<p>Exosomes released by epithelial keratinocytes and dermal fibroblasts significantly accelerate wound healing. Moreover, endogenous electric fields (EFs) were demonstrated to promote wound healing by directing the migration of epidermal cells toward the wound center, it is currently unclear whether EFs may facilitate wound healing by regulating the secretion of exosomes in these cells. In this study, we demonstrated that physiological-intensity EFs significantly enhanced exosome secretion from HaCaT cells, with the total protein content of the exosomes increased by approximately 1.5 times higher than that of the control group. Additionally, the exosomes derived from EF-stimulated HaCaT cells accelerated the wound healing rate of HaCaT and HSF cells, and the wound closure rate increased by approximately 20%. Mechanistically, we identified that EFs regulated exosome secretion by influencing the expression of exosome-related proteins—including ALIX and TSG101. Overall, our research results indicate that the electric field is an effective regulatory factor for enhancing exosome secretion and establish a novel high-exosome-producing strategy based on bioelectrics. This may lay the foundation for the translational application of exosomes in wound healing and other fields.</p> Graphical abstract <p></p>