Georg Isbary

A first prospective randomized controlled trial to decrease bacterial load using cold atmospheric argon plasma on chronic wounds in patients

Background  Bacterial colonization of chronic wounds slows healing. Cold atmospheric plasma has been shown in vitro to kill a wide range of pathogenic bacteria.

Successful and safe use of 2 min cold atmospheric argon plasma in chronic wounds: results of a randomized controlled trial

Background  The development of antibiotic resistance by microorganisms is an increasing problem in medicine. In chronic wounds, bacterial colonization is associated with impaired healing. Cold atmospheric plasma is an innovative promising tool to deal with these problems.

Plasma applications in medicine with a special focus on dermatology

The recent tremendous progress in understanding physical plasma phenomenon, together with the development of new plasma sources has put growing focus on the application of plasmas in health care. Active plasma components, such as molecules, atoms, ions, electrons and photons, reactive species, ultraviolet radiation, optical and infrared emission and heat have the ability of activating, controlling and catalysing reactions and complex biochemical procedures. Thermal and non‐thermal (i.e. cold) plasmas – both already widely established in medicine – are used for various therapeutic applications. Particularly in dermatology, plasma applications hold big potential, for example, in wound healing, such as efficient disinfection or sterilization, therapy of various skin infections or tissue regeneration. This review gives an overview on potential plasma applications in medicine – including the recent research on skin diseases – and summarizes possible interactions between plasmas and living tissue.

Plasma medicine: possible applications in dermatology

As a result of both the better understanding of complex plasma phenomena and the development of new plasma sources in the past few years, plasma medicine has developed into an innovative field of research showing high potential. While thermal plasmas have long been used in various medical fields (for instance for cauterization and sterilization of medical instruments), current research mainly focuses on application of non‐thermal plasmas.

Effects of cold atmospheric plasma on mucosal tissue culture

Thermal plasmas have been commonly used in medical applications such as plasma ablation and blood coagulation. Newer developments show that plasmas can be generated with ion temperatures close to room temperature: these non-thermal or so-called cold atmospheric plasmas (CAPs) therefore open up a wide range of further biomedical applications. Based on the understanding of the bactericidal, virucidal and fungicidal properties of CAPs, information about the effects of CAP on mucosal cells and tissue is still lacking. Therefore this study focuses on the interaction of CAP with healthy head and neck mucosal cells on a molecular level. To analyse this interaction in detail, fresh tissue samples from healthy nasal and pharyngeal mucosa were harvested during surgery, assembled to a three-dimensional tissue culture model (mini organ cultures) and treated with CAP for different treatment times. Effects on the viability, necrosis induction and mutagenic activity were evaluated with the trypan blue exclusion test, Annexin-V/PI staining and alkaline microgel electrophoresis (comet assay). Trypan blue exclusion test revealed that the CAP treatment significantly decreases the cell viability for all tested treatment times (5, 10, 30, 60 and 120s; p< 0.05), but only a treatment time of 120s showed a cytotoxic effect as the viability dropped below 90%. Annexin-V/PI staining revealed a significant increase in necrosis in CAP treated pharyngeal tissue cultures for treatment times of 60 and 120s ( p< 0.05). For nasal tissue this effect was already detected for a 30s treatment ( p< 0.05). Comet assay analysis showed no mutagenic effects after exposure to CAP. (Some figures may appear in colour only in the online journal)

Cold atmospheric air plasma sterilization against spores and other microorganisms of clinical interest

ABSTRACT Physical cold atmospheric surface microdischarge (SMD) plasma operating in ambient air has promising properties for the sterilization of sensitive medical devices where conventional methods are not applicable. Furthermore, SMD plasma could revolutionize the field of disinfection at health care facilities. The antimicrobial effects on Gram-negative and Gram-positive bacteria of clinical relevance, as well as the fungus Candida albicans, were tested. Thirty seconds of plasma treatment led to a 4 to 6 log10 CFU reduction on agar plates. C. albicans was the hardest to inactivate. The sterilizing effect on standard bioindicators (bacterial endospores) was evaluated on dry test specimens that were wrapped in Tyvek coupons. The experimental D 23 ° C values for Bacillus subtilis, Bacillus pumilus, Bacillus atrophaeus, and Geobacillus stearothermophilus were determined as 0.3 min, 0.5 min, 0.6 min, and 0.9 min, respectively. These decimal reduction times (D values) are distinctly lower than D values obtained with other reference methods. Importantly, the high inactivation rate was independent of the material of the test specimen. Possible inactivation mechanisms for relevant microorganisms are briefly discussed, emphasizing the important role of neutral reactive plasma species and pointing to recent diagnostic methods that will contribute to a better understanding of the strong biocidal effect of SMD air plasma.

Randomized placebo-controlled human pilot study of cold atmospheric argon plasma on skin graft donor sites

Cold atmospheric plasma has already been shown to decrease the bacterial load in chronic wounds. However, until now it is not yet known if plasma treatment can also improve wound healing. We aimed to assess the impact of cold atmospheric argon plasma on the process of donor site healing. Forty patients with skin graft donor sites on the upper leg were enrolled in our study. The wound sites were divided into two equally sized areas that were randomly assigned to receive either plasma treatment or placebo (argon gas) for 2 minutes. Donor site healing was evaluated independently by two blinded dermatologists, who compared the wound areas with regard to reepithelialization, blood crusts, fibrin layers, and wound surroundings. From the second treatment day onwards, donor site wound areas treated with plasma (n = 34) showed significantly improved healing compared with placebo‐treated areas (day 1, p = 0.25; day 2, p = 0.011; day 3, p < 0.001; day 4, p < 0.001; day 5, p = 0.004; day 6, p = 0.008; day 7, p = 0.031). Positive effects were observed in terms of improved reepithelialization and fewer fibrin layers and blood crusts, whereas wound surroundings were always normal, independent of the type of treatment. Wound infection did not occur in any of the patients, and no relevant side effects were observed. Both types of treatment were well tolerated. The mechanisms contributing to these clinically observed effects should be further investigated.

Contact-Free Inactivation of Candida albicans Biofilms by Cold Atmospheric Air Plasma

ABSTRACT Candida albicans is one of the main species able to form a biofilm on almost any surface, causing both skin and superficial mucosal infections. The worldwide increase in antifungal resistance has led to a decrease in the efficacy of standard therapies, prolonging treatment time and increasing health care costs. Therefore, the aim of this work was to demonstrate the applicability of atmospheric plasma at room temperature for inactivating C. albicans growing in biofilms without thermally damaging heat-sensitive materials. This so-called cold atmospheric plasma is produced by applying high voltage to accelerate electrons, which ionize the surrounding air, leading to the production of charged particles, reactive species, and photons. A newly developed plasma device was used, which exhibits a large plasma-generating surface area of 9 by 13 cm (117 cm2). Different time points were selected to achieve an optimum inactivation efficacy range of ≥3 log10 to 5 log10 reduction in CFU per milliliter, and the results were compared with those of 70% ethanol. The results obtained show that contact-free antifungal inactivation of Candida biofilms by cold atmospheric plasma is a promising tool for disinfection of surfaces (and items) in both health care settings and the food industry, where ethanol disinfection should be avoided.

Cold atmospheric plasma devices for medical issues

Cold atmospheric plasma science is an innovative upcoming technology for the medical sector. The plasma composition and subsequent effects on cells, tissues and pathogens can vary enormously depending on the plasma source, the plasma settings and the ambient conditions. Cold atmospheric plasmas consist of a highly reactive mix of ions and electrons, reactive molecules, excited species, electric fields and to some extent also UV radiation. In the last year, this partly ionized gas has been demonstrated to have a broad antimicrobial activity, while resistance and resistance development are unlikely. Furthermore, recent research has indicated that plasmas also have a strong influence on various cell lines and cell functions, including anticancer properties. This review summarizes the major plasma designs available and their main benefits, as well as assessing possible risks of this new technology.

A randomized two-sided placebo-controlled study on the efficacy and safety of atmospheric non-thermal argon plasma for pruritus.

Background  To look into new potential indications for physical plasma and because some reports suggest plasma having antipruritic effects, we investigated the treatment of pruritus that often represents a therapeutic challenge.