Curcumin-loaded copper/iron bimetallic nanoparticle-incorporated hydrogel scaffold: a sequential microenvironment reprogramming platform for accelerated chronic wound healing

Diabetic wound management represents a substantial clinical challenge owing to the deteriorative tissue microenvironment including the excessive reactive oxygen species (ROS), persistent inflammation, and potential bacterial infection. To address these issues, herein, a hybrid hydrogel scaffold (SF@NP-Cur) capable of sequentially reprogramming the wound microenvironment was developed through microfluidic 3D printing technique for infected chronic wound healing. Such scaffold incorporates curcumin-loaded copper/iron bimetallic nanoparticles (NP-Cur), which confers not only the oxidase- and peroxidase-like activities for efficient ROS scavenging, but also enables the multimodal antibacterial behavior via copper release and photothermal effects of NP-Cur. Simultaneously, the release NP-Cur contribute to the pro-migration effect on fibroblasts, accelerating wound healing by promoting collagen deposition and angiogenesis. Furthermore, the loaded curcumin within NP-Cur enables the polarization of M1 macrophages toward the pro-regenerative M2 phenotype. Benefitting from these properties, such hydrogel scaffold potently accelerates the reconstruction of infected diabetic wounds by reprogramming the wound microenvironment indicated by the reduced ROS, attenuated inflammation, plentiful M2-type macrophages, and enhanced neovascularization. Collectively, this immunomodulatory scaffold represents a promising dressing for reconstruction of impaired chronic tissue environments, offering a robust therapeutic strategy for chronic wound repair and regeneration.