An injectable and adaptable system for the sustained release of hydrogen sulfide for targeted diabetic wound therapy by improving the microenvironment of inflammation regulation and angiogenesis

Abstract

The combined effects of persistent chronic inflammation, oxidative stress, microcirculation disorders, and dysregulated cellular energy metabolism often hinder the repair of diabetic skin wounds. Traditional treatment methods are typically insufficient in simultaneously addressing these complex factors, resulting in delayed wound healing and a high propensity for recurrence and chronic ulceration. This study developed an innovative strategy based on reactive oxygen species (ROS)–responsive nanoparticles loaded with an ultraviolet (UV)-light-responsive hydrogen sulfide (H₂S) donor. This approach leverages the endogenous ROS present in diabetic wounds and external UV light as dual triggers to facilitate the controlled and stepwise release of H₂S. The material design explicitly targets the critical challenges in diabetic wound repair, including the inhibition of chronic inflammation, oxidative stress reduction, microcirculation improvement, and support of cellular energy metabolism, thereby significantly accelerating wound healing. This adaptive release of signaling molecules effectively modulates the wound regeneration microenvironment, enhancing the repair process and offering a promising solution for diabetic skin wound management.

Statement of significance

This study developed an innovative strategy based on reactive oxygen species (ROS)–responsive nanoparticles loaded with an ultraviolet (UV)-light-responsive hydrogen sulfide (H₂S) donor. This approach leverages the endogenous ROS present in diabetic wounds and external UV light as dual triggers to facilitate the controlled and stepwise release of H₂S. The material design explicitly targets the critical challenges in diabetic wound repair, including the inhibition of chronic inflammation, oxidative stress reduction, microcirculation improvement, and support of cellular energy metabolism, thereby significantly accelerating wound healing. This adaptive release of signaling molecules effectively modulates the wound regeneration microenvironment, enhancing the repair process and offering a promising solution for diabetic skin wound management.