Cold atmospheric plasma promotes migration persistence, through induced H₂O₂ and electric field

Cold atmospheric plasma (CAP) generates various products, including radiation, electrons, ions, an electric field, and reactive oxygen and nitrogen species. CAP promotes wound healing and has been implemented in several medical devices to treat acute or chronic wounds. Beyond the closure of the epidermal monolayer of keratinocytes, wound healing requires migration of dermal fibroblasts. The effect of CAP on fibroblast migration has been insufficiently characterized. Here, we show, using primary human dermal fibroblasts, that a 10-s exposure to CAP suffices to increase Arp2/3-dependent lamellipodium formation and migration persistence for several hours. In an attempt to identify the specific CAP-generated products involved in this activity, we found that reactive oxygen species and the electric field induced by plasma were critical for enhanced and sustained migration persistence. Taken separately, these two stimuli were only partially active in inducing migration persistence at the dose that CAP generates. However, their combination was sufficient to recapitulate the full enhancement of migration persistence obtained with CAP exposure, indicating that these two stimuli act in synergy and that they likely represent the active components of CAP to activate migration of dermal fibroblasts during wound healing.