A polyphenol-modified chitosan hybrid hydrogel with enhanced antimicrobial and antioxidant activities for rapid healing of diabetic wounds

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.