Temporally Programmed H2O2 and H2S-Releasing Hydrogel Dressing for Accelerated Infected Wound Healing

Endogenous signaling molecules are essential for coordinated wound healing, yet current donor-based dressings typically provide only single-mediator delivery with limited release duration. Here, a multifunctional hydrogel dressing, HEVCTM, is developed by free radical copolymerization of N -hydroxyethyl acrylamide (HEAA) with a hydrogen peroxide (H 2 O 2 ) releasing donor (VIM-CAT) and a hydrogen sulfide (H 2 S) releasing donor (TBA-MA). The hydrogel enables temporally programmed release, with rapid H 2 O 2 delivery within 24 h for early stage antibacterial action and sustained H 2 S release for up to 7 days to alleviate inflammation and promote angiogenesis during later healing stages. HEVCTM exhibits potent antibacterial activity against Escherichia coli (99.6%) and Staphylococcus aureus (99.97%), significantly enhances macrophage M2 polarization (52.4%), and shows favorable antioxidant, hemostatic, adhesive, and pro-angiogenic properties. Moreover, in an infected mouse wound model, HEVCTM significantly accelerated wound healing and promoted tissue regeneration. This work provides a bioactive hydrogel platform that matches the dynamic requirements of wound healing and effectively accelerates tissue repair.