Keratinocyte electrotaxis induced by physiological pulsed direct current electric fields

Endogenous electric fields (EFs) direct the migration (electrotaxis) of keratinocytes in skin wounds, and the exogenous application of EFs may therefore improve wound healing, but the potential benefits are limited by the side effects of constant direct current (DC) passing through tissues. In contrast, with pulsed DC (characterized by intermittent output), parameters can be adjusted to minimize the adverse effects of electric currents. However, it remains unknown whether pulsed DC can reliably induce keratinocyte electrotaxis. In this study, using primary keratinocytes in an electrotaxis chamber, we found that a pulsed DCEF at physiological strength (EF = 150 mV/mm, duty cycle = 60%, frequency = 0.1 Hz) could induce robust electrotaxis. This effect was dependent on both voltage and duty cycle, but not on frequency. As predicted, fewer electrochemical reactions and cytotoxic reactions were detected with pulsed DCEF than with constant DCEF. In summary, we here demonstrate for the first time, that pulsed DCEF can trigger keratinocyte electrotaxis comparable to that induced by constant DCEF, while minimizing the electrochemical side effects. These findings support the future development of a pulsed DCEF device to improve wound healing in human patients. •Pulsed directed current electric field (DCEF) can induce keratinocyte electrotaxis•Pulsed DCEF is superior to constant DCEF on inducing keratinocyte electrotaxis•ERK1/2 involved in keratinocyte electrotaxis under pulsed DCEF