State of the Art on the Understanding of Plasma Jet Interaction with Skin Tissue Models

This paper provides an overview of past and new experimental studies with kHz helium plasma jets and floating-electrode dielectric barrier discharge (DBD) in the context of biomedical applications with the aim to discuss the interaction of plasma jet with skin tissue models. The key motivation is to summarize and address perspectives on the understanding of the mode of action of nonthermal plasma from surface delivery to the biological response of deeper and deeper tissues. First, the significant impact of the target exposed to the plasma jet on the plasma characteristics is documented, highlighting the importance of considering this interaction for <i>in vivo</i> studies. Next, cell permeabilization was first reported and translated to the study of plasma jet permeation of reconstructed epidermis, human explants, and human tissues. Strong analogies are observed in all three substrates, demonstrating a potent but transient modulation of surface features and skin barrier function for a few minutes following a brief plasma exposure time of a few tens of seconds. Interestingly, the modulation of reactive oxygen and nitrogen species generation, so-called RONS, with the variation of the pulse repetition rate of the plasma jet shows no direct correlation with the permeation efficiency. This questions the role of RONS alone in the mode of action of nonthermal plasma for biological response in the few hundreds of microns to the few millimeter tissue layers as was previously also questioned for subcutaneous action of plasma in wound and tumor <i>in vivo</i> treatments. Finally, the combinative role of RONS with electrical factors (charging, current, electric field) is hypothesized and supported with the investigation of deeper living skin tissue oxygenation and vasodilation.