Graphical Abstract

High oxidative stress injury and bacterial infection are the main challenges that impair wound healing in diabetic patients. Therefore, a hydrogel with enhanced antimicrobial and antioxidant properties was developed for rapid healing of diabetic wounds. In this study, chitosan methacrylate-gallic acid (CSMA-GA) polymer with antioxidant activity, antimicrobial activity, and ultraviolet (UV)-triggered gelling properties was developed as a hydrogel precursor. Meanwhile, amphiphilic Pluronic F127 molecules were used to load hydrophobic chlorhexidine drug molecules to obtain F127/chlorhexidine nanoparticle (NP) with strong antibacterial activity. Subsequently, F127/chlorhexidine NPs were encapsulated in CSMA-GA hydrogel to further enhance its antibacterial activity. The hybrid hydrogel platform (CSMA-GA/F127/chlorhexidine (CMGFC)) exhibited high antibacterial efficiency (> 99.9%) and strong reactive oxygen species (ROS) scavenging ability (> 80.0%), which effectively protected cells from external oxidative stress (upregulated superoxide dismutase (SOD) and glutathione/oxidized glutathione disulfide (GSH/GSSG) levels and downregulated malondialdehyde (MDA) levels). Moreover, in vivo results proved that the CMGFC hydrogel significantly reduced inflammatory responses (downregulated interleukin-6 (IL-6) and upregulated interleukin-10 (IL-10) levels), promoted angiogenesis (upregulated vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (CD 31) levels), and wound healing (enhanced collagen deposition and tissue remodelling). Overall, the CMGFC hydrogel with enhanced antimicrobial and antioxidant properties demonstrated significant potential to enhance diabetic wound healing.
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