A photothermally enhanced oxygen-releasing and antibacterial hydrogel accelerating diabetic wound healing via energy metabolism regulation

Non-healing diabetic wounds represent a significant clinical challenge, with hypoxia-driven microenvironmental remodeling and persistent infection being the primary barriers to effective tissue repair. To address these issues, we developed a multifunctional near-infrared (NIR)-responsive hydrogel with enhanced oxygen-releasing properties, designed to locally modulate oxygen supply at the wound site while synergistically promoting healing through combined antibacterial and antioxidative activity. The hydrogel system was constructed by embedding core-shell oxygen-releasing nanoparticles (ORN) into a hyaluronic acid methacrylate (HAMA) hydrogel matrix, alongside selenium nanoparticles (Se NPs), to form a photothermally activatable composite (ORN@Se-HAMA). The ORN@Se-HAMA hydrogel demonstrates controlled oxygen release under near-infrared (NIR) irradiation while simultaneously scavenging free radicals. The incorporation of Se NPs and photothermal therapy enhances the hydrogel's synergistic antibacterial effects. This multifunctional ORN@Se-HAMA hydrogel integrates three therapeutic effects: controlled oxygen delivery, antibacterial synergy, and antioxidant activity. These properties collectively help improve local oxygenation, alleviate inflammation, and accelerate wound healing. Metabolomic and transcriptomic analyses further revealed that ORN@Se-HAMA-NIR treatment reprogrammed cellular energy metabolism, notably upregulating fatty acid metabolism, a critical driver of tissue repair. By intelligently regulating oxygen supply in response to hypoxia, combating bacterial infection, and restoring fatty acid metabolic homeostasis, this advanced dressing offers a novel, precise, and multi-faceted therapeutic strategy for managing diabetic wounds.