A silk fibroin/tannic acid hydrogel with acid-enhanced adhesion and procoagulant nanofiber reinforcement for gastric hemorrhage management.

Abstract

Effective endoscopic management of gastric hemorrhage necessitates a hemostat with rapid coagulation capabilities and sustained protection against gastric acid erosion. This study demonstrates that silk fibroin-tannic acid (SF-TA), which exhibits unique acid-triggered adhesion enhancement under acidic conditions, serves as a potential foundation for gastric hemorrhage management. This supramolecular structure displays an enhanced adhesion pattern to epithelial keratin-2 (EKRT2) at pH 1. The weakened electrostatic shielding effect and the rearrangement of water molecules induced by H⁺ significantly enhance the electrostatic interactions and van der Waals forces between the functional groups (-NH₂, -COOH, and Ar-OH) of SF-TA and EKRT2. This results in an over 50 % increase in adhesion strength under simulated gastric fluid (SGF, pH 1.3) compared to that in PBS (pH 7.3). The β-sheet repeat domain of SF offers a stable conformation, facilitating strong binding with TA, thereby maintaining integrity in gastric fluid for over 5 days. SF-TA is further reinforced with procoagulant silk fibroin nanofibers/protein corona (SFNPC), enabling rapid control of pig gastrorrhagia within 2 min, providing persistent protection in gastric fluid to prevent rebleeding, and facilitating gastric mucosal healing within 5 days. This study reveals the acid-triggered enhanced adhesion pattern of silk fibroin/tannic acid, offering a feasible approach for the further development of biomaterials for long-term gastric hemorrhage and conditions management. STATEMENT OF SIGNIFICANCE: This work presents a biomaterial-based hemostat with transformative potential for managing gastric hemorrhage. Its significance lies in the unique acid-triggered adhesive mechanism of the silk fibroin-tannic acid (SF-TA) complex, which exhibits enhanced adhesion to mucosal proteins under extreme gastric acidity (pH 1), a critical limitation of existing hemostatic agents. This supramolecular system ensures robust, long-lasting cohesion for over 5 days. Furthermore, when reinforced with procoagulant nanofibers (SFNPC), it achieves rapid hemostasis, provides a durable physical barrier against acid erosion and rebleeding, and actively promotes mucosal healing. This technology offers a comprehensive and efficient therapeutic strategy, addressing the key challenges of rapid coagulation and sustained protection in the harsh gastric environment.