Preparation of Apoptotic Extracellular Vesicles from Adipose Tissue and Their Efficacy in Promoting High-Quality Skin Wound Healing

Purpose: A lot of strategies have been attempted to achieve high-quality skin wound healing, among them, fat transplantation has been used for skin wound repair and scar management and has shown beneficial effects. However, the underlying mechanism is still unclear. Recently, studies found that transplanted cells underwent apoptosis within a short period and apoptotic extracellular vesicles (ApoEVs) might play the therapeutic role. Methods: In this study, we directly isolated apoptotic extracellular vesicles from adipose tissue (ApoEVs-AT) and evaluated their characteristics. In vivo, we investigated the therapeutic role of ApoEVs-AT in full-thickness skin wounds. The rate of wound healing, the quality of granulation tissue, and the area of scars were evaluated here. In vitro, we investigated the cellular behaviors of fibroblasts and endothelial cells induced by ApoEVs-AT, including cellular uptake, proliferation, migration, and differentiation. Results: ApoEVs-AT could be successfully isolated from adipose tissue and possessed the basic characteristics of ApoEVs. In vivo, ApoEVs-AT could accelerate skin wound healing, improve the quality of granulation tissue, and reduce the area of scars. In vitro, ApoEVs-AT could be engulfed by fibroblasts and endothelial cells, significantly enhancing their proliferation and migration. Moreover, ApoEVs-AT could promote adipogenic differentiation and inhibit the fibrogenic differentiation of fibroblasts. Conclusion: These findings indicated that ApoEVs could be successfully prepared from adipose tissue and showed the ability to promote high-quality skin wound healing by modulating fibroblasts and endothelial cells.