Shelf-Stable, Rapid-Gelling, and Robust Thrombin-Independent Fibrinogen-Based Hydrogels for Massive Hemorrhage Control.

Effective hemorrhage control remains an important unmet need in trauma care and emergency medicine. Therefore, it is essential to achieve rapid and effective hemostasis. Bioadhesives offer an attractive approach to wound sealing, achieving simultaneous leakage prevention, mechanical support, and hemostasis. However, available bioadhesives are limited in clinical applications by weak mechanical strength, insufficient biocompatibility, and strict storage condition. In this study, a thrombin-independent fibrinogen-based hydrogel was developed, featuring rapid gelation, robust mechanical strength, strong tissue adhesion, and excellent shelf stability. This hydrogel is prepared from knob-peptide-grafted gelatin methacryloyl (GMK) and fibrinogen methacryloyl (FM). GMK/FM hydrogel can quickly form the knob-hole crosslinking and then be reinforced through photo-crosslinking. Compared with clinical standard-of-care fibrin glue, GMK/FM hydrogel demonstrates comparably rapid gelation (< 2 s), alongside enhanced mechanical strength, tissue adhesion and storage stability (4 weeks at room temperature). In rat severe hemorrhage models of liver and abdominal aorta, GMK/FM hydrogel decreased hemostatic time and blood loss remarkably. It demonstrates exceptional hemostatic performance, outstanding biocompatibility, and storage stability, holding significant promise for clinical applications and emergency uses.