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Plasma from outer space – a reactive bundle of energy

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What is cold atmospheric plasma?

Solid, liquid, gaseous – these are the generally known states of aggregation.

When ice and water are heated, they change their physical state: ice melts and water evaporates. Almost all matter changes its state of aggregation in a similar way if enough energy is added.
If additional energy is added to a gas, plasma is created. This process leads to ionization of the molecules.

Plasma is therefore an ionized gas.

Plasma is a fourth state of matter that is created when energy is added to a gas.

Natural plasma is produced by phenomena such as lightning or the Northern Lights, i.e. the plasma occurring in nature is far too hot to be applied directly to living beings. It was only through the technical development of cold atmospheric plasma, i.e. plasma at room temperature and under atmospheric pressure, that it became possible to apply it to human skin.

But how does an extremely hot gas mixture become cold plasma?

To obtain cold plasma, just enough energy is added to a gas so that it is only partially ionized (one particle out of 10⁹ is ionized). This allows the temperature to be controlled so that it remains below 40°C.

This process triggers a cascade of chemical reactions that produce a so-called plasma cocktail consisting of light, heat, some ultraviolet radiation, electromagnetic fields, free electrons, ions and excited molecules – the so-called reactive species. This cocktail is poison for bacteria, including multi-resistant pathogens, and stimulates cell division in healthy human cells.

Cold plasma for medical purposes is deliberately “designed”.

This means that the proportion of reactive species is kept particularly high, as these represent the medically effective part of the plasma cocktail. On the other hand, the proportion of visible light, UV and heat radiation is minimized.

Sources on the topic

How does CAP work?

Cold plasma deactivates bacteria (including multi-resistant pathogens), fungi and viruses. It activates cell growth, blood circulation and cell metabolism, thereby stimulating wound healing.

Sources on the topic

If the plasma cocktail described above with a high proportion of reactive species encounters bacteria or multi-resistant pathogens (MRG for short), the cellular structures, including the DNA, are destroyed. Once the DNA has been destroyed, these microorganisms can no longer multiply – fortunately, this also applies to antibiotic-resistant bacteria. Even allergies and intolerances play no role in the treatment. A similarly good effect of cold plasma has also been demonstrated with many fungi and viruses.

During the cold plasma application with plasma care, more than 600 reactions take place in the treatment time of 60 seconds. All of them are important for the treatment of wounds.

The most important processes in the cell at a glance

Most fungal infections are difficult to treat, as fungi and spores have very resistant structures.

In addition to the bactericidal effect of CAP, including multi-resistant bacteria, fungi can also be inactivated by the application of cold plasma. Fungi are eukaryotes, which means that they have a cell nucleus that contains their DNA.

Treatment with CAP deforms the spores of fungi, causing them to break open, flatten and shrink. The DNA within the spores can also be destroyed. Reactive oxygen species (ROS) trigger various reactions in fungi. Depending on the dose, these can lead to the oxidation of intracellular membranes and proteins through to structural changes inside the cells and, in the further course, to apoptosis (programmed cell death).

The effect on healthy human cells is completely different. These cells are much better protected than bacteria due to their cellular structure. In them, the reactive species stimulate survival mechanisms and cell division.

In concrete terms, this means wound healing: The release of growth factors promotes cell renewal. The stimulation of angiogenesis leads to better blood circulation and, together with the improved cell metabolism, promotes wound closure and skin healing.

Cold plasma has no damaging effect on healthy cells and does not alter the genetic material.

Various in-vitro and in-vivo studies have shown that cold atmospheric plasmas are highly effective at inactivating bacteria (including multi-resistant germs) without any side effects. Eukaryotic (human) tissue is not damaged.

How is the cold plasma of the plasma care® product series generated?

Safety of cold plasma therapy with plasma care®

The plasma care® works with “tamed” high voltage to generate the cold plasma from the ambient air – which of course also means that safety is a top priority for us:

We influence the production of cold plasma in such a way that the UV radiation and ozone content in the plasma cocktail is kept very low.

The cold plasma of plasma care® has been tested in several years of preclinical and clinical studies and found to be effective and safe.

The gas mixture produced by plasma care® is at room temperature.

No current flows through the skin. The high voltage required for cold plasma extraction is only in the device. In addition, the spacer creates a defined distance to the skin surface.

The composition of the cold plasma is below the legally prescribed limits.

Sources on the topic

1 Zimmermann, J. L. et al. Test for bacterial resistance build-up against plasma treatment. New J. Phys. 14, 073037 (2012).
2. Maisch, T. et al. Decolonization of MRSA, S. aureus and E. coli by cold-atmospheric plasma using a porcine skin model in vitro. PloS One 7, e34610 (2012).
3. Heinlin, J. et al. Contact-free inactivation of Trichophyton rubrum and Microsporum canis by cold atmospheric plasma treatment. Future Microbiol. 8, 1097-1106 (2013).
4. Daeschlein, G. et al. Skin and wound decontamination of multidrug-resistant bacteria by cold atmospheric plasma coagulation. J. Dtsch. Dermatol. Ges. J. Ger. Soc. Dermatol. JDDG 13, 143-150 (2015).
5. Bunz, O. et al. Cold atmospheric plasma as antiviral therapy – effect on human herpes simplex virus type 1. J. Gen. Virol. 101, 208-215 (2020).
6. Isbary, G. et al. Randomized placebo-controlled clinical trial showed cold atmospheric argon plasma relieved acute pain and accelerated healing in herpes zoster. Clin. Plasma Med. 2, 50-55 (2014).
7. Lee, J. et al. Fast and easy disinfection of coronavirus-contaminated face masks using ozone gas produced by a dielectric barrier discharge plasma generator. http://medrxiv.org/lookup/doi/10.1101/2020.04.26.20080317 (2020) doi:10.1101/2020.04.26.20080317.
8. Arndt, S., Unger, P., Berneburg, M., Bosserhoff, A.-K. & Karrer, S. Cold atmospheric plasma (CAP) activates angiogenesis-related molecules in skin keratinocytes, fibroblasts and endothelial cells and improves wound angiogenesis in an autocrine and paracrine mode. J. Dermatol. Sci. 89, 181-190 (2018).
9. Maisch, T. et al. Investigation of toxicity and mutagenicity of cold atmospheric argon plasma. Environ. Mol. Mutagen. 58, 172-177 (2017).
10. Boxhammer, V. et al. Investigation of the mutagenic potential of cold atmospheric plasma at bactericidal dosages. Mutat. Res. 753, 23-28 (2013).
11. Isbary, G. et al. Cold atmospheric argon plasma treatment may accelerate wound healing in chronic wounds: Results of an open retrospective randomized controlled study in vivo. Clin. Plasma Med. 1, 25-30 (2013).
12. Heinlin, J. et al. Randomized placebo-controlled human pilot study of cold atmospheric argon plasma on skin graft donor sites. Wound Repair Regen. Off. Publ. Wound Heal. Soc. Eur. Tissue Repair Soc. 21, 800-807 (2013).

Source Fungi mode of action:
1. Maisch, T. et al. Decolonization of MRSA, S. aureus and E. coli by cold-atmospheric plasma using a porcine skin model in vitro. PloS One 7, e34610 (2012).
2. Becker, S. et al. Effects of cold atmospheric plasma (CAP) on bacteria and mucosa of the upper aerodigestive tract. Auris. Nasus. Larynx 46, 294-301 (2019).
3. 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).
4. Zimmermann, J. L. et al. Test for bacterial resistance build-up against plasma treatment. New J. Phys. 14, 073037 (2012).
5. Heinlin, J. et al. Contact-free inactivation of Trichophyton rubrum and Microsporum canis by cold atmospheric plasma treatment. Future Microbiol. 8, 1097-1106 (2013).
6. Shapourzadeh, A. et al. Inhibitory effects of cold atmospheric plasma on the growth, ergosterol biosynthesis, and keratinase activity in Trichophyton rubrum. Arch. Biochem. Biophys. 608, 27-33 (2016).
7. Daeschlein, G. et al. In Vitro Killing of Clinical Fungal Strains by Low-Temperature Atmospheric-Pressure Plasma Jet. IEEE Trans. Plasma Sci. 39, 815-821 (2011).
8. Kaloriti, D. et al. Mechanisms Underlying the Exquisite Sensitivity of Candida albicans to Combinatorial Cationic and Oxidative Stress That Enhances the Potent Fungicidal Activity of Phagocytes. mBio (2014) doi:10.1128/mBio.01334-14.
9. Misra, N. N., Yadav, B., Roopesh, M. S. & Jo, C. Cold Plasma for Effective Fungal and Mycotoxin Control in Foods: Mechanisms, Inactivation Effects, and Applications: Cold plasma for effective fungal…. Compr. rev. food sci. food saf. 18, 106-120 (2019).
10. Arndt, S., Unger, P., Berneburg, M., Bosserhoff, A.-K. & Karrer, S. Cold atmospheric plasma (CAP) activates angiogenesis-related molecules in skin keratinocytes, fibroblasts and endothelial cells and improves wound angiogenesis in an autocrine and paracrine mode. J. Dermatol. Sci. 89, 181-190 (2018).
11. Hasse, S. et al. Induction of proliferation of basal epidermal keratinocytes by cold atmospheric-pressure plasma. Clin. Exp. Dermatol. 41, 202-209 (2016).
12. 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).

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