Phase-engineered MoS₂ nanosheets/probiotic vesicles hydrogel for diabetic wound healing via dynamic ROS modulation

Diabetic wound repair remains a huge clinical challenge and drives demand for advanced therapies. Most novel nanomaterial-based dressings exploit elevated reactive oxygen species (ROS) for antibacterial efficacy are short of the intelligent of ROS modulation to regulate wound immune microenvironment. To address this, we developed a diabetic wound microenvironment-responsive hydrogel system integrating phase-engineered 1T-MoS₂ nanosheets and L. reuteri-derived extracellular vesicles (LEVs) to dynamically modulate ROS for diabetic wound healing. Featuring dynamic borate ester crosslinks, the hydrogel exhibits glucose-responsive degradation within diabetic wound microenvironments. Released 1T-MoS₂ nanosheets can catalyze endogenous H₂O₂ in diabetic wounds to generate ROS through their remarkable peroxidase (POD)-like activity under near-infrared (NIR) irradiation. Coupled with NIR enhanced glutathione (GSH) depletion ability, the rapid elimination of multiple pathogens and biofilms during the early stage of wound healing were enhanced. Besides, released LEVs promote macrophage to M2 phenotype polarization by restoring mitochondrial function, reducing intracellular ROS levels, and suppressing NF-κB activation, thereby alleviating the pro-inflammatory microenvironment and promoting diabetic wound healing. This integrated nanozyme-LEVs system synergistically addresses infection and immune dysregulation through adaptive ROS modulation, offering a precise and intelligent strategy for diabetic wound management.