A Retrievable and Non‐Swelling Zwitterionic Hydrogel With Attenuated Free Radical Damage for Long‐Term Immunoprotective Islet Encapsulation

Islet encapsulation transplantation holds great promise for restoring endogenous insulin production in type 1 diabetes patients. However, current hydrogel systems face considerable challenges, including radical‐induced islet damage during gelation, mechanical stress injury from excessive swelling, and inherent foreign body response. Herein, a retrievable zwitterionic hydrogel is developed via photoinitiated copolymerization of an acrylate‐modified carboxybetaine zwitterionic macromonomer (PCBOAA) with a small fraction of the hydrogen‐bonding monomer N‐acryloyl glycinamide (NAGA), enabling rapid gelation (8 s) and substantial mitigation of radical generation under blue‐light irradiation. Incorporation of NAGA into the hydrogel network via copolymerization reinforces hydrogen‐bonding interactions among polymer chains, which not only efficiently mitigates hydrogel overswelling but also prevents mechanical stress‐mediated islet injury. The resulting PCBOAA 8 ‐PNAGA 1 hydrogel displays high water content (>92.9%) to allow efficient mass transfer, sufficient flexibility and mechanical stability to endure dynamic mechanical environment of peritoneal cavity, along with outstanding antifouling performance to confer the significantly attenuated immune reaction and fibrous encapsulation. Islets encapsulated within the PCBOAA‐PNAGA hydrogel can achieve sustained correction of hyperglycemia, normalized glucose tolerance, and markedly reduce HbA1c levels (4.6%) for at least 3 months. Notably, the retrieved hydrogel implants maintain structural integrity, while islets still exhibit high viability and preserve dual insulin/glucagon secretory function.