Hydrogen Sulfide Nano-Engineered Dressings in Wound Healing: Translational Insights from Hydrogen Sulfide-rich Sulfurous Thermal Spring Water

Hydrogen sulfide (H2S) is increasingly recognized as a key endogenous gasotransmitter involved in tissue repair, angiogenesis, inflammation modulation, and cytoprotection. Its biological activity, mediated through enzymatic pathways including cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, supports the therapeutic rationale for exogenous H2S supplementation in impaired wound healing. Sulfurous thermal spring waters represent a traditional yet biologically relevant source of H2S exposure, particularly in dermatological and chronic wound conditions. However, the clinical translation of H2S therapy is limited by the molecule’s volatility and rapid degradation. Nano-engineered delivery systems have recently emerged as promising tools to enable controlled and sustained H2S release at the wound site [1-3]. We conducted a systematic review of the literature investigating H2S-releasing nanotechnology-based dressings for wound healing applications, interrogating major biomedical databases including PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar (2012–2026). A total of 8760 articles were found. After abstract reading and duplicate removal, 73 abstracts were eligible for full text review. Finally, 51 articles met the inclusion criteria, 38 of which focused on diabetic wounds. Hydrogels represented the most frequently employed delivery platform. Across experimental models, H2S-releasing nano-dressings consistently demonstrated enhanced fibroblast proliferation, accelerated re-epithelialization, improved angiogenesis, and modulation of inflammatory responses, with particularly promising results in diabetic wound models. These findings suggest that nano-engineered H2S delivery systems may reproduce and potentiate the regenerative effects historically observed with sulfurous thermal spring water, offering a translational bridge between traditional thermal medicine and advanced biomaterial-based therapies. Further clinical studies are warranted to define optimal delivery strategies and therapeutic protocols for chronic wound management.