Biomimetic artificial islet model with vascularized microcapsule structures for durable glycemic control

Abstract

Abstract 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.