NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China.
J Mater Chem B. 2020 Jun 7;8(21):4627-4641. doi: 10.1039/d0tb00561d. Epub 2020 May 6.
Frequent subcutaneous insulin injection and islet transplantation are promising therapeutic options for type 1 diabetes mellitus. However, poor patient compliance, insufficient appropriate islet β cell donors and body immune rejection limit their clinical applications. The design of a platform capable of encapsulating insulin-secreting cells and achieving real-time blood glucose regulation, is a so far unmet need. Herein, inspired by the natural processes of regulating blood glucose in pancreatic islet β cells, we developed a poly(N-isopropylacrylamide-co-dextran-maleic acid-co-3-acrylamidophenylboronic acid) (P(AAPBA-Dex-NIPAM)) hydrogel as a cell platform with glucose responsiveness and thermo-responsiveness for the therapy of diabetes. This platform showed good biocompatibility against insulin-secreting cells and presented glucose-dependent insulin release behaviour. The bioinspired P(AAPBA-Dex-NIPAM) hydrogel had a positive effect on real-time glycaemic regulation, as observed by intraperitoneal glucose tolerance tests. The non-fasting blood glucose of diabetic rats was restored to a normal level during the period of treatment. Additionally, the inflammatory response did not occur after administration of the platform. Collectively, we expected that the bio-mimetic platform combined with an insulin-secreting capability could be a new diabetic treatment strategy.
频繁的皮下胰岛素注射和胰岛移植是 1 型糖尿病有前途的治疗选择。然而，较差的患者依从性、足够数量的合适胰岛 β 细胞供体和机体免疫排斥限制了它们的临床应用。设计一个能够包封胰岛素分泌细胞并实现实时血糖调节的平台，是目前尚未满足的需求。受胰岛 β 细胞调节血糖的自然过程的启发，我们开发了一种聚（N-异丙基丙烯酰胺-co-葡聚糖-马来酸-co-3-丙烯酰胺基苯硼酸）（P（AAPBA-Dex-NIPAM））水凝胶作为具有葡萄糖响应性和温敏性的细胞平台，用于糖尿病治疗。该平台对胰岛素分泌细胞表现出良好的生物相容性，并表现出葡萄糖依赖性胰岛素释放行为。通过腹腔葡萄糖耐量试验观察到，生物仿生 P（AAPBA-Dex-NIPAM）水凝胶对实时血糖调节有积极作用。糖尿病大鼠的非禁食血糖在治疗期间恢复到正常水平。此外，平台给药后没有发生炎症反应。总之，我们期望这种具有仿生功能的平台与胰岛素分泌能力相结合，可以成为一种新的糖尿病治疗策略。
