Sustained-Release H₂S Nanospheres Regulate the Inflammatory Microenvironment of Wounds, Promote Angiogenesis and Collagen Deposition, and Accelerate Diabetic Wound Healing

Diabetic wounds are blocked in the inflammatory stage, growth factors are degraded, and blood vessels are difficult to regenerate, leading to continuous necrosis and nonhealing of the wound. Hydrogen sulfide (H₂S) plays an important role in the pathophysiological process of wound healing and has a long history of treating skin diseases. Although the sulfide salt solution is the preferred donor of exogenous H₂S, its rapid release rate, excess production, and difficulty in accurately controlling the dose limit its use. Herein, we developed H₂S sustained-release nanospheres NaHS@MS@LP for the treatment of diabetic wounds. NaHS@MS@LP nanosphere was composed of a NaHS-loaded mesoporous silicon core and a DSPE-PEG liposome outer membrane. When NaHS@MS@LP nanospheres were used to treat the wound of diabetic rats, mesoporous silicon was delivered into the cells and the loaded NaHS slowly released H₂S through hydrolysis, participating in all stages of wound healing. In conclusion, NaHS@MS@LP nanospheres regulated the inflammatory microenvironment of wound skin by inducing the transformation of macrophages into M2 type and promoted angiogenesis and collagen deposition to accelerate wound healing in diabetic rats. Our findings provide strategies for the treatment of chronic wounds, including but not limited to diabetic wounds.