Department of Developmental BioEngineering, Faculty of Science and Technology, Technical Medical Centre, University of Twente, Enschede, The Netherlands.
Department of Cell Biology - Inspired Tissue Engineering (cBITE), MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.
J Biomed Mater Res B Appl Biomater. 2021 Jan;109(1):117-127. doi: 10.1002/jbm.b.34686. Epub 2020 Jul 16.
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.
为了有效地应用微孔阵列细胞输送装置,必须根据其预期用途和植入位置来调整其生物降解率。本研究比较了两种具有不同降解特性的微孔阵列装置,一种适用于缓慢降解情况下可回收系统的制造,另一种适用于使用快速降解聚合物进行广泛重塑的细胞输送系统。聚乙二醇-聚对苯二甲酸丁二醇酯(PEOT-PBT)和聚(酯-氨酯)的薄膜在不同 pH 值的 PBS 中孵育 34 周,评估了其体外降解曲线。PEOT-PBT 薄膜随时间表现出最小的体外降解,而聚(酯-氨酯)薄膜随时间表现出广泛的降解和碎片化。随后,从这些聚合物中制造了微孔阵列细胞输送装置,并将其腹膜内植入 Albino Oxford 大鼠中,以在 12 周的时间内研究其生物相容性。PEOT-PBT 植入物能够随时间维持微孔结构。植入物引发了异物反应,导致多层纤维化,与周围组织整合。聚(酯-氨酯)植入物随时间显示出微孔结构的丧失,以及纤维化反应,直到开始碎片化,至少在植入后 4 周。得出的结论是,PEOT-PBT 植入物可用作可回收细胞输送装置,而聚(酯-氨酯)植入物可用作需要在 4-12 周内重塑的细胞输送装置。