Controlled Codelivery of Hydrogen Sulfide and Nitric Oxide for the Treatment of Full-Thickness Skin Wound

Chronic wounds present significant clinical challenges stemming from persistent inflammation, impaired angiogenesis, and disrupted tissue homeostasis. Nitric oxide (NO) and hydrogen sulfide (H2S) are important gaseous signalling molecules that play critical regulatory roles in the pathophysiology of numerous diseases. In the present study, we designed a novel prodrug, TSNO, which releases H2S and NO in a controlled manner under the catalysis of GSH and the engineered enzyme A4-β-GalH363A. Furthermore, a functional wound dressing was prepared by incorporating TSNO into an electrospun poly(ε-caprolactone) (PCL) mat, and the therapeutic efficacy was evaluated in a full-thickness skin wound model established in mice. Results showed that the functional wound dressing effectively accelerated the wound healing process by enhancing collagen synthesis, promoting angiogenesis, and regulating inflammation via controlled codelivery of H2S and NO. Taken together, the functional wound dressing developed in this study represents a promising candidate for treating large-scale skin wounds in the clinic.