Dual-Network Hydrogel Loaded With ROS-activated Hydrogen Sulfide Donor to Accelerate Wound Healing and Inhibit Scar Production.

The wound healing process consists of four continuous and overlapping stages-hemostasis, inflammation, proliferation, and remodeling-involving a variety of cells, growth factors, and the extracellular matrix. In recent years, growing evidence has shown that enhancing endogenous hydrogen sulfide (H2S) synthesis or providing exogenous H2S can promote angiogenesis, inhibit inflammation, reduce excessive oxidative stress, and support collagen deposition. However, the administration of exogenous H2S often presents challenges related to controlling its release duration and achieving targeted delivery. To achieve controlled and site-specific delivery of H2S to the wound area, a dual-network cross-linked injectable hydrogel formed by grafted ε-poly-L-lysine (designed as EG) and oxidized dextran (OD) (EGODF) loaded with a hydrogen sulfide donor (HSDF-NH2) to study its potential in wound healing is developed. The hydrogel exhibits excellent injectability, self-healing capability, and mechanical strength. Upon reactive oxygen species (ROS) stimulation, HSDF-NH2 releases both self-reporter fluorescence (HSDG-NH2) and H2S. Changes in the self-reporter fluorescence signal reflect H2S production and its entry into the body to exert therapeutic effects. Finally, using a wound model and a hypertrophic scar repair model, it is demonstrated that EGODF hydrogel is effective in promoting wound healing and inhibiting scar production.