Abstract
Chronic skin wound in the aged tissue is quite hard to repair because of the accumulation of senescent cells and incresing secretion of senescence-associated secretory phenotype-(SASP). Stem cell-derived small extracellular vesicles (sEVs) show the ability to alleviate cellular senescence with very low risk of tumorigenesis and immune responses. Urine-derived stem cells (USCs) are a subpopulation of mesenchymal stem cells and can be obtained easily and noninvasively. Therefore, USC derived sEVs are attractive for the treatment of aging-associated diseases. In addition, how to maximize the biological effects of sEVs in the wound remains a challenge. Human acellular amniotic membrane (HAAM) can effectively promote the wound healing, and its porous structure enables them to act as an ideal reservoir for sEVs delivery. In this study, we find that HAAM loaded with USC-sEVs can effectively accelerate the wound healing by ameliorating cellular senescence and reducing the secretion of SASP in aged skin wound. In vitro experiments, HAAM showed the ability to release USC-sEVs, which could rejuvenate senescent fibroblasts by activating Sirt1 and lead to the acceleration of pressure ulcer in aged mice. We present a more convenient and effective sEVs composited material for treating aged skin wound.
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