Multifunctional Co-FeS2 nanozyme-hydrogel composite promotes diabetic wound healing by synergistic antioxidant, antibacterial, and anti-inflammation therapy

Diabetic wounds are refractory and recurrent chronic conditions, characterized by insufficient tissue nutrition, persistent infection, and immune dysregulation. These challenges underscore the need for innovative, multifunctional wound dressings. In this study, we synthesized cobalt-doped FeS₂ (Co-FeS₂) nanozymes that exhibit superior peroxidase (POD)-like and superoxide dismutase (SOD)-like activities, enhanced photothermal performance, and greater antioxidant capacity compared to Fe₃O₄ and FeS₂. The Co-FeS₂ nanozyme was encapsulated together with H₂O₂ in a hydrogel matrix composed of polyvinyl alcohol (PVA)-borax modified with sodium alginate (SA) and tannic acid (TA), resulting in a material with strong skin adhesion, self-healing property, and excellent biodegradability. The incorporated H₂O₂ serves a dual purpose: it regulates the hydrogel's degradation kinetics and provides early-stage antibacterial activity through reactive oxygen species (ROS) generation, while subsequently being catalyzed by Co-FeS₂ to produce oxygen. This oxygen supply, along with ROS scavenging, promotes the polarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages, thereby resolving chronic inflammation. Both in vitro and in vivo evaluations demonstrated that the composite hydrogel possesses excellent biocompatibility, sustained antibacterial efficacy, antioxidant activity, anti-inflammatory regulation, and pro-angiogenic effects. These findings highlight its potential as a promising wound dressing for diabetic and other chronic wounds, effectively addressing multiple pathological challenges in the healing process.