pH-responsive and self-adaptive injectable sodium alginate/carboxymethyl chitosan hydrogel accelerates infected wound healing by bacteriostasis and immunomodulation

Abstract

Infected wound healing is a global medical challenge due to persistent bacterial infection and excess inflammation. Designing microenvironment-responsive and self-adaptive hydrogels with antibacterial and anti-inflammatory properties is expected to be an effective strategy to promote infected wound healing. In this study, a self-adaptive injectable sodium alginate/carboxymethyl chitosan hydrogel (SCSC) for pH-responsive release of curcumin has been prepared at room temperature by simple stirring. The incorporation of the crosslinker, Sr²⁺, enhances mechanical properties of SCSC hydrogel by tensing network structures, and provides synergistic biological activities. Meanwhile, SCSC hydrogel self-adapts in irregular wound shapes with outstanding ECM-like performance and releases effectively in the acidic microenvironment simulating the initial stage of infected wounds. SCSC hydrogel with good biocompatibility can promote cell migration, while relieving oxidative stress and mitochondria damage. Notably, SCSC hydrogel inhibits inflammatory factor expression and promotes M2 macrophage polarization by suppressing the NF-κB signaling pathway. Further, SCSC hydrogel significantly downregulates the over-expression of matrix metalloproteinase-9 (MMP-9), thereby helping promote ECM reconstruction. In vivo experiment results further demonstrate that SCSC hydrogel accelerates the re-epithelialization of infected wounds on the back of rats. Thus, the pH-responsive and self-adaptive SCSC hydrogel possesses great potential in the management and control of infected wounds.