H₂S/Curcumin Coreleasing Biomineralized Zinc Sulfide Nanostructures for Diabetic Wound Healing

Diabetic wound healing is a great challenge among diabetic patients, and it is a complex dynamic process involving inflammatory and angiogenesis responses. Anti-inflammation and pro-angiogenesis are key issues in diabetic wound healing. Herein, an H 2 S/curcumin coreleasing biomineralized zinc sulfide (named HZSC) is developed to promote diabetic wounds healing. The prepared HZSC features a nanoscale size of 166 ± 6.4 nm as well as a unique structure of HA loading Cur and coating ZnS biomineralized nanoclusters. After being applied in the mildly acidic diabetic wound tissue, the prepared HZSC controllably coreleases H 2 S and curcumin to promote macrophage polarization to the M2 phenotype, reduce reactive oxygen species levels, as well as enhance angiogenic factors. According to the results of both in vitro/vivo studies, HZSC can affect macrophage phenotype polarization, stimulate vascular endothelial cell migration and tube formation, accelerate the wound transition into the repair and proliferation stages, and then promote the diabetic wound healing. RNA sequencing analysis supports that HZSC downregulates TNF, NF-κB, and JAK-STAT pathways while upregulating genes associated with anti-inflammation and pro-angiogenesis. Our findings introduce a therapeutic approach to promote diabetic wound healing through H 2 S/curcumin coreleasing, improving anti-inflammation and pro-angiogenesis.