A bio-inspired injectable hydrogel as a cell platform for real-time glycaemic regulation

Zhang, Y (Zhang, Yu)^{[ 1,2 ]} ; Yang, J (Yang, Jun)^{[ 1,2 ]} ; Zhang, J (Zhang, Jun)^{[ 1,2 ]} ; Li, SW (Li, Shuangwen)^{[ 1,2 ]} ; Zheng, LS (Zheng, Lisi)^{[ 1,2 ]} ; Zhang, YL (Zhang, Yanlong)^{[ 3 ]} ; Meng, HP (Meng, Huipeng)^{[ 3 ]} ; Zhang, XG (Zhang, Xinge)^{[ 4 ]} ; Wu, ZM (Wu, Zhongming)^{[ 1,2 ]}

JOURNAL OF MATERIALS CHEMISTRY B, 2020, 8(21): 4627-4641

DOI: 10.1039/d0tb00561d

摘要

Frequent subcutaneous insulin injection and islet transplantation are promising therapeutic options for type 1 diabetes mellitus. However, poor patient compliance, insufficient appropriate islet beta 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 beta 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(6)-Dex-NIPAM(64)) 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.