Expired apheresis platelet-derived exosomes promote cutaneous wound healing

Exosomes derived from apheresis platelets (AP-Exos) can regulate cellular functions and promote tissue regeneration; however, the characteristics and therapeutic efficacy of exosomes from expired apheresis platelets remain unclear. This study evaluated the properties of exosomes derived from apheresis platelets stored for 7 days (D7-Exos) and their role in skin wound repair. Exosomes were isolated from apheresis platelets stored for 3 days (D3-Exos) and 7 days, and their morphology, particle size, growth factor content, and biological effects on keratinocytes, fibroblasts, and endothelial cells were examined. The potential involvement of the PI3K/Akt signaling pathway in HUVEC was investigated. A full-thickness skin defect model was established in rats to compare the therapeutic efficacy of D3-Exos, D7-Exos, and platelet lysate (PL). D7-Exos showed higher particle concentration and elevated levels of TGF-β1 and PDGF-BB compared with D3-Exos. They significantly promoted cell proliferation, enhanced collagen secretion in HSF, and increased VEGF secretion and angiogenic capacity in HUVEC. D7-Exos activated the PI3K/Akt signaling pathway in HUVEC and upregulated VEGF expression. In vivo, D7-Exos markedly accelerated wound closure, re-epithelialization, and collagen deposition, with better efficacy than D3-Exos and PL. D7-Exos are enriched with multiple growth factors, promote VEGF secretion in HUVEC via activation of the PI3K/Akt pathway, and accelerate wound healing, suggesting potential as a candidate therapeutic approach for skin injury, pending further preclinical validation and safety assessment.