From Hemostasis to Angiogenesis: A Self-Healing Hydrogel Loaded with Copper Sulfide-Based Nanoenzyme for Whole-Process Management of Diabetic Wounds

Diabetic wounds pose considerable healing challenges due to factors such as impaired angiogenesis, persistent inflammation, elevated levels of reactive oxygen species, and bacterial infections. In this study, we synthesized copper sulfide nanoparticles (NPs) using sericin as a biotemplate and functionalized them with tannic acid-Fe (TA-Fe) metal-phenolic network coatings to create CuS-based nanoenzymes (CuS-Se@TA-Fe NPs). These NPs were integrated into a composite hydrogel formed from polyvinyl alcohol, carboxymethyl chitosan, and borax. The hydrogen bonding between polyvinyl alcohol and carboxymethyl chitosan, combined with the borate ester bonds from borax and the electrostatic interactions with CuS-Se@TA-Fe NPs, resulted in a hydrogel with remarkable adhesion, self-healing capabilities, and shape retention (PCCuT hydrogel). Additionally, the PCCuT hydrogel demonstrated superoxide dismutase and catalase mimetic activities to eliminate excess free radicals, along with excellent photothermal conversion and antimicrobial properties due to the photothermal effect. Both in vitro and in vivo investigations indicated that the PCCuT hydrogel could enhance angiogenesis and promote the transformation of macrophages into the M2 anti-inflammatory phenotype. Notably, in a rat model of diabetic wound infection, the hydrogel exhibited substantial wound-healing benefits. In summary, the PCCuT hydrogel holds promise for advancing the treatment of diabetic wounds complicated by infection.