A self-healing injectable hydrogel integrated with enzymatic and nonenzymatic antioxidants as artificial antioxidant defense system for diabetic wound healing

Chronic diabetic wounds seriously threaten human health due to their intractable nature in a complex pathological microenvironment that contains oxidative stress, persistent inflammatory status, hypoxia and bacterial infections, of which oxidative damage contributing the most. Applied materials that can mimic the natural intracellular antioxidant defense system are perceived to have huge therapeutic potential. Herein, we present a novel strategy to prepare a versatile nanocomposite hydrogel by incorporating the nanoenzyme (manganese dioxide (MnO2)) and nonenzymatic antioxidant components (polydopamine (PDA)) in a dynamic hydrogel network composed of thioctic acid and tannic acid (TA). The prepared hydrogel exhibited outstanding adhesive and injectable properties, making it adapt perfectly to wounds with different shapes and depths. More importantly, encapsulation of PDA@MnO2 nanoparticles (NPs) conferred the hydrogel with superior antioxidant performance to effectively scavenge multiple types of reactive nitrogen and oxygen species (RNOS) and reduce the inflammatory response by regulating macrophage polarization. Meanwhile, the hydrogel showed highperformance catalyzing ability to transfer hydrogen peroxide (H2O2) into oxygen (O2), which could further alleviate hypoxic wound environment. Moreover, the nanocomposite hydrogel exhibited excellent near-infrared (NIR) photothermal antibacterial effect. Collectively, our findings indicate that the synthesized nanocomposite hydrogel shows potential for use in a clinical setting to treat diabetic wounds.