A bioactive Janus zwitterionic hydrogel enables multitargeted peritoneal microenvironment remodeling to prevent postoperative adhesion

Physical barriers are standard care for preventing postoperative peritoneal adhesion (PPA), yet their clinical efficacy is limited by poor wet-tissue adhesion, inadequate hemostasis and insufficient bioactivity triggering exudate and clots to cause excessive fibrin deposition. Herein, we reported a degradable, bioactive bilayer Janus hydrogel termed GTA-PCBDS that comprised a gelatin-tannic acid (GTA) hydrogel layer for strong wet-tissue adhesion, rapid hemostasis, and enhanced wound healing with a poly(carboxybetaine dithiolane) (PCBDS) hydrogel layer serving as an antifouling barrier to inhibit fibrous protein adsorption and fibroblast attachment, while also possessing prominent antioxidant and anti-inflammatory activities. In both primary and recurrent peritoneal adhesion models, this GTA-PCBDS Janus hydrogel demonstrated superior anti-adhesive efficacy, and further mechanistic investigations revealed that this Janus hydrogel effectively inhibited the accumulation of fibrin precursors through rapid hemostasis and alleviated early-stage inflammation by suppressing the CXCL2/CXCR2 signaling axis, thereby preventing the occurrence of peritoneal adhesions at the source. Collectively, this superior postoperative anti-adhesion efficacy might be attributed to a synergistic four-pronged approach: physical barrier isolation, rapid localized hemostasis, modulation of inflammatory cytokines, and regulation of the fibrinolysis process. This work establishes a biomaterial design strategy that integrates physiological synchronization with active microenvironmental modulation, moving beyond simple physical isolation.