Enhanced efficacy of fibrin hemostatic patch through rational design at the molecular level

Internal hemorrhage remains a critical challenge requiring immediate intervention. Recent advances in biomaterials have positioned fibrin hemostatic patches (FHPs) as a promising therapeutic option through targeted fibrinogen-to-fibrin conversion at the injured organ; however, insufficient understanding of the stoichiometric coupling between active components of FHP may limit its coagulation performance. Here, we report a novel FHP (nFHP) through orthogonal optimization of fibrinogen, thrombin, and calcium chloride. Systematic screening identified fibrinogen concentration as the primary determinant of clotting time, with fibrinogen-to-thrombin and fibrinogen-to-calcium chloride ratios further impacting. nFHP, fabricated with the optimal formulation (17 mg/cm² fibrinogen, 40 IU/cm² thrombin, 115 μg/cm² calcium chloride), achieved rapid fibrin network formation and superior adhesive strength on the porcine aorta, surpassing commercial FHP (cFHP). In vivo evaluations across hepatic resection, cardiac stab wound, and arterial hemorrhage models demonstrated nFHP's universal efficacy, achieving the minimal blood loss compared to commercial products. Our work identifies stoichiometric proportion as a key factor in fibrin-based biomaterial rational design and provides a translatable solution for uncontrolled internal hemorrhage.