Injectable thermogelling bioadhesive chitosan-based hydrogels for efficient hemostasis

Development of an injectable hemostatic for treating noncompressible or irregularly shaped bleeding wounds remains a pressing medical need. Herein, we report an injectable thermogelling chitosan/glycerophosphate formulation that enhances gel-forming capacity and wet tissue adherence by incorporation of dihydrocaffeic acid (DHCA). This was found to decrease gelation time by >2 times around 37 degrees C while increasing hydrogel internal network structure, with its tissue adhesive strength >2 times greater than that of the non-composite hydrogel or previously reported. The thermosensitive hydrogels significantly reduce whole blood coagulation time in vitro and both hemostasis time and blood loss in vivo using rat hepatic hemorrhage and tail amputation models. These improvements are biocompatible, without adversely affecting cell viability, blood components, biodegradability, or introducing notable inflammation, thus enabling injury healing. Moreover, our results displayed the potential of a facile approach to enhance thermogelling and bioadhesion of chitosan-based hydrogels via noncovalent supramolecular mechanisms.

Automated summary

A thermogelling chitosan/glycerophosphate formulation was developed by incorporating dihydrocaffeic acid (DHCA), which significantly enhanced gel-forming capacity and tissue adherence. The thermosensitive hydrogels showed improved hemostasis and reduced blood loss in both in vitro and in vivo models. The results demonstrated the potential of enhancing thermogelling and bioadhesion of chitosan-based hydrogels through noncovalent supramolecular mechanisms.