeation chromatography revealed that glucose and galactose were the most abundant monosaccharide in the neutral polysaccharides from the gel juice and skin juice, respectively. The acidic polysaccharides from the two juices consisted of glucuronic acid, galactose, glucose, mannose, and xylose with variable proportions. Conclusions Except glucuronic acid (15.4%) in flower acidic polysaccharide, the flower neutral and acidic polysaccharides contained galactose, glucose, and mannose as the main sugar components. Glucuronic acid was the major uronic acid in all acidic polysaccharides from different tissues. PMID:23095284

Flurbiprofen-loaded niosomes-in-gel system improves the ocular bioavailability of flurbiprofen in the aqueous humor.

PubMed

El-Sayed, Marwa M; Hussein, Amal K; Sarhan, Hatem A; Mansour, Heba F

2017-06-01

The present work aimed to prolong the contact time of flurbiprofen (FBP) in the ocular tissue to improve the drug anti-inflammatory activity. Different niosome systems were fabricated adopting thin-film hydration technique and using the nonionic surfactant Span 60. The morphology of the prepared niosomes was characterized by scanning electron microscopy (SEM). Physical characterization by differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy were conducted for the optimized formula (F5) that was selected on the basis of percent entrapment efficiency, vesicular size and total lipid content. F5 was formulated as 1% w/w Carpobol 934 gel. Pharmacokinetic parameters of FBP were investigated following ocular administration of F5-loaded gel system, F5 niosome dispersion or the corresponding FBP ocular drops to albino rabbits dispersion. Anti-inflamatory effect of F5-loaded carbopol gel was investigated by histopathological examination of the corneal tissue before and after the treatment of inflamed rabbit eye with the system. Results showed that cholesterol content, surfactant type. and total lipid contents had an apparent impact on the vesicle size of the formulated niosomes. Physical characterization revealed reduced drug crystallinity and incidence of interaction with other niosome contents. F5-loaded gel showed higher C max , area under the curve (AUC 0-12 ), and thus higher ocular bioavailability than those of the corresponding FBP ocular solution. F5-loaded gel showed a promising rapid anti-inflammatory effect in the inflamed rabbit eye. These findings will eradicate the necessity for frequent ocular drug instillation and thus, improve patient compliance.

Coating flow of an anti-HIV microbicide gel: boundary dilution and yield stress

NASA Astrophysics Data System (ADS)

Szeri, Andrew J.; Tasoglu, Savas; Park, Su Chan; Katz, David F.

2010-11-01

A recent study has confirmed, for the first time, that a vaginal gel formulation of the antiretroviral drug Tenofovir, when topically applied, significantly inhibits sexual HIV transmission to women [1]. However, the gel for this drug, and anti-HIV microbicide gels in general, have not been designed using an understanding of how gel spreading govern successful drug delivery. Elastohydrodynamic lubrication theory can be applied to model spreading of microbicide gels [2]. Here, we extend our initial analysis: we incorporate a yield stress, and we model the effects of gel dilution due to contact with vaginal fluid produced at the gel-tissue interface. Our model developed in [2] is supplemented with a convective-diffusive transport equation to characterize dilution, and solved using a multi-step scheme in a moving domain. The association between local dilution of gel and rheological properties is obtained experimentally. To model the common yield stress property of gels, we proceed by scaling analysis first. This establishes the conditions for validity of lubrication theory of a shear thinning yield stress fluid. This involves further development of the model in [2], incorporating a biviscosity model.[4pt] [1] Karim, et al., Science, 2010.[0pt] [2] Szeri, et al., Phy. of Fluids, 2008.

Direct-write bioprinting of cell-laden methacrylated gelatin hydrogels.

PubMed

Bertassoni, Luiz E; Cardoso, Juliana C; Manoharan, Vijayan; Cristino, Ana L; Bhise, Nupura S; Araujo, Wesleyan A; Zorlutuna, Pinar; Vrana, Nihal E; Ghaemmaghami, Amir M; Dokmeci, Mehmet R; Khademhosseini, Ali

2014-06-01

Fabrication of three dimensional (3D) organoids with controlled microarchitectures has been shown to enhance tissue functionality. Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture. Therefore, it represents an exciting alternative for organ fabrication. Despite the rapid progress in the field, the development of printing processes that can be used to fabricate macroscale tissue constructs from ECM-derived hydrogels has remained a challenge. Here we report a strategy for bioprinting of photolabile cell-laden methacrylated gelatin (GelMA) hydrogels. We bioprinted cell-laden GelMA at concentrations ranging from 7 to 15% with varying cell densities and found a direct correlation between printability and the hydrogel mechanical properties. Furthermore, encapsulated HepG2 cells preserved cell viability for at least eight days following the bioprinting process. In summary, this work presents a strategy for direct-write bioprinting of a cell-laden photolabile ECM-derived hydrogel, which may find widespread application for tissue engineering, organ printing and the development of 3D drug discovery platforms.

Evaluation of two types of swabs for sampling allograft musculoskeletal tissue.

PubMed

Varettas, Kerry

2015-01-01

Allograft musculoskeletal tissue is commonly sampled by a swab for bioburden screening. To determine if bioburden recovery could be improved at the pre-analytical stage, two swab systems were evaluated: the Amies gel swab and the ESwab. In vitro studies were performed to determine the recovery of each swab system with <100 colony-forming unit of challenge organisms using inoculated swabs and by sampling inoculated femoral heads. The standard culture protocol used in this laboratory was also evaluated after sampling of inoculated femoral heads. A prospective study was performed with both swab systems used in parallel to sample cadaveric allograft musculoskeletal tissue. The challenge organisms could be recovered from the in vitro inoculated studies. The standard culture protocol in this laboratory recovered all challenge organisms from both swab systems. One hundred and six paired Amies and ESwabs were collected from eight cadaveric donors with skin commensals the predominant isolates. The sampling of an inoculated femoral head was included to reflect routine swab sampling practice as was the inclusion of the standard method used in this laboratory. This appears to be the first study to compare Amies gel swabs with ESwabs to sample allograft femoral heads and in a prospective study with cadaveric allograft musculoskeletal tissue. Other comparative studies of swab systems have used a much higher inoculum to mimic an infection; however, sepsis is an exclusion criterion for allograft donors. It was found that the Amies gel swab and ESwab are both suitable sampling devices for bioburden testing of allograft musculoskeletal tissue. © 2014 Royal Australasian College of Surgeons.

ISOCT study of collagen crosslinking of collagen in cancer models (Conference Presentation)

NASA Astrophysics Data System (ADS)

Spicer, Graham; Young, Scott T.; Yi, Ji; Shea, Lonnie D.; Backman, Vadim

2016-03-01

The role of extracellular matrix modification and signaling in cancer progression is an increasingly recognized avenue for the progression of the disease. Previous study of field effect carcinogenesis with Inverse Spectroscopic Optical Coherence Tomography (ISOCT) has revealed pronounced changes in the nanoscale-sensitive mass fractal dimension D measured from field effect tissue when compared to healthy tissue. However, the origin of this difference in tissue ultrastructure in field effect carcinogenesis has remained poorly understood. Here, we present findings supporting the idea that enzymatic crosslinking of the extracellular matrix is an effect that presents at the earliest stages of carcinogenesis. We use a model of collagen gel with crosslinking induced by lysyl oxidase (LOXL4) to recapitulate the difference in D previously reported from healthy and cancerous tissue biopsies. Furthermore, STORM imaging of this collagen gel model verifies the morphologic effects of enzymatic crosslinking at length scales as small as 40 nm, close to the previously reported lower length scale sensitivity threshold of 35 nm for ISOCT. Analysis of the autocorrelation function from STORM images of collagen gels and subsequent fitting to the Whittle-Matérn correlation function shows a similar effect of LOXL4 on D from collagen measured with ISOCT and STORM. We extend this to mass spectrometric study of tissue to directly measure concentrations of collagen crosslink residues. The validation of ISOCT as a viable tool for non-invasive rapid quantification of collagen ultrastructure lends it to study other physiological phenomena involving ECM restructuring such as atherosclerotic plaque screening or cervical ripening during pregnancy.

Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells.

PubMed

Shkumatov, Artem; Thompson, Michael; Choi, Kyoung M; Sicard, Delphine; Baek, Kwanghyun; Kim, Dong Hyun; Tschumperlin, Daniel J; Prakash, Y S; Kong, Hyunjoon

2015-06-01

Multiple pulmonary conditions are characterized by an abnormal misbalance between various tissue components, for example, an increase in the fibrous connective tissue and loss/increase in extracellular matrix proteins (ECM). Such tissue remodeling may adversely impact physiological function of airway smooth muscle cells (ASMCs) responsible for contraction of airways and release of a variety of bioactive molecules. However, few efforts have been made to understand the potentially significant impact of tissue remodeling on ASMCs. Therefore, this study reports how ASMCs respond to a change in mechanical stiffness of a matrix, to which ASMCs adhere because mechanical stiffness of the remodeled airways is often different from the physiological stiffness. Accordingly, using atomic force microscopy (AFM) measurements, we found that the elastic modulus of the mouse bronchus has an arithmetic mean of 23.1 ± 14 kPa (SD) (median 18.6 kPa). By culturing ASMCs on collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we found that gels designed to be softer than average airway tissue significantly increased cellular secretion of vascular endothelial growth factor (VEGF). Conversely, gels stiffer than average airways stimulated cell proliferation, while reducing VEGF secretion and agonist-induced calcium responses of ASMCs. These dependencies of cellular activities on elastic modulus of the gel were correlated with changes in the expression of integrin-β1 and integrin-linked kinase (ILK). Overall, the results of this study demonstrate that changes in matrix mechanics alter cell proliferation, calcium signaling, and proangiogenic functions in ASMCs. Copyright © 2015 the American Physiological Society.

Early matrix change of a nanostructured bone grafting substitute in the rat.

PubMed

Xu, Weiguo; Holzhüter, Gerd; Sorg, Heiko; Wolter, Daniel; Lenz, Solvig; Gerber, Thomas; Vollmar, Brigitte

2009-11-01

A nanocrystalline bone substitute embedded in a highly porous silica gel matrix (NanoBone) has previously been shown to bridge bone defects by an organic matrix. As the initial host response on the bone graft substitute might be a determinant for subsequent bone formation, our present purpose was to characterize the early tissue reaction on this biomaterial. After implantation of 80 mg of NanoBone into the adipose neck tissue of a total of 35 rats, grafts were harvested for subsequent analysis at days 3, 6, 9, 12, and 21. The biomaterial was found encapsulated by granulation tissue which partly penetrated the implant at day 3 and completely pervaded the graft at day 12 on implantation. Histology revealed tartrate-resistant acid phosphatase (TRAP)-positive giant cells covering the biomaterial. ED1 (CD68) immunopositivity of these cells further indicated their osteoclast-like phenotype. Scanning electron microscopy revealed organic tissue components within the periphery of the graft already at day 9, whereas the central hematoma region still presented the silica-surface of the biomaterial. Energy dispersive X-ray spectroscopy further demonstrated that the silica gel was degraded faster in the peripheral granulation tissue than in the central hematoma and was replaced by organic host components by day 12. In conclusion, the silica gel matrix is rapidly replaced by carbohydrate macromolecules. This might represent a key step in the process of graft degradation on its way toward induction of bone formation. The unique composition and structure of this nanoscaled biomaterial seem to support its degradation by host osteoclast-like giant cells.

Highly efficient treatment of aerobic vaginitis with simple acidic buffered gels: The importance of pH and buffers on the microenvironment of vaginas.

PubMed

Sun, Xiaodong; Qiu, Haiying; Jin, Yiguang

2017-06-15

Aerobic vaginitis (AV) leads to uterus deep infection or preterm birth. Antibacterial agents are not optimal therapeutics of AV. Here, we report a series of temperature-sensitive in situ forming acidic buffered gels for topical treatment of AV, involving lactate, acetate, and citrate gels at pH 3.5, 5.0, and 6.5. AV rat models were prepared following vaginal infection with Staphylococcus aureus and Escherichia coli. In vitro/in vivo studies of the buffered gels were performed compared with ofloxacin gels and blank gels. All the buffered gels showed the lower in vitro antibacterial activities than ofloxacin gels but the better in vivo anti-S. aureus effects and similar anti-E. coli effects. The buffered gels improved Lactobacillus growth in the vaginas. Both the healthy rat vaginal pH and the pH of rat vaginas treated with the buffered gels were about 6.5 though the AV rat models or ones treated with ofloxacin gels still remained at the high pH more than 7.0. After treatments with the buffered gels, the vaginal smears changed to a clean state nearly without aerobic bacteria, the vaginal tissues were refreshed, and the immunoreactions were downregulated. The acidic buffered gels bring rapid decrease of local vaginal pH, high antibacterial activities, improvement of probiotics, and alleviation of inflammation. They are simple, highly efficient, and safe anti-AV formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Branched Polymers for Enhancing Polymer Gel Strength and Toughness

DTIC Science & Technology

2013-02-01

Molecular Massively Parallel Simulator ( LAMMPS ) program and the stress-strain relations were calculated with varying strain-rates (figure 6). A...Acronyms ARL U.S. Army Research Laboratory D3 hexamethylcyclotrisiloxane FTIR Fourier transform infrared GPC gel permeation chromatography LAMMPS

Physicochemical characterization of diclofenac sodium-loaded poloxamer gel as a rectal delivery system with fast absorption.

PubMed

Yong, Chul Soon; Sah, Hongkee; Jahng, Yurngdong; Chang, Hyeun Wook; Son, Jong-Keun; Lee, Seung Ho; Jeong, Tae Cheon; Rhee, Jong-Dal; Baek, Suk Hwan; Kim, Chong-Kook; Choi, Han-Gon

2003-05-01

Rectal poloxamer gel systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and were mucoadhesive to the rectal tissues without leakage after the dose. However, a poloxamer gel containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a poloxamer gel using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength, and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers, and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the poloxamer gel was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The poloxamer gels with less than 1.0% sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage, and were retained in the rectum of rats for at least 6 hr. Furthermore, poloxamer gel gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from poloxamer gel could be absorbed faster than that from the solid one in rats. Our results suggested that a rectal poloxamer gel system with sodium chloride and poloxamers was a more physically stable, convenient, and effective rectal dosage form for diclofenac sodium.

Adipose Extracellular Matrix/Stromal Vascular Fraction Gel Secretes Angiogenic Factors and Enhances Skin Wound Healing in a Murine Model.

PubMed

Sun, Mingliang; He, Yunfan; Zhou, Tao; Zhang, Pan; Gao, Jianhua; Lu, Feng

2017-01-01

Mesenchymal stem cells are an attractive cell type for cytotherapy in wound healing. The authors recently developed a novel, adipose-tissue-derived, injectable extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) for stem cell therapy. This study was designed to assess the therapeutic effects of ECM/SVF-gel on wound healing and potential mechanisms. ECM/SVF-gel was prepared for use in nude mouse excisional wound healing model. An SVF cell suspension and phosphate-buffered saline injection served as the control. The expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and monocyte chemotactic protein-1 (MCP-1) in ECM/SVF-gel were analyzed at different time points. Angiogenesis (tube formation) assays of ECM/SVF-gel extracts were evaluated, and vessels density in skin was determined. The ECM/SVF-gel extract promoted tube formation in vitro and increased the expression of the angiogenic factors VEGF and bFGF compared with those in the control. The expression of the inflammatory chemoattractant MCP-1 was high in ECM/SVF-gel at the early stage and decreased sharply during the late stage of wound healing. The potent angiogenic effects exerted by ECM/SVF-gel may contribute to the improvement of wound healing, and these effects could be related to the enhanced inflammatory response in ECM/SVF-gel during the early stage of wound healing.

Block copolymers for biomimetic composites

NASA Astrophysics Data System (ADS)

Calvert, Paul D.; Oner, Mualla; Burdon, Jeremy; Rieke, Peter C.; Farmer, Kelly

1993-07-01

Mineralized biological tissues can be regarded as composites where a fine reinforcement is laid down in a very controlled fashion within a tough polymeric matrix. Such materials include bone, antler, tooth enamel, mollusc shell, and crustacean shell. We have been exploring ways of forming similar structures by synthetic routes involving precipitation of reinforcing particles directly into a polymeric matrix. Part of this biomimetic approach requires polymer matrices which can exert a high degree of control over the mineralization process. Polymer gels have been formed from cross-linked methacrylates with various types of functionality within the gel. By incorporating calcium binding groups we have been producing gels which lead to preferential mineralization of the gel when it is incubated in a supersaturated solution of calcium oxalate or calcium carbonate. Similarly we have been incorporating silane groups within the gel in order to promote the deposition of silica in a gel body when it is immersed in a metastable solution of partly hydrolysed silicon alkoxides.

Structural Properties of Silk Electro-Gels

NASA Astrophysics Data System (ADS)

Tabatabai, A. P.; Urbach, J. S.; Blair, D. L.; Kaplan, D. L.

2013-03-01

The interest in Bombyx Mori silk emerges from its biocompatibility and its structural superiority to synthetic polymers. Our particular interest lies in understanding the capabilities of silk electro-gels because of their reversibility and tunable adhesion. We create an electro-gel by applying a DC electric potential across a reconstituted silk fibroin solution derived directly from Bombyx Mori cocoons. This process leads to the intermolecular self-assembly of fibroin proteins into a weak gel. In this talk we will present our results on the effects of applied shear on electro-gels. We quantify the structural properties while dynamically imaging shear induced fiber formation; known as fibrillogenesis. It is observed that the mechanical properties and microstructure of these materials are highly dependent on shear history. We will also discuss the role of surface modification, through micro-patterning, on the observed gel structure. Our results provide an understanding of both the viscoelastiticity and microstucture of reconstituted silks that are being utilized as tissue scaffolds. This work is supported by a grant from the AFOSR FA9550-07-1-0130.

Optimization of Large Gel 2D Electrophoresis for Proteomic Studies of Skeletal Muscle

PubMed Central

Reed, Patrick W.; Densmore, Allison; Bloch, Robert J.

2013-01-01

We describe improved methods for large format, 2-dimensional gel electrophoresis (2-DE) that improve protein solubility and recovery, minimize proteolysis, and reduce the loss of resolution due to contaminants and manipulations of the gels, and thus enhance quantitative analysis of protein spots. Key modifications are: (i) the use of 7M urea + 2 M thiourea, instead of 9M urea, in sample preparation and in the tops of the gel tubes; (ii) standardized deionization of all solutions containing urea with a mixed bed ion exchange resin and removal of urea from the electrode solutions; and (iii) use of a new gel tank and cooling device that eliminate the need to run two separating gels in the SDS dimension. These changes make 2D-GE analysis more reproducible and sensitive, with minimal artifacts. Application of this method to the soluble fraction of muscle tissues reliably resolves ~1800 protein spots in adult human skeletal muscle and over 2800 spots in myotubes. PMID:22589104

Topical Review: Polymer gel dosimetry

PubMed Central

Baldock, C; De Deene, Y; Doran, S; Ibbott, G; Jirasek, A; Lepage, M; McAuley, K B; Oldham, M; Schreiner, L J

2010-01-01

Polymer gel dosimeters are fabricated from radiation sensitive chemicals which, upon irradiation, polymerize as a function of the absorbed radiation dose. These gel dosimeters, with the capacity to uniquely record the radiation dose distribution in three-dimensions (3D), have specific advantages when compared to one-dimensional dosimeters, such as ion chambers, and two-dimensional dosimeters, such as film. These advantages are particularly significant in dosimetry situations where steep dose gradients exist such as in intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery. Polymer gel dosimeters also have specific advantages for brachytherapy dosimetry. Potential dosimetry applications include those for low-energy x-rays, high-linear energy transfer (LET) and proton therapy, radionuclide and boron capture neutron therapy dosimetries. These 3D dosimeters are radiologically soft-tissue equivalent with properties that may be modified depending on the application. The 3D radiation dose distribution in polymer gel dosimeters may be imaged using magnetic resonance imaging (MRI), optical-computerized tomography (optical-CT), x-ray CT or ultrasound. The fundamental science underpinning polymer gel dosimetry is reviewed along with the various evaluation techniques. Clinical dosimetry applications of polymer gel dosimetry are also presented. PMID:20150687

A novel thermo-sensitive hydrogel based on thiolated chitosan/hydroxyapatite/beta-glycerophosphate.

PubMed

Liu, Xujie; Chen, Yan; Huang, Qianli; He, Wei; Feng, Qingling; Yu, Bo

2014-09-22

In order to get a water-soluble in situ gel-forming system, a thiolated chitosan, chitosan-4-thio-butylamidine (CS-TBA) conjugate was synthesized and used to replace the unmodified chitosan in the application of the in situ gel-forming system. A novel thermo-sensitive hydrogel was prepared based on CS-TBA/hydroxyapatite (HA)/beta-glycerophosphate disodium (β-GP). The gel formation, rheological properties, morphology, degradation, cytotoxicity, as well as protein release process of the novel gel system were investigated in this study. The CS-TBA/HA/β-GP gel showed a higher storage modulus (G') and loss modulus (G″) and a decreased bovine serum albumin (BSA) release rate which was maintained the protein release for a longer time compared with the unmodified chitosan (CS)/HA/β-GP gel, due to the existence of thiol groups and/or disulfide bonds. The CS-TBA/HA/β-GP gel has a porous structure with a uniform distribution of nano-hydroxyapatite, an appropriate degradation rate and low cytotoxicity, showing potential applications in drug delivery and tissue engineering. Copyright © 2014 Elsevier Ltd. All rights reserved.

Electrospun Polyhydroxybutyrate/Poly(ε-caprolactone)/58S Sol-Gel Bioactive Glass Hybrid Scaffolds with Highly Improved Osteogenic Potential for Bone Tissue Engineering.

PubMed

Ding, Yaping; Li, Wei; Müller, Teresa; Schubert, Dirk W; Boccaccini, Aldo R; Yao, Qingqing; Roether, Judith A

2016-07-13

Electrospinning of biopolymer and inorganic substances is one of the efficient ways to combine various advantageous properties in one single fibrous structure with potential for tissue engineering applications. In the present study, to integrate the high stiffness of polyhydroxybutyrate (PHB), the flexibility of poly(ε-caprolactone) (PCL) and the bioactivity of 58S bioactive glass, PHB/PCL/58S sol-gel bioactive glass hybrid scaffolds were fabricated using combined electrospinning and sol-gel method. Physical features such as fiber diameter distribution, mechanical strength and Young's modulus were characterized thoroughly. FTIR analysis demonstrated the successful incorporation of 58S bioactive glass into the blend polymers, which greatly improved the hydrophilicity of PHB/PCL fibermats. The primary biological response of MG-63 osteoblast-like cells on the prepared fibrous scaffolds was evaluated, proving that the 58S glass sol containing hybrid scaffold were not only favorable to MG-63 cell adhesion but also slightly enhanced cell viability and significantly increased alkaline phosphate activity .

Robust Bonding of Tough Double Network Hydrogel to Bone

NASA Astrophysics Data System (ADS)

Nonoyama, Takayuki; Wada, Susumu; Kiyama, Ryuji; Kitamura, Nobuto; Kurokawa, Takayuki; Nakajima, Tasuku; Yasuda, Kazunori; Gong, Jian Ping

Tough Double Network (DN) hydrogels are one of candidates as next-generation artificial cartilage from the viewpoints of low friction, water storage capability and toughness. For practical use, the hydrogel must be strongly fixed at the joint. However, strong fixation of such hydrogel to other materials (tissues) has not been achieved yet because the surface property of hydrogel is almost equal to water due to its high water content. Therefore, robust adhesion for fixation and low friction for lithe motion are trade-off relation. Here, we report robust fixation of hydroxyapatite (HAp) mineralized DN hydrogel to the bone without any toxicity. HAp is main inorganic component of bone tissues and has osteoconductive capability. After 4 weeks implantation of HAp/DN gel into rabbit femoral groove, The robust fixation between bone and HAp/DN gel, more than strength of gel matrix, was achieved. The methodology is universal for new biomaterials, which should be fixed on bone, such as ligament and tendon systems.

Novel control of gel fraction and enhancement of bonding strength for constructing 3D architecture of tissue engineering scaffold with alginate tubular fiber.

PubMed

Li, Yu; Liu, Yuanyuan; Li, Shuai; Liang, Gang; Jiang, Chen; Hu, Qingxi

2016-01-01

Alginate tubular fiber has been successfully prepared via coaxial fluid crosslink mode, which is potentially used for the construction of vascularized tissue engineering scaffolds (VTES). However, its elastic and smooth surface is negative for the adhesion of fibers. In this study, the gel fractions were controlled in a novel way of two-step crosslink process in order to meet the needs of each processing link. Based on such consideration, an appropriate formulation was selected to direct write single fiber, which ensured the tubular structure with enough gel portion as well as adhesion between fibers with the reserved sol. Finally, the integrity of the scaffolds had a further development within the 2nd crosslink bath process, which would help to solve the question of poor shear resistance for hydrogel scaffolds. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Joint immobilization inhibits spontaneous hyaline cartilage regeneration induced by a novel double-network gel implantation.

PubMed

Arakaki, Kazunobu; Kitamura, Nobuto; Kurokawa, Takayuki; Onodera, Shin; Kanaya, Fuminori; Gong, Jian-Ping; Yasuda, Kazunori

2011-02-01

We have recently discovered that spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect in the rabbit, when we implant a novel double-network (DN) gel plug at the bottom of the defect. To clarify whether joint immobilization inhibits the spontaneous hyaline cartilage regeneration, we conducted this study with 20 rabbits. At 4 or 12 weeks after surgery, the defect in the mobile knees was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen, while no cartilage tissues were observed in the defect in the immobilized knees. Type-2 collagen, Aggrecan, and SOX9 mRNAs were expressed only in the mobile knees at each period. This study demonstrated that joint immobilization significantly inhibits the spontaneous hyaline cartilage regeneration induced by the DN gel implantation. This fact suggested that the mechanical environment is one of the significant factors to induce this phenomenon.

In vitro study of electroactive tetraaniline-containing thermosensitive hydrogels for cardiac tissue engineering.

PubMed

Cui, Haitao; Liu, Yadong; Cheng, Yilong; Zhang, Zhe; Zhang, Peibiao; Chen, Xuesi; Wei, Yen

2014-04-14

Injectable hydrogels made of degradable biomaterials can function as both physical support and cell scaffold in preventing infarct expansion and promoting cardiac repair in myocardial infarction therapy. Here, we report in situ hydrogels consisting of thermosensitive PolyNIPAM-based copolymers and electroactive tetraaniline (TA). Studies showed that the addition of 2-methylene-1,3-dioxepane (MDO) provided the PolyNIPAM-based gel with biodegradability, and the introduction of tetraaniline endowed these copolymers with desirable electrical properties and antioxidant activities. The encapsulated H9c2 cells (rat cardiac myoblast) remained highly viable in the gel matrices. In vivo gel formation and histological analyses were performed in rats by subcutaneous injection and excellent biocompatibility was observed. Furthermore, the proliferation and intracellular calcium transients of H9c2 cells were also studied with (and without) electrical stimuli. Both in vitro and in vivo results demonstrated that electroactive hydrogel may be used as a promising injectable biomaterial for cardiac tissue engineering.

Adipose‑derived stem cells and hyaluronic acid based gel compatibility, studied in vitro.

PubMed

Guo, Jiayan; Guo, Shu; Wang, Yuxin; Yu, Yanqiu

2017-10-01

Minimally invasive aesthetic and cosmetic procedures have increased in popularity. Injectable dermal fillers provide soft tissue augmentation, improve facial rejuvenation and wrinkles, and correct tissue defects. To investigate the use of adipose‑derived stem cells integrated with a hyaluronic acid based gel as a dermal filler, the present study used cytotoxicity studies, proliferation studies, adipogenic and osteogenic differentiation, apoptosis assays and scanning electron microscopy. Although hyaluronic acid induced low levels of apoptosis in adipose‑derived stem cells, its significantly promoted proliferation of adipose‑derived stem cells. Hyaluronic acid demonstrates little toxicity against adipose‑derived stem cells. Adipose‑derived stem cells were able to differentiate into adipocytes and osteoblasts. Furthermore, scanning electron microscopy revealed that adipose‑derived stem cells maintained intact structures on the surface of hyaluronic acid as well as in it, and demonstrated abundant cell attachments. The present study demonstrated the compatibility of adipose‑derived stem cells and hyaluronic acid based gels in vitro.

The Effect of 3D Hydrogel Scaffold Modulus on Osteoblast Differentiation and Mineralization Revealed by Combinatorial Screening

PubMed Central

Chatterjee, Kaushik; Lin-Gibson, Sheng; Wallace, William E.; Parekh, Sapun H.; Lee, Young J.; Cicerone, Marcus T.; Young, Marian F.; Simon, Carl G.

2011-01-01

Cells are known to sense and respond to the physical properties of their environment and those of tissue scaffolds. Optimizing these cell-material interactions is critical in tissue engineering. In this work, a simple and inexpensive combinatorial platform was developed to rapidly screen three-dimensional (3D) tissue scaffolds and was applied to screen the effect of scaffold properties for tissue engineering of bone. Differentiation of osteoblasts was examined in poly(ethylene glycol) hydrogel gradients spanning a 30-fold range in compressive modulus (≈ 10 kPa to ≈ 300 kPa). Results demonstrate that material properties (gel stiffness) of scaffolds can be leveraged to induce cell differentiation in 3D culture as an alternative to biochemical cues such as soluble supplements, immobilized biomolecules and vectors, which are often expensive, labile and potentially carcinogenic. Gel moduli of ≈ 225 kPa and higher enhanced osteogenesis. Furthermore, it is proposed that material-induced cell differentiation can be modulated to engineer seamless tissue interfaces between mineralized bone tissue and softer tissues such as ligaments and tendons. This work presents a combinatorial method to screen biological response to 3D hydrogel scaffolds that more closely mimics the 3D environment experienced by cells in vivo. PMID:20378163

Hydrogel Bioprinted Microchannel Networks for Vascularization of Tissue Engineering Constructs

PubMed Central

Bertassoni, Luiz E.; Cecconi, Martina; Manoharan, Vijayan; Nikkhah, Mehdi; Hjortnaes, Jesper; Cristino, Ana Luiza; Barabaschi, Giada; Demarchi, Danilo; Dokmeci, Mehmet R.; Yang, Yunzhi; Khademhosseini, Ali

2014-01-01

Vascularization remains a critical challenge in tissue engineering. The development of vascular networks within densely populated and metabolically functional tissues facilitate transport of nutrients and removal of waste products, thus preserving cellular viability over a long period of time. Despite tremendous progress in fabricating complex tissue constructs in the past few years, approaches for controlled vascularization within hydrogel based engineered tissue constructs have remained limited. Here, we report a three dimensional (3D) micromolding technique utilizing bioprinted agarose template fibers to fabricate microchannel networks with various architectural features within photo cross linkable hydrogel constructs. Using the proposed approach, we were able to successfully embed functional and perfusable microchannels inside methacrylated gelatin (GelMA), star poly (ethylene glycol-co-lactide) acrylate (SPELA), poly (ethylene glycol) dimethacrylate (PEGDMA) and poly (ethylene glycol) diacrylate (PEGDA) hydrogels at different concentrations. In particular, GelMA hydrogels were used as a model to demonstrate the functionality of the fabricated vascular networks in improving mass transport, cellular viability and differentiation within the cell-laden tissue constructs. In addition, successful formation of endothelial monolayers within the fabricated channels was confirmed. Overall, our proposed strategy represents an effective technique for vascularization of hydrogel constructs with useful applications in tissue engineering and organs on a chip. PMID:24860845

Hydrodynamic theory of active matter

NASA Astrophysics Data System (ADS)

Jülicher, Frank; Grill, Stephan W.; Salbreux, Guillaume

2018-07-01

We review the general hydrodynamic theory of active soft materials that is motivated in particular by biological matter. We present basic concepts of irreversible thermodynamics of spatially extended multicomponent active systems. Starting from the rate of entropy production, we identify conjugate thermodynamic fluxes and forces and present generic constitutive equations of polar active fluids and active gels. We also discuss angular momentum conservation which plays a role in the the physics of active chiral gels. The irreversible thermodynamics of active gels provides a general framework to discuss the physics that underlies a wide variety of biological processes in cells and in multicellular tissues.

Imaging of Selenium by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) in 2-D Electrophoresis Gels and Biological Tissues.

PubMed

Cruz, Elisa Castañeda Santa; Susanne Becker, J; Sabine Becker, J; Sussulini, Alessandra

2018-01-01

Selenium and selenoproteins are important components of living organisms that play a role in different biological processes. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a powerful analytical technique that has been employed to obtain distribution maps of selenium in biological tissues in a direct manner, as well as in selenoproteins, previously separated by their molecular masses and isoelectric points using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). In this chapter, we present the protocols to perform LA-ICP-MS imaging experiments, allowing the distribution visualization and determination of selenium and/or selenoproteins in biological systems.

Fabrication and characterization of biotissue-mimicking phantoms in the THz frequency range

NASA Astrophysics Data System (ADS)

Liakhov, E.; Smolyanskaya, O.; Popov, A.; Odlyanitskiy, E.; Balbekin, N.; Khodzitsky, M.

2016-08-01

The study revealed the most promising candidates for phantoms mimicking different biological tissues in the terahertz frequency range. Closest to biological tissues in terms of the refractive index appeared to be gelatin-based gels; in terms of the absorption coefficient they were agar-based gels. Gelatin is more stable in time, but requires special storage conditions to limit water evaporation. The dense structure of the agar-based phantom allows its use without mold and risk of damage. However, agar is a nutrient medium for bacteria and its parameters degrade even when the phantom form and water content are retained. Use of liquid suspensions of lecithin and milk powder are found to be extremely limited.

Highly Reactive Thiol-Norbornene Photo-Click Hydrogels: Toward Improved Processability.

PubMed

Van Hoorick, Jasper; Gruber, Peter; Markovic, Marica; Rollot, Mélanie; Graulus, Geert-Jan; Vagenende, Maxime; Tromayer, Maximilian; Van Erps, Jürgen; Thienpont, Hugo; Martins, José C; Baudis, Stefan; Ovsianikov, Aleksandr; Dubruel, Peter; Van Vlierberghe, Sandra

2018-06-10

In the present work, gelatin type B is modified with highly reactive norbornene functionalities (Gel-NB) following a one-pot synthesis approach to enable subsequent thiol-ene photo-click crosslinking. The modification strategy displays close control over the amount of introduced functionalities. Additionally, Gel-NB exhibits considerably improved processing capabilities in terms of two-photon polymerization when benchmarked to earlier-reported crosslinkable gelatin derivatives (e.g., gelatin-methacrylamide (Gel-MOD) and gelatin-methacrylamide-aminoethylmethacrylate (Gel-MOD-AEMA)). The improvement is especially apparent in terms of minimally required laser power (20 mW vs ≥60 mW (Gel-MOD) vs ≥40 mW (Gel-MOD-AEMA) at 100 mm s -1 scan speed) and processable concentration range (≥5 w/v% vs ≥10 w/v% (Gel-MOD/Gel-MOD-AEMA)). Furthermore, the proposed functionalization scheme maintains the excellent biocompatibility and cell interactivity of gelatin. Additionally, the norbornene functionalities have potential for straightforward postprocessing "thiol-ene" surface grafting of active molecules. As a consequence, a very promising material toward tissue engineering applications and more specifically, biofabrication, is presented. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation of a novel composite nanofiber gel-encapsulated human placental extract through layer-by-layer self-assembly

PubMed Central

LIU, GUOHUI; CHEN, XI; ZHOU, WU; YANG, SHUHUA; YE, SHUNAN; CAO, FAQI; LIU, YI; XIONG, YUAN

2016-01-01

Aqueous human placenta extract (HPE) has been previously used to treat chronic soft tissue ulcer; however, the optimal dosage of HPE has yet to be elucidated. The present study investigated a novel nanofiber gel composed through layer-by-layer (LbL) self-assembly, in which HPE was encapsulated. IKVAV, RGD, RAD16 and FGL-PA were screened and combined to produce an optimal vehicle nanofiber gel through LbL assembly. Subsequently, the aqueous HPE was encapsulated into this nanofiber at the appropriate concentration, and the morphology, particle size, drug loading efficacy, encapsulation rate, release efficiency and structure validation were detected. The encapsulation efficiency of all three HPE samples was >90%, the nanofiber gel exhibited a slow releasing profile, and the structure of HPE encapsulated in the nanofiber gel was unvaried. In conclusion, this type of novel composite nanocapsules may offer a promising delivery system for HPE. PMID:27073463

Solvent-free, supersoft and superelastic bottlebrush melts and networks

NASA Astrophysics Data System (ADS)

Daniel, William F. M.; Burdyńska, Joanna; Vatankhah-Varnoosfaderani, Mohammad; Matyjaszewski, Krzysztof; Paturej, Jarosław; Rubinstein, Michael; Dobrynin, Andrey V.; Sheiko, Sergei S.

2016-02-01

Polymer gels are the only viable class of synthetic materials with a Young's modulus below 100 kPa conforming to biological applications, yet those gel properties require a solvent fraction. The presence of a solvent can lead to phase separation, evaporation and leakage on deformation, diminishing gel elasticity and eliciting inflammatory responses in any surrounding tissues. Here, we report solvent-free, supersoft and superelastic polymer melts and networks prepared from bottlebrush macromolecules. The brush-like architecture expands the diameter of the polymer chains, diluting their entanglements without markedly increasing stiffness. This adjustable interplay between chain diameter and stiffness makes it possible to tailor the network's elastic modulus and extensibility without the complications associated with a swollen gel. The bottlebrush melts and elastomers exhibit an unprecedented combination of low modulus (~100 Pa), high strain at break (~1,000%), and extraordinary elasticity, properties that are on par with those of designer gels.

Powder XRD and dielectric studies of gel grown calcium pyrophosphate crystals

NASA Astrophysics Data System (ADS)

Parekh, Bharat; Parikh, Ketan; Joshi, Mihir

2013-06-01

Formation of calcium pyrophosphate dihydrate (CPPD) crystals in soft tissues such as cartilage, meniscus and synovial tissue leads to CPPD deposition diseases. The appearance of these crystals in the synovial fluid can give rise to an acute arthritic attack with pain and inflammation of the joints, a condition called pseudo-gout. The growth of CPP crystals has been carried out, in the present study, using the single diffusion gel growth technique, which can broadly mimic in vitro the condition in soft tissues. The crystals were characterized by different techniques. The FTIR study revealed the presence of various functional groups. Powder XRD study was also carried out to verify the crystal structure. The dielectric study was carried out at room temperature by applying field of different frequency from 500 Hz to 1 MHz. The dielectric constant, dielectric loss and a.c. resistivity decreased as frequency increased, whereas the a.c. conductivity increased as frequency increased.

Evaluation of several two-dimensional gel electrophoresis techniques in cardiac proteomics.

PubMed

Li, Zhao Bo; Flint, Paul W; Boluyt, Marvin O

2005-09-01

Two-dimensional gel electrophoresis (2-DE) is currently the best method for separating complex mixtures of proteins, and its use is gradually becoming more common in cardiac proteome analysis. A number of variations in basic 2-DE have emerged, but their usefulness in analyzing cardiac tissue has not been evaluated. The purpose of the present study was to systematically evaluate the capabilities and limitations of several 2-DE techniques for separating proteins from rat heart tissue. Immobilized pH gradient strips of various pH ranges, parameters of protein loading and staining, subcellular fractionation, and detection of phosphorylated proteins were studied. The results provide guidance for proteome analysis of cardiac and other tissues in terms of selection of the isoelectric point separating window for cardiac proteins, accurate quantitation of cardiac protein abundance, stabilization of technical variation, reduction of sample complexity, enrichment of low-abundant proteins, and detection of phosphorylated proteins.

Localized internal radiotherapy with 90Y particles embedded in a new thermosetting alginate gel: a feasibility study in pigs.

PubMed

Holte, Oyvind; Skretting, Arne; Bach-Gansmo, Tore; Hol, Per Kristian; Johnsrud, Kjersti; Tønnesen, Hanne Hjorth; Karlsen, Jan

2006-02-01

Internal radiotherapy requires the localization of the radionuclide to the site of action. A new injectable alginate gel formulation intended to undergo immediate gelation in tissues and capable of encapsulating radioactive particles containing 90Y was investigated. The formulation was injected intramuscularly, into the bone marrow compartment of the femur and intravenously, respectively, in pigs. The distribution of radioactivity in various tissues was determined. Following intramuscular injection, more than 90% of the radioactivity was found at the site of injection. Following injection into bone marrow, 30-40% of the radioactivity was retained at the site of injection, but a considerable amount of radioactivity was also detected in the lungs (35-45%) and the liver (5-18%). Following intravenous injection, 80-90% of the radioactivity was found in the lungs. The present formulation appears suitable for localized radiotherapy in organs and tissues having low perfusion.

Functionalized α-Helical Peptide Hydrogels for Neural Tissue Engineering

PubMed Central

2015-01-01

Trauma to the central and peripheral nervous systems often lead to serious morbidity. Current surgical methods for repairing or replacing such damage have limitations. Tissue engineering offers a potential alternative. Here we show that functionalized α-helical-peptide hydrogels can be used to induce attachment, migration, proliferation and differentiation of murine embryonic neural stem cells (NSCs). Specifically, compared with undecorated gels, those functionalized with Arg-Gly-Asp-Ser (RGDS) peptides increase the proliferative activity of NSCs; promote their directional migration; induce differentiation, with increased expression of microtubule-associated protein-2, and a low expression of glial fibrillary acidic protein; and lead to the formation of larger neurospheres. Electrophysiological measurements from NSCs grown in RGDS-decorated gels indicate developmental progress toward mature neuron-like behavior. Our data indicate that these functional peptide hydrogels may go some way toward overcoming the limitations of current approaches to nerve-tissue repair. PMID:26240838

Self-assembled high-strength hydroxyapatite/graphene oxide/chitosan composite hydrogel for bone tissue engineering.

PubMed

Yu, Peng; Bao, Rui-Ying; Shi, Xiao-Jun; Yang, Wei; Yang, Ming-Bo

2017-01-02

Graphene hydrogel has shown greatly potentials in bone tissue engineering recently, but it is relatively weak in the practical use. Here we report a facile method to synthesize high strength composite graphene hydrogel. Graphene oxide (GO), hydroxyapatite (HA) nanoparticles (NPs) and chitosan (CS) self-assemble into a 3-dimensional hydrogel with the assistance of crosslinking agent genipin (GNP) for CS and reducing agent sodium ascorbate (NaVC) for GO simultaneously. The dense and oriented microstructure of the resulted composite gel endows it with high mechanical strength, high fixing capacity of HA and high porosity. These properties together with the good biocompatibility make the ternary composite gel a promising material for bone tissue engineering. Such a simultaneous crosslinking and reduction strategy can also be applied to produce a variety of 3D graphene-polymer based nanocomposites for biomaterials, energy storage materials and adsorbent materials. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alginate nanobeads interspersed fibrin network as in situ forming hydrogel for soft tissue engineering.

PubMed

Deepthi, S; Jayakumar, R

2018-06-01

Hydrogels are a class of materials that has the property of injectability and in situ gel formation. This property of hydrogels is manipulated in this study to develop a biomimetic bioresorbable injectable system of alginate nanobeads interspersed in fibrin network. Alginate nanobeads developed by calcium cross-linking yielded a size of 200-500 nm. The alginate nanobeads fibrin hydrogel was formed using dual syringe apparatus. Characterization of the in situ injectable hydrogel was done by SEM, FTIR and Rheometer. The developed hydrogel showed mechanical strength of 19 kPa which provides the suitable compliance for soft tissue engineering. Cytocompatibility studies using human umbilical cord blood derived mesenchymal stem cells showed good attachment, proliferation and infiltration within the hydrogel similar to fibrin gel. The developed in situ forming hydrogel could be a suitable delivery carrier of stem cells for soft tissue regeneration.

Rationalization of reduced penetration of drugs through ceramide gel phase membrane.

PubMed

Paloncýová, Markéta; DeVane, Russell H; Murch, Bruce P; Berka, Karel; Otyepka, Michal

2014-11-25

Since computing resources have advanced enough to allow routine molecular simulation studies of drug molecules interacting with biologically relevant membranes, a considerable amount of work has been carried out with fluid phospholipid systems. However, there is very little work in the literature on drug interactions with gel phase lipids. This poses a significant limitation for understanding permeation through the stratum corneum where the primary pathway is expected to be through a highly ordered lipid matrix. To address this point, we analyzed the interactions of p-aminobenzoic acid (PABA) and its ethyl (benzocaine) and butyl (butamben) esters with two membrane bilayers, which differ in their fluidity at ambient conditions. We considered a dioleoylphosphatidylcholine (DOPC) bilayer in a fluid state and a ceramide 2 (CER2, ceramide NS) bilayer in a gel phase. We carried out unbiased (100 ns long) and biased z-constraint molecular dynamics simulations and calculated the free energy profiles of all molecules along the bilayer normal. The free energy profiles converged significantly slower for the gel phase. While the compounds have comparable affinities for both membranes, they exhibit penetration barriers almost 3 times higher in the gel phase CER2 bilayer. This elevated barrier and slower diffusion in the CER2 bilayer, which are caused by the high ordering of CER2 lipid chains, explain the low permeability of the gel phase membranes. We also compared the free energy profiles from MD simulations with those obtained from COSMOmic. This method provided the same trends in behavior for the guest molecules in both bilayers; however, the penetration barriers calculated by COSMOmic did not differ between membranes. In conclusion, we show how membrane fluid properties affect the interaction of drug-like molecules with membranes.

Difference in volatile profile between pericarp tissue and locular gel in tomato fruit

USDA-ARS?s Scientific Manuscript database

Aroma, a complex mixture of volatile compounds, plays an important role in the perception and acceptability of tomato products by consumers. Numerous studies have reported volatile profiles in tomatoes based on measurement of the whole fruit or pericarp tissue, however, little is understood regardin...

Toughening of Thermoresponsive Arrested Networks of Elastin-Like Polypeptides To Engineer Cytocompatible Tissue Scaffolds.

PubMed

Glassman, Matthew J; Avery, Reginald K; Khademhosseini, Ali; Olsen, Bradley D

2016-02-08

Formulation of tissue engineering or regenerative scaffolds from simple bioactive polymers with tunable structure and mechanics is crucial for the regeneration of complex tissues, and hydrogels from recombinant proteins, such as elastin-like polypeptides (ELPs), are promising platforms to support these applications. The arrested phase separation of ELPs has been shown to yield remarkably stiff, biocontinuous, nanostructured networks, but these gels are limited in applications by their relatively brittle nature. Here, a gel-forming ELP is chain-extended by telechelic oxidative coupling, forming extensible, tough hydrogels. Small angle scattering indicates that the chain-extended polypeptides form a fractal network of nanoscale aggregates over a broad concentration range, accessing moduli ranging from 5 kPa to over 1 MPa over a concentration range of 5-30 wt %. These networks exhibited excellent erosion resistance and allowed for the diffusion and release of encapsulated particles consistent with a bicontinuous, porous structure with a broad distribution of pore sizes. Biofunctionalized, toughened networks were found to maintain the viability of human mesenchymal stem cells (hMSCs) in 2D, demonstrating signs of osteogenesis even in cell media without osteogenic molecules. Furthermore, chondrocytes could be readily mixed into these gels via thermoresponsive assembly and remained viable in extended culture. These studies demonstrate the ability to engineer ELP-based arrested physical networks on the molecular level to form reinforced, cytocompatible hydrogel matrices, supporting the promise of these new materials as candidates for the engineering and regeneration of stiff tissues.

The use of hemoglobin saturation ratio as a means of measuring tissue perfusion in the development of heel pressure sores.

PubMed

Aliano, Kristen A; Stavrides, Steve; Davenport, Thomas

2013-09-01

The heel is a common site of pressure ulcers. The amount of pressure and time needed to develop these wounds is dependent on various factors including pressure surface, the patient's anatomy, and co-morbidities. We studied the use of the hemoglobin saturation ratio as a means of assessing heel perfusion in various pressure settings. The mixed perfusion ratio in the heels of 5 volunteers was assessed on 3 pressure surfaces and at the time of off-load. The surfaces studied included: stretcher pad, plastic backboard without padding, and pressure reduction gel. Each surface was measured for 5 minutes with a real-time reading. On the stretcher, the average StO2% decrease for each pressure surface was 26.2 ± 10 (range 18-43). The average StO2% decrease on the backboard was 22.8 ± 12.3 (range 8-37), and 24.0 ± 4.8 (range 19-30) on the gel pad. The StO2% drop plateaued with the stretcher and gel pad, but with the backboard there was a continued slow drop at 5 minutes. This study demonstrates that hemoglobin oxygenation ratio may be effective in assessing a tissue's direct perfusion in the setting of tissue pressure and may also be beneficial to better assess the effects of pressure-reduction surfaces. Further studies will be needed to determine time to skin breakdown as it pertains to pressure and tissue oxygenation.

Tissue engineering-based cartilage repair with mesenchymal stem cells in a porcine model.

PubMed

Chang, Chih-Hung; Kuo, Tzong-Fu; Lin, Feng-Huei; Wang, Jyh-Horng; Hsu, Yuan-Ming; Huang, Huei-Ting; Loo, Shiao-Tung; Fang, Hsu-Wei; Liu, Hwa-Chang; Wang, Wen-Chih

2011-12-01

This in vivo pilot study explored the use of mesenchymal stem cell (MSC) containing tissue engineering constructs in repair of osteochondral defects. Osteochondral defects were created in the medial condyles of both knees of 16 miniature pigs. One joint received a cell/collagen tissue engineering construct with or without pretreatment with transforming growth factor β (TGF-β) and the other joint from the same pig received no treatment or the gel scaffold only. Six months after surgery, in knees with no treatment, all defects showed contracted craters; in those treated with the gel scaffold alone, six showed a smooth gross surface, one a hypertrophic surface, and one a contracted crater; in those with undifferentiated MSCs, five defects had smooth, fully repaired surfaces or partially repaired surfaces, and one defect poor repair; in those with TGF-β-induced differentiated MSCs, seven defects had smooth, fully repaired surfaces or partially repaired surfaces, and three defects showed poor repair. In Pineda score grading, the group with undifferentiated MSC, but not the group with TGF-β-induced differentiated MSCs, had significantly lower subchondral, cell morphology, and total scores than the groups with no or gel-only treatment. The compressive stiffness was larger in cartilage without surgical treatment than the treated area within each group. In conclusion, this preliminary pilot study suggests that using undifferentiated MSCs might be a better approach than using TGF-β-induced differentiated MSCs for in vivo tissue engineered treatment of osteochondral defects. Copyright © 2011 Orthopaedic Research Society.

Real-Time Monitoring Of Regional Tissue Elasticity During FUS Focused Ultrasound Therapy Using Harmonic Motion Imaging

NASA Astrophysics Data System (ADS)

Maleke, Caroline; Pernot, Mathieu; Konofagou, Elisa

2006-05-01

The feasibility of the Harmonic Motion Imaging (HMI) technique for simultaneous monitoring and generation of focused ultrasound therapy using two separate focused ultrasound transducer elements has previously been shown. In this study, a new HMI technique is described that images tissue displacement induced by a harmonic radiation force induced using a single focused ultrasound element. First, wave propagation simulation models were used to compare the use of a single Amplitude-Modulated (AM) focused beam versus two overlapping focused beams as previously implemented for HMI. Simulation results indicated that, unlike in the two-beam configuration, the AM beam produced a consistent, stable focus for the applied harmonic radiation force. The AM beam thus offered the unique advantage of sustaining the application of the spatially-invariant radiation force. Experiments were then performed on gelatin gel phantoms and tissue in vitro bovine liver. The radiation force was generated by a 4.68 MHz focused transducer using a low-frequency Amplitude-Modulated (AM) RF-signal. RF data were acquired at 7.5 MHz with a PRF of 6.5 kHz and displacements were estimated using a 1D cross-correlation algorithm on successive RF signals. Furthermore, taking advantage of the real-time capability of our method, the change in the elastic properties was monitored during focused ultrasound (FUS) ablation of tissue in vitro bovine liver. Based on the harmonic displacements, their temperature-dependence, and the calculated acoustic radiation force, the change in the relative, regional stiffness could be monitored during heating and ablation, both using the displacement amplitude and the resulting phase shift change of the displacement relative to the radiation force temporal profile. In conclusion, the feasibility of using an AM radiation force for HMI for simultaneous monitoring and treatment during ultrasound therapy was demonstrated in phantoms and tissues in vitro. Further study of this method will include, ex vivo and in vivo, stiffness and temperature.

2D dose distribution images of a hybrid low field MRI-γ detector

NASA Astrophysics Data System (ADS)

Abril, A.; Agulles-Pedrós, L.

2016-07-01

The proposed hybrid system is a combination of a low field MRI and dosimetric gel as a γ detector. The readout system is based on the polymerization process induced by the gel radiation. A gel dose map is obtained which represents the functional part of hybrid image alongside with the anatomical MRI one. Both images should be taken while the patient with a radiopharmaceutical is located inside the MRI system with a gel detector matrix. A relevant aspect of this proposal is that the dosimetric gel has never been used to acquire medical images. The results presented show the interaction of the 99mTc source with the dosimetric gel simulated in Geant4. The purpose was to obtain the planar γ 2D-image. The different source configurations are studied to explore the ability of the gel as radiation detector through the following parameters; resolution, shape definition and radio-pharmaceutical concentration.

Monte Carlo simulation of two-component bilayers: DMPC/DSPC mixtures.

PubMed Central

Sugár, I P; Thompson, T E; Biltonen, R L

1999-01-01

In this paper, we describe a relatively simple lattice model of a two-component, two-state phospholipid bilayer. Application of Monte Carlo methods to this model permits simulation of the observed excess heat capacity versus temperature curves of dimyristoylphosphatidylcholine (DMPC)/distearoylphosphatidylcholine (DSPC) mixtures as well as the lateral distributions of the components and properties related to these distributions. The analysis of the bilayer energy distribution functions reveals that the gel-fluid transition is a continuous transition for DMPC, DSPC, and all DMPC/DSPC mixtures. A comparison of the thermodynamic properties of DMPC/DSPC mixtures with the configurational properties shows that the temperatures characteristics of the configurational properties correlate well with the maxima in the excess heat capacity curves rather than with the onset and completion temperatures of the gel-fluid transition. In the gel-fluid coexistence region, we also found excellent agreement between the threshold temperatures at different system compositions detected in fluorescence recovery after photobleaching experiments and the temperatures at which the percolation probability of the gel clusters is 0.36. At every composition, the calculated mole fraction of gel state molecules at the fluorescence recovery after photobleaching threshold is 0.34 and, at the percolation threshold of gel clusters, it is 0.24. The percolation threshold mole fraction of gel or fluid lipid depends on the packing geometry of the molecules and the interchain interactions. However, it is independent of temperature, system composition, and state of the percolating cluster. PMID:10096905

The use of normoxic polymer gel for measuring dose distributions of 1, 4 and 30 mm cones

NASA Astrophysics Data System (ADS)

Lee, C. C.; Wu, J. F.; Chang, K. P.; Chu, C. H.; Wey, S. P.; Liu, H. L.; Tung, C. J.; Wu, S. W.; Chao, T. C.

2014-11-01

This study demonstrates the use of normoxic polymer gel for measuring dose distributions of small fields that lack lateral electronic equilibrium. Two different types of normoxic polymer gel, MAGAT and PAGAT, are studied in a larger field (10 cm×10 cm) and 1, 4 and 30 mm cones to obtain cone factors, dose profiles and percentage depth doses. These results were then compared to KODAK XV film measurements and BEAMnrc Monte Carlo simulations. The results show that the sensitivity of PAGAT gel is 0.090±0.074 s-1 Gy-1, which may not be suitable for small-field dosimetry with a 0.3 mm resolution scanned using a 3 T MR imager in a dose range lower than 2.5 Gy. There are good agreements between cone factors estimated using KODAK XV film and MAGAT gel. In a dose profile comparison, good dose agreement among MAGAT gel, XV film and MC simulation can be seen in the central area for a 30 mm cone. In penumbra, the distance to agreement is at most 1.2 mm (4 pixel), and less than 0.3 mm (1 pixel) for 4 and 1 mm cones. In a percentage depth dose comparison, there were good agreements between MAGAT and MC up to a depth of 8 cm. Possible factors for gel uncertainty such as MRI magnetic field inhomogeneity and temperature were also investigated.

SU-E-J-210: Characterizing Tissue Equivalent Materials for the Development of a Dual MRI-CT Heterogeneous Anthropomorphic Phantom Designed Specifically for MRI Guided Radiotherapy Systems

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

Steinmann, A; Stafford, R; Yung, J

Purpose: MRI guided radiotherapy (MRIgRT) is an emerging technology which will eventually require a proficient quality auditing system. Due to different principles in which MR and CT acquire images, there is a need for a multi-imaging-modality, end-to-end QA phantom for MRIgRT. The purpose of this study is to identify lung, soft tissue, and tumor equivalent substitutes that share similar human-like CT and MR properties (i.e. Hounsfield units and relaxation times). Methods: Materials of interested such as common CT QA phantom materials, and other proprietary gels/silicones from Polytek, SmoothOn, and CompositeOne were first scanned on a GE 1.5T Signa HDxT MR.more » Materials that could be seen on both T1-weighted and T2-weighted images were then scanned on a GE Lightspeed RT16 CT simulator and a GE Discovery 750HD CT scanner and their HU values were then measured. The materials with matching HU values of lung (−500 to −700HU), muscle (+40HU) and soft tissue (+100 to +300HU) were further scanned on GE 1.5T Signa HDx to measure their T1 and T2 relaxation times from varying parameters of TI and TE. Results: Materials that could be visualized on T1-weighted and T2-weighted images from a 1.5T MR unit and had an appropriate average CT number, −650, −685, 46,169, and 168 HUs were: compressed cork saturated with water, Polytek Platsil™ Gel-00 combined with mini styrofoam balls, radiotherapy bolus material, SmoothOn Dragon-Skin™ and SmoothOn Ecoflex™, respectively. Conclusion: Post processing analysis is currently being performed to accurately map T1 and T2 values for each material tested. From previous MR visualization and CT examinations it is expected that Dragon-Skin™, Ecoflex™ and bolus will have values consistent with tissue and tumor substitutes. We also expect compressed cork statured with water, and Polytek™-styrofoam combination to have approximate T1 and T2 values suitable for lung-equivalent materials.« less

Fabrication and in vivo evaluation of an osteoblast-conditioned nano-hydroxyapatite/gelatin composite scaffold for bone tissue regeneration.

PubMed

Samadikuchaksaraei, Ali; Gholipourmalekabadi, Mazaher; Erfani Ezadyar, Elham; Azami, Mahmoud; Mozafari, Masoud; Johari, Behrooz; Kargozar, Saeid; Jameie, Seyed Behnamedin; Korourian, Alireza; Seifalian, Alexander M

2016-08-01

In this study, the effects of osteoblast-conditioning on mechanical behavior, biocompatibility, biodegradation and osteoinductive properties of a nano-hydroxyapatite/gelatin (HA/GEL) nanocomposite scaffold was investigated. The scaffold was fabricated using the layer solvent casting combined with the freeze-drying and lamination techniques. The scaffolds were conditioned by culture of osteoblasts on their surface and their elimination by a repeated freeze-thawing process. The potential of the osteoblast-conditioned HA/GEL (HA/GEL/OC) scaffold to support cell adhesion and growth and its cytotoxicity was assessed in vitro using rat mesenchymal stem cells. For in vivo studies, the HA/GEL/OC nanocomposite was implanted in the critical size bone defect created on rat calvarium and studied after 7, 30 and 90 days. The results showed that mechanical and in vitro biological properties of the scaffold were not affected by the process of conditioning. However, in vivo studies demonstrated that osteoblast-conditioning enhanced biocompatibility and osteoinductivity and of the nanocomposite scaffold. The osteoblast conditioning also accelerated collagen content during the bone healing. In the experimental group that received the HA/GEL/OC and MSCs, the newly formed bone occupied almost the entire defect (93.4 ± 3.3%) within 3 months. In conclusion, this study indicates that osteoblast-conditioning is a viable strategy for the development of bone tissue engineering scaffolds. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2001-2010, 2016. © 2016 Wiley Periodicals, Inc.

Development and Implementation of Non-Newtonian Rheology Into the Generalized Fluid System Simulation Program (GFSSP)

NASA Technical Reports Server (NTRS)

DiSalvo, Roberto; Deaconu, Stelu; Majumdar, Alok

2006-01-01

One of the goals of this program was to develop the experimental and analytical/computational tools required to predict the flow of non-Newtonian fluids through the various system components of a propulsion system: pipes, valves, pumps etc. To achieve this goal we selected to augment the capabilities of NASA's Generalized Fluid System Simulation Program (GFSSP) software. GFSSP is a general-purpose computer program designed to calculate steady state and transient pressure and flow distributions in a complex fluid network. While the current version of the GFSSP code is able to handle various systems components the implicit assumption in the code is that the fluids in the system are Newtonian. To extend the capability of the code to non-Newtonian fluids, such as silica gelled fuels and oxidizers, modifications to the momentum equations of the code have been performed. We have successfully implemented in GFSSP flow equations for fluids with power law behavior. The implementation of the power law fluid behavior into the GFSSP code depends on knowledge of the two fluid coefficients, n and K. The determination of these parameters for the silica gels used in this program was performed experimentally. The n and K parameters for silica water gels were determined experimentally at CFDRC's Special Projects Laboratory, with a constant shear rate capillary viscometer. Batches of 8:1 (by weight) water-silica gel were mixed using CFDRC s 10-gallon gelled propellant mixer. Prior to testing the gel was allowed to rest in the rheometer tank for at least twelve hours to ensure that the delicate structure of the gel had sufficient time to reform. During the tests silica gel was pressure fed and discharged through stainless steel pipes ranging from 1", to 36", in length and three diameters; 0.0237", 0.032", and 0.047". The data collected in these tests included pressure at tube entrance and volumetric flowrate. From these data the uncorrected shear rate, shear stress, residence time, and viscosity were evaluated using formulae for non-Newtonian, power law fluids. The maximum shear rates (corrected for entrance effects) obtained in the rheometer with the current setup were in the 150,000 to 170,000sec- range. GFSSP simulations were performed with a flow circuit simulating the capillary rheometer and using Power Law gel viscosity coefficients from the experimental data. The agreement between the experimental data and the simulated flow curves was within +/-4% given quality entrance effect data.

Engineered Fibrin Gels for Parallel Stimulation of Mesenchymal Stem Cell Proangiogenic and Osteogenic Potential

PubMed Central

Murphy, Kaitlin C.; Hughbanks, Marissa L.; Binder, Bernard Y.K.; Vissers, Caroline B.; Leach, J. Kent

2014-01-01

Mesenchymal stem/stromal cells (MSCs) are under examination for use in cell therapies to repair bone defects resulting from trauma or disease. MSCs secrete proangiogenic cues and can be induced to differentiate into bone-forming osteoblasts, yet there is limited evidence that these events can be achieved in parallel. Manipulation of the cell delivery vehicle properties represents a candidate approach for directing MSC function in bone healing. We hypothesized that the biophysical properties of a fibrin gel could simultaneously regulate the proangiogenic and osteogenic potential of entrapped MSCs. Fibrin gels were formed by supplementation with NaCl (1.2, 2.3, and 3.9% w/v) to modulate gel biophysical properties without altering protein concentrations. MSCs entrapped in 1.2% w/v NaCl gels were the most proangiogenic in vitro, yet cells in 3.9% w/v gels exhibited the greatest osteogenic response. Compared to the other groups, MSCs entrapped in 2.3% w/v gels provided the best balance between proangiogenic potential, osteogenic potential, and gel contractility. The contribution of MSCs to bone repair was then examined when deployed in 2.3% w/v NaCl gels and implanted into an irradiated orthotopic bone defect. Compared to acellular gels after 3 weeks of implantation, defects treated with MSC-loaded fibrin gels exhibited significant increases in vessel density, early osteogenesis, superior morphology, and increased cellularity of repair tissue. Defects treated with MSC-loaded gels exhibited increased bone formation after 12 weeks compared to blank gels. These results confirm that fibrin gel properties can be modulated to simultaneously promote both the proangiogenic and osteogenic potential of MSCs, and fibrin gels modified by supplementation with NaCl are promising carriers for MSCs to stimulate bone repair in vivo. PMID:25527322

Ionic liquid based multifunctional double network gel

NASA Astrophysics Data System (ADS)

Ahmed, Kumkum; Higashihara, Tomoya; Arafune, Hiroyuki; Kamijo, Toshio; Morinaga, Takashi; Sato, Takaya; Furukawa, Hidemitsu

2015-04-01

Gels are a promising class of soft and wet materials with diverse application in tissue engineering and bio-medical purpose. In order to accelerate the development of gels, it is required to synthesize multi-functional gels of high mechanical strength, ultra low surface friction and suitable elastic modulus with a variety of methods and new materials. Among many types of gel ionic gel made from ionic liquids (ILs) could be used for diverse applications in electrochemical devices and in the field of tribology. IL, a promising materials for lubrication, is a salt with a melting point lower than 100 °C. As a lubricant, ILs are characterized by an extremely low vapor pressure, high thermal stability and high ion conductivity. In this work a novel approach of making double network DN ionic gel using IL has been made utilizing photo polymerization process. A hydrophobic monomer Methyl methacrylate (MMA) has been used as a first network and a hydrophobic IL monomer, N,N-diethyl-N-(2-mthacryloylethyl)-N-methylammonium bistrifluoromethylsulfonyl)imide (DEMM-TFSI) has been used as a second network using photo initiator benzophenon and crosslinker triethylene glycol dimethacrylate (TEGDMA). The resulting DN ionic gel shows transparency, flexibility, high thermal stability, good mechanical toughness and low friction coefficient value which can be a potential candidate as a gel slider in different mechanical devices and can open a new area in the field of gel tribology.

Magnetoacoustic tomography with magnetic induction for high-resolution bioimepedance imaging through vector source reconstruction under the static field of MRI magnet.

PubMed

Mariappan, Leo; Hu, Gang; He, Bin

2014-02-01

Magnetoacoustic tomography with magnetic induction (MAT-MI) is an imaging modality to reconstruct the electrical conductivity of biological tissue based on the acoustic measurements of Lorentz force induced tissue vibration. This study presents the feasibility of the authors' new MAT-MI system and vector source imaging algorithm to perform a complete reconstruction of the conductivity distribution of real biological tissues with ultrasound spatial resolution. In the present study, using ultrasound beamformation, imaging point spread functions are designed to reconstruct the induced vector source in the object which is used to estimate the object conductivity distribution. Both numerical studies and phantom experiments are performed to demonstrate the merits of the proposed method. Also, through the numerical simulations, the full width half maximum of the imaging point spread function is calculated to estimate of the spatial resolution. The tissue phantom experiments are performed with a MAT-MI imaging system in the static field of a 9.4 T magnetic resonance imaging magnet. The image reconstruction through vector beamformation in the numerical and experimental studies gives a reliable estimate of the conductivity distribution in the object with a ∼ 1.5 mm spatial resolution corresponding to the imaging system frequency of 500 kHz ultrasound. In addition, the experiment results suggest that MAT-MI under high static magnetic field environment is able to reconstruct images of tissue-mimicking gel phantoms and real tissue samples with reliable conductivity contrast. The results demonstrate that MAT-MI is able to image the electrical conductivity properties of biological tissues with better than 2 mm spatial resolution at 500 kHz, and the imaging with MAT-MI under a high static magnetic field environment is able to provide improved imaging contrast for biological tissue conductivity reconstruction.

Piercing Ear Keloid: Excision Using Loupe Magnification and Topical Liquid Silicone Gel as Adjuvant

PubMed Central

Ramesh, Bellam A.; Mohan, J.

2018-01-01

Background: Keloid is an abnormal growth of scar at the site of skin injury, which usually does not regress. It proliferates beyond the original scar. The ear keloid usually develops after piercing injury to wear ornaments. A patient usually asks for removal of keloid, as it is aesthetically unpleasant. Patient may sometimes complain of itching and pain. Aim: The study was conducted to analyze results following excision of keloid with its tract and topical silicone gel as the postsurgical adjuvant. Materials and Methods: Ear keloids measuring less than 0.5cm or more than 5cm in maximum dimension were excluded from the study. Nonpiercing causes such as burns, trauma, and recurrent keloid were excluded from the study. The study was carried out on 22 patients who had keloid because of piercing injury, including 4 cases with both ear keloids. Of 26 ear keloids, 19 had the tract or connecting tissue. The lesion was excised under anesthesia using magnification. For all the operated cases, topical liquid silicone gel was used as postsurgical adjuvant therapy. The method of application of topical silicone gel was taught to each patient and was considered significant. Result: The magnification helped in identification of tract in 73% of the cases in this study. Twenty patients had successfully responded to proposed treatment, and two patients developed recurrence while using topical silicone gel as the adjuvant. These two patients were managed with conventional triamcinolone injection. Conclusion: The topical silicone gel as postsurgical adjuvant therapy avoided the use of painful postsurgical injection or radiotherapy for the 1–3cm primary ear keloids. The advantages of magnification were better clearance of keloid tissue, easier identification of tract and removal of keloid pseudopods, meticulous suturing, and comfortable elevation of a small local flap. PMID:29731586

Oral Transmucosal Detomidine Gel in New Zealand White Rabbits (Oryctolagus cuniculus).

PubMed

Williams, Morika D; Long, C Tyler; Durrant, Jessica R; McKeon, Gabriel P; Shive, Heather R; Griffith, Emily H; Messenger, Kristen M; Fish, Richard E

2017-07-01

Handling and restraining rabbits for routine procedures may be impossible without prior sedation, result in unnecessary stress or injury to the rabbit or handler, and increase experimental variability. Parenteral administration of sedatives can cause stress also, as well as localized pain and tissue damage, especially in fractious animals. Detomidine hydrochloride, an α2-adrenergic receptor agonist, is commercially available in an oral transmucosal (OTM) gel formulation that is FDA-approved for sedation and restraint in horses. This study investigated the efficacy and safety of detomidine gel as an alternative to injectable sedation in rabbits. Eight adult male New Zealand White rabbits each received 0.6, 1.2, or 1.8 mg/kg OTM detomidine gel. Physiologic parameters and sedation scores (SS) were assessed at 10-min intervals from before administration until 100 min afterward. Histopathology of cardiac tissue was scored through 12 d after dosing. Gel administration increased the SS in all rabbits, but none of the animals developed clinically effective sedation (SS of 10 or greater, based on 5 reflex responses on a 3- or 4-point scale). The SS did not differ among dosage groups, and the time-dose interaction was not statistically significant. Heart rate decreased rapidly in all rabbits, with no difference among dosage groups, and there was no effect of time or dosage on peripheral capillary oxygen saturation. Minimal to mild degenerative changes were seen in the myocardium of all treated rabbits, but myocyte necrosis, inflammation, fibrosis, and mural thrombi-reported previously in rabbits that had received parenteral detomidine-did not occur. OTM detomidine gel was safely and easily administered to rabbits, but the duration and level of sedation were unpredictable. The use of OTM detomidine as a sole agent to facilitate handling and restraint of rabbits does not offer advantages over existing parenteral regimens.

Topical tenofovir protects against vaginal simian HIV infection in macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis.

PubMed

Makarova, Natalia; Henning, Tara; Taylor, Andrew; Dinh, Chuong; Lipscomb, Jonathan; Aubert, Rachael; Hanson, Debra; Phillips, Christi; Papp, John; Mitchell, James; McNicholl, Janet; Garcia-Lerma, Gerardo J; Heneine, Walid; Kersh, Ellen; Dobard, Charles

2017-03-27

Chlamydia trachomatis and Trichomonas vaginalis, two prevalent sexually transmitted infections, are known to increase HIV risk in women and could potentially diminish preexposure prophylaxis efficacy, particularly for topical interventions that rely on local protection. We investigated in macaques whether coinfection with Chlamydia trachomatis/Trichomonas vaginalis reduces protection by vaginal tenofovir (TFV) gel. Vaginal TFV gel dosing previously shown to provide 100 or 74% protection when applied either 30 min or 3 days before simian HIV(SHIV) challenge was assessed in pigtailed macaques coinfected with Chlamydia trachomatis/Trichomonas vaginalis and challenged twice weekly with SHIV162p3 for up to 10 weeks (two menstrual cycles). Three groups of six macaques received either placebo or 1% TFV gel 30 min or 3 days before each SHIV challenge. We additionally assessed TFV and TFV diphosphate concentrations in plasma and vaginal tissues in Chlamydia trachomatis/Trichomonas vaginalis coinfected (n = 4) and uninfected (n = 4) macaques. Chlamydia trachomatis/Trichomonas vaginalis coinfections were maintained during the SHIV challenge period. All macaques that received placebo gel were SHIV infected after a median of seven challenges (one menstrual cycle). In contrast, no infections were observed in macaques treated with TFV gel 30 min before SHIV challenge (P < 0.001). Efficacy was reduced to 60% when TFV gel was applied 3 days before SHIV challenge (P = 0.07). Plasma TFV and TFV diphosphate concentrations in tissues and vaginal lymphocytes were significantly higher in Chlamydia trachomatis/Trichomonas vaginalis coinfected compared with Chlamydia trachomatis/Trichomonas vaginalis uninfected macaques. Our findings in this model suggest that Chlamydia trachomatis/Trichomonas vaginalis coinfection may have little or no impact on the efficacy of highly effective topical TFV modalities and highlight a significant modulation of TFV pharmacokinetics.

Intra-articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large osteochondral defect by implantation of a double-network gel.

PubMed

Fukui, Takaaki; Kitamura, Nobuto; Kurokawa, Takayuki; Yokota, Masashi; Kondo, Eiji; Gong, Jian Ping; Yasuda, Kazunori

2014-04-01

Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the osteochondral defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical osteochondral defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.

The effects of inhomogeneous boundary dilution on the coating flow of an anti-HIV microbicide vehicle

NASA Astrophysics Data System (ADS)

Tasoglu, Savas; Peters, Jennifer J.; Park, Su Chan; Verguet, Stéphane; Katz, David F.; Szeri, Andrew J.

2011-09-01

A recent study in South Africa has confirmed, for the first time, that a vaginal gel formulation of the antiretroviral drug Tenofovir, when topically applied, significantly inhibits sexual HIV transmission to women [Karim et al., Science 329, 1168 (2010)]. However, the gel for this drug and anti-HIV microbicide gels in general have not been designed using an understanding of how gel spreading and retention in the vagina govern successful drug delivery. Elastohydrodynamic lubrication theory can be applied to model spreading of microbicide gels [Szeri et al., Phys. Fluids 20, 083101 (2008)]. This should incorporate the full rheological behavior of a gel, including how rheological properties change due to contact with, and dilution by, ambient vaginal fluids. Here, we extend our initial analysis, incorporating the effects of gel dilution due to contact with vaginal fluid produced at the gel-tissue interface. Our original model is supplemented with a convective-diffusive transport equation to characterize water transport into the gel and, thus, local gel dilution. The problem is solved using a multi-step scheme in a moving domain. The association between local dilution of gel and rheological properties is obtained experimentally, delineating the way constitutive parameters of a shear-thinning gel are modified by dilution. Results show that dilution accelerates the coating flow by creating a slippery region near the vaginal wall akin to a dilution boundary layer, especially if the boundary flux exceeds a certain value. On the other hand, if the diffusion coefficient of boundary fluid is increased, the slippery region diminishes in extent and the overall rate of gel spreading decreases.

Objective assessment of leg edema using ultrasonography with a gel pad

PubMed Central

Iuchi, Terumi; Tsuchiya, Sayumi; Ohno, Naoki; Dai, Misako; Matsumoto, Masaru; Ogai, Kazuhiro; Sato, Aya; Sawazaki, Takuto; Miyati, Tosiaki; Tanaka, Shinobu; Sugama, Junko

2017-01-01

Ultrasonography (US) is useful for visual detection of edematous tissues to assess subcutaneous echogenicity. However, visualization of subcutaneous echogenicity is interpreted differently among operators because the evaluation is subjective and individual operators have unique knowledge. This study objectively assessed leg edema using US with a gel pad including fat for normalization of echogenicity in subcutaneous tissue. Five younger adults and four elderly people with leg edema were recruited. We compared assessments of US and limb circumference before and after the intervention of vibration to decrease edema in younger adults, and edema prior to going to sleep and reduced edema in the early morning in elderly people. These assessments were performed twice in elderly people by three operators and reliability, interrater differences, and bias were assessed. For US assessment, echogenicity in subcutaneous tissue was normalized to that of the gel pad by dividing the mean echogenicity of subcutaneous tissue by the mean echogenicity of the gel pad. In younger adults, the normalized subcutaneous echogenicity before the intervention was significantly higher than that after the intervention. In elderly people, echogenicity indicating edema was significantly higher than that after edema reduction. Edema was detected with accuracy rates of 76.9% in younger adults and 75.0% in elderly people. Meanwhile, limb circumference could be used to detect edema in 50.0% of healthy adults and 87.8% of elderly people. The intra-reliability was excellent (intraclass correlation coefficient > 0.9, p < 0.01), and the inter-reliability was good (intraclass correlation coefficient > 0.7, p < 0.01) for normalized subcutaneous echogenicity. Bland-Altman plots revealed that inter-rater differences and systematic bias were small. Normalized subcutaneous echogenicity with the pad can sensitively and objectively assess leg edema with high reliability. Therefore, this method has the potential to become a new gold standard for objective assessment of leg edema in clinical practice. PMID:28792959

Ocular and systemic pharmacokinetics of lidocaine hydrochloride ophthalmic gel in rabbits after topical ocular administration.

PubMed

Liu, Bing; Ding, Li; Xu, Xiaowen; Lin, Hongda; Sun, Chenglong; You, Linjun

2015-12-01

Lidocaine hydrochloride ophthalmic gel is a novel ophthalmic preparation for topical ocular anesthesia. The study is aimed at evaluating the ocular and systemic pharmacokinetics of lidocaine hydrochloride 3.5 % ophthalmic gel in rabbits after ocular topical administration. Thirty-six rabbits were randomly placed in 12 groups (3 rabbits per group). The rabbits were quickly killed according to their groups at 0 (predose), 0.0833, 0.167, 0.333, 0.667, 1, 1.5, 2, 3, 4, 6, and 8 h postdose and then the ocular tissue and plasma samples were collected. All the samples were analyzed by a validated LC-MS/MS method. The test result showed that the maximum concentration (C max) of lidocaine in different ocular tissues and plasma were all achieved within 20 min after drug administration, and the data of C max were (2,987 ± 1814) μg/g, (44.67 ± 12.91) μg/g, (26.26 ± 7.19) μg/g, (11,046 ± 2,734) ng/mL, and (160.3 ± 61.0) ng/mL for tear fluid, cornea, conjunctiva, aqueous humor, and plasma, respectively. The data of the elimination half-life in these tissues were 1.5, 3.2, 3.5, 1.9, and 1.7 h for tear fluid, cornea, conjunctiva, aqueous humor, and plasma, respectively. The intraocular lidocaine levels were significantly higher than that in plasma, and the elimination half-life of lidocaine in cornea, conjunctiva, and aqueous humor was relatively longer than that in tear fluid and plasma. The high intraocular penetration, low systemic exposure, and long duration in the ocular tissues suggested lidocaine hydrochloride 3.5 % ophthalmic gel as an effective local anesthetic for ocular anesthesia during ophthalmic procedures.

Touch Locating and Stretch Sensing Studies of Conductive Hydrogels with Applications to Soft Robots.

PubMed

Zhou, Yanmin; He, Bin; Yan, Zhe; Shang, Yinghui; Wang, Qigang; Wang, Zhipeng

2018-02-13

Soft robots possess great potential in environmental adaptations, while their environmental sensing abilities are critical. Conductive hydrogels have been suggested to possess sensing abilities. However, their application in soft robots is lacking. In this work, we fabricated a soft and stretchable gel material, introduced its sensing mechanisms, and developed a measurement setup. Both experimental and simulation studies indicate strong nonlinearity of touch locating on a square touch panel with Cartesian coordinates. To simplify the touch locating, we proposed a touch locating system based on round touch panels with polar coordinates. Mathematical calculations and finite element method (FEM) simulations showed that in this system the locating of a touch point was only determined by its polar radius. This was verified by experimental studies. As a resistor, a gel strip's resistance increases with stretching. To demonstrate their applications on soft robots, a 3D printed three-fingered soft gripper was employed with gel strips attached. During finger bending for rod grasping, the resistances of the gel strips increased, indicating stretching of the soft material. Furthermore, the strain and stress of a gel strip increased with a decrease of the rod diameter. These studies advance the application of conductive hydrogels on soft robots.

Dentine sialoprotein and collagen I expression after experimental pulp capping in humans using emdogain gel.

PubMed

Fransson, H; Petersson, K; Davies, J R

2011-03-01

To characterize the hard tissue formed in human teeth experimentally pulp capped either with calcium hydroxide or with Emdogain Gel (Biora AB, Malmö, Sweden) - a derivative of enamel matrix (EMD), using two markers for dentine; dentine sialoprotein (DSP) and type 1 collagen (Col I). Affinity-purified rabbit anti-Col I and anti-DSP polyclonal antibodies were used to stain histological sections from nine pairs of contra-lateral premolars that had been experimentally pulp amputated and randomly capped with EMDgel or calcium hydroxide. Twelve weeks after the teeth had been pulp capped, they were extracted, fixed, demineralized and serially sectioned prior to immunohistochemical staining. In the calcium hydroxide treated teeth DSP was seen in the new hard tissue which formed a bridge. DSP was also seen in the newly formed hard tissue in the EMDgel-treated teeth. Proliferated pulp tissue partly filled the space initially occupied by EMDgel and DSP-stained hard tissue was observed alongside exposed dentine surfaces as well as in isolated masses within the proliferated pulp tissue, although the new hard tissue did not cover the pulp exposure. DSP staining was also seen in the cells lining the hard tissue in both groups. Col I staining was seen in the newly formed hard tissue in both groups. The new hard tissue formed after pulp capping with EMDgel or calcium hydroxide contained DSP and Col I, considered to be markers for dentine. Thus, the newly formed hard tissue can be characterized as dentine rather than unspecific hard tissue. © 2010 International Endodontic Journal.

Measuring Dilution of Microbicide Gels with Optical Imaging

PubMed Central

Drake, Tyler K.; Shah, Tejen; Peters, Jennifer J.; Wax, Adam; Katz, David F.

2013-01-01

We present a novel approach for measuring topical microbicide gel dilution using optical imaging. The approach compares gel thickness measurements from fluorimetry and multiplexed low coherence interferometry in order to calculate dilution of a gel. As a microbicide gel becomes diluted at fixed thickness, its mLCI thickness measurement remains constant, while the fluorimetry signal decreases in intensity. The difference between the two measurements is related to the extent of gel dilution. These two optical modalities are implemented in a single endoscopic instrument that enables simultaneous data collection. A preliminary validation study was performed with in vitro placebo gel measurements taken in a controlled test socket. It was found that change in slope of the regression line between fluorimetry and mLCI based measurements indicates dilution. A dilution calibration curve was then generated by repeating the test socket measurements with serial dilutions of placebo gel with vaginal fluid simulant. This methodology can provide valuable dilution information on candidate microbicide products, which could substantially enhance our understanding of their in vivo functioning. PMID:24340006

Chemotaxis of active, self-oscillating polymer gels in solution

NASA Astrophysics Data System (ADS)

Dayal, Pratyush; Bhattacharya, Amitabh; Kuksenok, Olga; Balazs, Anna C.

2012-02-01

Fighting, fleeing and feeding are hallmarks of all living things; all these activities require some degree of mobility. Herein, we undertake the first computational study of self-oscillating polymer gels and show that this system can ``communicate'' to undergo a biomimetic, collective response to small-scale chemical changes. In this study we harness unique properties of polymer gels that undergo oscillatory Belousov-Zhabotinsky (BZ) reaction. The activator for the reaction is generated within these BZ cilia and diffuses between the neighboring gels. In order to simulate the dynamics of the BZ gels in surrounding fluid we have developed a nonlinear hybrid 3D model which captures the elasto-dynamics of polymer gel and diffusive exchange of BZ reagents between the gel and the fluid. We illustrate that multiple BZ gels in solution exhibit a distinct form of chemotaxis, moving towards the highest activator concentration in the solution. Similar ability to sense and move in response to chemical gradients constitutes a vital function in simple organisms, enabling them to find food and flee from poisons.

Sol–gel method to fabricate CaP scaffolds by robocasting for tissue engineering

PubMed Central

Fu, Qiang; Saiz, Eduardo; Tomsia, Antoni P.

2012-01-01

Highly porous calcium phosphate (CaP) scaffolds for bone-tissue engineering were fabricated by combining a robocasting process with a sol–gel synthesis that mixed Calcium Nitrate Tetrahydrate and Triethyl Phosphite precursors in an aqueous medium. The resulting gels were used to print scaffolds by robocasting without the use of binder to increase the viscosity of the paste. X-ray diffraction analysis confirmed that the process yielded hydroxyapatite and β-tricalcium phosphate biphasic composite powders. Thus, the scaffold composition after crystallization of the amorphous structure could be easily modified by varying the initial Ca/P ratio during synthesis. The compressive strengths of the scaffolds are ~6 MPa, which is in the range of human cancellous bone (2–12 MPa). These highly porous scaffolds (~73 vol% porosity) are composed of macro-pores of ~260 μm in size; such porosity is expected to enable bone ingrowth into the scaffold for bone repair applications. The chemistry, porosity, and surface topography of such scaffolds can also be modified by the process parameters to favor bone formation. The studied sol–gel process can be used to coat these scaffolds by dip-coating, which induces a significant enhancement of mechanical properties. This can adjust scaffold properties such as composition and surface morphology, which consequently may improve their performances. PMID:22311079

Sol-gel method to fabricate CaP scaffolds by robocasting for tissue engineering.

PubMed

Houmard, Manuel; Fu, Qiang; Saiz, Eduardo; Tomsia, Antoni P

2012-04-01

Highly porous calcium phosphate (CaP) scaffolds for bone-tissue engineering were fabricated by combining a robocasting process with a sol-gel synthesis that mixed Calcium Nitrate Tetrahydrate and Triethyl Phosphite precursors in an aqueous medium. The resulting gels were used to print scaffolds by robocasting without the use of binder to increase the viscosity of the paste. X-ray diffraction analysis confirmed that the process yielded hydroxyapatite and β-tricalcium phosphate biphasic composite powders. Thus, the scaffold composition after crystallization of the amorphous structure could be easily modified by varying the initial Ca/P ratio during synthesis. The compressive strengths of the scaffolds are ~6 MPa, which is in the range of human cancellous bone (2-12 MPa). These highly porous scaffolds (~73 vol% porosity) are composed of macro-pores of ~260 μm in size; such porosity is expected to enable bone ingrowth into the scaffold for bone repair applications. The chemistry, porosity, and surface topography of such scaffolds can also be modified by the process parameters to favor bone formation. The studied sol-gel process can be used to coat these scaffolds by dip-coating, which induces a significant enhancement of mechanical properties. This can adjust scaffold properties such as composition and surface morphology, which consequently may improve their performances.

Study of urological devices coated with fullerene-like nanoparticles.

PubMed

Goldbart, Ohad; Elianov, Olga; Shumalinsky, Dmitry; Lobik, Leonid; Cytron, Shmuel; Rosentsveig, Rita; Wagner, H Daniel; Tenne, Reshef

2013-09-21

Insertion of endoscopes and other medical devices into the human body are ubiquitous, especially among aged males. The applied force for the insertion/extraction of the device from the urethra must overcome endoscope-surface-human-tissue interactions. In daily practice a gel is applied on the endoscope surface, in order to facilitate its entry into the urethra, providing also for local anesthesia. In the present work, a new solid-state lubricant has been added to the gel, in order to reduce the metal-urethra interaction and alleviate the potential damage to the epithelial tissue. For that purpose, a urethra model was designed and fabricated, which allowed a quantitative assessment of the applied force for extraction of the endoscope from a soft polymer-based ring. It is shown that the addition of MoS2 nanoparticles with fullerene-like structure (IF-MoS2) and in particular rhenium-doped nanoparticles (Re:IF-MoS2) to Esracain gel applied on the metal-lead reduced the friction substantially. The Re:IF-MoS2 showed better results than the undoped fullerene-like nanoparticles and both performed better than the gel alone. The mechanism of friction reduction is attributed to fullerenes' ability to roll and act as a separator between the active parts of the model.

Study of urological devices coated with fullerene-like nanoparticles

NASA Astrophysics Data System (ADS)

Goldbart, Ohad; Elianov, Olga; Shumalinsky, Dmitry; Lobik, Leonid; Cytron, Shmuel; Rosentsveig, Rita; Wagner, H. Daniel; Tenne, Reshef

2013-08-01

Insertion of endoscopes and other medical devices into the human body are ubiquitous, especially among aged males. The applied force for the insertion/extraction of the device from the urethra must overcome endoscope-surface-human-tissue interactions. In daily practice a gel is applied on the endoscope surface, in order to facilitate its entry into the urethra, providing also for local anesthesia. In the present work, a new solid-state lubricant has been added to the gel, in order to reduce the metal-urethra interaction and alleviate the potential damage to the epithelial tissue. For that purpose, a urethra model was designed and fabricated, which allowed a quantitative assessment of the applied force for extraction of the endoscope from a soft polymer-based ring. It is shown that the addition of MoS2 nanoparticles with fullerene-like structure (IF-MoS2) and in particular rhenium-doped nanoparticles (Re:IF-MoS2) to Esracain gel applied on the metal-lead reduced the friction substantially. The Re:IF-MoS2 showed better results than the undoped fullerene-like nanoparticles and both performed better than the gel alone. The mechanism of friction reduction is attributed to fullerenes' ability to roll and act as a separator between the active parts of the model.

Recovery of Peripheral Nerve with Massive Loss Defect by Tissue Engineered Guiding Regenerative Gel

PubMed Central

Nevo, Zvi

2014-01-01

Objective. Guiding Regeneration Gel (GRG) was developed in response to the clinical need of improving treatment for peripheral nerve injuries and helping patients regenerate massive regional losses in peripheral nerves. The efficacy of GRG based on tissue engineering technology for the treatment of complete peripheral nerve injury with significant loss defect was investigated. Background. Many severe peripheral nerve injuries can only be treated through surgical reconstructive procedures. Such procedures are challenging, since functional recovery is slow and can be unsatisfactory. One of the most promising solutions already in clinical practice is synthetic nerve conduits connecting the ends of damaged nerve supporting nerve regeneration. However, this solution still does not enable recovery of massive nerve loss defect. The proposed technology is a biocompatible and biodegradable gel enhancing axonal growth and nerve regeneration. It is composed of a complex of substances comprising transparent, highly viscous gel resembling the extracellular matrix that is almost impermeable to liquids and gasses, flexible, elastic, malleable, and adaptable to various shapes and formats. Preclinical study on rat model of peripheral nerve injury showed that GRG enhanced nerve regeneration when placed in nerve conduits, enabling recovery of massive nerve loss, previously unbridgeable, and enabled nerve regeneration at least as good as with autologous nerve graft “gold standard” treatment. PMID:25105121

Platelet-Rich Plasma and Platelet Gel: A Review

PubMed Central

Everts, Peter A.M.; Knape, Johannes T.A.; Weibrich, Gernot; Schönberger, Jacques P.A.M.; Hoffmann, Johannes; Overdevest, Eddy P.; Box, Henk A.M.; van Zundert, André

2006-01-01

Abstract: Strategies to reduce blood loss and transfusion of allogeneic blood products during surgical procedures are important in modern times. The most important and well-known autologous techniques are preoperative autologous predonation, hemodilution, perioperative red cell salvage, postoperative wound blood autotransfusion, and pharmacologic modulation of the hemostatic process. At present, new developments in the preparation of preoperative autologous blood component therapy by whole blood platelet-rich plasma (PRP) and platelet-poor plasma (PPP) sequestration have evolved. This technique has been proven to reduce the number of allogeneic blood transfusions during open heart surgery and orthopedic operations. Moreover, platelet gel and fibrin sealant derived from PRP and PPP mixed with thrombin, respectively, can be exogenously applied to tissues to promote wound healing, bone growth, and tissue sealing. However, to our disappointment, not many well-designed scientific studies are available, and many anecdotic stories exist, whereas questions remain to be answered. We therefore decided to study perioperative blood management in more detail with emphasis on the application and production of autologous platelet gel and the use of fibrin sealant. This review addresses a large variety of aspects relevant to platelets, platelet-rich plasma, and the application of platelet gel. In addition, an overview of recent animal and human studies is presented. PMID:16921694

A photochemical crosslinking technology for tissue engineering: enhancement of the physico-chemical properties of collagen-based scaffolds

NASA Astrophysics Data System (ADS)

Chan, Barbara P.

2005-04-01

Collagen gel is a natural biomaterial commonly used in tissue engineering because of its close resemblance to nature, negligible immunogenecity and excellent biocompatibility. However, unprocessed collagen gel is mechanically weak, highly water binding and vulnerable to chemical and enzymatic attacks that limits its use in tissue engineering in particular tissues for weight-bearing purposes. The current project aimed to strengthen and stabilize collagen scaffolds using a photochemical crosslinking technique. Photochemical crosslinking is rapid, efficient, non-thermal and does not involve toxic chemicals, comparing with other crosslinking methods such as glutaraldehyde and gamma irradiation. Collagen scaffolds were fabricated using rat-tail tendon collagen. An argon laser was used to process the collagen gel after equilibrating with a photosensitizing reagent. Scanning electronic microscope was used to characterize the surface and cross-sectional morphology of the membranes. Physico-chemical properties of the collagen scaffolds such as water-binding capacity, mechanical properties and thermostability were studied. Photochemical crosslinking significantly reduced the water-binding capacity, a parameter inversely proportional to the extent of crosslinking, of collagen scaffolds. Photochemical crosslinking also significantly increased the ultimate stress and tangent modulus at 90% of the rupture strain of the collagen scaffolds. Differential scanning calorimetry analysis showed a significantly higher shrinkage temperature and absence of the denaturation peak during the thermoscan comparing with the controls. This means greater thermostability in the photochemically crosslinked collagen scaffolds. This study demonstrates that the photochemical crosslinking technology is able to enhance the physicochemical propterties of collagen scaffolds by strengthening, stabilizing and controlling the swelling ratio of the collagen scaffolds so as to enable their use for tissue engineering.

Augmentation of the hard palate thin masticatory mucosa in the potential connective tissue donor sites using two collagen materials-Clinical and histological comparison.

PubMed

Bednarz, Wojciech; Kobierzycki, Christopher; Dzięgiel, Piotr; Botzenhart, Ute; Gedrange, Tomasz; Ziętek, Marek

2016-11-01

Due to the similarity of keratinized gingival and palatal mucosa the latter can pose as a potential donor site for gingival recession coverage. However, its availability is restricted and a thin transplant bears the risk of being rejected. The aim of the present study was to compare the clinical and histological results of thin palatal mucosa augmentation, using lyophilized Biokol ® xenogenous collagen sponge and a suspension of xenogenous Gel 0 ® pure collagen with non-augmented tissue from the same patients. Ten patients simultaneously underwent bilateral augmentation procedures using Biokol ® and Gel 0 ® collagen material. The donor sites were augmented 8 weeks prior to the harvesting of the connective tissue graft (CTG) for the gingival recession coverage procedures. Prior to the implantation of the collagen material and during the course of harvesting the augmented CTG, tissue specimens were taken for histological examination. Prior to the commencement of the study and after it, the parameters of palatal gingival thickness at 4mm (PGT1), and at 8mm apical to the gingival margin (PGT2) around the teeth neighboring the operating fields were determined. In both groups the palatal mucosa had thickened significantly in both measuring sites. An intergroup comparison revealed greater thickening of the masticatory mucosa in the Biokol ® group at both measuring points. The histological image of the grafts, obtained from sites augmented using both test methods, revealed a typical pattern of mature fibrous connective tissue. No epithelial cells were found. Augmentation of thin masticatory mucosa using Biokol ® or Gel 0 ® collagen materials resulted in a significant thickening of the mucosa, which could be demonstrated to be greater in the first group. Copyright © 2016 Elsevier GmbH. All rights reserved.

The hen's egg chorioallantoic membrane (HET-CAM) test to predict the ophthalmic irritation potential of a cysteamine-containing gel: Quantification using Photoshop® and ImageJ.

PubMed

McKenzie, Barbara; Kay, Graeme; Matthews, Kerr H; Knott, Rachel M; Cairns, Donald

2015-07-25

A modified hen's egg chorioallantoic membrane (HET-CAM) test has been developed, combining ImageJ analysis with Adobe(®) Photoshop(®). The irritation potential of an ophthalmic medicine can be quantified using this method, by monitoring damage to blood vessels. The evaluation of cysteamine containing hyaluronate gel is reported. The results demonstrated that the novel gel formulation is non-irritant to the ocular tissues, in line with saline solution (negative control). In conclusion, the modification of the established HET-CAM test can quantify the damage to minute blood vessels. These results offer the possibility to formulate cysteamine in an ocular applicable gel formulation. Copyright © 2015 Elsevier B.V. All rights reserved.

Bone Marrow Stimulation Technique Augmented by an Ultrapurified Alginate Gel Enhances Cartilage Repair in a Canine Model.

PubMed

Baba, Rikiya; Onodera, Tomohiro; Matsuoka, Masatake; Hontani, Kazutoshi; Joutoku, Zenta; Matsubara, Shinji; Homan, Kentaro; Iwasaki, Norimasa

2018-05-01

The optimal treatment for a medium- or large-sized cartilage lesion is still controversial. Since an ultrapurified alginate (UPAL) gel enhances cartilage repair in animal models, this material is expected to improve the efficacy of the current treatment strategies for cartilage lesions. The bone marrow stimulation technique (BMST) augmented by UPAL gel can induce hyaline-like cartilage repair. Controlled laboratory study. Two cylindrical osteochondral defects were created in the patellar groove of 27 beagle dogs. A total of 108 defects were divided into 3 groups: defects without intervention (control group), defects with the BMST (microfracture group), and defects with the BMST augmented by implantation of UPAL gel (combined group). At 27 weeks postoperatively, macroscopic and histological evaluations, micro-computed tomography assessment, and mechanical testing were performed for each reparative tissue. The defects in the combined group were almost fully covered with translucent reparative tissues, which consisted of hyaline-like cartilage with well-organized collagen structures. The macroscopic score was significantly better in the combined group than in the control group ( P < .05). The histological scores in the combined group were significantly better than those in the control group ( P < .01) and microfracture group ( P < .05). Although the repaired subchondral bone volumes were not influenced by UPAL gel augmentation, the mechanical properties of the combined group were significantly better than those of the microfracture group ( P < .05). The BMST augmented by UPAL gel elicited hyaline-like cartilage repair that had characteristics of rich glycosaminoglycan and matrix immunostained by type II collagen antibody in a canine osteochondral defect model. The present results suggest that the current technique has the potential to be one of the autologous matrix-induced chondrogenesis techniques of the future and to expand the operative indications for the BMST without loss of its technical simplicity. The data support the clinical reality of 1-step minimally invasive cartilage-reparative medicine with UPAL gel without harvesting donor cells.

The Permeability Enhancing Mechanism of DMSO in Ceramide Bilayers Simulated by Molecular Dynamics

PubMed Central

Notman, Rebecca; den Otter, Wouter K.; Noro, Massimo G.; Briels, W. J.; Anwar, Jamshed

2007-01-01

The lipids of the topmost layer of the skin, the stratum corneum, represent the primary barrier to molecules penetrating the skin. One approach to overcoming this barrier for the purpose of delivery of active molecules into or via the skin is to employ chemical permeability enhancers, such as dimethylsulfoxide (DMSO). How these molecules exert their effect at the molecular level is not understood. We have investigated the interaction of DMSO with gel-phase bilayers of ceramide 2, the predominant lipid in the stratum corneum, by means of molecular dynamics simulations. The simulations satisfactorily reproduce the phase behavior and the known structural parameters of ceramide 2 bilayers in water. The effect of DMSO on the gel-phase bilayers was investigated at various concentrations over the range 0.0−0.6 mol fraction DMSO. The DMSO molecules accumulate in the headgroup region and weaken the lateral forces between the ceramides. At high concentrations of DMSO (≥0.4 mol fraction), the ceramide bilayers undergo a phase transition from the gel phase to the liquid crystalline phase. The liquid-crystalline phase of ceramides is expected to be markedly more permeable to solutes than the gel phase. The results are consistent with the experimental evidence that high concentrations of DMSO fluidize the stratum corneum lipids and enhance permeability. PMID:17513383

Fabrication of 3D Reconstituted Organoid Arrays by DNA-programmed Assembly of Cells (DPAC)

PubMed Central

Todhunter, Michael E; Weber, Robert J; Farlow, Justin; Jee, Noel Y; Cerchiari, Alec E; Gartner, Zev J

2016-01-01

Tissues are the organizational units of function in metazoan organisms. Tissues comprise an assortment of cellular building blocks, soluble factors, and extracellular matrix (ECM) that are composed into specific three dimensional (3D) structures. The capacity to reconstitute tissues in vitro with the structural complexity observed in vivo is key to understanding processes such as morphogenesis, homeostasis, and disease. In this unit, we describe DNA-programmed Assembly of Cells (DPAC), a method to fabricate viable, functional arrays of organoid-like tissues within 3D ECM gels. In DPAC, dissociated cells are chemically functionalized with degradable oligonucleotide “velcro,” allowing rapid, specific, and reversible cell adhesion to a two-dimensional (2D) template patterned with complementary DNA. An iterative assembly process builds up organoids, layer-by-layer, from this initial 2D template and into the third dimension. Cleavage of the DNA releases the completed array of tissues that are captured and fully embedded in ECM gels for culture and observation. DPAC controls the size, shape, composition, and spatial heterogeneity of organoids, and permits positioning constituent cells with single-cell resolution even within cultures several centimeters long. PMID:27622567

Dissolution of pulp tissue by aqueous solution of chlorhexidine digluconate and chlorhexidine digluconate gel.

PubMed

Okino, L A; Siqueira, E L; Santos, M; Bombana, A C; Figueiredo, J A P

2004-01-01

To evaluate the activity of various root canal irrigants on bovine pulp tissue. The irrigants tested were: 0.5, 1.0 and 2.5% sodium hypochlorite; 2% aqueous solution of chlorhexidine digluconate; 2% chlorhexidine digluconate gel (Natrosol); and distilled water as control. Bovine pulp fragments were weighed and placed in contact with 20 mL of each tested substance in a centrifuge at 150 r.p.m. until total dissolution. Dissolution speed was calculated by dividing pulp weight by dissolution time. Statistical analysis was performed using the Kruskal-Wallis test. Distilled water and both solutions of chlorhexidine did not dissolve the pulp tissue within 6 h. Mean dissolution speeds for 0.5, 1.0 and 2.5% sodium hypochlorite solutions were 0.31, 0.43 and 0.55 mg min(-1), respectively. The solvent ability of chlorhexidine solutions was similar to that of distilled water. The results for sodium hypochlorite solutions, chlorhexidine solutions and distilled water were statistically different (P>0.01). Both chlorhexidine preparations and distilled water were not able to dissolve pulp tissue. All sodium hypochlorite solutions were efficient in dissolving pulp tissue; the dissolution speed varied with the concentration of the solution.

Design of self-assembling beta-hairpin pepide-based hydrogels for tissue engineering applications

NASA Astrophysics Data System (ADS)

Butterick, Lisa Ann

The field of tissue engineering aims to repair damaged tissues and organs with diminished function. One approach used in tissue engineering is to introduce cells and/or growth factors to the damaged tissue in either one of two ways. The first method is an invasive procedure where cells are introduced to a preformed scaffold and cultured in vitro. The scaffold is then inserted into the host by making an incision at the site of interest, which must be as large as the preformed scaffold. The second method is a minimally invasive procedure where cells are suspended in a polymeric solution and injected via syringe. After leaving the syringe, the material undergoes a phase transition to form a hydrogel at the site of introduction. Regardless of the delivery mechanism employed, development of an appropriate scaffold conducive to cellular proliferation and extracellular matrix production is critical to the success of the implanted material in persuading the body to repair itself. In working toward this goal, we have developed a family of beta-hairpin peptides, based on the design MAX1, that undergoes intramolecular folding and self-assembly to form rigid hydrogels in response to changes in pH, ionic strength, and temperature. From a molecular design standpoint of view, site specific N-methylation of MAX1 was performed to determine the importance of forming hydrogen bonds during the self-assembly event and its effect on hydrogelation. The remainder of this thesis is dedicated to the development of materials and minimally methodologies to deliver gel/cell constructs via syringe to target sites to aid in tissue repair. A peptide, MAX7CNB was designed that undergoes folding and assembly in response to ultraviolet light to form hydrogel material. In addition, MAX8 was rationally designed to display the appropriate hydrogelation kinetics to achieve homogenous cellular encapsulation throughout the gel matrix. MAX8 gel/cell scaffolds can be easily delivered via syringe to secondary target sites while maintaining cellular homogeneity, viability and remain fixed at the site of introduction. Additionally, preliminary in vitro based studies employing mouse peritoneal macrophages suggest the MAX8 gels are non-inflammatory in nature and may not elicit an in vivo immune response upon implantation. It has been demonstrated throughout this thesis that by employing amino acids as fundamental building blocks, peptide sequences can be designed to undergo molecular recognition, resulting in hydrogel material for use in tissue engineering applications.

The role of quench rate in colloidal gels.

PubMed

Royall, C Patrick; Malins, Alex

2012-01-01

Interactions between colloidal particles have hitherto usually been fixed by the suspension composition. Recent experimental developments now enable the control of interactions in situ. Here we use Brownian dynamics simulations to investigate the effect of controlling interactions upon gelation, by "quenching" the system from an equilibrium fluid to a gel. We find that, contrary to the normal case of an instantaneous quench, where the local structure of the gel is highly disordered, controlled quenching results in a gel with a much higher degree of local order. Under sufficiently slow quenching, local crystallisation is found, which is strongly enhanced when a monodisperse system is used. The higher the degree of local order, the smaller the mean squared displacement, indicating an enhancement of gel stability.

Non-equilibrium thermodynamics in cells.

PubMed

Jülicher, Frank; Grill, Stephan W; Salbreux, Guillaume

2018-03-15

We review the general hydrodynamic theory of active soft materials that is motivated in partic- ular by biological matter. We present basic concepts of irreversible thermodynamics of spatially extended multicomponent active systems. Starting from the rate of entropy production, we iden- tify conjugate thermodynamic fluxes and forces and present generic constitutive equations of polar active fluids and active gels. We also discuss angular momentum conservation which plays a role in the the physics of active chiral gels. The irreversible thermodynamics of active gels provides a general framework to discuss the physics that underlies a wide variety of biological processes in cells and in multicellular tissues. © 2018 IOP Publishing Ltd.

3D printing of an interpenetrating network hydrogel material with tunable viscoelastic properties.

PubMed

Bootsma, Katherine; Fitzgerald, Martha M; Free, Brandon; Dimbath, Elizabeth; Conjerti, Joe; Reese, Greg; Konkolewicz, Dominik; Berberich, Jason A; Sparks, Jessica L

2017-06-01

Interpenetrating network (IPN) hydrogel materials are recognized for their unique mechanical properties. While IPN elasticity and toughness properties have been explored in previous studies, the factors that impact the time-dependent stress relaxation behavior of IPN materials are not well understood. Time-dependent (i.e. viscoelastic) mechanical behavior is a critical design parameter in the development of materials for a variety of applications, such as medical simulation devices, flexible substrate materials, cellular mechanobiology substrates, or regenerative medicine applications. This study reports a novel technique for 3D printing alginate-polyacrylamide IPN gels with tunable elastic and viscoelastic properties. The viscoelastic stress relaxation behavior of the 3D printed alginate-polyacrylamide IPN hydrogels was influenced most strongly by varying the concentration of the acrylamide cross-linker (MBAA), while the elastic modulus was affected most by varying the concentration of total monomer material. The material properties of our 3D printed IPN constructs were consistent with those reported in the biomechanics literature for soft tissues such as skeletal muscle, cardiac muscle, skin and subcutaneous tissue. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adult amphibian epidermal proteins: biochemical characterization and developmental appearance.

PubMed

Reeves, O R

1975-08-01

The keratin-like proteins (KLPs) from the epidermis of adult frogs of the species Xenopus laevis have been isolated and biochemically characterized by means of polyacrylamide gel electrophoresis, amino acid analysis, tryptic peptide mapping, amino-terminal end-group analysis and isoelectric focusing. One particular protein fraction of rather unusual amino acid composition found only in epidermal tissue was isolated in quantity by preparative gel electrophoresis and monospecific antibodies prepared against it. Using this anti-KLP antibody preparation it was possible to show that at least one kine of keratin-like protein characteristic of the adult epidermis first appears within the larval epidermis during metamorphosis. This is the first reported biochemical characterization of a tissue-specific protien from adult amphibian skin.

Microfluidic Bioprinting for Engineering Vascularized Tissues and Organoids.

PubMed

Zhang, Yu Shrike; Pi, Qingmeng; van Genderen, Anne Metje

2017-08-11

Engineering vascularized tissue constructs and organoids has been historically challenging. Here we describe a novel method based on microfluidic bioprinting to generate a scaffold with multilayer interlacing hydrogel microfibers. To achieve smooth bioprinting, a core-sheath microfluidic printhead containing a composite bioink formulation extruded from the core flow and the crosslinking solution carried by the sheath flow, was designed and fitted onto the bioprinter. By blending gelatin methacryloyl (GelMA) with alginate, a polysaccharide that undergoes instantaneous ionic crosslinking in the presence of select divalent ions, followed by a secondary photocrosslinking of the GelMA component to achieve permanent stabilization, a microfibrous scaffold could be obtained using this bioprinting strategy. Importantly, the endothelial cells encapsulated inside the bioprinted microfibers can form the lumen-like structures resembling the vasculature over the course of culture for 16 days. The endothelialized microfibrous scaffold may be further used as a vascular bed to construct a vascularized tissue through subsequent seeding of the secondary cell type into the interstitial space of the microfibers. Microfluidic bioprinting provides a generalized strategy in convenient engineering of vascularized tissues at high fidelity.

Direct-write Bioprinting of Cell-laden Methacrylated Gelatin Hydrogels

PubMed Central

Bertassoni, Luiz E.; Cardoso, Juliana C.; Manoharan, Vijayan; Cristino, Ana L.; Bhise, Nupura S.; Araujo, Wesleyan A.; Zorlutuna, Pinar; Vrana, Nihal E.; Ghaemmaghami, Amir M.

2014-01-01

Fabrication of three dimensional (3D) organoids with controlled microarchitectures has been shown to enhance tissue functionality. Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture. Therefore, it represents an exciting alternative for organ fabrication. Despite the rapid progress in the field, the development of printing processes that can be used to fabricate macroscale tissue constructs from ECM-derived hydrogels has remained a challenge. Here we report a strategy for bioprinting of photolabile cell-laden methacrylated gelatin (GelMA) hydrogels. We bioprinted cell-laden GelMA at concentrations ranging from 7 to 15% with varying cell densities and found a direct correlation between printability and the hydrogel mechanical properties. Furthermore, encapsulated HepG2 cells preserved cell viability for at least 8 days following the bioprinting process. In summary, this work presents a strategy for direct-write bioprinting of a cell-laden photolabile ECM-derived hydrogel, which may find widespread application for tissue engineering, organ printing and the development of 3D drug discovery platforms. PMID:24695367

Development of crosslinked methylcellulose hydrogels for soft tissue augmentation using an ammonium persulfate-ascorbic acid redox system.

PubMed

Gold, Gittel T; Varma, Devika M; Taub, Peter J; Nicoll, Steven B

2015-12-10

Hydrogels composed of methylcellulose are candidate materials for soft tissue reconstruction. Although photocrosslinked methylcellulose hydrogels have shown promise for such applications, gels crosslinked using reduction-oxidation (redox) initiators may be more clinically viable. In this study, methylcellulose modified with functional methacrylate groups was polymerized using an ammonium persulfate (APS)-ascorbic acid (AA) redox initiation system to produce injectable hydrogels with tunable properties. By varying macromer concentration from 2% to 4% (w/v), the equilibrium moduli of the hydrogels ranged from 1.47 ± 0.33 to 5.31 ± 0.71 kPa, on par with human adipose tissue. Gelation time was found to conform to the ISO standard for injectable materials. Cellulase treatment resulted in complete degradation of the hydrogels within 24h, providing a reversible corrective feature. Co-culture with human dermal fibroblasts confirmed the cytocompatibility of the gels based on DNA measurements and Live/Dead imaging. Taken together, this evidence indicates that APS-AA redox-polymerized methylcellulose hydrogels possess properties beneficial for use as soft tissue fillers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of xenogenous bovine platelet gel embedded within collagen implant on tendon healing: an in vitro and in vivo study

PubMed Central

Oryan, Ahmad; Meimandi-Parizi, Abdolhamid; Maffulli, Nicola

2015-01-01

Surgical reconstruction of large Achilles tendon defects is demanding. Platelet concentrates may be useful to favor healing in such conditions. The characteristics of bovine platelet-gel embedded within a collagen-implant were determined in vitro, and its healing efficacy was examined in a large Achilles tendon defect in rabbits. Two cm of the left Achilles tendon of 60 rabbits were excised, and the animals were randomly assigned to control (no implant), collagen-implant, or bovine-platelet-gel-collagen-implant groups. The tendon edges were maintained aligned using a Kessler suture. No implant was inserted in the control group. In the two other groups, a collagen-implant or bovine-platelet-gel-collagen-implant was inserted in the defect. The bioelectricity and serum platelet-derived growth factor levels were measured weekly and at 60 days post injury, respectively. After euthanasia at 60 days post injury, the tendons were tested at macroscopic, microscopic, and ultrastructural levels, and their dry matter and biomechanical performances were also assessed. Another 60 rabbits were assigned to receive no implant, a collagen-implant, or a bovine-platelet-gel-collagen-implant, euthanized at 10, 20, 30, and 40 days post injury, and their tendons were evaluated grossly and histologically to determine host-graft interactions. Compared to the control and collagen-implant, treatment with bovine-platelet-gel-collagen-implant improved tissue bioelectricity and serum platelet-derived growth factor levels, and increased cell proliferation, differentiation, and maturation. It also increased number, diameter, and density of the collagen fibrils, alignment and maturation of the collagen fibrils and fibers, biomechanical properties and dry matter content of the injured tendons at 60 days post injury. The bovine-platelet-gel-collagen-implant also increased biodegradability, biocompatibility, and tissue incorporation behavior of the implant compared to the collagen-implant alone. This treatment also decreased tendon adhesion, muscle fibrosis, and atrophy, and improved the physical activity of the animals. The bovine-platelet-gel-collagen-implant was effective in neotenon formation in vivo, which may be valuable in the clinical setting. PMID:25341879

Promotion of osteogenic differentiation of stem cells and increase of bone-bonding ability in vivo using urease-treated titanium coated with calcium phosphate and gelatin.

PubMed

Huang, Zhong-Ming; Qi, Yi-Ying; Du, Shao-Hua; Feng, Gang; Unuma, Hidero; Yan, Wei-Qi

2013-10-01

Because of its excellent biocompatibility and low allergenicity, titanium has been widely used for bone replacement and tissue engineering. To produce a desirable composite with enhanced bone response and mechanical strength, in this study bioactive calcium phosphate (CaP) and gelatin composites were coated onto titanium (Ti) via a novel urease technique. The cellular responses to the CaP/gelatin/Ti (CaP/gel/Ti) and bone bonding ability were evaluated with proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) on CaP/gel/Ti and CaP/Ti in vitro . The results showed that the optical density values, alkaline phosphatase expression and genes expression of MSCs on CaP/gel/Ti were similar to those on CaP/Ti, yet significantly higher than those on pure Ti ( p < 0.05). CaP/gel/Ti and CaP/Ti rods (2 mm in diameter, 10 mm in length) were also implanted into femoral shaft of rabbits and pure Ti rods served as control ( n = 10). Histological examination, scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) measurements were performed at 4 and 8 weeks after the operation. The histological and SEM observations demonstrated clearly that more new bone formed on the surface of CaP/gel/Ti than in the other two groups at each time point. The CaP/gel/Ti bonded to the surrounding bone directly with no intervening soft tissue layer. An interfacial layer, containing Ti, Ca and P, was found to form at the interface between bone and the implant on all three groups by EDS analysis. However, the content of Ca, P in the surface of CaP/gel/Ti implants was more than in the other two groups at each time point. The CaP/gel/Ti modified by the urease method was not only beneficial for MSCs proliferation and osteogenic differentiation, but also favorable for bone bonding ability on Ti implants in vivo , suggesting that Ti functionalized with CaP and gelatin might have a great potential in clinical joint replacement or dental implants.

Promotion of osteogenic differentiation of stem cells and increase of bone-bonding ability in vivo using urease-treated titanium coated with calcium phosphate and gelatin

NASA Astrophysics Data System (ADS)

Huang, Zhong-Ming; Qi, Yi-Ying; Du, Shao-Hua; Feng, Gang; Unuma, Hidero; Yan, Wei-Qi

2013-10-01

Because of its excellent biocompatibility and low allergenicity, titanium has been widely used for bone replacement and tissue engineering. To produce a desirable composite with enhanced bone response and mechanical strength, in this study bioactive calcium phosphate (CaP) and gelatin composites were coated onto titanium (Ti) via a novel urease technique. The cellular responses to the CaP/gelatin/Ti (CaP/gel/Ti) and bone bonding ability were evaluated with proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) on CaP/gel/Ti and CaP/Ti in vitro. The results showed that the optical density values, alkaline phosphatase expression and genes expression of MSCs on CaP/gel/Ti were similar to those on CaP/Ti, yet significantly higher than those on pure Ti (p < 0.05). CaP/gel/Ti and CaP/Ti rods (2 mm in diameter, 10 mm in length) were also implanted into femoral shaft of rabbits and pure Ti rods served as control (n = 10). Histological examination, scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) measurements were performed at 4 and 8 weeks after the operation. The histological and SEM observations demonstrated clearly that more new bone formed on the surface of CaP/gel/Ti than in the other two groups at each time point. The CaP/gel/Ti bonded to the surrounding bone directly with no intervening soft tissue layer. An interfacial layer, containing Ti, Ca and P, was found to form at the interface between bone and the implant on all three groups by EDS analysis. However, the content of Ca, P in the surface of CaP/gel/Ti implants was more than in the other two groups at each time point. The CaP/gel/Ti modified by the urease method was not only beneficial for MSCs proliferation and osteogenic differentiation, but also favorable for bone bonding ability on Ti implants in vivo, suggesting that Ti functionalized with CaP and gelatin might have a great potential in clinical joint replacement or dental implants.

Ultrarapid electrophoretic transfer of high and low molecular weight proteins using heat.

PubMed

Kurien, Biji T; Scofield, R Hal

2009-01-01

An ultrarapid method for the electrophoretic transfer of high and low molecular weight proteins to nitrocellulose membranes following sodium dodecyl sulfate (SDS) polyacrylamide gel is described here. The transfer was performed with heated (70-75 degrees C) normal transfer buffer from which methanol had been omitted. Complete transfer of high and low molecular weight antigens (molecular weight protein standards, a purified protein, and proteins from a human tissue extract) could be carried out in 10 min for a 7% (0.75 mm) SDS polyacrylamide gel. For 10 and 12.5% gels (0.75 mm) the corresponding time was 15 min. A complete transfer could be carried out in 20 min for 7, 10, and 12.5% gels (1.5 mm gels). The permeability of the gel is increased by heat, such that the proteins trapped in the polyacrylamide gel matrix can be easily transferred to the membrane. The heat mediated transfer method was compared with a conventional transfer protocol, under similar conditions. The conventional method transferred minimal low molecular weight proteins while retaining most of the high molecular weight proteins in the gel. In summary, this procedure is particularly useful for the transfer of high molecular weight proteins, very rapid, and avoids the use of methanol.

Western blotting of high and low molecular weight proteins using heat.

PubMed

Kurien, Biji T; Scofield, R Hal

2015-01-01

A method for the electrophoretic transfer of high and low molecular weight proteins to nitrocellulose membranes following sodium dodecyl sulfate (SDS) polyacrylamide gel is described here. The transfer was performed with heated (70-75 °C) normal transfer buffer from which methanol had been omitted. Complete transfer of high and low molecular weight antigens (molecular weight protein standards, a purified protein, and proteins from a human tissue extract) could be carried out in 10 min for a 7 % (0.75 mm) SDS polyacrylamide gel. For 10 and 12.5 % gels (0.75 mm) the corresponding time was 15 min. A complete transfer could be carried out in 20 min for 7, 10, and 12.5 % gels (1.5 mm gels). The permeability of the gel is increased by heat, such that the proteins trapped in the polyacrylamide gel matrix can be easily transferred to the membrane. The heat mediated transfer method was compared with a conventional transfer protocol, under similar conditions. The conventional method transferred minimal low molecular weight proteins while retaining most of the high molecular weight proteins in the gel. In summary, this procedure is particularly useful for the transfer of high molecular weight proteins, very rapid, and avoids the use of methanol.

Preparation and Properties of Nano-Hydroxyapatite/Gelatin/Poly(vinyl alcohol) Composite Membrane.

PubMed

Liao, Haotian; Shi, Kun; Peng, Jinrong; Qu, Ying; Liao, Jinfeng; Qian, Zhiyong

2015-06-01

In this study, the bone-like composite membrane based on blends of gelatin (Gel), nano-hydroxyapatite (n-HA) and poly(vinyl alcohol) (PVA) was fabricated by solvent casting and evaporation methods. The effect of n-HA content and the ratio of Gel/PVA on the properties of the composite was investigated. The Gel/PVA and n-HA/Gel/PVA composite membranes were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), water contact angle measurement and scanning electron microscopy (SEM). The mechanical properties of the composites were determined by tensile tests. The as prepared composite membranes exhibited hydrophobility, the water contact angle of composite membrane was 126.6 when its mass ratio of n-HA/Gel/PVA was 10/50/40. The tensile strength of composite membranes was greatly increased due to the introduction of n-HA, and the tensile strength was increased to 74.92 MPa when the mass ratio of n-HA/Gel/PVA was 10/50/40. SEM observation indicated that n-HA was dispersed in the membranes and a sea-island structure was formed in the n-HA/Gel/PVA composite membranes, resulting in a significant increase in tensile strength. The as-prepared n-HA/Gel/PVA composite membranes may be applied in the field of bone tissue engineering.

Fabrication of Orientation-Controlled 3D Tissues Using a Layer-by-Layer Technique and 3D Printed a Thermoresponsive Gel Frame.

PubMed

Tsukamoto, Yoshinari; Akagi, Takami; Shima, Fumiaki; Akashi, Mitsuru

2017-06-01

Herein, we report the fabrication of orientation-controlled tissues similar to heart and nerve tissues using a cell accumulation and three-dimensional (3D) printing technique. We first evaluated the 3D shaping ability of hydroxybutyl chitosan (HBC), a thermoresponsive polymer, by using a robotic dispensing 3D printer. HBC polymer could be laminated to a height of 1124 ± 14 μm. Based on this result, we fabricated 3D gel frames of various shapes, such as square, triangular, rectangular, and circular, for shape control of 3D tissue and then normal human cardiac fibroblasts (NHCFs) coated with extracellular matrix nanofilms were seeded in the frames. Observation of shape-controlled tissues after 1 day of cultivation showed that the orientation of fibroblasts was in one direction when a short-sided, thin, rectangular-shaped frame was used. Next, we tried to fabricate orientation-controlled tissue with a vascular network by coculturing NHCF and normal human cardiac microvascular endothelial cells. As a consequence of cultivation for 4 days, observation of cocultured tissue confirmed aligned cells and blood capillaries in orientation-controlled tissue. Our results clearly demonstrated that it would be possible to control the cell orientation by controlling the shape of the tissues by combining a cell accumulation technique and a 3D printing system. The results of this study suggest promising strategies for the fabrication of oriented 3D tissues in vitro. These tissues, mimicking native organ structures, such as muscle and nerve tissue with a cell alignment structure, would be useful for tissue engineering, regenerative medicine, and pharmaceutical applications.

Evaluation of gold nanotracers to track adipose-derived stem cells in a PEGylated fibrin gel for dermal tissue engineering applications

PubMed Central

Chung, Eunna; Nam, Seung Yun; Ricles, Laura M; Emelianov, Stanislav Y; Suggs, Laura J

2013-01-01

Evaluating the regenerative capacity of a tissue-engineered device in a noninvasive and synchronous manner is critical to determining the mechanisms for success in clinical applications. In particular, directly tracking implanted cells in a three-dimensional (3D) scaffold is desirable in that it enables the monitoring of cellular activity in a specific and localized manner. The authors’ group has previously demonstrated that the PEGylation of fibrin results in a 3D scaffold that supports morphologic and phenotypic changes in mesenchymal stem cells that may be advantageous in wound healing applications. Recently, the authors have evaluated adipose-derived stem cells (ASCs) as a mesenchymal cell source to regenerate skin and blood vessels due to their potential for proliferation, differentiation, and production of growth factors. However, tracking and monitoring ASCs in a 3D scaffold, such as a PEGylated fibrin gel, have not yet been fully investigated. In the current paper, nanoscale gold spheres (20 nm) as cell tracers for ASCs cultured in a PEGylated fibrin gel were evaluated. An advanced dual-imaging modality combining ultrasound and photoacoustic imaging was utilized to monitor rat ASCs over time. The ASCs took up gold nanotracers and could be detected up to day 16 with high sensitivity using photoacoustic imaging. There were no detrimental effects on ASC morphology, network formation, proliferation, and protein expression/secretion (ie, smooth muscle α-actin, vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9) associated with gold nanotracers. Therefore, utilization of gold nanotracers can be an effective strategy to monitor the regenerative process of a stem cell source in a 3D gel for vascular and dermal tissue engineering applications. PMID:23345978

Tuning mechanical performance of poly(ethylene glycol) and agarose interpenetrating network hydrogels for cartilage tissue engineering.

PubMed

Rennerfeldt, Deena A; Renth, Amanda N; Talata, Zsolt; Gehrke, Stevin H; Detamore, Michael S

2013-11-01

Hydrogels are attractive for tissue engineering applications due to their incredible versatility, but they can be limited in cartilage tissue engineering applications due to inadequate mechanical performance. In an effort to address this limitation, our team previously reported the drastic improvement in the mechanical performance of interpenetrating networks (IPNs) of poly(ethylene glycol) diacrylate (PEG-DA) and agarose relative to pure PEG-DA and agarose networks. The goal of the current study was specifically to determine the relative importance of PEG-DA concentration, agarose concentration, and PEG-DA molecular weight in controlling mechanical performance, swelling characteristics, and network parameters. IPNs consistently had compressive and shear moduli greater than the additive sum of either single network when compared to pure PEG-DA gels with a similar PEG-DA content. IPNs withstood a maximum stress of up to 4.0 MPa in unconfined compression, with increased PEG-DA molecular weight being the greatest contributing factor to improved failure properties. However, aside from failure properties, PEG-DA concentration was the most influential factor for the large majority of properties. Increasing the agarose and PEG-DA concentrations as well as the PEG-DA molecular weight of agarose/PEG-DA IPNs and pure PEG-DA gels improved moduli and maximum stresses by as much as an order of magnitude or greater compared to pure PEG-DA gels in our previous studies. Although the viability of encapsulated chondrocytes was not significantly affected by IPN formulation, glycosaminoglycan (GAG) content was significantly influenced, with a 12-fold increase over a three-week period in gels with a lower PEG-DA concentration. These results suggest that mechanical performance of IPNs may be tuned with partial but not complete independence from biological performance of encapsulated cells. © 2013 Elsevier Ltd. All rights reserved.

Fabrication and characterization of gels with integrated channels using 3D printing with microfluidic nozzle for tissue engineering applications.

PubMed

Attalla, R; Ling, C; Selvaganapathy, P

2016-02-01

The lack of a simple and effective method to integrate vascular network with engineered scaffolds and tissue constructs remains one of the biggest challenges in true 3D tissue engineering. Here, we detail the use of a commercially available, low-cost, open-source 3D printer modified with a microfluidic print-head in order to develop a method for the generation of instantly perfusable vascular network integrated with gel scaffolds seeded with cells. The print-head features an integrated coaxial nozzle that allows the fabrication of hollow, calcium-polymerized alginate tubes that can be easily patterned using 3D printing techniques. The diameter of the hollow channel can be precisely controlled and varied between 500 μm - 2 mm by changing applied flow rates or print-head speed. These channels are integrated into gel layers with a thickness of 800 μm - 2.5 mm. The structural rigidity of these constructs allows the fabrication of multi-layered structures without causing the collapse of hollow channels in lower layers. The 3D printing method was fully characterized at a range of operating speeds (0-40 m/min) and corresponding flow rates (1-30 mL/min) were identified to produce precise definition. This microfluidic design also allows the incorporation of a wide range of scaffold materials as well as biological constituents such as cells, growth factors, and ECM material. Media perfusion of the channels causes a significant viability increase in the bulk of cell-laden structures over the long-term. With this setup, gel constructs with embedded arrays of hollow channels can be created and used as a potential substitute for blood vessel networks.

Analysis of soybean tissue culture protein dynamics using difference gel electrophoresis.

PubMed

Miernyk, Ján A; Jett, Alissa A; Johnston, Mark L

2016-01-01

Excised hypocotyls from developing soybean (Glycine max (L.) merr. cv. Jack) were cultivated on agar-solidified medium until callus formed. The calli were then propagated in liquid medium until stable, relatively uniform, finely-divided suspension cultures were obtained. Cells were typically transferred to fresh medium at 7-day intervals. Cultures were harvested by filtration five days (early log phase) or eight days (late log phase) after transfer. In order to evaluate dynamic changes, both intracellular and extracellular proteins were analyzed by 2-dimensional difference gel electrophoresis. Selected spots were subjected to in-gel tryptic-digestion and the resultant peptides were analyzed by nLC-MS/MS. In follow-up studies gel-free shot-gun analyses led to identification of 367 intracellular proteins and 188 extracellular proteins. The significance of the described research is two-fold. First a gel-based proteomics method was applied to the study of the dynamics of the secretome (extracellular proteins). Second, results of a shot-gun non-gel based proteomic survey of both cellular and extracellular proteins are presented. Published by Elsevier B.V.

Nanostructured lipid carriers-based flurbiprofen gel after topical administration: acute skin irritation, pharmacodynamics, and percutaneous absorption mechanism.

PubMed

Song, Aihua; Su, Zhen; Li, Sanming; Han, Fei

2015-01-01

In order to assess the preliminary safety and effectiveness of nanostructured lipid carriers-based flurbiprofen gel (FP NLC-gel), the acute irritation test, in vivo pharmacodynamics evaluation and pharmacokinetic study were investigated after topical application. No dropsy and erythema were observed after continuous dosing 7 d of FP NLC-gel on the rabbit skin, and the xylene-induced ear drossy could be inhibited by FP NLC-gel at different dosages. The maximum concentration of FP in rats muscle was 2.03 μg/g and 1.55 μg/g after oral and topical administration, respectively. While the peak concentration in untreated muscle after topical administration was only 0.37 μg/mL. And at any time, following topical administration the mean muscle-plasma concentration ratio Cmuscle/CPlasma was obviously higher than that following oral administration. Results indicated that FP could directly penetrate into the subcutaneous muscle tissue from the administration site. Thus, the developed FP NLC-gel could be a safe and effective vehicle for topical delivery of FP.

Hybrid Macro-Porous Titanium Ornamented by Degradable 3D Gel/nHA Micro-Scaffolds for Bone Tissue Regeneration

PubMed Central

Yin, Bo; Ma, Pei; Chen, Jun; Wang, Hai; Wu, Gui; Li, Bo; Li, Qiang; Huang, Zhifeng; Qiu, Guixing; Wu, Zhihong

2016-01-01

Porous titanium is a kind of promising material for bone substitution, while its bio-inert property results in demand of modifications to improve the osteointegration capacity. In this study, gelatin (Gel) and nano-hydroxyapatite (nHA) were used to construct 3D micro-scaffolds in the pores of porous titanium in the ratios of Gel:nHA = 1:0, Gel:nHA = 1:1, and Gel:nHA = 1:3, respectively. Cell attachment and proliferation, and gene and protein expression levels of osteogenic markers were evaluated in MC3T3-E1 cells, followed by bone regeneration assessment in a rabbit radius defect model. All hybrid scaffolds with different composition ratio were found to have significant promotional effects in cell adhesion, proliferation and differentiation, in which the group with Gel:nHA = 1:1 showed the best performance in vitro, as well as the most bone regeneration volume in vivo. This 3D micro-scaffolds modification may be an innovative method for porous titanium ornamentation and shows potential application values in clinic. PMID:27092492

Hybrid Macro-Porous Titanium Ornamented by Degradable 3D Gel/nHA Micro-Scaffolds for Bone Tissue Regeneration.

PubMed

Yin, Bo; Ma, Pei; Chen, Jun; Wang, Hai; Wu, Gui; Li, Bo; Li, Qiang; Huang, Zhifeng; Qiu, Guixing; Wu, Zhihong

2016-04-15

Porous titanium is a kind of promising material for bone substitution, while its bio-inert property results in demand of modifications to improve the osteointegration capacity. In this study, gelatin (Gel) and nano-hydroxyapatite (nHA) were used to construct 3D micro-scaffolds in the pores of porous titanium in the ratios of Gel:nHA = 1:0, Gel:nHA = 1:1, and Gel:nHA = 1:3, respectively. Cell attachment and proliferation, and gene and protein expression levels of osteogenic markers were evaluated in MC3T3-E1 cells, followed by bone regeneration assessment in a rabbit radius defect model. All hybrid scaffolds with different composition ratio were found to have significant promotional effects in cell adhesion, proliferation and differentiation, in which the group with Gel:nHA = 1:1 showed the best performance in vitro, as well as the most bone regeneration volume in vivo. This 3D micro-scaffolds modification may be an innovative method for porous titanium ornamentation and shows potential application values in clinic.

The use of supersaturation for the vaginal application of microbicides: a case study with dapivirine.

PubMed

Grammen, Carolien; Plum, Jakob; Van Den Brande, Jeroen; Darville, Nicolas; Augustyns, Koen; Augustijns, Patrick; Brouwers, Joachim

2014-11-01

In this study, we investigated the potential of supersaturation for the formulation of the poorly water-soluble microbicide dapivirine (DPV) in an aqueous vaginal gel in order to enhance its vaginal tissue uptake. Different excipients such as hydroxypropylmethylcellulose, polyethylene glycol 1000, and cyclodextrins were evaluated for their ability to inhibit precipitation of supersaturated DPV in the formulation vehicle as such as well as in biorelevant media. In vitro permeation assessment across HEC-1A cell layers demonstrated an enhanced DPV flux from supersaturated gels compared with suspension gels. The best performing supersaturated gel containing 500 μM DPV (supersaturation degree of 4) in the presence of sulfobutyl ether-beta-cyclodextrin (2.5%) appeared to be stable for at least 3 months. In addition, the gel generated a significant increase in vaginal drug uptake in rabbits as compared with suspension gels. We conclude that supersaturation is a possible strategy to enhance the vaginal concentration of hydrophobic microbicides, thereby increasing permeation into the vaginal submucosa. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Surface-attached orthogonal gradient hydrogels

NASA Astrophysics Data System (ADS)

Chinnayan Kannan, Pandiyarajan; Genzer, Jan

Gradient materials play a significant role in the creation of artificial implants due to their potential to reduce stress concentration when two or more structures with different mechanical properties are joined together, e . g . , tendon, a fibrous protein that connects the soft and hard muscle tissues in our body. We employ free radical polymerization to synthesize random copolymers containing 90% of N-isopropyl acrylamide (NIPAAm), 5% photo-active methacrylyloxybenzophenone (MABP) and 5% thermally-active styrenesulfonylazide (SSAz) crosslinkers. The presence of MABP and SSAz facilitates adjusting gel density on a flat support in two orthogonal directions by spatially and independently controlling UV dosage and temperature. The swelling behavior (α) of the gels in water and methanol is examined using a spectroscopic ellipsometry and the degree of swelling depends on the extent of crosslinking that ranges from α = 1-1.2 (highly crosslinked gels) to α = 4-5 (loosely crosslinked gels). We compare the network properties surface-attached gels and un-attached identical counterparts and confirm that the linear swelling ratio of surface-attached networks is higher than that of the corresponding un-attached gels.

Irradiation Sterilized Gelatin-Water-Glycerol Ternary Gel as an Injectable Carrier for Bone Tissue Engineering.

PubMed

Zhao, Yantao; Han, Liwei; Yan, Jun; Li, Zhonghai; Wang, Fuli; Xia, Yang; Hou, Shuxun; Zhong, Hongbin; Zhang, Feimin; Gu, Ning

2017-01-01

Injectable gelatin gels offer an attractive option for filling bone defects. The challenge is to fabricate gelatin gels with optimal gelation properties, which can be irradiation sterilized. Here, a gelatin-water-glycerol (GWG) gel is reported for use as a broad-spectrum injectable carrier. This ternary gel is high in glycerol and low in water, and remains stable after gamma irradiation at doses (25 kGy). As an injectable gel, it remains a viscous solution at gelatin concentrations ≤2.0%, at room temperature. Its storage modulus increases dramatically and eventually exceeds the loss modulus around 46-50 °C, indicating a transition from a liquid-like state to an elastic gel-like state. This ternary gel ranges significantly in terms of storage modulus (12-1700 Pa) while demonstrating a narrow pH range (5.58-5.66), depending on the gelatin concentration. Therefore, it can be loaded with a variety of materials. It is highly cytocompatible compared with saline in vivo and culture media in vitro. When loaded with demineralized bone matrix, the composites show favorable injectability, and excellent osteogenesis performance, after irradiation. These features can be attributed to high hydrophilicity and fast degradability. These findings justify that this ternary gel is promising as an irradiation-sterilized and universal injectable delivery system. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of chest compression effect on airway management with air-Q, aura-i, i-gel, and Fastrack intubating supraglottic devices by novice physicians: a randomized crossover simulation study.

PubMed

Komasawa, Nobuyasu; Ueki, Ryusuke; Kaminoh, Yoshiroh; Nishi, Shin-Ichi

2014-10-01

In the 2010 American Heart Association guidelines, supraglottic devices (SGDs) such as the laryngeal mask are proposed as alternatives to tracheal intubation for cardiopulmonary resuscitation. Some SGDs can also serve as a means for tracheal intubation after successful ventilation. The purpose of this study was to evaluate the effect of chest compression on airway management with four intubating SGDs, aura-i (aura-i), air-Q (air-Q), i-gel (i-gel), and Fastrack (Fastrack), during cardiopulmonary resuscitation using a manikin. Twenty novice physicians inserted the four intubating SGDs into a manikin with or without chest compression. Insertion time and successful ventilation rate were measured. For cases of successful ventilation, blind tracheal intubation via the intubating SGD was performed with chest compression and success or failure within 30 s was recorded. Chest compression did not decrease the ventilation success rate of the four intubating SGDs (without chest compression (success/total): air-Q, 19/20; aura-i, 19/20; i-gel, 18/20; Fastrack, 19/20; with chest compression: air-Q, 19/20; aura-i, 19/20; i-gel, 16/20; Fastrack, 18/20). Insertion time was significantly lengthened by chest compression in the i-gel trial (P < 0.05), but not with the other three devices. The blind intubation success rate with chest compression was the highest in the air-Q trial (air-Q, 15/19; aura-i, 14/19; i-gel, 12/16; Fastrack, 10/18). This simulation study revealed the utility of intubating SGDs for airway management during chest compression.

Cholesteric liquid crystal gels with a graded mechanical stress

NASA Astrophysics Data System (ADS)

Agez, Gonzague; Relaix, Sabrina; Mitov, Michel

2014-02-01

In cholesteric liquid-crystalline gels, the mechanical role of the polymer network over the structure of the whole gel has been ignored. We show that it is the stress gradient exerted by the network over the helical structure that drives the broadening of the optical band gap, as evidenced by the absence of a gradient in chiral species. Model calculations and finite-difference time-domain simulations show that the network acts as a spring with a stiffness gradient. The present results indicate a revision to the common understanding of the physical properties of liquid-crystalline gels is necessary when a concentration gradient in a polymer network is present.

Cholesteric liquid crystal gels with a graded mechanical stress.

PubMed

Agez, Gonzague; Relaix, Sabrina; Mitov, Michel

2014-02-01

In cholesteric liquid-crystalline gels, the mechanical role of the polymer network over the structure of the whole gel has been ignored. We show that it is the stress gradient exerted by the network over the helical structure that drives the broadening of the optical band gap, as evidenced by the absence of a gradient in chiral species. Model calculations and finite-difference time-domain simulations show that the network acts as a spring with a stiffness gradient. The present results indicate a revision to the common understanding of the physical properties of liquid-crystalline gels is necessary when a concentration gradient in a polymer network is present.

Measurements of Elastic Moduli of Silicone Gel Substrates with a Microfluidic Device

PubMed Central

Gutierrez, Edgar; Groisman, Alex

2011-01-01

Thin layers of gels with mechanical properties mimicking animal tissues are widely used to study the rigidity sensing of adherent animal cells and to measure forces applied by cells to their substrate with traction force microscopy. The gels are usually based on polyacrylamide and their elastic modulus is measured with an atomic force microscope (AFM). Here we present a simple microfluidic device that generates high shear stresses in a laminar flow above a gel-coated substrate and apply the device to gels with elastic moduli in a range from 0.4 to 300 kPa that are all prepared by mixing two components of a transparent commercial silicone Sylgard 184. The elastic modulus is measured by tracking beads on the gel surface under a wide-field fluorescence microscope without any other specialized equipment. The measurements have small and simple to estimate errors and their results are confirmed by conventional tensile tests. A master curve is obtained relating the mixing ratios of the two components of Sylgard 184 with the resulting elastic moduli of the gels. The rigidity of the silicone gels is less susceptible to effects from drying, swelling, and aging than polyacrylamide gels and can be easily coated with fluorescent tracer particles and with molecules promoting cellular adhesion. This work can lead to broader use of silicone gels in the cell biology laboratory and to improved repeatability and accuracy of cell traction force microscopy and rigidity sensing experiments. PMID:21980487

The β‐1,3‐glucanosyltransferases (Gels) affect the structure of the rice blast fungal cell wall during appressorium‐mediated plant infection

PubMed Central

Samalova, Marketa; Mélida, Hugo; Vilaplana, Francisco; Bulone, Vincent; Soanes, Darren M.; Talbot, Nicholas J.

2016-01-01

Abstract The fungal wall is pivotal for cell shape and function, and in interfacial protection during host infection and environmental challenge. Here, we provide the first description of the carbohydrate composition and structure of the cell wall of the rice blast fungus Magnaporthe oryzae. We focus on the family of glucan elongation proteins (Gels) and characterize five putative β‐1,3‐glucan glucanosyltransferases that each carry the Glycoside Hydrolase 72 signature. We generated targeted deletion mutants of all Gel isoforms, that is, the GH72+, which carry a putative carbohydrate‐binding module, and the GH72− Gels, without this motif. We reveal that M. oryzae GH72 + GELs are expressed in spores and during both infective and vegetative growth, but each individual Gel enzymes are dispensable for pathogenicity. Further, we demonstrated that a Δgel1Δgel3Δgel4 null mutant has a modified cell wall in which 1,3‐glucans have a higher degree of polymerization and are less branched than the wild‐type strain. The mutant showed significant differences in global patterns of gene expression, a hyper‐branching phenotype and no sporulation, and thus was unable to cause rice blast lesions (except via wounded tissues). We conclude that Gel proteins play significant roles in structural modification of the fungal cell wall during appressorium‐mediated plant infection. PMID:27568483

Engineering 3D Cellularized Collagen Gels for Vascular Tissue Regeneration.

PubMed

Meghezi, Sébastien; Seifu, Dawit G; Bono, Nina; Unsworth, Larry; Mequanint, Kibret; Mantovani, Diego

2015-06-16

Synthetic materials are known to initiate clinical complications such as inflammation, stenosis, and infections when implanted as vascular substitutes. Collagen has been extensively used for a wide range of biomedical applications and is considered a valid alternative to synthetic materials due to its inherent biocompatibility (i.e., low antigenicity, inflammation, and cytotoxic responses). However, the limited mechanical properties and the related low hand-ability of collagen gels have hampered their use as scaffold materials for vascular tissue engineering. Therefore, the rationale behind this work was first to engineer cellularized collagen gels into a tubular-shaped geometry and second to enhance smooth muscle cells driven reorganization of collagen matrix to obtain tissues stiff enough to be handled. The strategy described here is based on the direct assembling of collagen and smooth muscle cells (construct) in a 3D cylindrical geometry with the use of a molding technique. This process requires a maturation period, during which the constructs are cultured in a bioreactor under static conditions (without applied external dynamic mechanical constraints) for 1 or 2 weeks. The "static bioreactor" provides a monitored and controlled sterile environment (pH, temperature, gas exchange, nutrient supply and waste removal) to the constructs. During culture period, thickness measurements were performed to evaluate the cells-driven remodeling of the collagen matrix, and glucose consumption and lactate production rates were measured to monitor the cells metabolic activity. Finally, mechanical and viscoelastic properties were assessed for the resulting tubular constructs. To this end, specific protocols and a focused know-how (manipulation, gripping, working in hydrated environment, and so on) were developed to characterize the engineered tissues.

Paraffin-gel tissue-mimicking material for ultrasound-guided needle biopsy phantom.

PubMed

Vieira, Sílvio L; Pavan, Theo Z; Junior, Jorge E; Carneiro, Antonio A O

2013-12-01

Paraffin-gel waxes have been investigated as new soft tissue-mimicking materials for ultrasound-guided breast biopsy training. Breast phantoms were produced with a broad range of acoustical properties. The speed of sound for the phantoms ranged from 1425.4 ± 0.6 to 1480.3 ± 1.7 m/s at room temperature. The attenuation coefficients were easily controlled between 0.32 ± 0.27 dB/cm and 2.04 ± 0.65 dB/cm at 7.5 MHz, depending on the amount of carnauba wax added to the base material. The materials do not suffer dehydration and provide adequate needle penetration, with a Young's storage modulus varying between 14.7 ± 0.2 kPa and 34.9 ± 0.3 kPa. The phantom background material possesses long-term stability and can be employed in a supine position without changes in geometry. These results indicate that paraffin-gel waxes may be promising materials for training radiologists in ultrasound biopsy procedures. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Viscoelastic properties of rabbit vocal folds after augmentation.

PubMed

Hertegård, Stellan; Dahlqvist, Ake; Laurent, Claude; Borzacchiello, Assunta; Ambrosio, Luigi

2003-03-01

Vocal fold function is closely related to tissue viscoelasticity. Augmentation substances may alter the viscoelastic properties of vocal fold tissues and hence their vibratory capacity. We sought to investigate the viscoelastic properties of rabbit vocal folds in vitro after injections of various augmentation substances. Polytetrafluoroethylene (Teflon), cross-linked collagen (Zyplast), and cross-linked hyaluronan, hylan b gel (Hylaform) were injected into the lamina propria and the thyroarytenoid muscle of rabbit vocal folds. Dynamic viscosity of the injected vocal fold as a function of frequency was measured with a Bohlin parallel-plate rheometer during small-amplitude oscillation. All injected vocal folds showed a decreasing dynamic viscosity with increasing frequency. Vocal fold samples injected with hylan b gel showed the lowest dynamic viscosity, quite close to noninjected control samples. Vocal folds injected with polytetrafluoroethylene showed the highest dynamic viscosity followed by the collagen samples. The data indicated that hylan b gel in short-term renders the most natural viscoelastic properties to the vocal fold among the substances tested. This is of importance to restore/preserve the vibratory capacity of the vocal folds when glottal insufficiency is treated with injections.

Dosimetric characteristics of PASSAG as a new polymer gel dosimeter with negligible toxicity

NASA Astrophysics Data System (ADS)

Farhood, Bagher; Abtahi, Seyed Mohammad Mahdi; Geraily, Ghazale; Ghorbani, Mehdi; Mahdavi, Seied Rabi; Zahmatkesh, Mohammad Hasan

2018-06-01

Despite many advantages of polymer gel dosimeters, their clinical use is only not realized now. Toxicity of polymer gel dosimeters can be considered as one of their main limitations for use in routine clinical applications. In the current study, a new polymer gel dosimeter is introduced with negligible toxicity. For this purpose, 2-Acrylamido-2-Methy-1-PropaneSulfonic acid (AMPS) sodium salt monomer was replaced instead of acrylamide monomer used in PAGAT gel dosimeter by using %6 T and %50 C to the gel formula and the new formulation is called PASSAG (Poly AMPS Sodium Salt and Gelatin) polymer gel dosimeter. The irradiation of gel dosimeters was carried out using a Co-60 therapy machine. MRI technique was used to quantify the dose responses of the PASSAG gel dosimeter. Then, the MRI responses (R2) of the gel dosimeter was analyzed at different dose values, post-irradiation times, and scanning temperatures. The results showed that the new gel formulation has a negligible toxicity and it is also eco-friendly. In addition, carcinogenicity and genetic toxicity tests are negative for the monomer used in PASSAG. The radiological properties of PASSAG gel dosimeter showed that this substance can be considered as a soft tissue/water equivalent material. Furthermore, dosimetric evaluation of the new polymer gel dosimeter revealed an excellent linear R2-dose response in the evaluated dose range (0-15 Gy). The R2-dose sensitivity and dose resolution of PASSAG gel dosimeter were 0.081 s-1Gy-1 (in 0-15 Gy dose range) and 1 Gy (in 0-10 Gy dose range), respectively. Moreover, it was shown that the R2-dose sensitivity and dose resolution of the new gel dosimeter improves over time after irradiation. It was also found that the R2 response of the PASSAG gel dosimeter has less dependency to the 18, 20, and 24 °C scanning temperature in comparison to that of room temperature (22 °C).

Retina tissue engineering by conjunctiva mesenchymal stem cells encapsulated in fibrin gel: Hypotheses on novel approach to retinal diseases treatment.

PubMed

Soleimannejad, Mostafa; Ebrahimi-Barough, Somayeh; Nadri, Samad; Riazi-Esfahani, Mohammad; Soleimani, Masoud; Tavangar, Seyed Mohammad; Ai, Jafar

2017-04-01

Retinitis pigmentosa (RP) and age related macular degeneration (AMD) are two retinal diseases that progress by photoreceptor cells death. In retinal transplantation studies, stem and progenitor cells inject into the sub retinal space or vitreous and then these cells can be migrate to the site of retinal degeneration and locate in the host retina and restitute vision. Our hypothesis suggests that using human conjunctiva stem cells (as the source for increasing the number of human stem cells progenitor cells in retina dysfunction diseases) with fibrin gel and also assessing its relating in vitro (cellular and molecular processes) and in vivo (vision tests and pathology) could be a promising strategy for treatment of AMD and RP disorders. In this idea, we describe a novel approach for retina tissue engineering with differentiation of conjunctiva mesenchymal stem cells (CJMSCs) into photoreceptor-like cells in fibrin gel with induction medium contain taurine. For assessment of differentiation, immunocytochemistry and real time PCR are used for the expression of Rhodopsin, RPE65, Nestin as differentiated photoreceptor cell markers in 2D and 3D culture. The results show that fibrin gel will offer a proper 3D scaffold for CJMSCs derived photoreceptor cell-like cells. Application of immune-privileged, readily available sources of adult stem cells like human conjunctiva stem cells with fibrin gel would be a promising strategy to increase the number of photoreceptor progenitor cells and promote involuntary angiogenesis needed in retina layer repair and regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

[The effect of locally applied Grisaldone or choline salicylate gel on bone healing after tooth extraction in animal experiments].

PubMed

Cendelin, E; Fröhlich, M

1977-01-01

Comparative histological and experimental animal studies of the effects upon bone wound healing of topically applied choline salicylate gel and Grisaldon showed that Grisaldon tends to hinder the course of reparation of bone, whereas choline salicylate gel has no appreciable influence upon the time course of wound healing. This essential difference is considered to be due predominantly to the exactly opposite behavior shown by the two pharmaceutical preparations in regard to their solubility in water. The difficultly watersoluble Grisaldon tends to exert a longer-drawn-out irritant effect upon the tissue and can be detected in alveoli even after twenty-eight days from administration thereof. By contrast, choline salicylate gel, which is known to be readily soluble in water, will be eliminated already after two days from administration thereof.

Gas-liquid chromatographic and gas-liquid-mass spectometric determination of fenvalerate and permethrin residues in grasshoppers and duck tissue samples

USGS Publications Warehouse

Reichel, W.L.; Kolbe, E.J.; Stafford, C.J.

1981-01-01

A procedure is described for determining fenvalerate and permethrin residues in grasshoppers and duck tissues. Samples are Soxhlet-extracted with hexane and cleaned up by gel permeation chromatography with an in-line alumina column. Samples are analyzed by gas-liquid chromatography with electron capture detection, and confirmed by gas-liquid chromatography-mass spectrometry. The average recovery from fortified tissues was 97%.

Polymer architecture of magnetic gels: a review

NASA Astrophysics Data System (ADS)

Weeber, Rudolf; Hermes, Melissa; Schmidt, Annette M.; Holm, Christian

2018-02-01

In this review article, we provide an introduction to ferrogels, i.e. polymeric gels with embedded magnetic particles. Due to the interplay between magnetic and elastic properties of these materials, they are promising candidates for engineering and biomedical applications such as actuation and controlled drug release. Particular emphasis will be put on the polymer architecture of magnetic gels since it controls the degrees of freedom of the magnetic particles in the gel, and it is important for the particle-polymer coupling determining the mechanisms available for the gel deformation in magnetic fields. We report on the different polymer architectures that have been realized so far, and provide an overview of synthesis strategies and experimental techniques for the characterization of these materials. We further focus on theoretical and simulational studies carried out on magnetic gels, and highlight their contributions towards understanding the influence of the gels’ polymer architecture.

Gelation under shear

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

Butler, B.D.; Hanley, H.J.M.; Straty, G.C.

An experimental small angle neutron scattering (SANS) study of dense silica gels, prepared from suspensions of 24 nm colloidal silica particles at several volume fractions {theta} is discussed. Provided that {theta}{approx_lt}0.18, the scattered intensity at small wave vectors q increases as the gelation proceeds, and the structure factor S(q, t {yields} {infinity}) of the gel exhibits apparent power law behavior. Power law behavior is also observed, even for samples with {theta}>0.18, when the gel is formed under an applied shear. Shear also enhances the diffraction maximum corresponding to the inter-particle contact distance of the gel. Difficulties encountered when trying tomore » interpret SANS data from these dense systems are outlined. Results of computer simulations intended to mimic gel formation, including computations of S(q, t), are discussed. Comments on a method to extract a fractal dimension characterizing the gel are included.« less

Cells on Gels: Cell Behavior at the Air-Gel Interface

NASA Astrophysics Data System (ADS)

O'Bryan, Christopher; Hormel, Tristan; Bhattacharjee, Tapomoy; Sawyer, W.; Angelini, Thomas

Numerous different types of cells are often grown at air-liquid interfaces. For example, a common way to create cell spheroids is to disperse cells in a droplet of liquid media that hangs from the lid of a culture dish - the ``hanging drop'' method. Some types of epithelial cells form monolayers at the bottom of hanging drops, instead of spheroids. Corneal epithelial cells stratify and exhibit a tissue-like phenotype when attached to liquid permeable culture surfaces positioned at the air-liquid media interface (air-lifted culture). These widely used culture methods make experimentation challenging - imaging through hanging drops and air-lifted culture dishes is prohibitive. However, similar results may be achieved by culturing cells on hydrogel surfaces at the air-gel interface. In this talk we will describe a method for culturing cells at air-gel interfaces. We seed human corneal epithelial cells (hTCEpi) onto the surfaces of hydrogel networks and jammed microgels, exposed to air. Preliminary observations of cell behavior at the air-gel interface will be presented.

A Ballistics Examination of Firearm Injuries Involving Breast Implants.

PubMed

Pannucci, Christopher J; Cyr, Adam J; Moores, Neal G; Young, Jason B; Szegedi, Martin

2018-03-01

This ballistics study examines whether saline breast implants can decrease tissue penetration in firearm injuries. We hypothesize that the fluid column within a saline breast implant can alter bullet velocity and/or bullet pattern of mushrooming. The two experimental groups included saline implants with 7.4 cm projection and a no implant group. The experimental design allowed the bullet to pass-through an implant and into ballistics gel (n = 10) or into ballistics gel without passage through an implant (n = 11). Shots that passed through an implant had 20.6% decreased penetration distance when compared to shots that did not pass-through an implant; this difference was statistically significant (31.9 cm vs. 40.2 cm, p < 0.001). Implant group bullets mushroomed prior to gel entry, but the no implant group mushroomed within the gel. Bullet passage through a saline breast implant results in direct bullet velocity reduction and earlier bullet mushrooming; this causes significantly decreased ballistics gel penetration. © 2017 American Academy of Forensic Sciences.

Confined compression and torsion experiments on a pHEMA gel in various bath concentrations.

PubMed

Roos, Reinder W; Petterson, Rob; Huyghe, Jacques M

2013-06-01

The constitutive behaviour of cartilaginous tissue is the result of complex interaction between electrical, chemical and mechanical forces. Electrostatic interactions between fixed charges and mobile ions are usually accounted for by means of Donnan osmotic pressure. Recent experimental data show, however, that the shear modulus of articular cartilage depends on ionic concentration even if the strain is kept constant. Poisson-Boltzmann simulations suggest that this dependence is intrinsic to the double-layer around the proteoglycan chains. In order to verify this premise, this study measures whether--at a given strain--this ionic concentration-dependent shear modulus is present in a polymerized hydroxy-ethyl-methacrylate gel or not. A combined 1D confined compression and torque experiment is performed on a thin cylindrical hydrogel sample, which is brought in equilibrium with, respectively, 1, 0.1 and 0.03 M NaCl. The sample was placed in a chamber that consists of a stainless steel ring placed on a sintered glass filter, and on top a sintered glass piston. Stepwise ionic loading was cascaded by stepwise 1D compression, measuring the total stress after equilibration of the sample. In addition, a torque experiment was interweaved by applying a harmonic angular displacement and measuring the torque, revealing the relation between aggregate shear modulus and salt concentration at a given strain.

Porous bodies of hydroxyapatite produced by a combination of the gel-casting and polymer sponge methods

PubMed Central

González Ocampo, Jazmín I.; Escobar Sierra, Diana M.; Ossa Orozco, Claudia P.

2015-01-01

A combination of gel-casting and polymeric foam infiltration methods is used in this study to prepare porous bodies of hydroxyapatite (HA), to provide a better control over the microstructures of samples. These scaffolds were prepared by impregnating a body of porous polyurethane foam with slurry containing HA powder, and using a percentage of solids between 40% and 50% w/v, and three different types of monomers to provide a better performance. X-Ray Diffraction (XRD), and Fourier Transformed Infrared (FTIR) and Scanning Electron Microscopy (SEM) were employed to evaluate both the powder hydroxyapatite and the scaffolds obtained. In addition, porosity and interconnectivity measurements were taken in accordance with the international norm. Bioactivity was checked using immersion tests in Simulated Body Fluids (SBF). After the sintering process of the porous bodies, the XRD results showed peaks characteristic of a pure and crystalline HA (JCPDS 9-432) as a single phase. SEM images indicate open and interconnected pores inside the material, with pore sizes between 50 and 600 μm. Also, SEM images demonstrate the relatively good bioactivity of the HA scaffolds after immersion in SBF. All results for the porous HA bodies suggest that these materials have great potential for use in tissue engineering. PMID:26966570

Mechanically Oriented 3D Collagen Hydrogel for Directing Neurite Growth.

PubMed

Antman-Passig, Merav; Levy, Shahar; Gartenberg, Chaim; Schori, Hadas; Shefi, Orit

2017-05-01

Recent studies in the field of neuro-tissue engineering have demonstrated the promising effects of aligned contact guidance cue to scaffolds of enhancement and direction of neuronal growth. In vivo, neurons grow and develop neurites in a complex three-dimensional (3D) extracellular matrix (ECM) surrounding. Studies have utilized hydrogel scaffolds derived from ECM molecules to better simulate natural growth. While many efforts have been made to control neuronal growth on 2D surfaces, the development of 3D scaffolds with an elaborate oriented topography to direct neuronal growth still remains a challenge. In this study, we designed a method for growing neurons in an aligned and oriented 3D collagen hydrogel. We aligned collagen fibers by inducing controlled uniaxial strain on gels. To examine the collagen hydrogel as a suitable scaffold for neuronal growth, we evaluated the physical properties of the hydrogel and measured collagen fiber properties. By combining the neuronal culture in 3D collagen hydrogels with strain-induced alignment, we were able to direct neuronal growth in the direction of the aligned collagen matrix. Quantitative evaluation of neurite extension and directionality within aligned gels was performed. The analysis showed neurite growth aligned with collagen matrix orientation, while maintaining the advantageous 3D growth.

Gel filtration applied to the study of lipases and other esterases

PubMed Central

Downey, W. K.; Andrews, P.

1965-01-01

1. Sephadex G-100 and G-200 gel-filtration columns were calibrated for molecular-weight estimation with proteins of known molecular weights, and used to study the composition of several lipase or esterase preparations. 2. Enzymes from cow's milk, rat adipose tissue and pig pancreas were detected in the column effluents by their ability to liberate free acid from emulsified tributyrin at pH 8·5. 3. Four tributyrinases were detected in preparations from individual cow's milks. Molecular weights 62000, 75000 and 112000 were estimated for three of them, but although the fourth may be of unusually low molecular weight an estimate was not possible. 4. Extracts of rat adipose tissue apparently contained six tributyrinases (molecular weights 39000, 47000, 55000, 68000, 75000 and 200000) but the relative amounts of these enzymes varied widely from rat to rat. 5. Tributyrinase activity in juice expressed from pig pancreatic tissue was due mainly to one enzyme (molecular weight 42000). On the other hand, activity in extracts of acetone-dried pancreas was confined to material of molecular weight > 106, which may be an aggregated form of the lower-molecular-weight enzyme. 6. Activity in fractionated wheat-germ extracts was assayed with emulsified triacetin substrate, and was evidently due to one enzyme (molecular weight 51000). 7. Some problems arising in the application of gel filtration to the study of lipase–esterase systems were indicated. PMID:14340054

Identification of proteins from 4200-year-old skin and muscle tissue biopsies from ancient Egyptian mummies of the first intermediate period shows evidence of acute inflammation and severe immune response.

PubMed

Jones, Jana; Mirzaei, Mehdi; Ravishankar, Prathiba; Xavier, Dylan; Lim, Do Seon; Shin, Dong Hoon; Bianucci, Raffaella; Haynes, Paul A

2016-10-28

We performed proteomics analysis on four skin and one muscle tissue samples taken from three ancient Egyptian mummies of the first intermediate period, approximately 4200 years old. The mummies were first dated by radiocarbon dating of the accompany-\\break ing textiles, and morphologically examined by scanning electron microscopy of additional skin samples. Proteins were extracted, separated on SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) gels, and in-gel digested with trypsin. The resulting peptides were analysed using nanoflow high-performance liquid chromatography-mass spectrometry. We identified a total of 230 unique proteins from the five samples, which consisted of 132 unique protein identifications. We found a large number of collagens, which was confirmed by our microscopy data, and is in agreement with previous studies showing that collagens are very long-lived. As expected, we also found a large number of keratins. We identified numerous proteins that provide evidence of activation of the innate immunity system in two of the mummies, one of which also contained proteins indicating severe tissue inflammation, possibly indicative of an infection that we can speculate may have been related to the cause of death.This article is part of the themed issue 'Quantitative mass spectrometry'. © 2016 The Author(s).

Identification of proteins from 4200-year-old skin and muscle tissue biopsies from ancient Egyptian mummies of the first intermediate period shows evidence of acute inflammation and severe immune response

PubMed Central

Jones, Jana; Mirzaei, Mehdi; Ravishankar, Prathiba; Xavier, Dylan; Lim, Do Seon; Shin, Dong Hoon; Bianucci, Raffaella

2016-01-01

We performed proteomics analysis on four skin and one muscle tissue samples taken from three ancient Egyptian mummies of the first intermediate period, approximately 4200 years old. The mummies were first dated by radiocarbon dating of the accompany-\\break ing textiles, and morphologically examined by scanning electron microscopy of additional skin samples. Proteins were extracted, separated on SDS–PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) gels, and in-gel digested with trypsin. The resulting peptides were analysed using nanoflow high-performance liquid chromatography–mass spectrometry. We identified a total of 230 unique proteins from the five samples, which consisted of 132 unique protein identifications. We found a large number of collagens, which was confirmed by our microscopy data, and is in agreement with previous studies showing that collagens are very long-lived. As expected, we also found a large number of keratins. We identified numerous proteins that provide evidence of activation of the innate immunity system in two of the mummies, one of which also contained proteins indicating severe tissue inflammation, possibly indicative of an infection that we can speculate may have been related to the cause of death. This article is part of the themed issue ‘Quantitative mass spectrometry’. PMID:27644972

Touch Locating and Stretch Sensing Studies of Conductive Hydrogels with Applications to Soft Robots

PubMed Central

He, Bin; Yan, Zhe; Shang, Yinghui; Wang, Qigang; Wang, Zhipeng

2018-01-01

Soft robots possess great potential in environmental adaptations, while their environmental sensing abilities are critical. Conductive hydrogels have been suggested to possess sensing abilities. However, their application in soft robots is lacking. In this work, we fabricated a soft and stretchable gel material, introduced its sensing mechanisms, and developed a measurement setup. Both experimental and simulation studies indicate strong nonlinearity of touch locating on a square touch panel with Cartesian coordinates. To simplify the touch locating, we proposed a touch locating system based on round touch panels with polar coordinates. Mathematical calculations and finite element method (FEM) simulations showed that in this system the locating of a touch point was only determined by its polar radius. This was verified by experimental studies. As a resistor, a gel strip’s resistance increases with stretching. To demonstrate their applications on soft robots, a 3D printed three-fingered soft gripper was employed with gel strips attached. During finger bending for rod grasping, the resistances of the gel strips increased, indicating stretching of the soft material. Furthermore, the strain and stress of a gel strip increased with a decrease of the rod diameter. These studies advance the application of conductive hydrogels on soft robots. PMID:29438318

Photochemical synthesis of simple organic free radicals on simulated planetary surfaces - An ESR study

NASA Technical Reports Server (NTRS)

Tseng, S.-S.; Chang, S.

1975-01-01

Electron spin resonance (ESR) spectroscopy provided evidence for formation of hydroxyl radicals during ultraviolet photolysis (254 nm) at -170 C of H2O adsorbed on silica gel or of silica gel alone. The carboxyl radical was observed when CO or CO2 or a mixture of CO and CO2 adsorbed on silica gel at -170 C was irradiated. The ESR signals of these radicals slowly disappeared when the irradiated samples were warmed to room temperature. However, reirradiation of CO or CO2, or the mixture CO and CO2 on silica gel at room temperature then produced a new species, the carbon dioxide anion radical, which slowly decayed and was identical with that produced by direct photolysis of formic acid adsorbed on silica gel. The primary photochemical process may involve formation of hydrogen and hydroxyl radicals. Subsequent reactions of these radicals with adsorbed CO or CO2 or both yield carboxyl radicals, CO2H, the precursors of formic acid. These results confirm the formation of formic acid under simulated Martian conditions and provide a mechanistic basis for gauging the potential importance of gas-solid photochemistry for chemical evolution on other extraterrestrial bodies, on the primitive earth, and on dust grains in the interstellar medium.

Junctionless Diode Enabled by Self-Bias Effect of Ion Gel in Single-Layer MoS2 Device.

PubMed

Khan, Muhammad Atif; Rathi, Servin; Park, Jinwoo; Lim, Dongsuk; Lee, Yoontae; Yun, Sun Jin; Youn, Doo-Hyeb; Kim, Gil-Ho

2017-08-16

The self-biasing effects of ion gel from source and drain electrodes on electrical characteristics of single layer and few layer molybdenum disulfide (MoS 2 ) field-effect transistor (FET) have been studied. The self-biasing effect of ion gel is tested for two different configurations, covered and open, where ion gel is in contact with either one or both, source and drain electrodes, respectively. In open configuration, the linear output characteristics of the pristine device becomes nonlinear and on-off ratio drops by 3 orders of magnitude due to the increase in "off" current for both single and few layer MoS 2 FETs. However, the covered configuration results in a highly asymmetric output characteristics with a rectification of around 10 3 and an ideality factor of 1.9. This diode like behavior has been attributed to the reduction of Schottky barrier width by the electric field of self-biased ion gel, which enables an efficient injection of electrons by tunneling at metal-MoS 2 interface. Finally, finite element method based simulations are carried out and the simulated results matches well in principle with the experimental analysis. These self-biased diodes can perform a crucial role in the development of high-frequency optoelectronic and valleytronic devices.

Three-dimensional collagenous niche and azacytidine selectively promote time-dependent cardiomyogenesis from human bone marrow-derived MSC spheroids.

PubMed

Joshi, Jyotsna; Mahajan, Gautam; Kothapalli, Chandrasekhar R

2018-04-17

Endogenous adult cardiac regenerative machinery is not capable of replacing the lost cells following myocardial infarction, often leading to permanent alterations in structure-function-mechanical properties. Regenerative therapies based on delivering autologous stem cells within an appropriate 3D milieu could meet such demand, by enabling homing and directed differentiation of the transplanted cells into lost specialized cell populations. Since type I collagen is the predominant cardiac tissue matrix protein, we here optimized the 3D niche which could promote time-dependent evolution of cardiomyogenesis from human bone marrow-derived mesenchymal stem cells (BM-MSC). 3D collagen gel physical and mechanical characteristics were assessed using SEM and AFM, respectively, while the standalone and combined effects of collagen concentration, culture duration, and 5-azacytidine (aza) dose on the phenotype and genotype of MSC spheroids were quantified using immunofluorescence labeling and RT-PCR analysis. Increasing collagen concentration led to a significant increase in Young's modulus (p < 0.01) but simultaneous decrease in the mean pore size, resulting in stiffer gels. Spheroid formation significantly modulated MSC differentiation and genotype, mostly due to better cell-cell interactions. Among the aza dosages tested, 10 μM appears to be optimal, while 3 mg/ml gels resulted in significantly lower cell viability compared to 1 or 2 mg/ml gels. Stiffer gels (2 and 3 mg/ml) and exposure to 10 μM aza upregulated early and late cardiac marker expressions in a time-dependent fashion. On the other hand, cell-cell signaling within the MSC spheroids seem to have a strong role in influencing mature cardiac markers expression, since neither aza nor gel stiffness seem to significantly improve their expression. Western blot analysis suggested that canonical Wnt/β-catenin signaling pathway might be primarily mediating the observed benefits of aza on cardiac differentiation of MSC spheroids. In conclusion, 2 mg/ml collagen and 10 μM aza appears to offer optimal 3D microenvironment in terms of cell viability and time-dependent evolution of cardiomyogenesis from human BM-MSCs, with significant applications in cardiac tissue engineering and stem cell transplantation for regenerating lost cardiac tissue. © 2018 Wiley Periodicals, Inc.

Local structure of percolating gels at very low volume fractions

NASA Astrophysics Data System (ADS)

Griffiths, Samuel; Turci, Francesco; Royall, C. Patrick

2017-01-01

The formation of colloidal gels is strongly dependent on the volume fraction of the system and the strength of the interactions between the colloids. Here we explore very dilute solutions by the means of numerical simulations and show that, in the absence of hydrodynamic interactions and for sufficiently strong interactions, percolating colloidal gels can be realised at very low values of the volume fraction. Characterising the structure of the network of the arrested material we find that, when reducing the volume fraction, the gels are dominated by low-energy local structures, analogous to the isolated clusters of the interaction potential. Changing the strength of the interaction allows us to tune the compactness of the gel as characterised by the fractal dimension, with low interaction strength favouring more chain-like structures.

Sequential Delivery of BMP-2 and IGF-1 Using a Chitosan Gel with gelatin Microspheres Enhances Early osteoblastic Differentiation

DTIC Science & Technology

2012-01-18

Vunjak- Novakovic G, Freed LE. Growth factors for sequential cellular de- and re-differentiation in tissue engineering. Biochem Biophys Res Commun...2002;294(1):149–54. [35] Martin I, Suetterlin R, Baschong W, Heberer M, Vunjak- Novakovic G, Freed LE. Enhanced cartilage tissue engineering by sequential

Live biospeckle laser imaging of root tissues.

PubMed

Braga, Roberto A; Dupuy, L; Pasqual, M; Cardoso, R R

2009-06-01

Live imaging is now a central component for the study of plant developmental processes. Currently, most techniques are extremely constraining: they rely on the marking of specific cellular structures which generally apply to model species because they require genetic transformations. The biospeckle laser (BSL) system was evaluated as an instrument to measure biological activity in plant tissues. The system allows collecting biospeckle patterns from roots which are grown in gels. Laser illumination has been optimized to obtain the images without undesirable specular reflections from the glass tube. Data on two different plant species were obtained and the ability of three different methods to analyze the biospeckle patterns are presented. The results showed that the biospeckle could provide quantitative indicators of the molecular activity from roots which are grown in gel substrate in tissue culture. We also presented a particular experimental configuration and the optimal approach to analyze the images. This may serve as a basis to further works on live BSL in order to study root development.

Introduction of N-cadherin-binding motif to alginate hydrogels for controlled stem cell differentiation.

PubMed

Lee, Jae Won; An, Hyoseok; Lee, Kuen Yong

2017-07-01

Control of stem cell fate and phenotype using biomimetic synthetic extracellular matrices (ECMs) is an important tissue engineering approach. Many studies have focused on improving cell-matrix interactions. However, proper control of cell-cell interactions using synthetic ECMs could be critical for tissue engineering, especially with undifferentiated stem cells. In this study, alginate hydrogels were modified with a peptide derived from the low-density lipoprotein receptor-related protein 5 (LRP5), which is known to bind to N-cadherin, as a cell-cell interaction motif. In vitro changes in the morphology and differentiation of mouse bone marrow stromal cells (D1 stem cells) cultured in LRP5-alginate hydrogels were investigated. LRP5-alginate gels successfully induced stem cell aggregation and enhanced chondrogenic differentiation of D1 stem cells, compared to RGD-alginate gels, at low cell density. This approach to tailoring synthetic biomimetic ECMs using cell-cell interaction motifs may be critical in tissue engineering approaches using stem cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Local application of osteoprotegerin-chitosan gel in critical-sized defects in a rabbit model

PubMed Central

2017-01-01

Background Osteoprotegerin (OPG) is used for the systemic treatment of bone diseases, although it has many side effects. The aim of this study was to investigate a newly formulated OPG-chitosan gel for local application to repair bone defects. Recent studies have reported that immunodetection of osteopontin (OPN) and osteocalcin (OC) can be used to characterise osteogenesis and new bone formation. Methods The osteogenic potential of the OPG-chitosan gel was evaluated in rabbits. Critical-sized defects were created in the calvarial bone, which were either left unfilled (control; group I), or filled with chitosan gel (group II) or OPG-chitosan gel (group III), with rabbits sacrificed at 6 and 12 weeks. Bone samples from the surgical area were decalcified and treated with routine histological and immunohistochemical protocols using OC, OPN, and cathepsin K (osteoclast marker) antibodies. The toxicity of the OPG-chitosan gel was evaluated by biochemical assays (liver and kidney function tests). Results The mean bone growth in defects filled with the OPG-chitosan gel was significantly higher than those filled with the chitosan gel or the unfilled group (p < 0.05). At 6 and 12 weeks, the highest levels of OC and OPN markers were found in the OPG-chitosan gel group, followed by the chitosan gel group. The number of osteoclasts in the OPG-chitosan gel group was lower than the other groups. The results of the liver and kidney functional tests indicated no signs of harmful systemic effects of treatment. In conclusion, the OPG-chitosan gel has many characteristics that make it suitable for bone repair and regeneration, highlighting its potential benefits for tissue engineering applications. PMID:28674665

Desire for penile girth enhancement and the effects of the self-injection of hyaluronic Acid gel.

PubMed

Coskuner, Enis Rauf; Canter, Halil Ibrahim

2012-07-01

Penile girth enhancement is a controversial subject but demands for enhancement are increasing steadily. Although various fillers have been widely used for soft tissue augmentation, there is no reliable material for this particular situation. Here we report a case of an acute hypersensitivity reaction in a man after his first self-injection of a filler material, which, he claimed, was hyaluronic acid gel for penile girth enhancement and glans penis augmentation.

Sol-gel processing of bioactive glass nanoparticles: A review.

PubMed

Zheng, Kai; Boccaccini, Aldo R

2017-11-01

Silicate-based bioactive glass nanoparticles (BGN) are gaining increasing attention in various biomedical applications due to their unique properties. Controlled synthesis of BGN is critical to their effective use in biomedical applications since BGN characteristics, such as morphology and composition, determining the properties of BGN, are highly related to the synthesis process. In the last decade, numerous investigations focusing on BGN synthesis have been reported. BGN can mainly be produced through the conventional melt-quench approach or by sol-gel methods. The latter approaches are drawing widespread attention, considering the convenience and versatility they offer to tune the properties of BGN. In this paper, we review the strategies of sol-gel processing of BGN, including those adopting different catalysts for initiating the hydrolysis and condensation of silicate precursors as well as those combining sol-gel chemistry with other techniques. The processes and mechanism of different synthesis approaches are introduced and discussed in detail. Considering the importance of the BGN morphology and composition to their biomedical applications, strategies put forward to control the size, shape, pore structure and composition of BGN are discussed. BGN are particularly interesting biomaterials for bone-related applications, however, they also have potential for other biomedical applications, e.g. in soft tissue regeneration/repair. Therefore, in the last part of this review, recently reported applications of BGN in soft tissue repair and wound healing are presented. Copyright © 2017 Elsevier B.V. All rights reserved.

Magnetoacoustic imaging of human liver tumor with magnetic induction

NASA Astrophysics Data System (ADS)

Hu, Gang; Cressman, Erik; He, Bin

2011-01-01

Magnetoacoustic tomography with magnetic induction (MAT-MI) is an imaging technique under development to achieve imaging of electrical impedance contrast in biological tissues with spatial resolution close to ultrasound imaging. However, previously reported MAT-MI experimental results are obtained either from low salinity gel phantoms, or from normal animal tissue samples. In this study, we report the experimental study on the performance of the MAT-MI imaging method for imaging in vitro human liver tumor tissue. The present promising experimental results suggest the feasibility of MAT-MI to image electrical impedance contrast between the cancerous tissue and its surrounding normal tissues.

Acoustic properties of healthy and reconstructed cleft lip

NASA Astrophysics Data System (ADS)

Thijssen, Johan M.; van Hees, Nancy J.; Weijers, Gert G.; Huyskens, Rinske W.; Nillesen, Maartje; Katsaros, Christos; de Korte, Chris L.

2006-03-01

The feasibility of echographic imaging of the tissues in healthy lip and in reconstructed cleft lip and estimating the dimensions and the normalized echo level of these tissues is investigated. Echographic images of the upper lip were made with commercial medical ultrasound equipment, using a linear array transducer (7-11 MHz bandwidth) and a non-contact gel coupling. Tissue dimensions were measured by means of software calipers. Echo levels were calibrated and corrected for beam characteristics, gel path and tissue attenuation by using a tissue-mimicking phantom. At central position of philtrum, mean thickness (and standard deviation) of lip loose connective tissue layer, orbicularis oris muscle and dense connective layer was 4.0 (sd 0.1) mm, 2.3 (sd 0.7) mm, 2.2 (sd 0.7) mm, respectively, in healthy lip at rest. Mean (sd) echo level of muscle and dense connective tissue layer with respect to echo level of lip loose connective tissue layer was in relaxed condition: - 19.3 (sd 0.6) dB and - 10.7 (sd 4.0) dB, respectively. Echo level of loose connective tissue layer was +25.6 (sd 4.2) dB relative to phantom echo level obtained in the focus of the transducer. Color mode echo images were calculated, after adaptive filtering of the images, which show the tissues in separate colors and highlight the details of healthy lip and reconstructed cleft lip. Quantitative assessment of thickness and echo level of various lip tissues is feasible after proper calibration of the echographic equipment. Diagnostic potentials of the developed quantitative echographic techniques for non-invasive evaluation of the outcome of cleft lip reconstruction are promising.

Temperature rise in pulp and gel during laser-activated bleaching: in vitro.

PubMed

Sari, Tugrul; Celik, Gozde; Usumez, Aslıhan

2015-02-01

The aim of this study was to evaluate the increase in temperature induced by various light sources during in-office bleaching treatment, under simulated blood microcirculation in pulp conditions. Ten freshly extracted human maxillary central incisors were used for the study. The roots of the teeth were removed from approximately 2 mm below the cementoenamel junction and fixed on an apparatus for the simulation of blood microcirculation in pulp. A J-type thermocouple wire was inserted into the pulp chamber through an artificial access at the lingual surfaces of the teeth, and another thermocouple wire was fixed on the labial surface of the teeth meanwhile. An in-office bleaching agent, intense red in color and with 30% water content, was applied to the labial surfaces of the teeth, and repeating measurements were made for each tooth using three different light sources: Er:YAG laser (40 mJ, 10 Hz, 20 s), 810-nm diode laser (4 W, 20 s, CW), and high-intensity light-emitting diodes (LED) (1,100 mW/cm(2), 20 s) as the control. Temperature increase in the pulp chamber and within the bleaching gel during light application were recorded and statistically evaluated. The highest pulp temperature increases were recorded for the diode laser group (2.61 °C), followed by the Er:YAG laser (1.86 °C) and LED (1.02 °C) groups (p < 0.05; analysis of variance (ANOVA), Tukey's honestly significant difference (HSD)). Contradictorily, the lowest gel temperature increases were recorded for diode laser (6.21 °C) and followed by LED (12.38 °C) and Er:YAG (20.11 °C) groups (p < 0.05; ANOVA, Tukey's HSD). Despite the significant differences among the groups, the temperature increases recorded for all groups were below the critical value of 5.6 °C that can cause irreversible harmful changes in pulp tissue. It can be concluded that, with regard to temperature increase, all the light sources evaluated in this study can be used safely for in-office bleaching treatment within the described parameters.

Soft Tissue Augmentation Using Silk Gels: An In Vitro and In Vivo Study

PubMed Central

Etienne, Olivier; Schneider, Aurore; Kluge, Jonathan A.; Bellemin-Laponnaz, Claire; Polidori, Camille; Leisk, Gary G.; Kaplan, David L.; Garlick, Jonathan A.; Egles, Christophe

2010-01-01

Background Restoration of a three-dimensional shape with soft tissue augmentation is a challenge for surgical reconstruction and esthetic improvement of intraoral mucosa and perioral skin tissues. A connective tissue graft or free gingival graft, classically used for such indications, requires a donor site, which may lead to various clinical complications. Methods In this article, a new three-dimensional scaffold made of silk fibroin that could be of great interest for these indications was studied. Mechanical tests were conducted to characterize the physical properties of the materials. The biocompatibility of such scaffolds was positively assessed in vitro using a combination of immunostaining, 5-bromo-2′-deoxyuridine proliferation assays, and histologic staining. Finally, the shaped material was grafted subcutaneously in nude mice for a long-time implantation study. Results Human fibroblasts embedded in this material had a survival rate up to 68.4% and were able to proliferate and synthesize proteins. One month after subcutaneous implantation, the three-dimensional soft tissue augmentation was stable, and histologic analysis revealed revascularization of the area through the biomaterial. A mild inflammatory reaction disappeared after 12 weeks. Conclusion The results indicate that silk-gel material was able to create a lasting three-dimensional soft tissue augmentation and is a promising biomaterial for periodontal and maxillofacial therapies, either as a scaffold for cells or alone as a biomaterial. PMID:19905955

Global PROTOMAP profiling to search for biomarkers of early-recurrent hepatocellular carcinoma.

PubMed

Taoka, Masato; Morofuji, Noriaki; Yamauchi, Yoshio; Ojima, Hidenori; Kubota, Daisuke; Terukina, Goro; Nobe, Yuko; Nakayama, Hiroshi; Takahashi, Nobuhiro; Kosuge, Tomoo; Isobe, Toshiaki; Kondo, Tadashi

2014-11-07

This study used global protein expression profiling to search for biomarkers to predict early recurrent hepatocellular carcinoma (HCC). HCC tissues surgically resected from patients with or without recurrence within 2 years (early recurrent) after surgery were compared with adjacent nontumor tissue and with normal liver tissue. We used the PROTOMAP strategy for comparative profiling, which integrates denaturing polyacrylamide gel electrophoresis migratory rates and high-resolution, semiquantitative mass-spectrometry-based identification of in-gel-digested tryptic peptides. PROTOMAP allows examination of global changes in the size, topography, and abundance of proteins in complex tissue samples. This approach identified 8438 unique proteins from 45 708 nonredundant peptides and generated a proteome-wide map of changes in expression and proteolytic events potentially induced by intrinsic apoptotic/necrotic pathways. In the early recurrent HCC tissue, 87 proteins were differentially expressed (≥20-fold) relative to the other tissues, 46 of which were up-regulated or specifically proteolyzed and 41 of which were down-regulated. This data set consisted of proteins that fell into various functional categories, including signal transduction and cell organization and, notably, the major catalytic pathways responsible for liver function, such as the urea cycle and detoxification metabolism. We found that aberrant proteolysis appeared to occur frequently during recurrence of HCC in several key signal transducers, including STAT1 and δ-catenin. Further investigation of these proteins will facilitate the development of novel clinical applications.

A kinetic modeling of chondrocyte culture for manufacture of tissue-engineered cartilage.

PubMed

Kino-Oka, Masahiro; Maeda, Yoshikatsu; Yamamoto, Takeyuki; Sugawara, Katsura; Taya, Masahito

2005-03-01

For repairing articular cartilage defects, innovative techniques based on tissue engineering have been developed and are now entering into the practical stage of clinical application by means of grafting in vitro cultured products. A variety of natural and artificial materials available for scaffolds, which permit chondrocyte cells to aggregate, have been designed for their ability to promote cell growth and differentiation. From the viewpoint of the manufacturing process for tissue-engineered cartilage, the diverse nature of raw materials (seeding cells) and end products (cultured cartilage) oblige us to design a tailor-made process with less reproducibility, which is an obstacle to establishing a production doctrine based on bioengineering knowledge concerning growth kinetics and modeling as well as designs of bioreactors and culture operations for certification of high product quality. In this article, we review the recent advances in the manufacturing of tissue-engineered cartilage. After outlining the manufacturing processes for tissue-engineered cartilage in the first section, the second and third sections, respectively, describe the three-dimensional culture of chondrocytes with Aterocollagen gel and kinetic model consideration as a tool for evaluating this culture process. In the final section, culture strategy is discussed in terms of the combined processes of monolayer growth (ex vivo chondrocyte cell expansion) and three-dimensional growth (construction of cultured cartilage in the gel).

CLOSED-LOOP STRIPPING ANALYSIS (CLSA) OF ...

EPA Pesticide Factsheets

Synthetic musk compounds are used as inexpensive fragrance materials for the production of perfumes and as additives to soap, detergent, and shampoo. They have been found in surface water, fish tissues, and human breast milk. The ubiquity of this class of compounds in the environment is attributable to high use and release into the environment. Current techniques for separating these compounds from fish tissues require tedious sample clean-up procedures. To obtain fat-free extracts, gel permeation chromatography (GPC), column chromatography using alumina, and silica gel, and thin layer chromatography (TLC clean-up procedures are frequently employed. Despite the considerable effort and resources devoted to these processes, a fraction of the lipids and lipid-like compounds frequently remains in the extracts. These low-level lipids foul injection liners, contaminate columns, and yield elevated baselines during gas chromatographic analysis of synthetic musk compounds. In this study, a simple method for the determination of synthetic musk compounds in fish tissues has been developed. Closed-loop stripping of saponified fish tissues in a I -L Wheaton purge- and-trap vessel, is used to strip compounds with high vapor pressures such as synthetic musks from the matrix onto a solid sorbent (Abselut Nexus). This technique is useful for screening biological tissues that contain lipids for musk compounds. Analytes are desorbed from the sorbent trap sequentially with polar an

Uninduced adipose-derived stem cells repair the defect of full-thickness hyaline cartilage.

PubMed

Zhang, Hai-Ning; Li, Lei; Leng, Ping; Wang, Ying-Zhen; Lv, Cheng-Yu

2009-04-01

To testify the effect of the stem cells derived from the widely distributed fat tissue on repairing full-thickness hyaline cartilage defects. Adipose-derived stem cells (ADSCs) were derived from adipose tissue and cultured in vitro. Twenty-seven New Zealand white rabbits were divided into three groups randomly. The cultured ADSCs mixed with calcium alginate gel were used to fill the full-thickness hyaline cartilage defects created at the patellafemoral joint, and the defects repaired with gel or without treatment served as control groups. After 4, 8 and 12 weeks, the reconstructed tissue was evaluated macroscopically and microscopically. Histological analysis and qualitative scoring were also performed to detect the outcome. Full thickness hyaline cartilage defects were repaired completely with ADSCs-derived tissue. The result was better in ADSCs group than the control ones. The microstructure of reconstructed tissue with ADSCs was similar to that of hyaline cartilage and contained more cells and regular matrix fibers, being better than other groups. Plenty of collagen fibers around cells could be seen under transmission electron microscopy. Statistical analysis revealed a significant difference in comparison with other groups at each time point (t equal to 4.360, P less than 0.01). These results indicate that stem cells derived from mature adipose without induction possess the ability to repair cartilage defects.

Heat-mediated, ultra-rapid electrophoretic transfer of high and low molecular weight proteins to nitrocellulose membranes.

PubMed

Kurien, Biji T; Scofield, R Hal

2002-08-01

Here, we report an ultra-rapid method for the transfer of high and low molecular weight proteins to nitrocellulose membranes following sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In this procedure, the electro-transfer was performed with heated (70-75 degrees C) normal transfer buffer from which methanol had been omitted. Complete transfer of high and low molecular weight proteins (a purified protein, molecular weight protein standards and proteins from a human tissue extract) could be carried out in 10 min for a 0.75-mm, 7% SDS-PAGE gel. For 10% and 12.5% gels (0.75 mm), the corresponding time was 15 min. In the case of 1.5-mm gels, a complete transfer could be carried out in 20 min for 7%, 10% and 12.5% gels. The permeability of the gel is increased by heat, such that the proteins trapped in the polyacrylamide gel matrix can be easily transferred to the membrane. When the heat-mediated transfer method was compared with a conventional transfer protocol, under similar conditions, we found that the latter method transferred minimal low molecular weight proteins while retaining most of the high molecular weight proteins in the gel. In summary, this procedure is very rapid, avoids the use of methanol and is particularly useful for the transfer of high molecular weight proteins.

Evaluation of characteristics of high-energy electron beams using N-isopropyl-acrylamide gel dosimeter

NASA Astrophysics Data System (ADS)

Shih, Tian-Yu; Yen, Tsung-Hsien; Liu, Yan-Lin; Luzhbin, Dmytro; Wu, Jay

2017-11-01

The advantage of electron beam radiotherapy is that the absorbed dose rapidly decreases with the increasing depth, which can prevent damage to deeper organs and tissues. Accurately evaluating the absorbed dose in the superficial tumor is imperative. This study assessed the characteristics of electron beams by using the N-isopropyl-acrylamide (n-NIPAM) gel dosimeter. The n-NIPAM gel was composed of 6% gelatin, 5% monomer, and 2.5% cross-linker with 5 mM tetrakis (hydroxymethyl) phosphonium chloride for deoxygenation. The gel was irradiated with 6-, 9-, and 12-MeV electron beams with dose rates of 100-600 MU/min, respectively. The energy dependence and dose rate dependence were assessed. The beam profiles and percentage depth doses were measured and compared with the results of the Gafchromic film and ionization chamber. The linearity of the n-NIPAM gel under 6-, 9-, and 12-MeV electrons was larger than 0.990 with 2% variation in sensitivity. The sensitivity of the gel under 100-600 MU/min showed 5% variations. The energy and dose rate dependence can be negligible. The beam profiles and percentage depth doses measured by the n-NIPAM gel matched well with the results of the ionization chamber and film. This study reveals the possibility of using the n-NIPAM gel dosimeter for electron beam measurements in clinical radiotherapy.

In Vitro and In Vivo Evaluation of Commercially Available Fibrin Gel as a Carrier of Alendronate for Bone Tissue Engineering.

PubMed

Kim, Beom Su; Shkembi, Feride; Lee, Jun

2017-01-01

Alendronate (ALN) is a bisphosphonate drug that is widely used for the treatment of osteoporosis. Furthermore, local delivery of ALN has the potential to improve the bone regeneration. This study was designed to investigate an ALN-containing fibrin (fibrin/ALN) gel and evaluate the effect of this gel on both in vitro cellular behavior using human mesenchymal stem cells (hMSCs) and in vivo bone regenerative capacity. Fibrin hydrogels were fabricated using various ALN concentrations (10 -7 -10 -4  M) with fibrin glue and the morphology, mechanical properties, and ALN release kinetics were characterized. Proliferation and osteogenic differentiation of and cytotoxicity in fibrin/ALN gel-embedded hMSCs were examined. In vivo bone formation was evaluated using a rabbit calvarial defect model. The fabricated fibrin/ALN gel was transparent with Young's modulus of ~13 kPa, and these properties were not affected by ALN concentration. The in vitro studies showed sustained release of ALN from the fibrin gel and revealed that hMSCs cultured in fibrin/ALN gel showed significantly increased proliferation and osteogenic differentiation. In addition, microcomputed tomography and histological analysis revealed that the newly formed bone was significantly enhanced by implantation of fibrin/ALN gel in a calvarial defect model. These results suggest that fibrin/ALN has the potential to improve bone regeneration.

In Vitro and In Vivo Evaluation of Commercially Available Fibrin Gel as a Carrier of Alendronate for Bone Tissue Engineering

PubMed Central

Kim, Beom Su; Shkembi, Feride

2017-01-01

Alendronate (ALN) is a bisphosphonate drug that is widely used for the treatment of osteoporosis. Furthermore, local delivery of ALN has the potential to improve the bone regeneration. This study was designed to investigate an ALN-containing fibrin (fibrin/ALN) gel and evaluate the effect of this gel on both in vitro cellular behavior using human mesenchymal stem cells (hMSCs) and in vivo bone regenerative capacity. Fibrin hydrogels were fabricated using various ALN concentrations (10−7–10−4 M) with fibrin glue and the morphology, mechanical properties, and ALN release kinetics were characterized. Proliferation and osteogenic differentiation of and cytotoxicity in fibrin/ALN gel-embedded hMSCs were examined. In vivo bone formation was evaluated using a rabbit calvarial defect model. The fabricated fibrin/ALN gel was transparent with Young's modulus of ~13 kPa, and these properties were not affected by ALN concentration. The in vitro studies showed sustained release of ALN from the fibrin gel and revealed that hMSCs cultured in fibrin/ALN gel showed significantly increased proliferation and osteogenic differentiation. In addition, microcomputed tomography and histological analysis revealed that the newly formed bone was significantly enhanced by implantation of fibrin/ALN gel in a calvarial defect model. These results suggest that fibrin/ALN has the potential to improve bone regeneration. PMID:28210623

Evaluation of a topical treatment for the relief of sensitive skin

PubMed Central

Heinicke, Ingrid R; Adams, Damian H; Barnes, Tanya M; Greive, Kerryn A

2015-01-01

Background Approximately, 50% of the population claim to have sensitive skin, which has created an important challenge for dermatologists and the cosmetic industry. This study evaluates the properties of QV Face Rescue Gel (Rescue Gel) that contains a combination of moisturizing and anti-irritant ingredients, and which is used to relieve the symptoms of sensitive facial skin. Methods The ability of Rescue Gel to induce collagen types I and III in cultured neonatal human foreskin fibroblasts compared to transforming growth factor beta 1, a known potent inducer of collagen types I and III, was measured using immunofluorescence staining. Furthermore, healthy volunteers were recruited to measure the potential for Rescue Gel to reduce erythema induced by solar-simulated ultraviolet radiation on the skin compared to 0.5% hydrocortisone cream (positive control) as well as it’s ability to decrease transepidermal water loss compared to baseline levels. In addition, the formulation was tested for its potential to be 1) nonstinging using a facial sting/discomfort assay performed on volunteers who reacted positively to lactic acid, 2) nonirritating as determined by repeat insult patch tests, and 3) noncomedogenic. Results Rescue Gel significantly induced collagen types I and III in cultured human foreskin fibroblasts similarly to transforming growth factor beta 1. In volunteers, Rescue Gel was shown to significantly reduce erythema induced by solar-simulated ultraviolet radiation similarly to 0.5% hydrocortisone, and to significantly reduce transepidermal water loss compared to baseline levels. Further, the formulation was found to be nonstinging, nonirritating, and noncomedogenic. No adverse events were observed. Conclusion In this study, Rescue Gel has been shown to exhibit properties that make it effective for use on sensitive or irritated facial skin, without exacerbation of the symptoms associated with sensitive skin. PMID:26251625

Surface-deacetylated chitin nanofibers reinforced with a sulfobutyl ether β-cyclodextrin gel loaded with prednisolone as potential therapy for inflammatory bowel disease.

PubMed

Tabuchi, Ryo; Anraku, Makoto; Iohara, Daisuke; Ishiguro, Takako; Ifuku, Shinsuke; Nagae, Tomone; Uekama, Kaneto; Okazaki, Shoko; Takeshita, Keizo; Otagiri, Masaki; Hirayama, Fumitoshi

2017-10-15

Surface-deacetylated chitin nanofibers (SDACNFs) reinforced with a sulfobutyl ether β-cyclodextrin (SBE-β-CD) (NFs-CDs) gel were developed to obtain a controlled release carrier of prednisolone (PD) for the treatment of colitis. PD was released slowly from the gel at both pH 1.2 and 6.8. The in vitro slow release of PD from the NFs-CDs gel was reflected in the in vivo absorption of the drug after oral administration to rats. These results suggest that a simple gel composed of a mixture of SDACNFs and SBE-β-CD has the potential for use in the controlled release of PD. We also evaluated the therapeutic effects of the NFs-CDs gel containing PD on dextran sulfate sodium (DSS)-induced colitis model mice. The administration of the NFs-CDs gel at intervals of 3days from the beginning of the DSS treatment resulted in a significant improvement, not only in colitis symptoms but also histopathological changes in colon tissue. In addition, the therapeutic effects of the NFs-CDs gel on colitis can be attributed to decreased levels of neutrophil infiltration and the development of oxidative stress. These efficacy profiles of the NFs-CDs gel containing PD suggest that it has the potential for use in the treatment of, not only colitis, but also a variety of other disorders associated with inflammation and oxidative injuries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytocompatibility, antibacterial activity and biodegradability of self-assembling beta-hairpin peptide-based hydrogels for tissue regenerative applications

NASA Astrophysics Data System (ADS)

Salick, Daphne Ann

Every year, millions of people suffer from tissue loss or failure. One approach to repair damaged or diseased tissue is through tissue/organ transplantation. However, one of the major problems which exist with this approach is that there are more people in need of a transplant than there are donors. Over the past several decades, scientists and doctors have come together to find a way to overcome this challenge. This collaboration has led to the development of biomimetic scaffolds, which closely mimic the desired tissue of interest to act as a substitute for the unfunctional tissue, with hopes to improve the quality of life. The Schneider and Pochan labs have developed a biomimetic scaffold using self-assembling beta-hairpin peptides. The self-assembly event can be triggered in response to physiological conditions, which is dictated by the monomer, to form non covalently crosslinked mechanically rigid hydrogels. In vitro studies showed that hydrogels were cytocompatible and may not elicit a pro-inflammatory response from murine macrophages. These material properties show promise for the use of these hydrogels in tissue engineering. When implanting a material into a host, a major concern is the introduction of infection. Infection, if not prevented or halted, results in poor tissue integration and function, ultimately leading to implant removal from the host. Interestingly, the beta-hairpin hydrogels were shown to exhibit antibacterial properties against pathogens commonly found in hospital environments. This inherently antibacterial hydrogel is advantageous because it may help decrease or diminish bacterial contamination when implanted in vivo, which may help to increase the success of implants. Also, a unique and exciting feature of these peptide-based hydrogels is their ability to shear-thin and self-heal. Hydrogels can be directly formed in a syringe and be subsequently delivered to a tissue defect in a minimally invasive manner where they will recover to their original mechanical rigidity. The resultant syringe-delivered gel was also shown to possess antibacterial properties. Aside from the material's inherent antibacterial activity, these peptide-based scaffolds display degradation that can be controlled using an exogenously added enzyme. This suggests that by using peptide design, the gel network degradation can be controlled to allow for the proper formation of functional tissue. The work described in this thesis shows these described attributes, as well as, the potential of these peptide-based gels for use as tissue substitutes.

Finding the position of tumor inhomogeneities in a gel-like model of a human breast using 3-D pulsed digital holography.

PubMed

Hernández-Montes, Maria del Socorro; Pérez-López, Carlos; Santoyo, Fernando Mendoza

2007-01-01

3-D pulsed digital holography is a noninvasive optical method used to measure the depth position of breast tumor tissue immersed in a semisolid gel model. A master gel without inhomogeneities is set to resonate at an 810 Hz frequency; then, an identically prepared gel with an inhomogeneity is interrogated with the same resonant frequency in the original setup. Comparatively, and using only an out-of-plane sensitive setup, gel surface displacement can be measured, evidencing an internal inhomogeneity. However, the depth position cannot be measured accurately, since the out-of-plane component has the contribution of in-plane surface displacements. With the information gathered, three sensitivity vectors can be obtained to separate contributions from x, y, and z vibration displacement components, individual displacement maps for the three orthogonal axes can be built, and the inhomogeneity's depth position can be accurately measured. Then, the displacement normal to the gel surface is used to find the depth profile and its cross section. Results from the optical data obtained are compared and correlated to the inhomogeneity's physically measured position. Depth position is found with an error smaller than 1%. The inhomogeneity and its position within the gel can be accurately found, making the method a promising noninvasive alternative to study mammary tumors.

Comparative Skeletal Muscle Proteomics Using Two-Dimensional Gel Electrophoresis

PubMed Central

Murphy, Sandra; Dowling, Paul; Ohlendieck, Kay

2016-01-01

The pioneering work by Patrick H. O’Farrell established two-dimensional gel electrophoresis as one of the most important high-resolution protein separation techniques of modern biochemistry (Journal of Biological Chemistry 1975, 250, 4007–4021). The application of two-dimensional gel electrophoresis has played a key role in the systematic identification and detailed characterization of the protein constituents of skeletal muscles. Protein changes during myogenesis, muscle maturation, fibre type specification, physiological muscle adaptations and natural muscle aging were studied in depth by the original O’Farrell method or slightly modified gel electrophoretic techniques. Over the last 40 years, the combined usage of isoelectric focusing in the first dimension and sodium dodecyl sulfate polyacrylamide slab gel electrophoresis in the second dimension has been successfully employed in several hundred published studies on gel-based skeletal muscle biochemistry. This review focuses on normal and physiologically challenged skeletal muscle tissues and outlines key findings from mass spectrometry-based muscle proteomics, which was instrumental in the identification of several thousand individual protein isoforms following gel electrophoretic separation. These muscle-associated protein species belong to the diverse group of regulatory and contractile proteins of the acto-myosin apparatus that forms the sarcomere, cytoskeletal proteins, metabolic enzymes and transporters, signaling proteins, ion-handling proteins, molecular chaperones and extracellular matrix proteins. PMID:28248237

Repair of surgical wounds in rats using a 10% unripe Musa sapientum peel gel.

PubMed

Von Atzingen, Dênia Amélia Novato Castelli; Mendonça, Adriana Rodrigues dos Anjos; Mesquita Filho, Marcos; Alvarenga, Vinícius Alves; Assis, Vinícius Almeida; Penazzo, Afonso Esteves; Muzetti, Julio Henrique; Rezende, Thaisa Sousa

2015-09-01

To investigate the efficacy of a 10% gel of unripe banana (Musa sapientum) peel in treating surgical wounds in rats. A longitudinal, prospective, randomized triple-blind study was conducted with 60 Wistar rats (Rattus norvegicus albinus) weighing approximately 400g. The animals were randomly divided into: control group (treated with gel containing no active ingredient) and study group (treated with 10% gel of unripe banana peel). The gel was applied every three days to a 4x4-cm surgical wound created on the back of each animal (day 0) in both groups. Tissue samples were collected for histological analysis on days 14, 21 and 28. On day 14, more extensive vascular proliferation (p=0.023), presence of mononuclear cells (p=0.000), fibroblast proliferation (p=0.012), re-epithelialization (p=0.000), and decreased presence of polymorphonuclear cells (p=0.010) were observed in the study group than in controls. No significant between-group difference in the presence of polymorphonuclear cells was found on day 21. Fibroblast proliferation was significantly greater (p=0.006) in the study group than in the control group on day 28. The 10% gel of unripe banana peel showed anti-inflammatory activity and stimulated wound healing in rat skin when compared with a gel containing no active ingredient.

Diffusion and convection in collagen gels: implications for transport in the tumor interstitium.

PubMed Central

Ramanujan, Saroja; Pluen, Alain; McKee, Trevor D; Brown, Edward B; Boucher, Yves; Jain, Rakesh K

2002-01-01

Diffusion coefficients of tracer molecules in collagen type I gels prepared from 0-4.5% w/v solutions were measured by fluorescence recovery after photobleaching. When adjusted to account for in vivo tortuosity, diffusion coefficients in gels matched previous measurements in four human tumor xenografts with equivalent collagen concentrations. In contrast, hyaluronan solutions hindered diffusion to a lesser extent when prepared at concentrations equivalent to those reported in these tumors. Collagen permeability, determined from flow through gels under hydrostatic pressure, was compared with predictions obtained from application of the Brinkman effective medium model to diffusion data. Permeability predictions matched experimental results at low concentrations, but underestimated measured values at high concentrations. Permeability measurements in gels did not match previous measurements in tumors. Visualization of gels by transmission electron microscopy and light microscopy revealed networks of long collagen fibers at lower concentrations along with shorter fibers at high concentrations. Negligible assembly was detected in collagen solutions pregelation. However, diffusion was similarly hindered in pre and postgelation samples. Comparison of diffusion and convection data in these gels and tumors suggests that collagen may obstruct diffusion more than convection in tumors. These findings have significant implications for drug delivery in tumors and for tissue engineering applications. PMID:12202388

Reflective terahertz (THz) imaging: system calibration using hydration phantoms

NASA Astrophysics Data System (ADS)

Bajwa, Neha; Garritano, James; Lee, Yoon Kyung; Tewari, Priyamvada; Sung, Shijun; Maccabi, Ashkan; Nowroozi, Bryan; Babakhanian, Meghedi; Sanghvi, Sajan; Singh, Rahul; Grundfest, Warren; Taylor, Zachary

2013-02-01

Terahertz (THz) hydration sensing continues to gain traction in the medical imaging community due to its unparalleled sensitivity to tissue water content. Rapid and accurate detection of fluid shifts following induction of thermal skin burns as well as remote corneal hydration sensing have been previously demonstrated in vivo using reflective, pulsed THz imaging. The hydration contrast sensing capabilities of this technology were recently confirmed in a parallel 7 Tesla Magnetic Resonance (MR) imaging study, in which burn areas are associated with increases in local mobile water content. Successful clinical translation of THz sensing, however, still requires quantitative assessments of system performance measurements, specifically hydration concentration sensitivity, with tissue substitutes. This research aims to calibrate the sensitivity of a novel, reflective THz system to tissue water content through the use of hydration phantoms for quantitative comparisons of THz hydration imagery.Gelatin phantoms were identified as an appropriate tissue-mimicking model for reflective THz applications, and gel composition, comprising mixtures of water and protein, was varied between 83% to 95% hydration, a physiologically relevant range. A comparison of four series of gelatin phantom studies demonstrated a positive linear relationship between THz reflectivity and water concentration, with statistically significant hydration sensitivities (p < .01) ranging between 0.0209 - 0.038% (reflectivity: %hydration). The THz-phantom interaction is simulated with a three-layer model using the Transfer Matrix Method with agreement in hydration trends. Having demonstrated the ability to accurately and noninvasively measure water content in tissue equivalent targets with high sensitivity, reflective THz imaging is explored as a potential tool for early detection and intervention of corneal pathologies.

Soft particles at a fluid interface

NASA Astrophysics Data System (ADS)

Mehrabian, Hadi; Harting, Jens; Snoeijer, Jacco H.

2015-11-01

Particles added to a fluid interface can be used as a surface stabilizer in the food, oil and cosmetic industries. As an alternative to rigid particles, it is promising to consider highly deformable particles that can adapt their conformation at the interface. In this study, we compute the shapes of soft elastic particles using molecular dynamics simulations of a cross-linked polymer gel, complemented by continuum calculations based on the linear elasticity. It is shown that the particle shape is not only affected by the Young's modulus of the particle, but also strongly depends on whether the gel is partially or completely wetting the fluid interface. We find that the molecular simulations for the partially wetting case are very accurately described by the continuum theory. By contrast, when the gel is completely wetting the fluid interface the linear theory breaks down and we reveal that molecular details have a strong influence on the equilibrium shape.

Study of a two-bed silica gel-water adsorption chiller: performance analysis

NASA Astrophysics Data System (ADS)

Sah, Ramesh P.; Choudhury, Biplab; Das, Ranadip K.

2018-01-01

In this study, a lumped parameter simulation model has been developed for analysis of the thermal performance of a single-stage two-bed adsorption chiller. Since silica gel has low regeneration temperature and water has high latent heat of vaporisation, silica gel-water pair has been chosen as the working pair of the adsorption chiller. Low-grade waste heat or solar heat at around 70-80°C can be used to run this adsorption chiller. In this model, the effects of operating parameters on the performance of the chiller have been studied. The simulated results show that the cooling capacity of the chiller has an optimum value of 5.95 kW for a cycle time of 1600 s with the hot, cooling, and chilled water inlet temperatures at 85°C, 25°C, and 14°C, respectively. The present model can be utilised to investigate and optimise adsorption chillers.

Characterization of konjac glucomannan-gelatin IPN physical hydrogel scaffold

NASA Astrophysics Data System (ADS)

Chen, Xiliang; Chen, Qinghua; Yan, Tingting; Liu, Jinkun

2017-06-01

A novel IPN hydrogel scaffold is prepared by freeze-drying method, in which konjac galactomannan (KGM) and gelatin are physically crosslinked respectively. This scaffold is thermostable, and the structure of this scaffold is analysed by scanning electron microscope, Fourier transform infrared spectrum, and X-ray diffraction method. The FT-IR results show that hydrogen bonds are formed between KGM and gelatin molecules, which hinder the formation of their respective crosslinking. This is consistent with the XRD results that the crystallinity gets lower in the IPN gels compared with pure gelatin and KGM gels. The morphologies of freeze-dried hydrogels are observed by SEM and the mechanical properties of the scaffolds are tested to analyse the relationship between the structures and properties. Although this novel IPN hydrogel is physical gel, it shows rubber-like performance as chemical gels. And it is nontoxic, so it can be used as the scaffold for cartilage tissue engineering that embedded in human bodies.

In vitro and in vivo characteristics of a thermogelling rectal delivery system of etodolac.

PubMed

Barakat, Nahla S

2009-01-01

Rectal etodolac-Poloxamer gel systems composed of Poloxamer and bioadhesive polymers were developed and evaluated. Hydroxypropylmethyl cellulose, poly)vinyl) pyrrolidone, methyl cellulose, hydroxyethylcellulose, and carbopol were examined as mucoadhesive polymers. The characteristics of the rectal gels differed according to the properties of mucoadhesive polymers. The physicochemical properties such as gelation temperature, gel strength, and bioadhesive force of various formulations were investigated. The analysis of release mechanism showed that the release of etodolac was proportional to the square root of time, indicating that etodolac might be released from the suppositories by Fickian diffusion. The anti-inflammatory effect of etodolac-Poloxamer gel system was also studied in rats. Moreover, liquid suppository of etodolac did not cause any morphological damage to the rectal tissues. These results suggested that in situ gelling liquid suppository with etodolac and mucoadhesive polymer was a physically safe, convenient, and effective rectal dosage form for etodolac.

A Novel Adjuvant-Solution Layer Strategy for Improving the Efficacy of Cryosurgery.

PubMed

Ramajayam, K K; Kumar, A; Sarangi, S K; Thirugnanam, A

During cryosurgery, studies reported earlier suggest increased destruction inside the tumour due to adjuvants or the prevention of damage to neighbouring healthy tissue through different methods. This study advocates a novel strategy that increases the freezing inside agarose gel phantoms by addition of glycine and limits the freezing to the desired location using a perfluorohexane layer during cryosurgery. Cryosurgery of glycine containing gels is carried out with and without perfluorohexane layer and the thermal history is measured using K-type thermocouples connected to a data acquisition system. The presence of glycine causes increased freezing during cryosurgery with an ice ball depth of 16 mm, while with a perfluorohexane layer at this gel interface, this depth is 13 mm, indicating the ability of this layer to limit freezing. It can be concluded that glycine addition results in substantial temperature decrease and perfluorohexane layer insulates the glycine gel effectively during cryosurgical cooling.

The effect of polymer composition on the gelation behavior of PLGA-g-PEG biodegradable thermoreversible gels.

PubMed

Tarasevich, B J; Gutowska, A; Li, X S; Jeong, B-M

2009-04-01

Graft copolymers consisting of a poly(D,L-lactic acid-co-glycolic acid) backbone grafted with polyethylene glycol side chains were synthesized and formed thermoreversible gels in aqueous solutions that exhibited solution behavior at low temperature and sol-to-gel transitions at higher temperature. The composition of the polymer and relative amounts of polylactic acid, glycolic acid, and ethylene glycol were varied by controlling the precursor concentrations and reaction temperature. The gelation temperature could be systematically tailored from 15 to 34 degrees C by increasing the concentration of polyethylene glycol in the graft copolymer. The gelation temperature also depended on the polymer molecular weight and concentration. This work has importance for the development of water soluble gels with tailored compositions and gelation temperatures for use in tissue engineering and as injectable depots for drug delivery. Copyright 2008 Wiley Periodicals, Inc.

Repair of large full-thickness articular cartilage defects in the rabbit: the effects of joint distraction and autologous bone-marrow-derived mesenchymal cell transplantation.

PubMed

Yanai, T; Ishii, T; Chang, F; Ochiai, N

2005-05-01

We produced large full-thickness articular cartilage defects in 33 rabbits in order to evaluate the effect of joint distraction and autologous culture-expanded bone-marrow-derived mesenchymal cell transplantation (ACBMT) at 12 weeks. After fixing the knee on a hinged external fixator, we resected the entire surface of the tibial plateau. We studied three groups: 1) with and without joint distraction; 2) with joint distraction and collagen gel, and 3) with joint distraction and ACBMT and collagen gel. The histological scores were significantly higher in the groups with ACBMT collagen gel (p < 0.05). The area of regenerated soft tissue was smaller in the group allowed to bear weight (p < 0.05). These findings suggest that the repair of large defects of cartilage can be enhanced by joint distraction, collagen gel and ACBMT.

Design and validation of a multiplexed low coherence interferometry instrument for in vivo clinical measurement of microbicide gel thickness distribution

PubMed Central

Drake, Tyler K.; DeSoto, Michael G.; Peters, Jennifer J.; Henderson, Marcus H.; Murtha, Amy P.; Katz, David F.; Wax, Adam

2011-01-01

We present a multiplexed, Fourier-domain low coherence interferometry (mLCI) instrument for in vivo measurement of intravaginal microbicide gel coating thickness distribution over the surface of the vaginal epithelium. The mLCI instrument uses multiple delivery fibers to acquire depth resolved reflection profiles across large scanned tissue areas. Here mLCI has been adapted into an endoscopic system with a custom imaging module for simultaneous, co-registered measurements with fluorimetric scans of the same surface. The resolution, optical signal-to-noise, and cross-talk of the mLCI instrument are characterized to evaluate performance. Validation measurements of gel thickness are made using a calibration socket. Initial results from a clinical study are presented to show the in vivo capability of the dual-modality system for assessing the distribution of microbicide gel vehicles in the lower human female reproductive tract. PMID:22025989