Forced hemostasis via enhanced erythrocyte adhesion: A procyanidin-based composite sponge for managing hemorrhage in...

Uncontrolled hemorrhage, particularly under coagulopathic conditions, remains a clinical challenge. Although commercial gelatin sponge (GS) is highly biocompatible, its passive hemostatic mechanism limits efficacy in managing severe hemorrhage. Here, we report a polyphenol-modified gelatin sponge (PG) fabricated via a facile one-step procyanidin conjugation. The optimal sponge formulation, PG3, exhibits enhanced hydrophilicity, rapid fluid absorption, and robust mechanical properties. Mechanistically, the hemostatic mechanism is primarily driven by the synergistic effect between Ca²⁺ and the polyphenol-modified surface, which markedly enhances protein adsorption and erythrocyte adhesion, without altering the intrinsic or extrinsic coagulation pathways. In a rat femoral artery injury model, PG3 significantly reduced bleeding time and blood loss by 62.3% in healthy rats and by 47.0% in heparinized coagulopathy rats, outperforming commercial GS. Additionally, PG3 exhibited excellent cytocompatibility, antioxidant capacity, and biodegradability. This work highlights a simple yet effective strategy for developing composite hemostatic materials, promising for the clinical management of severe bleeding, especially in challenging coagulopathic scenarios.