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

Abstract

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.