Hydrogel-Mediated Delivery of Baicalein for the Effective Therapy of MRSA-Infected Diabetic Wounds by Immune Response and Moderate Photothermal Effect

Persistent bacterial infections and the imbalance in immune regulation induced by oxidative stress present a significant challenge in diabetic wound healing. In this study, we developed a novel dual-network hydrogel system composed of chitosan/polyacrylic acid (PEC) and polyoxometalate PMo12 (PMo12-PEC) loaded with baicalein (BA), designated as PMo12-BA-PEC, for the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic wounds. The hydrogel demonstrated enhanced mechanical strength and elasticity, facilitating effective wound adherence and accommodating tissue movement. Upon 808 nm near-infrared (NIR) light irradiation, the photothermal properties of PMo12 enabled controlled low-temperature hyperthermia and accelerated BA release. Remarkably, the hydrogel achieved an antibacterial efficacy of 99.45% ± 0.12% against MRSA following 5 minutes of NIR exposure, while exhibiting potent antioxidant and anti-inflammatory capabilities to scavenge reactive oxygen species and mitigate inflammatory responses. Comprehensive evaluation revealed that the PMo12-BA-PEC hydrogel significantly promoted angiogenesis, enhanced collagen deposition, inhibited bacterial growth, and modulated immune regulation, thereby accelerating the wound healing process in diabetic rat models. These findings suggest that the PMo12-BA-PEC hydrogel represents a promising biomaterial platform for clinical management of diabetic wounds and potential treatment of oxidative stress-related disorders.