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

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.