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

The EGODF hydrogel, an injectable and self-healing system, enables controlled H₂S release and fluorescence self-reporting upon ROS stimulation. Designed for wound healing, it enhances angiogenesis, reduces inflammation, and mitigates oxidative stress. In vivo studies demonstrate its effectiveness in accelerating wound closure and minimizing scar formation, offering a promising therapeutic strategy.

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.