Development of an atmospheric nonthermal multineedle dielectric barrier discharge jet for large area treatment of skin diseases
Graphical abstract
Introduction
Recently, interest in various plasma-based technologies has been rapidly increasing. In particular, atmospheric pressure low temperature plasmas have recently received considerable attention in the field of plasma medicine (or bioplasma) due to the results of research on the treatment and modification of biological targets including tissues and cells through the generation of controlled chemically active species. Although various medical studies using plasma have been conducted, there is still a shortage of relevant literature on treatment of skin diseases such as psoriasis; thus, there is a strong demand for research on psoriasis treatment using plasma [1].
Woedtke et al. [2] performed various biological studies using a pen shaped plasma jet called kINPen. They reported that reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by the low temperature plasma jet induced oxidative damage and modification of the cytoplasmatic membrane, proteins, and DNA. They also confirmed the low temperature plasma jet to be effective for wound healing and cell regeneration through in vivo and in vitro experiments. Cheng et al. [3] reported the effect of an Ar atmospheric pressure plasma jet on promoting diabetic wound healing in rats through the ROS generated by the plasma. Additionally, Lee et al. [4] demonstrated the use of a nonthermal plasma jet to suppress psoriasis like skin inflammation using a mouse model. It was also proven that the increase in epithelial cell thickness and the expression of inflammatory molecules were suppressed in response to the treatment using the nonthermal plasma jet. Even though many researchers have demonstrated that plasma technology can be applied to wound healing, microbial sterilization, and cancer cell removal, treatment of skin inflammatory diseases has not been studied extensively. Thus, the need for research on skin diseases such as psoriasis is continuing to increase. Psoriasis is an immune mediated autoimmune skin disease induced by chronic activation of inflammatory cell infiltration and dysregulation of epidermal keratinocytes in the skin and occurs over a large area on the human skin. Therefore, it is necessary to develop a plasma generation source capable of treating a large area. Although plasma sources with new designs and features are continually being developed, the one most widely used in the biomedical field is the common pen type nonthermal atmospheric pressure plasma jet (NT-APPJ). This type of source is popular because an NT-APPJ can be generated from a long distance of about several centimeters on human skin, so it is relatively safe against electric shock according to the structure of plasma source and directly induces biological effects on human skin. However, a pen type NT-APPJ can characteristically affect the high density plasma only in a very localized area of about 0.1 mm to a few millimeters; thus, its application to skin diseases is limited [5,6].
To overcome this challenge, in this study, we developed a multineedle DBD jet, which is a type of NT-APPJ that can stably generate large amounts of active species and radicals, which induce chemical and biological reactions. The developed plasma jet is designed to treat relatively large areas using a multineedle structure, as shown in Fig. 1(a). Various analyses were performed using He, Ar, N2, and air to characterize the multineedle DBD jet. To confirm the stable generation of plasma and power consumption with different discharge gases, the electrical characteristics were analyzed, and qualitative optical analysis of optical emission spectra (OES) was performed to confirm the generation of active species and radicals. In addition, optimized operating conditions were established based on the results of the characterization. Finally, we determined whether the developed plasma jet could inhibit STAT3 activation in vitro and ameliorate psoriasis like skin inflammation in mice. Imiquimod is a ligand for toll-like receptors of immune cells, and induces strong activation of the immune system, which causes significant markers of psoriatic pathogenesis including hyperproliferation and immune cell infiltration. Therefore, we used an imiquimod-induced psoriasis mouse model to determine whether multineedle DBD jet could treat the inflammatory skin disease.
Section snippets
Structure of the multineedle DBD jet
Fig. 1(a) shows schematic drawings of the multineedle DBD jet developed in this study. The plasma jet consisted of a high voltage (H.V) electrode, a ground electrode, a dielectric, an insulator, a gas injection port, and a high voltage power supply. The power supply shown in the figure was a commercially available 25 kHz AC transformer (NTO-500, NT electronics, South Korea) and was connected to the H.V and ground electrodes. The high voltage electrode was composed of stainless steel and was in
Stable plasma generation and characteristics with changes in discharge gas
NT-APPJ generates ROS, RNS, UV, electrons, and charged ions according to the operating conditions. Despite many plasma medicine studies utilizing NT-APPJ, it has not yet been clarified exactly what mechanism and which active species would be useful for medical treatment or alleviation. However, various studies have shown that plasma generated ROS plays a role in wound healing, cancer cell elimination, and sterilization [7]. In particular, OH radicals are strongly oxidizing (E0 = 2.80 V) and
Conclusions
In this research, we developed a multineedle DBD jet that can be used in plasma medicine and applied it to the treatment of psoriasis. The jet was stably formed in a wide range while enlarging the narrow processing area, which is a fatal drawback of the existing atmospheric pressure plasma jet. Optimal operating conditions were established based on electrical and optical analysis, and it was confirmed that ROS, which is useful for the treatment of psoriasis, was generated by He and Ar plasma.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
Funding: This study was supported by the R&D Program of Plasma Convergence and Fundamental Research through the National Fusion Research Institute of South Korea (NFRI) funded by the Korean Government, and the Basic Science Research Program (2017M3A9F7079339) through the National Research Foundation of Korea funded by the Ministry of Science, ICT, and Future Planning (MSIP).
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