Виробництво та характеризація прокоагулянтних біоматеріалів, модифікованих активатором протромбіну

Background. While several biomaterials used in routine medical settings provide only moderate hemostatic effects, military and disaster medicine require next-generation hemostatic biomaterials with substantially enhanced efficacy to achieve rapid, reliable control of massive hemorrhage. Modification of biomaterials using the enzymatic prothrombin activator (EA) was proposed as a universal approach to improve their procoagulant properties. Objective. The aim of the present work was in vitro and in vivo testing of EA-modified bioactive (carbon sorbent, silicon dioxide), bioinert (cellulose, hydroxyapatite), and biodegradable (collagen, gelatin) biomaterials. Methods. The prothrombin activator was purified using ion-exchange chromatography. A chromogenic substrate assay was used to detect EA washout; modified aggregometry was used to assess the hemostatic properties of modified biomaterials. A rat model of massive liver bleeding was used to evaluate the hemostatic properties of modified biomaterials. Results. EA modification proved feasible across all tested biomaterial classes, with adsorptive immobilization observed. EA-modified biomaterials demonstrated markedly superior hemostatic activity compared to their unmodified forms, significantly shortening bleeding times and reducing blood loss in both in vitro and in vivo settings. Among the matrices evaluated, carbon sorbent and collagen emerged as the most promising carriers: they enabled stable, non-covalent EA binding while fully preserving the enzyme's procoagulant catalytic function, leading to the most pronounced enhancement in hemostatic performance. These findings highlight carbon-sorbent- and collagen-based EA composites as leading candidates for advanced hemostatic agents in high-acuity trauma scenarios. Conclusions. The combination of biomaterials with an enzymatic prothrombin activator creates a new material that preserves the matrix's properties while imparting strong procoagulant activity. Collagen and carbon sorbent were shown to be efficient non-covalent binders of EA and can be used as hemostatic agents in surgery or emergency medicine.