“Atmospheric-pressure dielectric barrier discharge (DBD) in air is investigated for medical applications, especially for skin treatment. When the DBD was tested on mouse skin, a homogeneous discharge accompanied by filamentary microdischarges is observed. For characterization of the homogeneous discharge, averaged plasma parameters (namely electron density and electron velocity distribution function) and gas temperature are determined by optical emission spectroscopy, microphotography and numerical simulation. Chemical kinetics in the active plasma volume and in the afterglow is simulated. Fluxes of biologically useful molecules like nitric oxide (NO) and ozone reaching the treated surface and irradiation by UV photons are determined. Skin biopsy results show that DBD treatment causes no inflammation and no changes in the skin-collagen.”
" The lipids of the stratum corneum comprise the most important components of the skin barrier. In patients with ichthyoses or atopic dermatitis, the composition of the skin barrier lipids is disturbed resulting in dry, scaly, itching erythematous skin. Using the latest X-Ray Photoelectron Spectroscopy (XPS) technology, we investigated the physiological skin lipid composition of human skin and the effects of cold atmospheric plasma treatment on the lipid composition. Skin lipids were stripped off forearms of six healthy volunteers using the cyanoacrylate glue technique, plasma treated or not and then subjected to detailed XPS analysis. We found that the human lipid skin barrier consisted of 84.4% carbon (+1.3 SEM%), 10.8% oxygen (+1.0 SEM%) and 4.8% nitrogen (+0.3 SEM%). The composition of physiological skin lipids was not different in males and females. Plasma treatment resulted in significant changes in skin barrier lipid stoichiometry. The total carbon amount was reduced to 76.7%, and the oxygen amount increased to 16.5%. There was also a slight increase in nitrogen to 6.8%. These changes could be attributed to reduced C-C bonds and increased C-O, C=O, C-N and N-C-O bonds. The moderate increase in nitrogen was caused by an increase in C-N and N-C-O bonds. Our results show for the first time that plasma treatment leads to considerable changes in the human skin lipid barrier. Our proof of principle investigations established the technical means to analyse, if plasma-induced skin lipid barrier changes may be beneficial in the treatment of ichthyotic or eczematous skin."
" The dielectric barrier discharge (DBD) plasma source for biomedical application is characterized using optical emission spectroscopy, plasma-chemical simulation and voltage–current measurements. This plasma source possesses only one electrode covered by ceramic. Human body or some other object with enough high electric capacitance or connected to ground can serve as the opposite electrode. DBD consists of a number of microdischarge channels distributed in the gas gap between the electrodes and on the surface of the dielectric. To characterize the plasma conditions in the DBD source, an aluminium plate is used as an opposite electrode. Electric parameters, the diameter of microdischarge channel and plasma parameters (electron distribution function and electron density) are determined. The gas temperature is measured in the microdischarge channel and calculated in afterglow phase. The heating of the opposite electrode is studied using probe measurement. The gas and plasma parameters in the microdischarge channel are studied at varied distances between electrodes. According to an energy balance study, the input microdischarge electric energy dissipates mainly in heating of electrodes (about 90%) and partially (about 10%) in the production of chemical active species (atoms and metastable molecules)."
"These data indicate that the repetitive use of non-thermal atmospheric plasma boosts and prolongs cutaneous microcirculation and might therefore be a potential tool to promote wound healing."
" CAP increases cutaneous tissue oxygen saturation and capillary blood flow at the radial forearm of healthy volunteers. These results support recently published data on wound healing after CAP treatment. However, further studies are needed to determine if this treatment can improve the reduced microcirculation in diabetic foot ulcers. Moreover, repetitive application protocols have to be compared with a single session treatment approach."
" Dielectric barrier discharge (DBD) devices generate air plasma above the skin containing active and reactive species including nitric oxide (NO). Since NO plays an essential role in skin physiology, a topical application of NO by plasma may be useful in the treatment of skin infections, impaired microcirculation and wound healing. Thus, after safety assessments of plasma treatment using human skin specimen and substitutes, NO-penetration through the epidermis, the loading of skin tissue with NO-derivates in vitro and the effects on human skin in vivo were determined. After the plasma treatment (0-60 min) of skin specimen or reconstructed epidermis no damaging effects were found (TUNEL/MTT). By Franz diffusion cell experiments plasma-induced NO penetration through epidermis and dermal enrichment with NO related species (nitrite 6-fold, nitrate 7-fold, nitrosothiols 30-fold) were observed. Furthermore, skin surface was acidified (~pH 2.7) by plasma treatment (90 s). Plasma application on the forearms of volunteers increased microcirculation fourfold in 1-2 mm and twofold in 6-8 mm depth in the treated skin areas. Regarding the NO-loading effects, skin acidification and increase in dermal microcirculation, plasma devices represent promising tools against chronic/infected wounds. However, efficacy of plasma treatment needs to be quantified in further studies and clinical trials."
"In the frame of plasma source development for dermatological applications in the field of plasma medicine, operational safety of the devices is of superior priority. For sources based on the concept of dielectric barrier discharges (DBD), electric potentials with amplitudes in the range of some kV are arranged in close proximity to the skin of patients, wherein dielectric strength of the electrodes and leakage currents are crucial for electrical applicability. In this work, ceramic electrodes of 10 mm in diameter and varying ceramic thickness are operated at input powers up to 300 mW against non‐biological counter electrodes. In a combined experimental and numerical approach, electric fields inside the ceramic are determined, whereas values are well below the dielectric strength of the material. The spectrally weighted plasma emission is within limit values of exposure to human skin as long as daily treatment does not exceeded 7 h. Neutral gas temperatures of up to 310 K are determined which underline the minor thermal impact of the plasma exposure. In contrast, values for reduced electric fields are of the order of some hundred Townsend and thus the electrons can initiate various secondary effects such as chemical reaction chains. Consequently, ozone concentrations in the discharges are quantified between 230 ppm and 1140 ppm in close proximity to the actual discharge volume and the results are discussed in the frame of risk assessment for therapeutic applications in dermatology."
"The effects of low-temperature plasma treatment on microorganisms typically related to skin diseases are studied qualitatively by the inhibition of growth and viability assays to evaluate the potential for classifying as a prospective antiseptic agent. A variety of microorganisms enveloping gram- negative and gram-positive bacteria as well as one genus of yeast and fungus each were exposed to plasma in vitro. In a comparative approach, two power supplies, both of which produce high voltage pulses yet at different temporal characteristics, are applied for the growth study. While operation with both devices led to growth inhibition of all microbes, the results indicate a superior antimicrobial efficacy for high voltage pulse lengths in the nanosecond scale. Fluorescence assays reveal the efficacy of nanosecond-pulse driven plasma in reducing germ viability. Furthermore, the technical background for patents related to low-temperature plasma technology in the field of plasma medicine is discussed."
"Ozone is a major component produced by low-temperature plasmas operating in oxygen-containing gas mixtures. For correlation with biological or clinical results of plasma medical therapies as well as for evaluation of application security, tempo-spatially resolved ozone concentrations need to be considered. When operating a single-electrode dielectric barrier discharge (SE-DBD), the electric field characteristics are dependent on the geometrical setup as well as the electrical properties of the counter electrode. Thus, the counter electrode also affects the plasma input power and hence the total production of chemical species. Therefore, we studied the power input and the tempo-spatial characteristics of ozone concentrations during operation of a SE-DBD operated at voltage pulses in the us regime against a clean metal electrode and a metal electrode covered with porcine skin samples. At energy densities of up to 1.85 J/cm2, the ozone concentrations in the plasma volume amount to as much as 293 ppm whereas at a distance of 5 and 20 cm, respectively, from the discharge, concentrations have decreased beneath recommended safety limits of 0.1 ppm. Furthermore, significantly lower ozone concentrations could be observed when skin samples were used as part of the counter electrode"
"For the operation of the 10 mm Al2O3 electrode, it was determined after a spectral weighting of the radiation according to the physiological effectiveness that a daily treatment using the same parameter set of 22 hours appears harmless. Since there were no significant differences in the spectral distribution of the two experiments and the intensities when operating with the flexible injection-molded electrode are many times lower, it can be assumed that there is no regulation of the daily treatment duration due to the plasma UV emission during the treatment results. "
In: Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery 45 (10), S. 1724–1730. DOI:
"The use of cold atmospheric plasma might offer a reliable, conservative treatment option in complicated wound healing disturbances in cranio-maxillo-facial surgery."
"Cold atmospheric plasma could offer a reliable conservative treatment option for complicated wound healing disturbances. This was exemplarily shown in the case of radial forearm free flap donor site morbidity with exposed flexor tendons in the present study."
"The direct treatment of excised human full-thickness skin with CAP, specifically a DBD, can lead to pore formation and enhances transdermal transport of sodium fluorescein."
"A CAP treatment in isolated human SC was shown to dramatically reduce electrical resistance and yield a regular pattern of locally permeabilized regions. These regions were greater in number than the natural number of skin appendages and admitted the passage of small hydrophilic substances with Stokes’ radii up to 1.4 nm through human SC subsequent to 2×90 s CAP treatment. Proof-of-principle experiments with full-thickness skin (FTS) confirm these results."
"Our results provide mechanistic insight into the potential of an emerging interdisciplinary technology - plasma medicine - as a prospective tool or treatment option. While it might become a safe and pain-free method to enhance skin permeation of drug substances, this is also a mechanism to keep in mind when tailoring plasma sources for other uses."
"These three courses make it clear that therapy with CAP - presumably due to different therapy regimes - can have various effects on tissue reconstruction. In the future, it will be necessary to clarify by means of randomized studies to what extent CAP is used for indications in which rapid re-epithelialization is to be promoted (e.g. split skin removal sites, status after laser resurfacing), for surgical wounds with slow secondary healing (e.g. secondary healing surgery - wounds in acne inversa) and of course in complex wounds, can show a therapeutic advantage. "
"Both the APPJ and DBD were highly effective in eradicating PF and AF from the fingertips of healthy volunteers. No plasma-resistant isolates were observed. Cold plasma appears to have potential for skin disinfection. For hand hygiene purposes, plasma exposure times would need to be reduced significantly by technical means."
"DBD with the largest electrode produced the largest IAs. VW showed results similar to 2 different modes of the kINPen 09. IAs of VW were enlargeable by attaching a larger electrode. Against biofilms, VW was less effective than DBD but more effective than ethanol 70% and polyhexanide."
"diCAP treatment of intact skin notably enhances microcirculation for a therapeutically relevant period. This effect is specific to the plasma treatment and not an effect of the applied pressure. Prolonged treatment durations lead to more pronounced effects."
"Cold atmospheric plasma displays favourable antibacterial effects. We demonstrated that plasma treatment with the PlasmaDerm® VU-2010 device is safe and effective in patients with chronic venous leg ulcers. Thus, larger controlled trials and the development of devices with larger application surfaces are warranted."
" In plasma treatment antiinflammatory, antipruritic, antimicrobial, tissue stimulation, stimulation of microcirculation, and other therapeutic effects are achieved in a single treatment due to the combined action of ultraviolet radiation, reactive oxygen species (e.g. ozone), reactive nitrogen species, and electric fields. In line with other reports, we have already demonstrated the use of direct plasma treatment in skin disinfection, in atopic eczema (superinfected dermatitis), in modulating the epidermal barrier, as well as in chronic wound treatment. We as well as others did not notice any side effects of plasma treatment so far. In summary, cold atmospheric pressure plasma constitutes a new and innovative treatment option especially for superinfected skin diseases. These promising relatively new clinical applications warrant further carefully conducted translational research to delineate the modes of actions of plasma as well as potential long term side effects. This should lead to norms for the technical devices to allow a standardized treatment of given diseases in the mid-term."
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