Non-thermal plasma (NTP) has nonspecific antibacterial effects, and can be applied as an effective tool for the treatment of chronic wounds and other skin pathologies. In this study we analysed the effect of NTP on the healing of the full-thickness acute skin wound model in rats. We utilised a single jet NTP system generating atmospheric pressure air plasma, with ion volume density 5 · 1017 m-3 and gas temperature 30-35 °C. The skin wounds were exposed to three daily plasma treatments for 1 or 2 minutes and were evaluated 3, 7 and 14 days after the wounding by histological and gene expression analysis. NTP treatment significantly enhanced epithelization and wound contraction on day 7 when compared to the untreated wounds. Macrophage infiltration into the wound area was not affected by the NTP treatment. Gene expression analysis did not indicate an increased inflammatory reaction or a disruption of the wound healing process; transient enhancement of inflammatory marker upregulation was found after NTP treatment on day 7. In summary, NTP treatment had improved the healing efficacy of acute skin wounds without noticeable side effects and concomitant activation of pro-inflammatory signalling. The obtained results highlight the favourability of plasma applications for wound therapy in clinics.

2nd Medical Faculty Charles University Prague Czech Republic

Institute of Experimental Medicine Academy of Sciences of the Czech Republic Prague Czech Republic

Institute of Physics Academy of Sciences of the Czech Republic Prague Czech Republic

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Emmert S. et al.. Atmospheric pressure plasma in dermatology: Ulcus treatment and much more. Clin Plasma Med 1, 24–29 (2013).

Haertel B., von Woedtke T., Weltmann K. D. & Lindequist U. Non-Thermal Atmospheric-Pressure Plasma Possible Application in Wound Healing. Biomol Ther 22, 477–490 (2014). PubMed PMC

Guerrero-Preston R. et al.. Cold atmospheric plasma treatment selectively targets head and neck squamous cell carcinoma cells. Int J Mol Med 34, 941–946 (2014). PubMed PMC

Yan D., Sherman J. H. & Keidar M. Cold atmospheric plasma, a novel promising anti-cancer treatment modality. Oncotarget (2016). PubMed PMC

Zhitong C., Xiaoqian C., Li L. & Michael K. Cold atmospheric plasma discharged in water and its potential use in cancer therapy. J Phys D Appl Phys 50, 015208 (2017).

Fridman A., Chirokov A. & Gutsol A. Non-thermal atmospheric pressure discharges. J Phys D Appl Phys 38, R1–R24 (2005).

Tian W. & Kushner M. J. Atmospheric pressure dielectric barrier discharges interacting with liquid covered tissue. J Phys D Appl Phys 47 (2014).

De Geyter N. & Morent R. Nonthermal Plasma Sterilization of Living and Nonliving Surfaces. Annu Rev Biomed Eng 14, 255–274 (2012). PubMed

Lunov O. et al.. Non-thermal plasma mills bacteria: Scanning electron microscopy observations. Appl Physs Lett 106, 053703 (2015).

Lunov O. et al.. The interplay between biological and physical scenarios of bacterial death induced by non-thermal plasma. Biomaterials 82, 71–83 (2016). PubMed

Kalghatgi S. et al.. Effects of non-thermal plasma on mammalian cells. Plos One 6, e16270 (2011). PubMed PMC

Ahn H. J. et al.. Atmospheric-pressure plasma jet induces apoptosis involving mitochondria via generation of free radicals. PLoS One 6, e28154 (2011). PubMed PMC

Ahn H. J. et al.. Targeting cancer cells with reactive oxygen and nitrogen species generated by atmospheric-pressure air plasma. Plos One 9, e86173 (2014). PubMed PMC

Dunnill C. et al.. Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process. Int Wound J (2015). PubMed PMC

Kurahashi T. & Fujii J. Roles of Antioxidative Enzymes in Wound Healing. J Dev Biol 3, 57 (2015).

Shao P. L. et al.. Enhancement of Wound Healing by Non-Thermal N2/Ar Micro-Plasma Exposure in Mice with Fractional-CO2-Laser-Induced Wounds. PloS one 11, e0156699 (2016). PubMed PMC

Arndt S. et al.. Cold atmospheric plasma (CAP) changes gene expression of key molecules of the wound healing machinery and improves wound healing in vitro and in vivo. PLoS One 8, e79325 (2013). PubMed PMC

Yu Y. et al.. Non-thermal plasma suppresses bacterial colonization on skin wound and promotes wound healing in mice. J Huazhong Univ Sci Technolog Med Sci 31, 390–394 (2011). PubMed

Xu G. M. et al.. Dual effects of atmospheric pressure plasma jet on skin wound healing of mice. Wound Repair Regen 23, 878–884 (2015). PubMed

Isbary G. et al.. Successful and safe use of 2 min cold atmospheric argon plasma in chronic wounds: results of a randomized controlled trial. Br J Dermatol 167, 404–410 (2012). PubMed PMC

Isbary G. et al.. A first prospective randomized controlled trial to decrease bacterial load using cold atmospheric argon plasma on chronic wounds in patients. Br J Dermatol 163, 78–82 (2010). PubMed

Brehmer F. et al.. Alleviation of chronic venous leg ulcers with a hand-held dielectric barrier discharge plasma generator (PlasmaDerm((R)) VU-2010): results of a monocentric, two-armed, open, prospective, randomized and controlled trial (NCT01415622). J Eur Acad Dermatol Venereol 29, 148–155 (2015). PubMed

Daeschlein G. et al.. Skin and wound decontamination of multidrug-resistant bacteria by cold atmospheric plasma coagulation. J Dtsch Dermatol Ges 13, 143–150 (2015). PubMed

Kalghatgi S., Friedman G., Fridman A. & Clyne A. M. Endothelial cell proliferation is enhanced by low dose non-thermal plasma through fibroblast growth factor-2 release. Ann Biomed Eng 38, 748–757 (2010). PubMed

Gweon B. et al.. Plasma effects on subcellular structures. Appl Phys Lett 96 (2010).

Zhong S. Y. et al.. Surface air plasma-induced cell death and cytokine release of human keratinocytes in the context of psoriasis. Br J Dermatol 174, 542–552 (2016). PubMed

Lunov O. et al.. Cell death induced by ozone and various non-thermal plasmas: therapeutic perspectives and limitations. Sci Rep-Uk 4, 7129 (2014). PubMed PMC

Lunov O. et al.. Towards the understanding of non-thermal air plasma action: effects on bacteria and fibroblasts. Rsc Adv 6, 25286–25292 (2016).

Reinke J. M. & Sorg H. Wound repair and regeneration. Eur Surg Res 49, 35–43 (2012). PubMed

Schmidt A., Bekeschus S., Wende K., Vollmar B. & von Woedtke T. A cold plasma jet accelerates wound healing in a murine model of full-thickness skin wounds. Exp Dermatol 26, 156–162 (2017). PubMed

Luo J. D. & Chen A. F. Nitric oxide: a newly discovered function on wound healing. Acta Pharmacol Sin 26, 259–264 (2005). PubMed

Luk P. P., Sinha S. N. & Lord R. Upregulation of inducible nitric oxide synthase (iNOS) expression in faster-healing chronic leg ulcers. J Wound Care 14, 373–375, 378–381 (2005). PubMed

Perez-Gomez E. et al.. Impaired wound repair in adult endoglin heterozygous mice associated with lower NO bioavailability. J Invest Dermatol 134, 247–255 (2014). PubMed

Heuer K. et al.. The topical use of non-thermal dielectric barrier discharge (DBD): Nitric oxide related effects on human skin. Nitric Oxide-Biol Ch 44, 52–60 (2015). PubMed

Hsu Y. C., Hsiao M., Wang L. F., Chien Y. W. & Lee W. R. Nitric oxide produced by iNOS is associated with collagen synthesis in keloid scar formation. Nitric Oxide-Biol Ch 14, 327–334 (2006). PubMed

Critical Analysis of Non-Thermal Plasma-Driven Modulation of Immune Cells from Clinical Perspective

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