Mechanism of action of adipose-derived mesenchymal stem cell supernatant/PF-127/HAhydrogel in promoting skin wound healing

Skin wound repair is challenging due to low efficiency and scarring. ADMSC-CM, which is rich in bioactive factors, has limited direct use because of rapid degradation. A thermosensitive PF-127/HA hydrogel delivery system for ADMSC-CM was developed. ADMSCs were isolated and characterized. The hydrogel's thermosensitivity, microstructure, and in vitro release profile were assessed. A full-thickness mouse skin defect model was used to compare wound healing, histopathology, and gene expression. Transcriptome profiling was performed. The hydrogel group showed faster wound closure, enhanced neovascularization, collagen deposition, and hair follicle regeneration. In the inflammatory phase (24h), genes such as Cks2, Pdzk1ip1, and Saa3 activated the MAPK pathway. In the regeneration phase (120h), genes including Krt77, Dapl1, and Ctsk promoted keratin formation and ECM remodeling. Differentially expressed genes (DEGs) were enriched in pathways related to tight junctions and Th17 cell differentiation. The ADMSC-CM/PF-127/HA hydrogel, with its thermosensitivity, porous structure, and sustained release capability, effectively preserves ADMSC-CM bioactivity, regulates key gene expression, and promotes skin wound repair, offering a promising cell-free regenerative therapy strategy.