Biomimetic zona pellucida-encapsulated islets for sustained glycaemic control in immunocompetent mice

Islet transplantation is a promising therapy for treating type 1 diabetes. Thin capsules, although offering numerous advantages over thicker ones in islet transplantation, pose persistent challenges for ensuring long-term cell protection. Here we show a biomimetic approach for cell protection using thin capsules, inspired by the biological development of the zona pellucida. A thin 20-μm hydrogel capsule is spontaneously generated on the cell surface with 100% encapsulation efficiency through aptamer-directed molecular recognition, crosslinking and hardening. The entire encapsulation process takes place droplet-free and stress-free under physiological conditions, without exposure to harsh factors or any loss of cellular viability or function. Immunocompetent diabetic mice receiving encapsulated allogeneic islets achieved normoglycaemia, with most sustaining it for more than 100 days.