Multiple Mesenchymal Stem Cell Derived Extracellular Vesicle Administration Accelerates Healing and Ameliorates Tissue Scarring Compared with Single Application in Full Thickness Cutaneous Wounds

Background Impaired wound healing is still challenging for patients and health care providers. Healing is a complex multiphasic process that is mediated by paracrine signaling. In recent years, human umbilical cord mesenchymal stem cell (hUC-MSC) derived extracellular vesicles (EVs) have shown promising effects on healing acceleration by modifying intercellular interactions. However, they will be promptly washed out after local injection and are almost depleted from the injured site in five days. Therefore, single-dose administration may fail to affect all phases of the healing process. In this study, we evaluated the advantages of multi-administration over its single injection following full-thickness cutaneous wound induction in rats. Methods EVs were isolated from human umbilical cord mesenchymal stem cells and characterized. These particles were administered locally in the EV-treated wounds. The level of inflammatory (TNF-α and TGF-β) and angiogenesis (CD31) factors were evaluated through the study to compare multiple dose EV administered, single dose EV administered, and control wounds with each other. Results In vivo results demonstrate that triple EV administration significantly attenuates inflammation and improves angiogenesis and collagen deposition in the injured area (p < 0.05). Conclusion This study suggests that multiple injections of EVs promotes wound closure and decreases scar formation mainly by maintaining adequate concentration in the wounded area.