Serotonin-functionalized starch-based hemostatic sponges enhance platelet activation in the management of non-compressible hemorrhage

Massive hemorrhage poses a serious threat to human health and even life. Access to rapid and potent hemostatic materials is crucial for lowering mortality rates. Starch-based materials exhibit good biocompatibility and are extensively utilized in hemostatic. However, existing starch-based hemostatic products suffer from limited hemostatic efficacy. Serotonin, an indoleamine naturally occurring in the human body, is recognized for its potent platelet-activating properties. Therefore, this study focused on enhancing the procoagulant activity of starch by incorporating serotonin into the starch backbone via esterification and amidation reactions, yielding a novel serotonin-loaded starch-based hemostatic sponge (SLS sponge). The SLS sponges featured exceptional porosity (>= 80 %) and water absorption capacity (>= 2000 %), which rapidly initiated the coagulation cascade reaction, promoted the adhesion and aggregation of red blood cells and platelets, and intensified platelet activation. This multifaceted approach synergistically enhanced hemostasis via both active and passive coagulation mechanisms. Notably, the SLS sponges adhered firmly to the wound surfaces without pressure. Compared with gelatin sponges, the SLS sponges significantly reduced blood loss by approximately 40.5 % and shortened the time to achieve hemostasis by approximately 28.9 %. These findings indicate that the newly developed SLS sponges are a promising active hemostatic material, particularly effective in managing non-compressible hemorrhages.