Helium/Argon-Generated Cold Atmospheric Plasma Facilitates Cutaneous Wound Healing

Bih-Show Lou; Jang-Hsing Hsieh; Chun-Ming Chen; Chun-Wei Hou; Hui-Yu Wu; Pang-Yun Chou; Chih-Ho Lai; Jyh-Wei Lee

doi:10.3389/fbioe.2020.00683

Helium/Argon-Generated Cold Atmospheric Plasma Facilitates Cutaneous Wound Healing

Front Bioeng Biotechnol. 2020 Jun 30:8:683. doi: 10.3389/fbioe.2020.00683. eCollection 2020.

Authors

Bih-Show Lou^{1

2}, Jang-Hsing Hsieh^{3

4}, Chun-Ming Chen³, Chun-Wei Hou¹, Hui-Yu Wu⁵, Pang-Yun Chou⁶, Chih-Ho Lai^{5

7

8

9}, Jyh-Wei Lee^{3

4

6

10}

Affiliations

¹ Chemistry Division, Center for General Education, Chang Gung University, Taoyuan, Taiwan.
² Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
³ Center for Plasma and Thin Film Technologies, Ming Chi University of Technology, New Taipei, Taiwan.
⁴ Department of Materials Engineering, Ming Chi University of Technology, New Taipei, Taiwan.
⁵ Department of Microbiology and Immunology, College of Medicine, Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
⁶ Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁷ Department of Pediatrics, Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan.
⁸ Department of Medical Research, School of Medicine, China Medical University and Hospital, Taichung, Taiwan.
⁹ Department of Nursing, Asia University, Taichung, Taiwan.
¹⁰ Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan.

Abstract

Cold atmospheric plasma jet (CAPJ) or non-thermal plasma jet has been employed in various biomedical applications based on their functions in bactericidal activity and wound healing. However, the effect of CAPJ generated by a particular composition of gases on wound closure and the underlying mechanisms that regulate wound healing signals remain elusive. In the present study, we investigated the impact of helium (He)- or a gas mixture of He and argon (He/Ar)-generated CAPJ on cell proliferation, which is a pivotal step during the wound healing process. With careful treatment duration control, He/Ar-CAPJ effectively induced keratinocyte proliferation and migration mediated through the activation of epithelial-to-mesenchymal transition (EMT) and cell cycle progression, which was evidenced by a decrease in E-cadherin levels and increases in N-cadherin, cyclin D1, Ki-67, Cdk2, and p-ERK levels. Rat wound healing studies showed that He/Ar-CAPJ treatment facilitated granulation tissue formation and mitigated inflammation in cutaneous tissue, resulting in accelerated wound closure. These findings highlight the possibility that He/Ar-CAPJ can be developed as a therapeutic agent for enhancing wound healing.

Keywords: cell cycle; cell proliferation; cold atmospheric plasma jet; keratinocyte; wound healing.