A serotonin-modified hyaluronic acid hydrogel for multifunctional hemostatic adhesives inspired by a platelet coagulation mediator

Abstract

Bleeding control is very important during operations and surgical treatments of wounds and traumatic injuries. This need has led to development and practical uses of various hemostatic agents. However, the currently available hemostatic agents have several limitations related to biocompatibility and hemostatic performance due to the presence of cytotoxic and immunogenic components and the individual differences in the blood coagulation system. In this study, a hydrogel system inspired by a blood clotting mediator in platelets was developed as a new class of hemostatic adhesive with improved performance and multi-functionality. The proposed hydrogel system was prepared using serotonin-conjugated hyaluronic acid, both of which are highly biocompatible as they are natural components of the body. Serotonin facilitates hemostasis by acting as a blood clotting mediator in platelets and acts as a crosslinker to form adhesive hydrogels. The serotonin-conjugated hyaluronic acid hydrogel exhibited significantly improved hemostatic capability in vivo with normal and hemophilic injuries compared with a commercially available fibrin-based hemostatic agent and prevented abnormal tissue adhesion after hemostasis. This hydrogel system, inspired by the platelet clotting mechanism, is a novel hemostatic adhesive that overcomes several limitations of existing hemostatic agents and could substantially improve bleeding control, thereby improving outcomes of surgical procedures.