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

Abstract

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.