ADSC-Exo-bFGF promotes skin wound healing and correlates with the PI3K/AKT signaling pathway activation

Wound healing is a complex physiological process involving a variety of tissue repair cells. Adipose-derived stem cell (ADSC)-derived exosomes have demonstrated potential in promoting wound healing. Basic fibroblast growth factor (bFGF) is known to facilitate tissue regeneration. Nevertheless, the biological functions and detailed mechanisms of ADSC-Exo-bFGF in cutaneous wound healing remain largely unelucidated. The study aimed to construct a bFGF-glycosylphosphatidylinositol (GPI)-anchored exosome system (ADSC-Exo-bFGF) and further explore its therapeutic efficacy and underlying molecular mechanisms in skin wound healing. A eukaryotic expression plasmid carrying bFGF-GPI fusion gene was constructed and transfected into ADSCs. Secreted exosomes were isolated and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. Hematoxylin and Eosin (H&E) staining and Masson's trichrome staining were used for histological assessment. Inflammatory cytokines in wound tissues and cell supernatants were quantified by enzyme-linked immunosorbent assay (ELISA). Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. Scratch assay was applied for determining cell migration ability. The protein levels of bFGF and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway related proteins were assessed using western blot assay. Characteristic exosomal surface markers were positively expressed in isolated ADSC-Exo-bFGF, which also exhibited abundant bFGF protein expression. In vivo results confirmed that compared with control groups, ADSC-Exo-bFGF treatment significantly accelerated skin wound healing, reduced inflammatory infiltration, and enhanced collagen deposition, exerting better therapeutic effects than unmodified ADSC-derived exosomes. In vitro experiments further verified that ADSC-Exo-bFGF promoted proliferation and migration of human skin fibroblasts (HSFs) and suppressed inflammatory factor secretion, with superior biological activity relative to empty exosomes. Western blot results revealed that ADSC-Exo-bFGF markedly elevated the phosphorylation levels of p-PI3K and p-AKT in both HSFs and mouse wound tissues, suggesting that the PI3K/AKT signaling pathway is likely involved in this biological process. Our findings revealed that bFGF-GPI-anchored exosomes accelerate skin wound healing via suppressing inflammatory responses, which is accompanied by the activation of the PI3K/AKT signaling cascade. This research offers a novel promising therapeutic strategy for clinical cutaneous wound treatment.