Defective wound healing poses a significant burden on patients and healthcare systems. In recent years, a novel reactive oxygen and nitrogen species (ROS/RNS) based therapy has received considerable attention among dermatologists for targeting chronic wounds. The multifaceted ROS/RNS are generated using gas plasma technology, a partially ionized gas operated at body temperature. This review integrates preclinical and clinical evidence into a set of working hypotheses mainly based on redox processes aiding in elucidating the mechanisms of action and optimizing gas plasmas for therapeutic purposes. These hypotheses include increased wound tissue oxygenation and vascularization, amplified apoptosis of senescent cells, redox signaling, and augmented microbial inactivation. Instead of a dominant role of a single effector, it is proposed that all mechanisms act in concert in gas plasma-stimulated healing, rationalizing the use of this technology in therapy-resistant wounds. Finally, addressable current challenges and future concepts are outlined, which may further promote the clinical utilization, efficacy, and safety of gas plasma technology in wound care in the future.

Medical gas plasma-stimulated wound healing: Evidence and mechanisms.

Plasma, the fourth and most pervasive state of matter in the visible universe, is a fascinating medium that is connected to the beginning of our universe itself. Man-made plasmas are at the core of many technological advances that include the fabrication of semiconductor devices, which enabled the modern computer and communication revolutions. The introduction of low temperature, atmospheric pressure plasmas to the biomedical field has ushered a new revolution in the healthcare arena that promises to introduce plasma-based therapies to combat some thorny and long-standing medical challenges. This article presents an overview of where research is at today and discusses innovative concepts and approaches to overcome present challenges and take the field to the next level. It is written by a team of experts who took an in-depth look at the various applications of plasma in hygiene, decontamination, and medicine, made critical analysis, and proposed ideas and concepts that should help the research community focus their efforts on clear and practical steps necessary to keep the field advancing for decades to come. 

https://ieeexplore.ieee.org/ielx7/7433213/9701857/09650590.pdf

Low-Temperature Plasma for Biology, Hygiene, and Medicine: Perspective and Roadmap

Plasma medicine is gaining increasing attention and is moving from basic research into clinical practice. While areas of application are diverse, much research has been conducted assessing the use of cold atmospheric pressure plasma (CAP) in wound healing and cancer treatment—two applications with entirely different goals. In wound healing, a tissue-stimulating effect is intended, whereas cancer therapy aims at killing malignant cells. In this review, we provide an overview of the latest clinical and some preclinical research on the efficacy of CAP in wound healing and cancer therapy. Furthermore, we discuss the current understanding of molecular signaling mechanisms triggered by CAP that grant CAP its antiseptic and tissue regenerating or anti-proliferative and cell death-inducing properties. For the efficacy of CAP in wound healing, already substantial evidence from clinical studies is available, while evidence for therapeutic effects of CAP in oncology is mainly from in vitro and in vivo animal studies. Efforts to elucidate the mode of action of CAP suggest that different components, such as ultraviolet (UV) radiation, electromagnetic fields, and reactive species, may act synergistically, with reactive species being regarded as the major effector by modulating complex and concentration-dependent redox signaling pathways.

https://www.mdpi.com/2076-3417/10/19/6898/pdf

Cold Atmospheric Pressure Plasma in Wound Healing and Cancer Treatment

Cold atmospheric plasma jet (CAPJ) or non-thermal plasma jet has been employed in various biomedical applications based on their functions in bactericidal activity and wound healing However, the effect of CAPJ generated by a particular composition of gases on wound closure and the underlying mechanisms that regulate wound healing signals remain elusive In the present study, we investigated the impact of helium (He)- or a gas mixture of He and argon (He/Ar)-generated CAPJ on cell proliferation, which is a pivotal step during the wound healing process With careful treatment duration control, He/Ar-CAPJ effectively induced keratinocyte proliferation and migration mediated through the activation of epithelial-to-mesenchymal transition (EMT) and cell cycle progression, which was evidenced by a decrease in E-cadherin levels and increases in N-cadherin, cyclin D1, Ki-67, Cdk2, and p-ERK levels Rat wound healing studies showed that He/Ar-CAPJ treatment facilitated granulation tissue formation and mitigated inflammation in cutaneous tissue, resulting in accelerated wound closure These findings highlight the possibility that He/Ar-CAPJ can be developed as a therapeutic agent for enhancing wound healing

/pdf/helium-argon-generated-cold-atmospheric-plasma-facilitates-1knyjt38pa.pdf

Helium/Argon-Generated Cold Atmospheric Plasma Facilitates Cutaneous Wound Healing.

Plasma,
the fourth and most pervasive state of matter in the visible universe, is a
fascinating medium that is connected to the beginning of our universe itself.
Man-made plasmas are at the core of many technological advances that include
the fabrication of semiconductor devices, which enabled the modern computer and
communication revolutions. The introduction of low temperature, atmospheric
pressure plasmas to the biomedical field has ushered a new revolution in the
healthcare arena that promises to introduce plasma-based therapies to combat
some thorny and long-standing medical challenges. This paper presents an
overview of where research is at today and discusses innovative concepts and
approaches to overcome present challenges and take the field to the next level.
It is written by a team of experts who took an in-depth look at the various
biomedical applications, made critical analysis, and proposed ideas and
concepts that should help the research community focus their efforts on clear
and practical steps necessary to keep the field advancing for decades to
come.

/pdf/low-temperature-plasma-for-biology-hygiene-and-medicine-1azj6bfubh.pdf

Low Temperature Plasma for Biology, Hygiene, and Medicine: Perspective and Roadmap

Using the Taguchi method to narrow experimental parameters, the antimicrobial efficiency of a cold atmospheric plasma jet (CAPJ) treatment was investigated. An L9 array with four parameters of CAPJ treatments, including the application voltage, CAPJ-sample distance, argon (Ar) gas flow rate, and CAPJ treatment time, were applied to examine the antimicrobial activity against Escherichia coli (E. coli). CAPJ treatment time was found to be the most influential parameter in its antimicrobial ability by evaluation of signal to noise ratios and analysis of variance. 100% bactericidal activity was achieved under the optimal bactericidal activity parameters including the application voltage of 8.5 kV, CAPJ-sample distance of 10 mm, Ar gas flow rate of 500 sccm, and CAPJ treatment time of 300 s, which confirms the efficacy of the Taguchi method in this design. In terms of the mechanism of CAPJ’s antimicrobial ability, the intensity of hydroxyl radical produced by CAPJ positively correlated to its antimicrobial efficiency. The CAPJ antimicrobial efficiency was further evaluated by both DNA double-strand breaks analysis and scanning electron microscopy examination of CAPJ treated bacteria. CAPJ destroyed the cell wall of E. coli and further damaged its DNA structure, thus leading to successful killing of bacteria. This study suggests that optimal conditions of CPAJ can provide effective antimicrobial activity and may be grounds for a novel approach for eradicating bacterial infections.

https://www.mdpi.com/2077-0383/8/11/1930/pdf

Parameters Affecting the Antimicrobial Properties of Cold Atmospheric Plasma Jet.

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Helium/Argon-Generated Cold Atmospheric Plasma Facilitates Cutaneous Wound Healing.

Parameters Affecting the Antimicrobial Properties of Cold Atmospheric Plasma Jet.