Plasma Medicine: A Field of Applied Redox Biology

Abstract

Plasma medicine comprises the application of physical plasma directly on or in the human body for therapeutic purposes. Three most important basic plasma effects are relevant for medical applications: i) inactivation of a broad spectrum of microorganisms, including multidrug-resistant pathogens, ii) stimulation of cell proliferation and angiogenesis with lower plasma treatment intensity, and iii) inactivation of cells by initialization of cell death with higher plasma treatment intensity, above all in cancer cells. Based on own published results as well as on monitoring of relevant literature the aim of this topical review is to summarize the state of the art in plasma medicine and connect it to redox biology. One of the most important results of basic research in plasma medicine is the insight that biological plasma effects are mainly mediated via reactive oxygen and nitrogen species influencing cellular redox-regulated processes. Plasma medicine can be considered a field of applied redox biology.

Keywords: Plasma medicine; cold atmospheric plasma (CAP); redox biology; review.

Figure 1. Example photographs of the most common cold atmospheric plasma source principles for biomedical applications: volume DBD (A), surface DBD (B), and plasma jet (C).

Figure 2. Schematic of interactions between the kINPen plasma effluent with aqueous liquid. There are four reaction regions: (A) core plasma region, (B) effluent and plasma-ambient air interaction zone, (C) plasma/gas/liquid interface, and (D) bulk liquid. Seven processes are dominant for the generation of ROS and RNS, and their transfer: (1), (2) mass transfer from plasma to liquid based on gas/plasma component dissolution and gas and liquid flow, respectively, (3) photolysis based on the plasma UV radiation, (4); positive ions and clusters, which induce sputtering processes releasing water, gases, or electrons from the liquid, (5) negative ions, clusters, and cluster transport, (6) water evaporation, and (7) electron impact or transport. (Adapted from 32).

Figure 3. CAP treatment induces an early translocation of Nrf2 from the cytoplasm to the nucleus (lower images) in skin tissues (A, 3 s CAP treatment), dermal fibroblasts (B, 60 s CAP treatment) and in epidermal keratinocytes (C, 60 s CAP treatment) in contrast to untreated controls (upper images). Immunofluorescent staining of nuclei (blue: DAPI - 4’,6-Diamidino-2-phenylindole), Nrf2 (green in A, red in B, C), and F-actin cytoskeleton (green in B, C: Phalloidin-FITC). Scale bars=100 μm (See 117 for experimental details).

Figure 4. CAP treatment improves wound healing processes via redox-regulated pathways. Enhanced wound healing by CAP involves a distinct temporal pattern of inflammation, a promoting of pro-angiogenetic factors, and a balance of cellular proliferation and apoptotic events. The cellular redox homeostasis is maintained and cells are defended from damage by a strong modulation of the nuclear E2-related factor (Nrf2) pathway.

Figure 5. Different aspects of CAP-triggered oxidative stress, its control, adaptive response and physiological consequences. (Adapted from176).