Effects of electrical stimulation on human skin keratinocyte growth and the secretion of cytokines and growth factors

Electrical stimulation (ES) has been widely explored and found effective in promoting wound healing. However, the role of ES on keratinocytes, a major player in wound healing, has not been well established. The present work investigated the cellular and molecular behaviors of human skin keratinocytes being exposed to ES. HaCaT keratinocytes were seeded on a novel electrically conductive and soft PPy-PU/PLLA membrane and cultured under electrical intensities of 100 or 200 mV mm-1for 6 and 24 h. The factors assessed after ES include cell proliferation, colony formation, cytokines, keratins, as well as phosphorylated ERK1/2 (pERK1/2) kinases. The results showed that the electrically stimulated cells exhibited a higher proliferative ability and secreted more IL-6, IL-1α, IL-8, GROα, FGF2, and VEGF-A. Interestingly, the 24 h ES induced a 'stimulus memory' by showing a significant rise in colony-forming efficiency in post-ES cells that were sub-cultured. Additionally, after stopping the 24 h ES, the productions of keratin 5 and keratin 14 were continuously increased for 3 d. The productions of keratin 10 and keratin 13 were significantly increased post the 6 h ES. Finally, the ES increased pERK1/2 kinases. The overall results demonstrated that the proliferation of keratinocytes and their secretion of cytokines and growth factors can be activated through appropriate ES to benefit skin wound healing.