Immunomodulation and Fibroblast Subtype Regulation by a Photoliquefiable Hydrogel Realize Anti‐Scar Skin Regeneration of Refractory Infected Wounds

Abstract

Abstract Effective wound repair and preventive strategies against scarring remain challenging especially for chronic refractory wounds, as aberrant healing often encounters with persistent bacterial infection, extensive inflammatory response, impaired angiogenesis, and fibrotic scar formation. Herein, a photoliquefiable hydrogel dressing (denoted as PCS gel) is proposed as promising therapeutic strategy for rapid anti‐scar skin regeneration of refractory wounds. Specifically, the gel exerts robust antibacterial effect via mild thermogenesis for multidrug‐resistant biofilm eradication, and timely regulates tissue redox homeostasis. Upon efficient alleviation of local immoderate inflammation, PCS gel fosters a favorable pro‐regenerative microenvironment by bridging swift transition of the inflammatory stage to the proliferative stage, and thus significantly promotes neoangiogenesis as well as epithelialization. Importantly, the gel simultaneously alters pro‐regenerative fibroblast subpopulations by effective suppression of CD36 receptor during this stage, and hence blocks JUN overexpression‐mediated dermal fibrotic scarring. Notably, by thorough testing on both murine infected wound models (including acute wounds, diabetic chronic wounds) and rabbit ear hyperplastic scar wound model, PCS gel aided by thermogenesis facilitates rapid normal skin‐like epithelial closure with no perceptible hyperplastic scars. Therefore, our work emphasizes the promising regenerative strategy of immunomodulation and fibroblast lineage regulation by the PCS gel platform for rapid anti‐scar wound repair.