Full-thickness skin defects caused by trauma or burns remain a clinical challenge due to limited donor sources and complications associated with traditional skin grafting. Herein, an injectable bioactive hydrogel was developed to promote skin regeneration and reduce scar formation. The hydrogel was formed by dynamic Schiff base bonding between oxidized hyaluronic acid (OHA) and adipic acid dihydrazide-grafted hyaluronic acid (HA-ADH), followed by photo-cross-linking of methacrylated decellularized matrix (dECMMA) to enhance mechanical stability. The optimized hydrogel showed good injectability, shear-thinning behavior, and reversible sol–gel transition. It exhibited excellent cytocompatibility and hemocompatibility and promoted fibroblast proliferation and migration while modulating macrophage polarization toward an anti-inflammatory M2 phenotype in vitro. In vivo studies demonstrated that the hydrogel maintained a moist wound environment and promoted progressive wound closure, while histological examination revealed more organized tissue architecture and reduced fibrotic deposition compared with the untreated control group, suggesting favorable skin regeneration with reduced scar formation. Overall, this injectable OHA/HA-ADH/dECMMA hydrogel demonstrates excellent biocompatibility and regenerative potential, offering a promising alternative to skin grafts for the treatment of full-thickness skin defects.
Qiu et al. (Mon,) studied this question.