A multifunctional protein-based hydrogel with Au nanozyme-mediated self generation of H₂S for diabetic wound healing

Diabetics usually suffer from chronic impaired wound healing due to facile infection, excessive inflammation, diabetic neuropathy, and peripheral vascular disease. Hence, the development of effective diabetic wound therapy remains a critical clinical challenge. Hydrogen sulfide (H₂S) regulates inflammation, oxidative stress, and angiogenesis, suggesting a potential role in promoting diabetic wound healing. Herein, we propose a first example of fabricating an antibiotic-free antibacterial protein hydrogel with self-generation of H₂S gas (H₂S-Hydrogel) for diabetic wound healing by simply mixing bovine serum albumin‑gold nanoclusters (BSA-AuNCs) with Bis[tetrakis(hydroxymethyl)phosphonium] sulfate (THPS) at room temperature within a few minutes. In this process, the amino group in BAS and the aldehyde group in THPS are crossed together by Mannich reaction. At the same time, tris(hydroxymethyl) phosphorus (trivalent phosphorus) from THPS hydrolysis could reduce disulfide bonds in BSA to sulfhydryl groups, and then the sulfhydryl group generates H₂S gas under the catalysis of BSA-AuNCs. THPS in H₂S-Hydrogel can destroy bacterial biofilms, while H₂S can inhibit oxidative stress, promote proliferation and migration of epidermal/endothelial cells, increase angiogenesis, and thus significantly increase wound closure. It would open a new perspective on the development of effective diabetic wound dressing.