Despite significant progress in skin wound healing, it is still a challenge to construct multifunctional bioactive dressings based on a highly aligned protein fiber coated hydrogel matrix for antifibrosis skin wound regeneration that is indistinguishable to native skin. In this study, a "dual-wheel-driven" strategy is adopted to modify the surface of methacrylated gelatin (GelMA) hydrogel with highly aligned magnetic nanocomposites-protein fiber assemblies (MPF) consisting of photothermal responsive antibacteria superparamagnetic nanocomposites-fibrinogen (Fg) complexes as the building blocks. Whole-phase healing properties of the modified hydrogel dressing, GelMA-MPF (GMPF), stem from the integration of Fg protein with RGD peptide activity decorated on the surface of the antibacterial magnetic nanoactuator, facilitating facile and reproducible dressing preparation by self-assembly and involving biochemical, morphological, and biophysical cues. Payload and substantial release of copper ions for in situ catalytic production of nitric oxide (NO) from the fiber inorganic skeleton adsorbed by Fg molecules collectively regulate the proliferation, migration, reorganization, and transdifferentiation behavior of fibroblasts and fulfill antifibrosis in the process of skin wound healing and subcutaneous appendage regeneration. In full-thickness skin lesion mouse models, the complete regeneration of skin tissue with regenerated hair follicle cells and capillary blood vessels is realized in a temporally and spatially ordered manner.
Keywords: antifibrosis; highly aligned fibers; magnetic nanoactuator; multifunctional hydrogel dressing; nitric oxide; skin wound healing.