Microsecond pulse electrical stimulation modulates cell migration

Abstract Wound healing is a complicated process for maintaining skin integrity after injury, for which electrical stimulations (ES) are ascribed to promote wound healing by facilitating cell migration. Time-shortening of the stimulation treatment from current hours to minutes for efficient wound healing but free of cell damage in return, is however rather a challenge. Here, a novel mechanism of ultrashort pulse electric field (PEF), microsecond PEF at higher voltage, is proposed and realized to promote wound healing under a much short time (seconds) for the total treatment. We revealed that microsecond PEF regulated actin cytoskeleton reorganization and focal adhesion turnover, promoting fibroblasts migration in 2D cell cultures under the pulse stimulation. This accelerated fibroblast migration was accompanied by the mutual promotion with extracellular matrix (ECM) alignment in 3D microenvironments, which cooperatively benefit the eventual wound healing, and these findings were further confirmed by the enhanced skin wound healing in a classic mouse model. Additionally, we coined an actin- and collagen-dependent mechanism of microsecond PEF-mediated wound healing. The quantitative mechanism proposed here for our novel microsecond pulse electric filed (μsPEF) methodology orients the new practical electric treatment in a wide range of biomedical applications, such as wound healing, regenerative medicine, and tissue engineering.