Fabrication of PLGA-chitosan-tranexamic acid composite sponge and its mechanism for rapid hemostasis

Persistent intraoperative hemorrhage is the major cause of trauma-related mortality, emphasizing the need for hemostatic dressings with improved efficacy. In this study, we designed a PLGA-CTS-TXA composite sponge, which was fabricated by grafting of poly (lactic- co -glycol acid) (PLGA) and hemostatic small molecule tranexamic acid (TXA) onto chitosan (CTS), for rapid hemostasis. The sponge integrates the advantages of CTS, PLGA and TXA, showcasing superior porosity (nearly 85 %) and water absorption capacity (3197 ± 105 % within 30 s). It also demonstrates good biocompatibility (hemolysis <1.2 %, RCV > 125 %), low blood clotting index (12.4 %) and abbreviated clotting times (<30 s). The incorporation of TXA substantially augmented the hemostatic capability of the composite sponge. Compared to CTS alone, PLGA-CTS-TXA demonstrated a significantly reduced hemostatic time in both rat tail and mouse liver hemostatic models. Its hemostatic mechanism was further analyzed from the perspective of the actual interface created by the interaction between the material and the biological fluid (ie., protein corona). The results demonstrated that the swift hemostatic mechanism involves modulation of erythrocyte and platelet aggregation/adhesion and fibrin degradation, etc. , thereby influencing the coagulation cascade. This research extends the utility of TXA in hemostasis and offers novel idea into the development and hemostatic mechanism of new high-efficiency hemostatic dressings.