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Elevated angiogenesis was reported in twelve eligible studies through multiple signaling pathways such as PI3K/Akt, MAPK/ERK, and JAK/STAT. The well-known signaling pathway to inhibit scar formation was TGF-β2/SMAD2. However, all included studies were not blinded enough which may have introduced bias. Therefore, the transition of EV's efficacy into the clinics is deeply rooted in the following important factors 1) pre-clinical studies with a lower risk of bias and longer follow-up time, and 2) consistent, reproducible, and feasible man