The leaky gate: Engineering biomaterial barriers for pancreatic fistula

Postoperative pancreatic fistula (POPF) represents the most prevalent and perilous complication following pancreatic resection, frequently precipitating severe infection, hemorrhage, and multiple organ dysfunction syndrome, thereby substantially increasing patient mortality and healthcare burden. Conventional surgical interventions and pharmacological therapies have inherent limitations in the prophylaxis and management of POPF and its secondary infectious sequelae. In recent years, biomaterials have emerged as innovative therapeutic modalities for this clinical challenge because of their engineerable physicochemical properties. This review aims to systematically elucidate recent advances in biomaterial-based strategies for POPF prevention and treatment, with particular emphasis on their dual mechanistic functions: (i) serving as physical barriers to achieve immediate sealing, adhesion, and mechanical support of the surgical site, thereby precluding pancreatic fluid extravasation; and (ii) actively modulating the local microenvironment through the incorporation of bioactive agents or intrinsic functionalization, exerting synergistic anti-infection, anti-inflammatory, and tissue regeneration and neovascularization effects. Furthermore, this article critically analyzes current challenges pertaining to biocompatibility, degradation controllability, and clinical translational efficiency while future design trajectories toward precision medicine-oriented and stimuli-responsive multifunctional biomaterials are prospected.