Application of adipose mesenchymal stem cell-derived exosomes-loaded β-chitin nanofiber hydrogel for wound healing.

INTRODUCTION Clarifying the role and mechanism of exosome gel in wound repair can provide a new effective strategy for wound treatment. MATERIALS AND METHODS The cellular responses of adipose mesenchymal stem cell-derived exosomes (AMSC-exos) and the wound healing ability of AMSC-exos-loaded β-chitin nanofiber (β-ChNF) hydrogel were studied in vitro in mouse fibroblasts cells (L929) and in vivo in rat skin injury model. The transcriptome and proteome of rat skin were studied with the use of sequenator and LC-MS/MS, respectively. RESULTS 80 and 160 μg/mL AMSC-exos could promote the proliferation and migration of mouse fibroblasts cells. Furthermore, AMSC-exos-loaded β-ChNF hydrogel resulted in a significant acceleration rate of wound closure, notably acceleration of re-epithelialization, and increased collagen expression based on the rat full-thickness skin injury model. The transcriptomics and proteomics studies revealed the changes of the expression of 18 genes, 516 transcripts and 250 proteins. The metabolic pathways, tight junction, NF-κB signaling pathways were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway. Complement factor D (CFD) and downstream Aldolase A (Aldoa) and Actn2 proteins in rats treated with AMSC-exos-loaded β-ChNF hydrogel were noticed and further confirmed by ELISA and Western blot. CONCLUSION These findings suggested that AMSC-exos-loaded β-ChNF hydrogel could promote wound healing with the mechanism which is related to the effect of AMSC-exos on CFD and downstream proteins.