Injectable Ca/ε-aminocaproic acid/dextran phosphate hydrogel for effective acute bleeding control

The development of new hemostatic agents is crucial for advancing medical treatments and improving outcomes in surgical and trauma settings, where controlling bleeding is often a critical challenge. Herein, we developed and characterized the physicochemical properties and hemostatic potential of Ca/ε-aminocaproic acid/dextran phosphate composite hydrogels. The phosphorylation of dextran in the system tributyl phosphate - orthophosphoric acid - phosphorus (V) oxide - chloroform at 30 °C with the formation of hydrogels was studied in detail. We explored physical and chemical properties of the hydrogels, including rheology, swelling, and morphology. Additionally, the sorption kinetics and isotherms of ε-aminocaproic acid by the hydrogels were studied, revealing a maximum sorption capacity of 80 %. The hydrogels rapidly released ε-aminocaproic acid in vitro at 37 °C in PBS. Significantly, they demonstrated in vitro effectiveness by reducing blood clotting time, enhancing the clotting index, and showing minimal hemolysis. In vivo tests further indicated that these hydrogels markedly decreased bleeding time and average blood loss in a rat liver hemorrhage model, surpassing control experiments. These results suggest that Ca/ε-aminocaproic acid/dextran phosphate hydrogels are effective in controlling bleeding and show promise as a future hemostatic agent.