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Cameron A. Best - One of the best experts on this subject based on the ideXlab platform.
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differential outcomes of venous and arterial tissue engineered vascular grafts highlight the importance of coupling long term implantation studies with computational modeling
Acta Biomaterialia, 2019Co-Authors: Mark W. Maxfield, Cameron A. Best, Ethan W Dean, Kevin A Rocco, Hirotsugu Kurobe, Jason M Szafron, Jacob C Zbinden, Shuhei TaraAbstract:Abstract Electrospinning is commonly used to generate Polymeric scaffolds for tissue engineering. Using this approach, we developed a small-diameter tissue engineered vascular graft (TEVG) composed of poly-e-caprolactone-co- l -lactic acid (PCLA) fibers and longitudinally assessed its performance within both the venous and arterial circulations of immunodeficient (SCID/bg) mice. Based on in vitro analysis demonstrating complete loss of graft strength by 12 weeks, we evaluated neovessel formation in vivo over 6-, 12- and 24-week periods. Mid-term observations indicated physiologic graft function, characterized by 100% patency and luminal matching with adjoining native vessel in both the venous and arterial circulations. An active and robust remodeling process was characterized by a confluent endothelial cell monolayer, macrophage infiltrate, and extracellular matrix deposition and remodeling. Long-term follow-up of venous TEVGs at 24 weeks revealed viable neovessel formation beyond graft Degradation when implanted in this high flow, low-pressure environment. Arterial TEVGs experienced catastrophic graft failure due to aneurysmal dilatation and rupture after 14 weeks. Scaffold parameters such as porosity, fiber diameter, and Degradation rate informed a previously described computational model of vascular growth and remodeling, and simulations predicted the gross differential performance of the venous and arterial TEVGs over the 24-week time course. Taken together, these results highlight the requirement for in vivo implantation studies to extend past the critical time period of Polymer Degradation, the importance of differential neotissue deposition relative to the mechanical (pressure) environment, and further support the utility of predictive modeling in the design, use, and evaluation of TEVGs in vivo. Statement of Significance Herein, we apply a biodegradable electrospun vascular graft to the arterial and venous circulations of the mouse and follow recipients beyond the point of Polymer Degradation. While venous implants formed viable neovessels, arterial grafts experienced catastrophic rupture due to aneurysmal dilation. We then inform a previously developed computational model of tissue engineered vascular graft growth and remodeling with parameters specific to the electrospun scaffolds utilized in this study. Remarkably, model simulations predict the differential performance of the venous and arterial constructs over 24 weeks. We conclude that computational simulations should inform the rational selection of scaffold parameters to fabricate tissue engineered vascular grafts that must be followed in vivo over time courses extending beyond Polymer Degradation.
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differential outcomes of venous and arterial tissue engineered vascular grafts highlight the importance of coupling long term implantation studies with computational modeling
Acta Biomaterialia, 2019Co-Authors: Mark W. Maxfield, Cameron A. Best, Ethan W Dean, Kevin A Rocco, Hirotsugu Kurobe, Jason M Szafron, Jacob Zbinden, Shuhei TaraAbstract:Abstract Electrospinning is commonly used to generate Polymeric scaffolds for tissue engineering. Using this approach, we developed a small-diameter tissue engineered vascular graft (TEVG) composed of poly-e-caprolactone-co-L-lactic acid (PCLA) fibers and longitudinally assessed its performance within both the venous and arterial circulations of immunodeficient (SCID/bg) mice. Based on in vitro analysis demonstrating complete loss of graft strength by 12 weeks, we evaluated neovessel formation in vivo over 6-, 12- and 24-week periods. Mid-term observations indicated excellent physiologic graft function, characterized by 100% patency and excellent luminal matching with adjoining native vessel in both the venous and arterial circulations. An active and robust remodeling process was characterized by a confluent endothelial cell monolayer, macrophage infiltrate, and extracellular matrix deposition and remodeling. Long-term follow-up of venous TEVGs at 24 weeks revealed viable neovessel formation beyond graft Degradation when implanted in this high flow, low-pressure environment. Arterial TEVGs experienced catastrophic graft failure due to aneurysmal dilatation and rupture after 14 weeks. Scaffold parameters such as porosity, fiber diameter, and Degradation rate informed a previously described computational model of vascular growth and remodeling, and simulations predicted the gross differential performance of the venous and arterial TEVGs over the 24-week time course. Taken together, these results highlight the requirement for in vivo implantation studies to extend past the critical time period of Polymer Degradation, the importance of differential neotissue deposition relative to the mechanical (pressure) environment, and further support the utility of predictive modeling in the design, use, and evaluation of TEVGs in vivo . Statement of Significance Herein, we apply a biodegradable electrospun vascular graft to the arterial and venous circulations of the mouse and follow recipients beyond the point of Polymer Degradation. While venous implants formed viable neovessels, arterial grafts experienced catastrophic rupture due to aneurysmal dilation. We then inform a previously developed computational model of tissue engineered vascular graft growth and remodeling with parameters specific to the electrospun scaffolds utilized in this study. Remarkably, model simulations predict the differential performance of the venous and arterial constructs over 24 weeks. We conclude that computational simulations should inform the rational selection of scaffold parameters to fabricate tissue engineered vascular grafts that must be followed in vivo over time courses extending beyond Polymer Degradation.
Shuhei Tara - One of the best experts on this subject based on the ideXlab platform.
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differential outcomes of venous and arterial tissue engineered vascular grafts highlight the importance of coupling long term implantation studies with computational modeling
Acta Biomaterialia, 2019Co-Authors: Mark W. Maxfield, Cameron A. Best, Ethan W Dean, Kevin A Rocco, Hirotsugu Kurobe, Jason M Szafron, Jacob C Zbinden, Shuhei TaraAbstract:Abstract Electrospinning is commonly used to generate Polymeric scaffolds for tissue engineering. Using this approach, we developed a small-diameter tissue engineered vascular graft (TEVG) composed of poly-e-caprolactone-co- l -lactic acid (PCLA) fibers and longitudinally assessed its performance within both the venous and arterial circulations of immunodeficient (SCID/bg) mice. Based on in vitro analysis demonstrating complete loss of graft strength by 12 weeks, we evaluated neovessel formation in vivo over 6-, 12- and 24-week periods. Mid-term observations indicated physiologic graft function, characterized by 100% patency and luminal matching with adjoining native vessel in both the venous and arterial circulations. An active and robust remodeling process was characterized by a confluent endothelial cell monolayer, macrophage infiltrate, and extracellular matrix deposition and remodeling. Long-term follow-up of venous TEVGs at 24 weeks revealed viable neovessel formation beyond graft Degradation when implanted in this high flow, low-pressure environment. Arterial TEVGs experienced catastrophic graft failure due to aneurysmal dilatation and rupture after 14 weeks. Scaffold parameters such as porosity, fiber diameter, and Degradation rate informed a previously described computational model of vascular growth and remodeling, and simulations predicted the gross differential performance of the venous and arterial TEVGs over the 24-week time course. Taken together, these results highlight the requirement for in vivo implantation studies to extend past the critical time period of Polymer Degradation, the importance of differential neotissue deposition relative to the mechanical (pressure) environment, and further support the utility of predictive modeling in the design, use, and evaluation of TEVGs in vivo. Statement of Significance Herein, we apply a biodegradable electrospun vascular graft to the arterial and venous circulations of the mouse and follow recipients beyond the point of Polymer Degradation. While venous implants formed viable neovessels, arterial grafts experienced catastrophic rupture due to aneurysmal dilation. We then inform a previously developed computational model of tissue engineered vascular graft growth and remodeling with parameters specific to the electrospun scaffolds utilized in this study. Remarkably, model simulations predict the differential performance of the venous and arterial constructs over 24 weeks. We conclude that computational simulations should inform the rational selection of scaffold parameters to fabricate tissue engineered vascular grafts that must be followed in vivo over time courses extending beyond Polymer Degradation.
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differential outcomes of venous and arterial tissue engineered vascular grafts highlight the importance of coupling long term implantation studies with computational modeling
Acta Biomaterialia, 2019Co-Authors: Mark W. Maxfield, Cameron A. Best, Ethan W Dean, Kevin A Rocco, Hirotsugu Kurobe, Jason M Szafron, Jacob Zbinden, Shuhei TaraAbstract:Abstract Electrospinning is commonly used to generate Polymeric scaffolds for tissue engineering. Using this approach, we developed a small-diameter tissue engineered vascular graft (TEVG) composed of poly-e-caprolactone-co-L-lactic acid (PCLA) fibers and longitudinally assessed its performance within both the venous and arterial circulations of immunodeficient (SCID/bg) mice. Based on in vitro analysis demonstrating complete loss of graft strength by 12 weeks, we evaluated neovessel formation in vivo over 6-, 12- and 24-week periods. Mid-term observations indicated excellent physiologic graft function, characterized by 100% patency and excellent luminal matching with adjoining native vessel in both the venous and arterial circulations. An active and robust remodeling process was characterized by a confluent endothelial cell monolayer, macrophage infiltrate, and extracellular matrix deposition and remodeling. Long-term follow-up of venous TEVGs at 24 weeks revealed viable neovessel formation beyond graft Degradation when implanted in this high flow, low-pressure environment. Arterial TEVGs experienced catastrophic graft failure due to aneurysmal dilatation and rupture after 14 weeks. Scaffold parameters such as porosity, fiber diameter, and Degradation rate informed a previously described computational model of vascular growth and remodeling, and simulations predicted the gross differential performance of the venous and arterial TEVGs over the 24-week time course. Taken together, these results highlight the requirement for in vivo implantation studies to extend past the critical time period of Polymer Degradation, the importance of differential neotissue deposition relative to the mechanical (pressure) environment, and further support the utility of predictive modeling in the design, use, and evaluation of TEVGs in vivo . Statement of Significance Herein, we apply a biodegradable electrospun vascular graft to the arterial and venous circulations of the mouse and follow recipients beyond the point of Polymer Degradation. While venous implants formed viable neovessels, arterial grafts experienced catastrophic rupture due to aneurysmal dilation. We then inform a previously developed computational model of tissue engineered vascular graft growth and remodeling with parameters specific to the electrospun scaffolds utilized in this study. Remarkably, model simulations predict the differential performance of the venous and arterial constructs over 24 weeks. We conclude that computational simulations should inform the rational selection of scaffold parameters to fabricate tissue engineered vascular grafts that must be followed in vivo over time courses extending beyond Polymer Degradation.
Klauspeter Schmitz - One of the best experts on this subject based on the ideXlab platform.
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biodegradable Polymeric coatings on cochlear implant surfaces and their influence on spiral ganglion cell survival
Journal of Biomedical Materials Research Part B, 2014Co-Authors: P Ceschi, A Bohl, Katrin Sternberg, A Neumeister, Volkmar Senz, Klauspeter Schmitz, M Kietzmann, Verena Scheper, Thomas Lenarz, Timo StoverAbstract:To improve the electrode–nerve interface of cochlear implants (CI), the role of poly(L-lactide) (PLLA) and poly(4-hydroxybutyrate) (P(4HB)) as potential coating matrices for CI was assessed both in vitro and in vivo in terms of Degradation behavior and effects on spiral ganglion neurons, the main target of the electrical stimulation with a CI. Growth rates of fibroblasts on the Polymers were investigated and a direct-contact test with freshly isolated spiral ganglion cells (SGC) was performed. In addition, the effects of the Polymer Degradation inside the inner ear were evaluated in vivo. The Polymer Degradation was assessed by use of scanning electron microscopy in combination with an energy-dispersive X-ray analysis. In vitro, no influence of the Polymers was detected on fibroblasts' viability and on SGC survival rate. In vivo, SGC density was decreased only 6 months after implantation in the basal and middle turns of the cochlea in comparison to normal-hearing animals but not between implanted groups (coated or uncoated). The analysis of the electrode models showed that in vivo P(4HB) is characterized by a gradual Degradation completed after 6 months; whereas, the PLLA coatings burst along their longitudinal axis but showed only little Degradation within the same time frame. In conclusion, both Polymers seem to justify further evaluation as possible coating for CI electrodes. Of the two options, due to its excellent coating adhesion/stability and optimal Degradation behavior, P(4HB) may prove to be the more promising biodegradable Polymer for designing a drug delivery system from the surface of CI electrodes. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1255–1267, 2014.
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in vitro study of drug eluting stent coatings based on poly l lactide incorporating cyclosporine a drug release Polymer Degradation and mechanical integrity
Journal of Materials Science: Materials in Medicine, 2007Co-Authors: Katrin Sternberg, Sven Kramer, Claudia Nischan, Niels Grabow, Thomas Langer, G Hennighausen, Klauspeter SchmitzAbstract:In this study, absorbable Polymer stent coatings for localized drug delivery based on poly(l-lactide) (PLLA) and cyclosporine A (CsA) were developed and tested in vitro. Metallic stents were coated with different compositions of PLLA/CsA (70/30, 60/40, 50/50% w/w) and β-sterilized. The specimens were used to assess the drug release kinetics with HPLC. Sterilization influenced Polymer Degradation was measured with GPC. Mechanical integrity of the stent coatings was studied with SEM. The interconnection of the coated stents with a balloon-catheter was characterized by the measurement of stent dislodgment force. A migration assay was used to determine the inhibitory effect of the model drug CsA on smooth muscle cell (SMC) migration. The release of CsA was established over time periods up to 24 days in sodium chloride solution and in porcine blood plasma. An inhibition of SMC migration (max. 26–33%) was found for CsA concentrations of 4 × 10−5 to 4 × 10−7 mol/l. Marked molecular weight reduction (70–80%) of the PLLA matrix occurred after β-sterilization. We also observed a substantial decrease of in vitro Degradation time. The maintenance of the mechanical integrity of the Polymer coating during crimping and dilation of the specimens could be verified, and a sufficient stent dislodgment force of 0.8–0.9 N was measured.
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in vitro study of drug eluting stent coatings based on poly l lactide incorporating cyclosporine a drug release Polymer Degradation and mechanical integrity
Journal of Materials Science: Materials in Medicine, 2007Co-Authors: Katrin Sternberg, Sven Kramer, Claudia Nischan, Niels Grabow, Thomas Langer, G Hennighausen, Klauspeter SchmitzAbstract:In this study, absorbable Polymer stent coatings for localized drug delivery based on poly(L-lactide) (PLLA) and cyclosporine A (CsA) were developed and tested in vitro. Metallic stents were coated with different compositions of PLLA/CsA (70/30, 60/40, 50/50% w/w) and beta-sterilized. The specimens were used to assess the drug release kinetics with HPLC. Sterilization influenced Polymer Degradation was measured with GPC. Mechanical integrity of the stent coatings was studied with SEM. The interconnection of the coated stents with a balloon-catheter was characterized by the measurement of stent dislodgment force. A migration assay was used to determine the inhibitory effect of the model drug CsA on smooth muscle cell (SMC) migration. The release of CsA was established over time periods up to 24 days in sodium chloride solution and in porcine blood plasma. An inhibition of SMC migration (max. 26-33%) was found for CsA concentrations of 4 x 10(-5) to 4 x 10(-7) mol/l. Marked molecular weight reduction (70-80%) of the PLLA matrix occurred after beta-sterilization. We also observed a substantial decrease of in vitro Degradation time. The maintenance of the mechanical integrity of the Polymer coating during crimping and dilation of the specimens could be verified, and a sufficient stent dislodgment force of 0.8-0.9 N was measured.
Justin Hanes - One of the best experts on this subject based on the ideXlab platform.
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synthesis and characterization of peg based ether anhydride terPolymers novel Polymers for controlled drug delivery
Macromolecules, 2004Co-Authors: Jennifer Fiegel, Justin HanesAbstract:A series of biodegradable poly(ether−anhydrides) composed of poly(ethylene glycol) (PEG), sebacic acid (SA), and 1,3-bis(carboxyphenoxy)propane (CPP) were synthesized for use in advanced drug delivery applications. PEG (Mn = 8000 Da) was incorporated to reduce Polymeric particle clearance rates by the immune system and improve particle resuspension and aerosolization efficiencies. CPP and SA were selected to render the Polymer insoluble in water and allow control over Polymer Degradation and drug release rates. In particular, CPP incorporation caused a significant decrease in Polymer Degradation rates and release kinetics of model drugs incorporated into poly(ether−anhydride) microparticles. TerPolymers were synthesized with weight-average molecular weights over 65 kDa without catalyst. The first thermal transition in Polymers containing ≤10 wt % PEG was ∼80 °C (well above typical storage conditions and body temperature), and there was no evidence of a glass transition (−100 to 200 °C). Several of the pol...
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a theoretical model of erosion and macromolecular drug release from biodegrading microspheres
Journal of Pharmaceutical Sciences, 1997Co-Authors: Richard P Batycky, Robert Langer, Justin Hanes, David A EdwardsAbstract:A theoretical model is outlined for predicting the time evolution of total mass, mean molecular weight, and drug release for the case of a spherical bulk-eroding microsphere, prepared by a double emulsification procedure and containing a hydrophilic drug, such as a protein or peptide. Explicit analytical formulae are derived for calculating the time evolution of measurable macroscopic characteristics, such as drug release or mean molecular weight. Microsphere hydration, Polymer erosion, and drug release phases are each described. Results indicate that Polymer Degradation by only random-chain scission or only end scission (or unzipping) cannot explain experimentally observed kinetics of particle mass loss and molecular weight change; thus, a combined model (incorporating both random and end scission) is proposed. A general methodology for determining the microscopic transport coefficients (such as Polymer Degradation rate constant or drug diffusion coefficient) from erosion and release data is outlined. This paradigm is applied to the specific case of 50:50 poly(D,L-lactic-co-glycolic acid (PLGA) microspheres encapsulating glycoprotein 120 (gp 120), a candidate AIDS vaccine. Predictions permit comparisons with experimental data for mean weight- and number-averaged molecular weights, as well as for mass loss and protein release. Other comparisons are made with data appearing in the literature for release of tetanus toxoid from PLA and PLGA microspheres of variable molecular weight. Agreement between theory and experiment is observed.
Katrin Sternberg - One of the best experts on this subject based on the ideXlab platform.
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biodegradable Polymeric coatings on cochlear implant surfaces and their influence on spiral ganglion cell survival
Journal of Biomedical Materials Research Part B, 2014Co-Authors: P Ceschi, A Bohl, Katrin Sternberg, A Neumeister, Volkmar Senz, Klauspeter Schmitz, M Kietzmann, Verena Scheper, Thomas Lenarz, Timo StoverAbstract:To improve the electrode–nerve interface of cochlear implants (CI), the role of poly(L-lactide) (PLLA) and poly(4-hydroxybutyrate) (P(4HB)) as potential coating matrices for CI was assessed both in vitro and in vivo in terms of Degradation behavior and effects on spiral ganglion neurons, the main target of the electrical stimulation with a CI. Growth rates of fibroblasts on the Polymers were investigated and a direct-contact test with freshly isolated spiral ganglion cells (SGC) was performed. In addition, the effects of the Polymer Degradation inside the inner ear were evaluated in vivo. The Polymer Degradation was assessed by use of scanning electron microscopy in combination with an energy-dispersive X-ray analysis. In vitro, no influence of the Polymers was detected on fibroblasts' viability and on SGC survival rate. In vivo, SGC density was decreased only 6 months after implantation in the basal and middle turns of the cochlea in comparison to normal-hearing animals but not between implanted groups (coated or uncoated). The analysis of the electrode models showed that in vivo P(4HB) is characterized by a gradual Degradation completed after 6 months; whereas, the PLLA coatings burst along their longitudinal axis but showed only little Degradation within the same time frame. In conclusion, both Polymers seem to justify further evaluation as possible coating for CI electrodes. Of the two options, due to its excellent coating adhesion/stability and optimal Degradation behavior, P(4HB) may prove to be the more promising biodegradable Polymer for designing a drug delivery system from the surface of CI electrodes. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1255–1267, 2014.
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in vitro study of drug eluting stent coatings based on poly l lactide incorporating cyclosporine a drug release Polymer Degradation and mechanical integrity
Journal of Materials Science: Materials in Medicine, 2007Co-Authors: Katrin Sternberg, Sven Kramer, Claudia Nischan, Niels Grabow, Thomas Langer, G Hennighausen, Klauspeter SchmitzAbstract:In this study, absorbable Polymer stent coatings for localized drug delivery based on poly(l-lactide) (PLLA) and cyclosporine A (CsA) were developed and tested in vitro. Metallic stents were coated with different compositions of PLLA/CsA (70/30, 60/40, 50/50% w/w) and β-sterilized. The specimens were used to assess the drug release kinetics with HPLC. Sterilization influenced Polymer Degradation was measured with GPC. Mechanical integrity of the stent coatings was studied with SEM. The interconnection of the coated stents with a balloon-catheter was characterized by the measurement of stent dislodgment force. A migration assay was used to determine the inhibitory effect of the model drug CsA on smooth muscle cell (SMC) migration. The release of CsA was established over time periods up to 24 days in sodium chloride solution and in porcine blood plasma. An inhibition of SMC migration (max. 26–33%) was found for CsA concentrations of 4 × 10−5 to 4 × 10−7 mol/l. Marked molecular weight reduction (70–80%) of the PLLA matrix occurred after β-sterilization. We also observed a substantial decrease of in vitro Degradation time. The maintenance of the mechanical integrity of the Polymer coating during crimping and dilation of the specimens could be verified, and a sufficient stent dislodgment force of 0.8–0.9 N was measured.
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in vitro study of drug eluting stent coatings based on poly l lactide incorporating cyclosporine a drug release Polymer Degradation and mechanical integrity
Journal of Materials Science: Materials in Medicine, 2007Co-Authors: Katrin Sternberg, Sven Kramer, Claudia Nischan, Niels Grabow, Thomas Langer, G Hennighausen, Klauspeter SchmitzAbstract:In this study, absorbable Polymer stent coatings for localized drug delivery based on poly(L-lactide) (PLLA) and cyclosporine A (CsA) were developed and tested in vitro. Metallic stents were coated with different compositions of PLLA/CsA (70/30, 60/40, 50/50% w/w) and beta-sterilized. The specimens were used to assess the drug release kinetics with HPLC. Sterilization influenced Polymer Degradation was measured with GPC. Mechanical integrity of the stent coatings was studied with SEM. The interconnection of the coated stents with a balloon-catheter was characterized by the measurement of stent dislodgment force. A migration assay was used to determine the inhibitory effect of the model drug CsA on smooth muscle cell (SMC) migration. The release of CsA was established over time periods up to 24 days in sodium chloride solution and in porcine blood plasma. An inhibition of SMC migration (max. 26-33%) was found for CsA concentrations of 4 x 10(-5) to 4 x 10(-7) mol/l. Marked molecular weight reduction (70-80%) of the PLLA matrix occurred after beta-sterilization. We also observed a substantial decrease of in vitro Degradation time. The maintenance of the mechanical integrity of the Polymer coating during crimping and dilation of the specimens could be verified, and a sufficient stent dislodgment force of 0.8-0.9 N was measured.