RESUMEN
To effectively apply microwell array cell delivery devices their biodegradation rate must be tailored towards their intended use and implantation location. Two microwell array devices with distinct degradation profiles, either suitable for the fabrication of retrievable systems in the case of slow degradation, or cell delivery systems capable of extensive remodeling using a fast degrading polymer, were compared in this study. Thin films of a poly(ethylene glycol)-poly(butylene terephthalate) (PEOT-PBT) and a poly(ester urethane) were evaluated for their in vitro degradation profiles over 34 weeks incubation in PBS at different pH values. The PEOT-PBT films showed minimal in vitro degradation over time, while the poly(ester urethane) films showed extensive degradation and fragmentation over time. Subsequently, microwell array cell delivery devices were fabricated from these polymers and intraperitoneally implanted in Albino Oxford rats to study their biocompatibility over a 12-week period. The PEOT-PBT implants shown to be capable to maintain the microwell structure over time. Implants provoked a foreign body response resulting in multilayer fibrosis that integrated into the surrounding tissue. The poly(ester urethane) implants showed a loss of the microwell structures over time, as well as a fibrotic response until the onset of fragmentation, at least 4 weeks post implantation. It was concluded that the PEOT-PBT implants could be used as retrievable cell delivery devices while the poly(ester urethane) implants could be used for cell delivery devices that require remodeling within a 4-12 week period.
Asunto(s)
Materiales Biocompatibles/química , Poliésteres/química , Polietilenglicoles/química , Poliuretanos/química , Andamios del Tejido/química , Animales , Biodegradación Ambiental , Humanos , Técnicas In Vitro , Fenómenos Mecánicos , Pruebas Mecánicas , Modelos Animales , Tereftalatos Polietilenos/química , Prótesis e Implantes , Ratas , Regeneración , Resistencia a la Tracción , Ingeniería de TejidosRESUMEN
IMPACT STATEMENT: This research deals with finding a proper bioengineering strategy to improve the outcome of islets transplantation for treatment of type 1 diabetes. It is focused on the mimicking of islet extracellular matrix niche in microwell islet delivery devices to improve their endocrine function.
Asunto(s)
Colágeno Tipo IV/metabolismo , Matriz Extracelular/metabolismo , Glucosa/farmacología , Secreción de Insulina/efectos de los fármacos , Islotes Pancreáticos/citología , Laminina/metabolismo , Andamios del Tejido , Anciano , Bioingeniería , Células Cultivadas , Colágeno Tipo IV/química , Matriz Extracelular/química , Femenino , Humanos , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Laminina/química , Masculino , Poliésteres/química , Poliésteres/metabolismo , Poliuretanos/química , Poliuretanos/metabolismo , Edulcorantes/farmacologíaRESUMEN
IMPACT STATEMENT: This research deals with finding a proper bioengineering strategy for the creation of improved ß-cell replacement therapy in type 1 diabetes. It specifically deals with the microenvironment of ß-cells and its relationship to their endocrine function.