Orchestrating diabetic wound healing via MoS2 and Zn2+ integrated poly(vinyl alcohol)/dextran hydrogels: decoupling the efficacy-biosafety paradox in mild photothermal therapy.

The healing of diabetic wounds is impeded by a pathological triad of recalcitrant bacterial infections, oxidative stress, and chronic inflammation. While photothermal therapy (PTT) is a promising non-antibiotic alternative, its clinical translation is constrained by a critical efficacy-biosafety paradox: high-temperature ablation (>60 °C) induces collateral tissue damage, whereas biosafe mild-temperature PTT (<50 °C) fails to achieve complete pathogen eradication due to bacterial heat-shock defenses. To reconcile this, we engineered a multifunctional hybrid hydrogel by incorporating flower-like MoS2@ZnO heterostructures into a dynamic dextran (Dex) and poly(vinyl alcohol) (PVA) network (PD@MoS2-ZnO), executing a "sensitization-before-attack" strategy. Sustained Zn2+ release selectively permeabilizes bacterial membranes, rendering pathogens hypersensitive to subsequent mild photothermal treatment (∼50 °C). In vitro assays demonstrated that this synergistic mechanism achieved exceptional antibacterial efficiency, eliminating 97.54% of E. coli and 98.98% of S. aureus. In a S. aureus-infected diabetic mouse model, the hydrogel treatment resulted in a 98.05% reduction in bacterial load and significantly accelerated wound closure, with the residual wound area diminishing to 1.11% after 15 days. Histological analyses further confirmed that the dressing promoted collagen deposition, re-epithelialization, and angiogenesis. This work establishes that an interfacial-sensitization platform provides a potent and biosafe strategy for managing complex diabetic wound infections without compromising host tissue viability.