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 filed (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 field (μsPEF) methodology orients the new practical electric treatment in a wide range of biomedical applications, such as wound healing, regenerative medicine, and tissue engineering.

Enhanced Cell Viability and Migration of Primary Bovine Annular Fibrosus Fibroblast-like Cells Induced by Microsecond Pulsed Electric Field Exposure

“…Xiang et al report increased fibroblast cell migration speed with a single 100 μsPEF at 0.75 kV/cm stimulation, whereas fibroblasts exposed to 1.5 kV/cm stimulation express a remarkable decrease in migration speed. 46 When pulse parameters are selected such that a higher cell viability is maintained, μsPEF stimulation could promote an increased migration speed of primary AF cells over a long period, which has the potential to significantly reduce clinical treatment time and bolster regenerative tissue engineering.…”

Electrical Stimulation in Cartilage Tissue Engineering

“…It is established that low electric fields (either continuous or periodic) alter cell transmembrane potential, which leads to the opening of voltage-gated ion channels or changes in the enzymatic activity of phosphatases, containing a voltage-sensor domain [ 66 ]. High electric fields might have thermal effects and cause tissue damage; however, when high-intensity stimulation is applied for short intervals, it can trigger positive effects, similar to those induced by longer low electric field strength stimulation [ 67 ]. Depending on the pulsed electric field strength, the duration and the number of pulses can be reduced, providing flexibility in the development of parametric protocols ( Table 2 ) [ 68 ].…”