Bioinspired Hydrogel Prepared by Core‐Shell Nanofibers: Accelerating Wound Healing via Macrophage Polarization Modulation

ABSTRACT The fascia, a hierarchical composite structure present in the skin, can promote the rapid repair of damaged tissues and reduce the formation of scars. However, its important role in wound repair has been severely neglected. Therefore, we develop a wound dressing with a nanofiber network structure that mimics the skin fascia. Using methacryloyl chondroitin sulfate as a hydrogel substrate, a light‐clickable fascia‐inspired nanofibrous hydrogel (CA‐DAF‐BSA @ PFD) is constructed by electrospinning a dextran shell loaded with pirfenidone albumin nanoparticles (BSA @ PFD) to form a core‐shell fiber network. The hydrogel demonstrates good viscoelasticity, injectability, swelling resistance, antibacterial activity, and biocompatibility. In vitro cell studies demonstrate that CA‐DAF‐BSA @ PFD hydrogel induces macrophage polarization toward the M2 phenotype and inhibits fibroblast differentiation into myofibroblasts. In vivo, CA‐DAF‐BSA @ PFD hydrogel can significantly promote granulation tissue regeneration and effectively reduce the formation of scar tissue by inhibiting excessive collagen deposition and abnormal fibrosis. This core‐shell fiber hydrogel exhibits significant potential as an advanced wound dressing, offering a novel therapeutic strategy for achieving both high‐efficiency and biocompatible tissue repair.