Photo-controlled multifunctional hydrogel for photothermal sterilization and microenvironment amelioration of infected diabetic wounds

Diabetic foot ulcers are linked to a high disability rate, with no effective treatment currently available. Addressing infection, reducing oxidative stress, and safely managing chronic inflammation remain major challenges. In this study, a composite hydrogel dressing was developed using natural substances or clinically approved components (dopamine, D-alpha-tocopheryl polyethylene glycol succinate, and rhein). Upon near-infrared laser irradiation, the composite system rapidly heats and solidifies into a gel with photothermal antibacterial properties. Additionally, the decomposition of hydrogen peroxide releases oxygen, alleviating wound hypoxia. The hydrogel exhibited strong bactericidal activity against multiple bacterial strains. Without laser irradiation, the hydrogel effectively scavenged various free radicals and intracellular reactive oxygen species, restoring redox balance. Furthermore, it significantly reduced the expression of inflammatory cytokines, including interleukin-6 and interleukin-1β. In a diabetic mouse wound model infected with S. aureus, the mild photothermal therapy, combined with the antibacterial action of rhein, effectively managed bacterial infections, reduced inflammation, and promoted wound healing. Consequently, the photo-controlled therapeutic approach, offering antibacterial, antioxidant, and anti-inflammatory effects, holds promise for the effective treatment and management of infected diabetic wounds.