Light‐Activated Transient Unilateral Adhesive Recombinant Collagen‐Based Hydrogel for Reversible Fibrosis Induction and Full‐Cycle Management of Pancreatic Fistula

Abstract Currently, no effective treatment for pancreatic fistula (PF) exists, which has a mortality rate >40%. Existing protein‐based physical barriers face the challenges of rapid degradation, lack of self‐adhesiveness, and the inability to promote PF healing. To overcome this, a novel enzyme‐resistant and highly bioactive hydrogel (CGO@Pg‐Cu(II)) is developed using glycidyl methacrylate recombinant collagen (enzyme‐cleavage‐free) and oxidized pullulan as backbone molecules, which is further loaded with a penicillin G‐Cu(II) infinite coordination polymer nanomedicine. This hydrogel can adapt to irregular PF wounds through injectable self‐leveling and achieve transient unilateral adhesion via light‐activated radical crosslinking with tissue‐inherent molecules. In vitro and in vivo studies demonstrate its ability to provide full‐cycle PF management by serving as a long‐lasting physical barrier while offering antimicrobial properties, rapid hemostasis, anti‐inflammatory effects, reversible fibrosis induction, and enhancing pancreatic tissue repair. The anti‐PF efficacy of the CGO@Pg‐Cu(II) hydrogel at day 7 is 100%, highlighting its strong potential for clinical postoperative PF prevention.