Abstract
Chronic non-healing wounds represent a severe complication of diabetes mellitus, which frequently progress to infection, limb amputation, and even mortality. The dysregulated wound microenvironment, marked by persistent inflammation and oxidative stress, severely impedes tissue repair, and the presence of MRSA biofilm infection further worsens these impairments and poses major clinical challenges. To address these challenges, we constructed a multifunctional injectable hydrogel (SOT) that integrates antibiofilm, antioxidant, and immunomodulatory properties. This hydrogel is formed through dynamic covalent crosslinking between thiolated hyaluronic acid (HA-SH) and dopamine-modified oxidized dextran (ODex-DA), which enables favorable injectability, self-healing, and in situ gelation. Tannic acid-silver nanoparticles (TA-Ag NPs) incorporated into the system impart antibiofilm and reactive oxygen species (ROS)-scavenging properties. In a diabetic MRSA biofilm infection model, the SOT hydrogel eradicated biofilms, reduced excessive ROS, and promoted wound closure. These findings suggest that this immuno-instructive hydrogel platform may offer a promising therapeutic approach for the treatment of MRSA biofilm-infected chronic diabetic wounds.