A Multifunctional Bilayer Hydrogel for Effective Pancreatic Fistula Prevention and Post‐Surgical Adhesion Control

Despite remarkable advancements in hydrogel-based medical applications in recent years, their clinical translation for pancreatic fistula management remains challenging owing to the moist surgical environment and complex post-pancreatectomy pathophysiology. To address the clinical need for reliable wet-adhesion materials to prevent postoperative pancreatic fistula after distal pancreatectomy (DP-POPF) and postoperative adhesive intestinal obstruction, we developed an asymmetric bilayer hydrogel (BH) patch that integrates an adhesive pancreatic layer (APL) and an anti-adhesion layer (AAL). The APL combines N-hydroxysuccinimide-mediated covalent bonding with xanthan gum-driven interfacial dehydration for robust wet-tissue adhesion, the AAL, composed of poly(sulfobetaine methacrylate)-carboxymethyl chitosan, prevents fibrosis via surface hydration; the BH hydrogel incorporates Ceffe, a cell-free fat extract possessing anti-inflammatory and proangiogenic properties. The BH patch exhibits exceptional mechanical strength, prolonged post-swelling adhesion retention, and enzymatic resistance. In vitro and in vivo studies confirm its outstanding biocompatibility, antibacterial efficacy, and adhesion prevention in rat models. In a DP rat model, the Ceffe@BH group displayed significantly reduced POPF incidence versus the normal saline and hand-sewn anastomosis groups, as demonstrated by reduced drain fluid amylase, attenuated inflammation (↓TNF-α/IL-6), enhanced angiogenesis, and effective adhesion prevention. This suture-free, multifunctional hydrogel presents a standardized solution for POPF with broad potential for wet-tissue surgical applications.