Dual dynamic covalent hydrogel enabling pH-responsive release of carboxymethyl chitosan and caffeic acid for synergistic antibacterial activity and wound healing.

Hydrogels have shown broad application prospects in the treatment of complex wounds due to their good biocompatibility and adhesion. In this study, we developed the CMCS-FPBA-CA hydrogel by incorporating a dual dynamic covalent cross-linking system based on Schiff base and borate ester bonds. This design confers pH-responsive behavior to the acidic wound microenvironment. Under acidic conditions, the cleavage of Schiff base and boronate ester bonds enables the release of carboxymethyl chitosan (CMCS) and caffeic acid (CA), which act synergistically to inhibit bacterial growth and accelerate wound healing. In vitro, the hydrogel demonstrated strong antibacterial activity, with inhibition rates of 95.4% against S. aureus and 98.12% against E. coli, while maintaining a hemolysis rate below 5%. In vivo results confirmed its ability to suppress bacterial infection and enhance collagen deposition, achieving a wound healing rate exceeding 95% within 14-15 d. In conclusion, this CMCS-FPBA-CA hydrogel presents an innovative strategy for designing smart polysaccharide-based hydrogels with significant potential for wound treatment and other biomedical applications.