1 Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, People’s Republic of China
2 Institute of Glucose and Lipid Metabolism, Southeast University, Nanjing 210009, People’s Republic of China
3 Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, and the Shanghai Key Laboratory of Medical Epigenetics, The International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People’s Republic of China
4 Department of Clinical Laboratory, Nanjing Drum Tower Hospital, The Affiliated of Medical School, Nanjing University, Nanjing 210008, People’s Republic of China
Funds:
This work was supported by National Natural Science Foundation Major International (Regional) Joint Research Program (82320108003), National Natural Science Foundation (82170845, 82000740, 81970717), the Key Research & Development Program (No. BE2022853) and Medical Key Discipline (ZDXK202203) of Jiangsu Province.
Islet transplantation is a promising strategy for diabetes mellitus treatment as it can recapitulate endogenous insulin secretion and provide long-term glycemic control. Islet models constructed in biomaterial scaffolds that reproduce biological characteristics of native islets is a feasible option to circumvent the dilemma of donor shortage and the requirement of chronic immunosuppression. Herein, we developed bioinspired artificial microcapsule-based islet models with microvessels for glycemic control using microfluidic electrospray strategy. Microfluidic electrospray can generate uniform hydrogel microcapsules with core-shell structure for encapsulating islet cells. The cell-laden microcapsules enabled the efficient transportation of nutrient, oxygen, and insulin; as well as the incorporation with microvessels for prompting glucose responsiveness and molecular exchange. We demonstrated by in vivo experiments that the blood glucose, food intake, and body weight of diabetic mouse models were alleviated, and the glucose tolerance was promoted after the engraftment of islet microcapsules. We further demonstrated the improved functionality of transplanted islet model in insulin secretion, immune escape, and microcirculation using standard histological and molecular analysis. These results indicated that the microcapsules with microvessels are promising artificial islet models and are valuable for treating diabetes.