A natural synergistic repair hydrogel with disulfide COF core breaks the vicious cycle of diabetic wounds in rabbits

Diabetic chronic wounds present a formidable clinical challenge driven by a self-perpetuating cycle of hyperglycaemia-induced oxidative stress, persistent inflammation, and recurrent infection. Conventional wound dressings often fail to address these complexities, primarily due to their lack of inherent multifunctionality and stimuli-responsive capabilities. To overcome these limitations, we develop a smart, redox-responsive hydrogel that integrates a disulfide-bridged covalent organic framework (S-COF) loaded with various natural bioactives, including curcumin, gallic acid, vanillin, and carboxymethyl chitosan. This multifunctional hydrogel facilitates sustained and on-demand therapeutic release in direct response to the wound microenvironment, while exerting synergistic antioxidant, antibacterial, and anti-inflammatory effects. In vitro assays using clinical diabetic blood samples demonstrated efficient reactive oxygen species scavenging, pathogen inhibition, and increased superoxide dismutase activity. In a diabetic rabbit wound model, this COF-based hydrogel significantly accelerated healing by reducing the inflammatory phase and promoting angiogenesis and collagen deposition, resulting in approximately 90% wound closure, a marked improvement over the 50% closure in untreated controls. Additionally, the hydrogel exhibited excellent biocompatibility, evidenced by a hemolysis rate of <1%. This natural-product-derived, redox-responsive platform simultaneously targets multiple pathological pathways, offering a robust and versatile strategy for advanced diabetic wound therapy.