Polysaccharide-Based Self-Healing Hydrogel for pH-Induced Smart Release of Lauric Acid to Accelerate Wound Healing

It is highly desirable yet significantly challenging to fabricate an injectable, self-healing, controlled-release wound dressing that is responsive to the alkaline pH of the wounds. Herein, we propose a facile approach to prepare pH-responsive chitosan-oxidized carboxymethyl cellulose (CS-o-CMC) hydrogel constructs in which gelation was achieved via electrostatic and Schiff base formation. Importantly, the Schiff base was formed in acidic medium and the final pH of pregel solution was intrinsically raised to 7.0-7.4 due to the cross-linking by β-glycerol phosphate. The self-healing behavior of the hydrogel was an enthalpy-driven process and efficient in alkaline compared to acidic pH. The pH responsiveness offered a controlled release of lauric acid (LA) from CS-o-CMC/LA hydrogel and regulated the M2 polarization. Overall, reduction in inflammation led to rapid vascularization, reepithelialization, and significantly accelerated wound healing in rats. Our findings demonstrate a promising strategy for developing injectable, immunomodulatory wound dressings tailored to the challenging environment of wounds.