Oxidized chitosan: Combining an "Adhesion-and-Kill" antibacterial strategy with immunoregulation and angiogenesis to enhance methicillin-resistant Staphylococcus Aureus-infected wound healing.

The emergence of antibiotic-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA), presents a significant challenge in clinical wound management due to their resistance to conventional antibiotics and ability to form persistent biofilms. This study explores the antibacterial properties and wound-healing potential of oxidized chitosan (OCTS), fabricated by oxidizing chitosan with hydrogen peroxide (H₂O₂), which introduces carboxyl groups to enhance its solubility, adhesion, and antibacterial activity. In vitro experiments demonstrate that OCTS exhibits lower MIC concentration (20 mg/mL vs. 80 mg/mL), superior bactericidal efficiency, stronger adhesion to MRSA, and greater biofilm inhibition than conventional chitosan (CTS), while retaining excellent biocompatibility and hemocompatibility. Multi-omics analyses (proteomics and metabolomics) reveal that OCTS disrupts key metabolic, structural, and redox pathways in MRSA. In a MRSA infection model on mouse skin, OCTS effectively eradicated MRSA in wound sites, reduced inflammation, promoted M2 macrophage polarization, and enhanced angiogenesis, culminating in a rapid wound healing rate of 89.2 ± 3.0 % by day 7. Its low cytotoxicity and excellent biosafety in mice further support its clinical translation. These findings highlight OCTS as a promising multifunctional biomaterial for MRSA-infected wound management, integrating antibacterial, immunoregulatory, and regenerative functions through a unique adhesion-and-kill mechanism.