Cold plasma

Plasma: The 4th state of matter

Plasma is the fourth state of matter after solid, liquid and gas. Plasma is a gaseous state where ions circulate freely, i.e. an ionized gas. This ionization can be caused by an increase in temperature or strong electromagnetic changes.

Solid

Liquid

Gas

Plasma

Lightning and the aurora borealis are examples of atmospheric plasma that can be found in nature.
Other examples are fluorescent lamps or plasma televisions.

COLD ATMOSPHERIC PLASMA THERAPY (CAP)

Cold atmospheric plasma is therefore a partially ionized gas, below 40°C, highly electrically conductive. The technology most commonly used in medicine is DBD (Dielectric Barrier Discharge), where the electrode is protected by an insulating layer of glass (dielectric) and the patient serves as a counter electrode.

The primary plasma applies voltage to the dielectric and the secondary plasma is generated by discharges between the device and the patient (conducting surface), which generates the biological and therapeutic action of the cold plasma. Due to the low electrical currents and its low temperature (<40ºC) this technology can be applied on living tissues and is widely accepted by patients.

Fundamentals and mechanisms of action

The various biological effects of CAP are based on the synergistic effects of the plasma components.

Therapeutic cold plasma consists of, among other things, ions, electrons, reactive oxygen and nitrogen species (ROS and RNS), UV radiation and electromagnetic fields.

First level: Cold plasma therapy

Efficacy down to the basal layer of the skin and adjacent tissue up to 1cm.

Antisepsis
The strong antiseptic effect of oxygen and nitrogen radicals formed on the surface and in the tissue is not affected by microbial resistance problems and achieves a pronounced deep effect down to the basal layer of the skin: This leads to an effective elimination of multi-resistant bacteria and biofilms.
Direct cell activation
Directly stimulated cells show increased proliferation and improved cell communication, which favorably influences inflammation and healing processes.
Angiogenesis
Immediate and sustained hyperaemia occurs with the formation of new blood vessels, improved oxygenation and enhanced microcirculation. Scars are revitalized and reduced through increased blood circulation and improved cellular structure.
Stimulates the Immune System
Cytokines locally attract macrophages and other immune cells.
Regulates inflammation
Through reduction of proinflammatory cytokines, inhibition of immune cell activation, regulation of oxidative stress and modulation of the inflammation process.
pH reduction
The pH is reduced to a range more favourable for wound healing.
Debridement
Damaged cells are eliminated earlier with the help of macrophages because their DNA is more sensitive to the effects of CAP.
Antisepsis Stimulates the Immune System Debridement Regulates inflammation Direct cell activation pH reduction Angiogenesis
Antisepsis Stimulates the Immune System Debridement Regulates inflammation Direct cell activation pH reduction Angiogenesis

Second level: High-frequency pulses (electrotherapy)

Tissue penetration deeper than 1 cm.
The powerful electromagnetic field can be used therapeutically for its effect on muscle tissue and nerves.
The source should be DBD with selectable pulse (Hz), ideally stimulating from 10 to 40Hz for muscle tension, recovery and stimulation after nerve damage and prevention of denervation of associated muscles.

Antimicrobial effects: Bacteria
  • Brun P, Bernabè G, Marchiori C, Scarpa M, Zuin M, Cavazzana R, Zaniol B, Martines E. Antibacterial efficacy and mechanisms of action of low power atmospheric pressure cold plasma: membrane permeability, biofilm penetra­tion and antimicrobial sensitization. J Appl Microbiol. 2018 Aug;125(2):398-408. PMID: 29655267. doi: 10.1111/jam.13780
  • Haghighi L, Azizi A, Vatanpour M, Ramezani G. Antibacterial Efficacy of Cold Atmospheric Plasma, Photodynamic Therapy with Two Photosensitizers, and Diode Laser on Primary Mandibular Second Molar Root Canals Infec­ted with Enterococcus faecalis: An in Vitro Study. Int J Dent. 2023 Apr 21:2023:5514829. PMID: 37123349. doi: 10.1155/2023/5514829
Antimicrobial effects: Viruses
  • Alekseev O, Donovan K, Limonnik V, Azizkhan-Clifford J. Nonthermal Dielectric Barrier Discharge (DBD) Plasma Su­ppresses Herpes Simplex Virus Type 1 (HSV-1) Replication in Corneal Epithelium. Transl Vis Sci Technol. 2014 Mar 27;3(2):2. PMID: 24757592. doi: 10.10.1167/tvst.3.2.2
  • Bunz O, Mese K, Zhang W, Piwowarczyk A, Ehrhardt A. Effect of cold atmospheric plasma (CAP) on human adenovi­ruses is adenovirus type-dependent. PLoS One. 2018 Oct 26;13 (10):e0202352. PMID: 30365500. doi: 10.1371/jour­nal.pone.0202352
  • Aboubakr HA, Mor SK, Higgins LA, Armien A, Youssef MM, Bruggeman PJ, Goyal SM. Cold argon-oxygen plasma species oxidize and disintegrate capsid protein of feline calicivirus. PLoS One. 2018 Mar 22;13(3):e0194618. PMID: 29566061. doi: 10.1371/journal.pone.0194618
Antimicrobial effects: Fungi
  • Lee T-H, Hyun J-E, Kang Y-H, Baek S-J, Hwang C-Y. In vitro antifungal activity of cold atmospheric microwave plasma and synergistic activity against Malassezia pachydermatis when combined with chlorhexidine gluconate. Vet Med Sci. 2022 Mar;8(2):524-529. PMID: 35089639. doi: 10.1002/vms3.719
  • Šimončicová J, Kaliňáková B, Medvecká V, Lakatoš B, Kryštofová S, Hoppanová L, Palušková V, Hudecová D, Ďurina P, Zahoranová A. Cold plasma treatment triggers antioxidative defense system and induces changes in hyphal surface and subcellular structures of Aspergillus flavus. Appl Microbiol Biotechnol. 2018 Aug;102(15):6647-6658. PMID: 29858953. doi: 10.1007/s00253-018-9118-y
  • Gnat S, Lagowski D, Dylag M, Zielinski J, Studzinski M, Nowakiewicz A. Cold atmospheric pressure plasma (CAPP) as a new alternative treatment method for onychomycosis caused by Trichophyton verrucosum: in vitro studies. 2021 Dec;49(6):1233-1240. PMID: 34499324. doi: 10.1007/s15010-021-01691-w
Antimicrobial effects: Parasites
  • Ten Bosch L, Habedank B, Siebert D, Mrotzek J, Viöl W. Cold Atmospheric Pressure Plasma Comb – A Physical Approach for Pediculosis Treatment. Int J Environ Res Public Health 2018 Dec 21;16(1):19. PMID: 30577656. doi: 10.3390/ijerph16010019
  • Daeschlein G, Scholz S, Arnold A, von Woedtke T, Kindel E, Niggmeier M, Weltmann K-D, Jünger M. In Vitro Activity of Atmospheric Pressure Plasma Jet (APPJ) Plasma Against Clinical Isolates of Demodex Folliculorum. IEEE Transac­tions on Plasma Science, Vol. 38, No. 10, October 2010. doi: 10.1109/TPS.2010.2061870
Neovascularization and angiogenesis
  • Schmidt A, Liebelt G, Striesow J, Freund E, von Woedtke T, Wende K, Bekeschus S. The molecular and physiologi­cal consequences of cold plasma treatment in murine skin and its barrier function. Free Radic Biol Med. 2020 Dec: 161:32-49. PMID: 33011275. doi: 10.1016/j.freeradbiomed.2020.09.026
  • Chatraie M, Torkaman G, Khani M, Salehi H, Shokri B. In vivo study of non-invasive effects of non-thermal plasma in pressure ulcer treatment. Sci Rep. 2018 Apr 4;8(1):5621. PMID: 29618775. doi: 10.1038/s41598-018-24049-z
  • Schmidt A, Niessner F, von Woedtke Th, Bekeschus S. Hyperspectral Imaging of Wounds Reveals Augmented Tissue Oxygenation Following Cold Physical Plasma Treatment in Vivo. IEEE TRANSACTIONS ON RADIATION AND PLASMA MEDICAL SCIENCES, VOL. 5, NO. 3, MAY 2021
  • T. von Woedtke, A. Schmidt, S. Bekeschus, K. Wende, K.D. Weltmann, Plasma medicine: a field of applied redox biology, Vivo 33 (2019) 1011–1026, doi: 10.21873/invivo.11570
Modulation of inflammatory cytokines
  • Schmidt A, von Woedtke T, Vollmar B, Hasse S, Bekeschus S. Nrf2 signaling and inflammation are key events in physical plasma-spurred wound healing. Theranostics. 2019 Jan 30;9(4):1066-1084. PMID: 30867816. doi: 10.7150/thno.29754
  • Ding C, Huang P, Feng L, Jin T, Zhou Y, He Y, Wu Z, Liu Y. Immediate intervention effect of dielectric barrier discharge on acute inflammation in rabbit’s ear wound, AIP Advances 10. 2020, 025008. doi: 10.1063/1.5139953
Cellular apoptosis
  • Haertel B, von Woedtke T, Weltmann K-D, Lindequist U. Non-thermal atmosperic-pressure plasma possible application in wound healing. Biomol Ther (Seoul). 2014 Nov;22(6):477-90. PMID: 25489414. doi: 10.4062/biomolther.2014.105
  • Gay-Mimbrera J, Garcia MC, Isla-Tejera B, Rodero-Serrano A, Garcia-Nieto AV, Ruano J. Clinical and Biological Princi­ples of Cold Atmospheric Plasma Application in Skin Cancer. Adv Ther. 2016 Jun;33(6):894-909. PMID: 27142848. doi: 10.1007/s12325-016-0338-1
Nerve regeneration
  • Lee S-T, Jang Y-S, Kim U-K, Kim H-J, Ryu M-H, Kim G-C, Hwang D-S. Non-thermal plasma application enhances the recovery of transected sciatic nerves in rats. Exp Biol Med (Maywood). 2021 Jun;246(11):1287-1296. PMID: 33653158. doi: 10.1177/1535370221996655
  • Ding C, Ni L, Liu Q, et al. Cold air plasma improving rheumatoid arthritis via mitochondrial apoptosis pathway. Bioeng Transl Med. 2023;8(1):e10366. doi:10.1002/btm2.10366
  • Faramarzi F, Zafari P, Alimohammadi M, et al. Inhibitory Effects of Cold Atmospheric Plasma on Inflammation and Tu­mor‑Like Feature of Fibroblast‑Like Syn

Cold plasma therapy equipment for small animals

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Cold plasma therapy device for horses

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