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January 2015 - September 2020
January 2014 - January 2015
January 2012 - December 2013
Publications
Publications (127)
Introduction: Diabetes mellitus is a chronic disease that can disrupt physiologic wound healing. Medical gas plasma technology produces therapeutic reactive species that support wound healing.
Objective: Previous studies have shown that increasing the transcriptional activity of the redox regulator nuclear factor erythroid 2-related factor 2 (Nrf2)...
The recent pandemic has highlighted the urgent need to elucidate the pathophysiological mechanisms underlying viral effects in humans and is driving the search for innovative antiviral therapies. Several studies have investigated the ability of gas plasma, a partially ionized gas that simultaneously generates several reactive species, to be a new a...
Introduction: Hippo is a signaling pathway that is evolutionarily conserved and plays critical roles in wound healing and tissue regeneration. Disruption of the transcriptional activity of both Hippo-associated factors, the yes-associated protein (YAP), and the transcriptional co-activator with PDZ binding motif (TAZ) has been associated with cardi...
In response to injury, efficient migration of skin cells to rapidly close the wound and restore barrier function requires a range of coordinated processes in cell spreading and migration. Gas plasma technology produces therapeutic reactive species that promote skin regeneration by driving proliferation and angiogenesis. However, the underlying mole...
Wound healing is strongly associated with the presence of a balanced content of reactive species in which oxygen-dependent, redox-sensitive signaling represents an essential step in the healing cascade. Numerous studies have demonstrated that cold physical plasma supports wound healing due to its ability to deliver a beneficial mixture of reactive...
The principal aim of this chapter is to provide a comprehensive overview of medical gas plasma technology for wound healing in animal models, veterinary medicine, and humans. Impaired or defective wound healing in skin injuries substantially burdens patients and the whole healthcare system. In recent years, the novel reactive oxygen and nitrogen sp...
New therapies such as medical gas plasma treatment command a safety assessment, regardless of their efficacy. This includes, for instance, electrical safety of plasma devices, a reproducible plasma generation to apply similar dosages, appropriate UV generation profiles, and therefore also the absence of genotoxic effects. This last feature is impor...
The environmental presence of nano- and micro-plastic particles (NMPs) is suspected to have a negative impact on human health. Environmental NMPs are difficult to sample and use in life science research, while commercially available plastic particles are too morphologically uniform. Additionally, this NMPs exposure exhibited biological effects, inc...
Diabetes can disrupt physiological wound healing, caused by decreased levels or impaired activity of angiogenic factors. This can contribute to chronic inflammation, poor formation of new blood vessels, and delayed re-epithelialization. The present study describes the preclinical application of medical gas plasma to treat a dermal, full-thickness e...
Background
Reactive oxygen species (ROS) are implicated in cancer therapy and as drivers of microenvironmental tumour cell adaptations. Medical gas plasma is a multi-ROS generating technology that has been shown effective for palliative tumour control in head and neck cancer (HNC) patients before tumour cells adapted to the oxidative stress and gro...
Environmental pollution by microplastics (MPs) is a growing concern regarding their impact on aquatic and terrestrial systems and human health. Typical exposure routes of MPs are dermal contact, digestion, and inhalation. Recent in vitro and in vivo studies observed alterations in immunity after MPs exposure, but systemic studies using primary huma...
Polystyrene nano- and micro-sized plastic particles (NMP) are one of the common plastic materials produced that dramatically pollute the environment, water, and oceanic habitats worldwide. NMP are continuously absorbed by the body through a number of routes, especially via intestinal ingestion, dermal uptake, and inhalation into the lung. Several s...
Nano- and microplastic particles (NMP) are strong environmental contaminants affecting marine ecosystems and human health. The negligible use of biodegradable plastics and the lack of knowledge about plastic uptake, accumulation, and functional consequences led us to investigate the short- and long-term effects in freshly isolated skin cells from m...
Plastic microparticles (MP) and nanoparticles (NP) have become a matter of environmental as well as human health concern. Recently, evidence of MP and NP was found in human blood. The potential harmful impacts of MP and NP on human health remain largely unexplored. The principal focus of the present study was to investigate the toxicity and genotox...
The ubiquitous nature of microplastic particles (MP) is a growing environmental and ecological concern due to their impact on aquatic and terrestrial systems and potentially on human health. The potential impact on human health may be due to MP daily exposure by several routes, but little is known about the cellular effects. Previous in vitro and i...
Introduction
Medical gas plasma therapy has been successfully applied to several types of cancer in preclinical models. First palliative tumor patients suffering from advanced head and neck cancer benefited from this novel therapeutic modality. The gas plasma-induced biological effects of reactive oxygen and nitrogen species (ROS/RNS) generated in...
Oxidative stress is described to have physiological, pathological, and therapeutic consequences in nearly all types of cancer. Yet, the expression signatures associated with oxidative stress sensitivity in cancer cells are understudied. To this end, we cultured more than 30 tumor cell lines and analyzed their basal expression on several levels: 1....
The ubiquitous nature of micro- (MP) and nanoplastics (NP) is a growing environmental concern. However, their potential impact on human health remains unknown. Research increasingly focused on using rodent models to understand the effects of exposure to individual plastic polymers. In vivo data showed critical exposure effects depending on particle...
Reactive oxygen and nitrogen species (ROS) are essential components of life. In contrast to the long-stated opinion that these reactive molecules are mere by-products of cellular respiration and tissue damage, this view has been updated in the last decade. ROS are critical signaling molecules regulating biochemical processes, and their production i...
The principal aim of this chapter is to provide a comprehensive overview of safety aspects and potential health risks in humans related to the exposure to cold physical plasma. Numerous studies were concerned with these critical aspects, as it is pivotal for the general acceptance of cold physical plasma among biologists, physicists, physicians, an...
Reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) are well-described agents in physiology and pathology. Chronic inflammation causes incessant H2O2 generation associated with disease occurrences such as diabetes, autoimmunity, and cancer. In cancer, conditioning of the tumor microenvironment, e.g., hypoxia and ROS generation, has been...
Peri-implantitis may result in the loss of dental implants. Cold atmospheric pressure plasma (CAP) was suggested to promote re-osseointegration, decrease antimicrobial burden, and support wound healing. However, the long-term risk assessment of CAP treatment in the oral cavity has not been addressed. Treatment with two different CAP devices was com...
The loss of skin integrity is inevitable in life. Wound healing is a necessary sequence of events to reconstitute the body’s integrity against potentially harmful environmental agents and restore homeostasis. Attempts to improve cutaneous wound healing are therefore as old as humanity itself. Furthermore, nowadays, targeting defective wound healing...
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 ga...
Cold physical plasma-derived ROS inactivate cells, which might be beneficial in oncology. However, several aspects of plasma oncotherapy remain elusive. These include the identification of a ROS composition with maximum toxicity and the molecular mechanisms that govern the degree of plasma-induced cell death. Using two human leukemia cell lines and...
Reactive oxygen species (ROS/RNS) are produced during inflammation and elicit protein modifications, but the immunological consequences are largely unknown. Gas plasma technology capable of generating an unmatched variety of ROS/RNS is deployed to mimic inflammation and study the significance of ROS/RNS modifications using the model protein chicken...
Gas plasma is a partially ionized gas increasingly recognized for targeting cancer. Several hypotheses attempt to explain the link between plasma treatment and cytotoxicity in cancer cells, all focusing on cellular membranes that are the first to be exposed to plasma-generated reactive oxygen species (ROS). One proposes high levels of aquaporins, m...
Recent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source ( V jet) to trea...
The requirements for new technologies to serve as anticancer agents go far beyond their toxicity potential. Novel applications also need to be safe on a molecular and patient level. In a broader sense, this also relates to cancer metastasis and inflammation. In a previous study, the toxicity of an atmospheric pressure argon plasma jet in four human...
Cold plasma technology is an emerging tool facilitating the spatially controlled delivery of a multitude of re-active species (ROS) to the skin. While the therapeutic efficacy of plasma treatment has been observed in several types of diseases, the fundamental consequences of plasma-derived ROS on skin physiology remain unknown. We aimed to bridge t...
Cutaneous squamous cell carcinoma (SCC) is the most prevalent cancer worldwide, increasing the cost of healthcare services and with a high rate of morbidity. Its etiology is linked to chronic ultraviolet (UV) exposure that leads to malignant transformation of keratinocytes. Invasive growth and metastasis are severe consequences of this process. The...
Efficient vascularization of skin tissue supports wound healing in response to injury. This includes elevated blood circulation, tissue oxygenation, and perfusion. Cold physical plasma promotes wound healing in animal models and humans. Physical plasmas are multicomponent systems that generate several physicochemical effectors, such as ions, electr...
Medical technologies from physics are imperative in the diagnosis and therapy of many types of diseases. In 2013, a novel cold physical plasma treatment concept is accredited for clinical therapy. This gas plasma jet technology generates large amounts of different reactive oxygen and nitrogen species (ROS). Using a melanoma model, gas plasma techno...
Physical plasmas generate unique mixes of reactive oxygen and nitrogen species (RONS or ROS). Only a bit more than a decade ago, these plasmas, operating at body temperature, started to be considered for medical therapy with considerably little mechanistic redox chemistry or biomedical research existing on that topic at that time. Today, a vast bod...
Phosphorylated histone 2AX ( γ H2AX) is a long-standing marker for DNA double-strand breaks (DSBs) from ionizing radiation in the field of radiobiology. This led to the perception of γ H2AX being a general marker of direct DNA damage with the treatment of other agents such as low-dose exogenous ROS that unlikely act on cellular DNA directly. Cold p...
Cold physical plasma has limited tumor growth in many preclinical models and is, therefore, suggested as a putative therapeutic option against cancer. Yet, studies investigating the cells’ metastatic behavior following plasma treatment are scarce, although being of prime importance to evaluate the safety of this technology. Therefore, we investigat...
Plasma medicine comprises the application of physical plasma directly on or in the human body for therapeutic purposes. Three most important basic plasma effects are relevant for medical applications: i) inactivation of a broad spectrum of microorganisms, including multidrug-resistant pathogens, ii) stimulation of cell proliferation and angiogenesi...
Background: Monocyte-derived macrophages are key regulators and producers of reactive oxygen and nitrogen species (ROS/RNS). Pre-clinical and clinical studies suggest that cold physical plasma may be beneficial in the treatment of inflammatory conditions via the release of ROS/RNS. However, it is unknown how plasma treatment affects monocytes and t...
Investigating cold argon plasma (CAP) for medical applications is a rapidly growing, innovative field of research. The controllable supply of reactive oxygen and nitrogen species through CAP has the potential for utilization in tumour treatment. Maxillofacial surgery is limited if tumours grow on vital structures such as the arteria carotis. Here C...
Supplementary figures and tables.
Small reactive oxygen and nitrogen species (ROS/RNS) driven signaling plays a significant role in wound healing processes by controlling cell functionality and wound phase transitions. The application of cold atmospheric pressure plasma (CAP), a partially ionized gas expelling a variety of ROS and RNS, was shown to be effective in chronic wound man...
Increasing numbers of cancer deaths worldwide demand for new treatment avenues. Cold physical plasma is a partially ionized gas expelling a variety of reactive oxygen and nitrogen species, which can be harnesses therapeutically. Plasmas and plasma-treated liquids have antitumor properties in vitro and in vivo. Yet, global response signatures to pla...
Chronic wounds and ulcers are major public health threats. Being a substantial burden for patients and health care systems alike, better understanding of wound pathophysiology and new avenues in the therapy of chronic wounds are urgently needed. Cold physical plasmas are particularly effective in promoting wound closure, irrespective of its etiolog...
Leukocytes are professionals in recognizing and removing pathogenic or unwanted material. They are present in virtually all tissues, and highly motile to enter or leave specific sites throughout the body. Less than a decade ago, physical plasmas entered the field of medicine to deliver their delicate mix of reactive species and other physical agent...
Non-healing wounds continue to be a clinical challenge for patients and medical staff. These wounds have a heterogeneous etiology, including diabetes and surgical trauma wounds. It is therefore important to decipher molecular signatures that reflect the macroscopic process of wound healing. To this end, we collected wound sponge dressings routinely...
Background: Over the past years, plasma medicine has developed from an unknown and little accepted medical field into an integral part of medical research and subsequently of clinical treatment. The cellular mechanisms mediated by plasma treatment in wound healing are well investigated, and plasma sources specifically developed for treating wound h...
Promising cold physical plasma sources have been developed in the field of plasma medicine. An important prerequisite to their clinical use is lack of genotoxic effects in cells. During optimization of one or even different plasma sources for a specific application, large numbers of samples need to be analyzed. There are soft and easy-to-assess mar...
Non-thermal plasmas are a valuable component of the biomedical research and application toolbox. In the past years, a plethora of fundamental and applied knowledge on plasmas was gathered. An important prerequisite for their clinical applicability is safety. The chapter comprises the current knowledge on potential threats arising from the use of pl...
With a supply of energy, physical plasma is formed by the ionization of atoms or molecules of a gas. Plasmas applicable in medicine are generated in an atmospheric environment. Biological plasma effects that are potentially useful for medical applications are mainly mediated via changes to the liquid cell and tissue environment by reactive (redox-a...
In plasma medicine, ionized gases with temperatures close to that of vertebrate systems are applied to cells and tissues. Cold plasmas generate reactive species known to redox regulate biological processes in health and disease. Pre-clinical and clinical evidence points to beneficial effects of plasma treatment in the healing of chronic ulcer of th...
Plasma medicine is a rapidly advancing field. As one promising application, cold plasma has been ascribed a beneficial role in wound healing in which monocytes/macrophages play an important part. Wound healing and many other physiological and pathological processes are subject to redox control. Cold plasma expels reactive species of many kinds, the...
Recent results in the field of plasma medicine are increasingly motivating the use of cold physical plasma in clinical settings. Especially two major health issues, non-healing wounds and cancers, are in focus of current research. The outcome of both diseases is highly dependent on inflammation, a process that is priory driven by leukocytes. It is...
Metastatic melanoma is an aggressive and deadly disease. Therapeutic advance has been achieved by antitumor chemo- and radiotherapy. These modalities involve the generation of reactive oxygen and nitrogen species, affecting cellular viability, migration, and immunogenicity. Such species are also created by cold physical plasma, an ionized gas capab...
A particularly promising medical application of cold physical plasma is the support of wound healing. This is presumably achieved by modulating inflammation as well as skin cell signaling and migration. Plasma derived reactive oxygen and nitrogen species (ROS/RNS) are assumed the central biologically active plasma components. We hypothesized that m...
Cold physical plasma has been suggested as a powerful new tool in oncology. However, some cancer cells such as THP-1 leukaemia cells have been shown to be resistant towards plasma-induced cell death, thereby serving as a good model for optimizing plasmas in order to foster pro-apoptotic anticancer effects. A helium/oxygen radio frequency driven atm...
Multiple evidence in animal models and in humans suggest a beneficial role of cold physical plasma in wound treatment. Yet, risk assessment studies are important to further foster therapeutic advancement and acceptance of cold plasma in clinics. Accordingly, we investigated the long-term side effects of repetitive plasma treatment over 14 consecuti...
Cold plasma as an alternative therapy option may be useful in the treatment of skin wounds. Previous studies have provided evidence that cold plasma supports the healing of wounds owing to its beneficial mixture of reactive species and modulation of inflammation in cells and tissues. To date cold plasma did display neither genotoxic nor mutagenic e...
Cold plasma has been successfully applied in several fields of medicine that require, e.g. pathogen inactivation, implant functionalization, or alteration of cellular activity. Previous studies have provided evidence that plasma supports the healing of wounds owing to its beneficial mixtures of reactive species and modulation of inflammation in cel...
Exposure to cold physical plasma has been proposed to be of therapeutical value in oncology via the generation of a number of biologically relevant redox-active molecules. Cancer cells can be recognized and eliminated by cells of the immune system, and accordingly many tumors are populated with these cells, among them T helper cells (TH cells). The...
Targeting cancer cells with cold physical plasma emerged as a promising application in plasma medicine. To understand its mode of action with regard to cellular redoxregulation, two leukemia cell lines (Jurkat and THP-1 cells) were plasma-treated and their gene expression was compared. Transcriptomics revealed strikingly similar expression levels o...
Wound healing is a central physiological process that restores the
barrier properties of the skin after injury and infection.[1] Defective
wound healing is a burden to millions of patients worldwide with
diabetes mellitus being a major risk factor for chronic wounds.[2]
Besides wound bed infections, especially neuropathy and angiopathy
accompanied...
Durch Zufuhr von elektrischer Energie kommt es zur Ionisation von Atomen oder Molekülen eines selbst nicht unmittelbar wirksamen Gases: Physikalisches Plasma entsteht. Medizinisch eingesetzte Plasmen werden unter atmosphärischen Bedingungen generiert. Biologische und medizinisch nutzbare Plasmaeffekte werden überwiegend über Veränderungen der flüss...
Gap junctional intercellular communication (GJIC) is an important mechanism that is involved and affected in many diseases and injuries. So far, the effect of nanosecond pulsed electric fields (nsPEFs) on the communication between cells was not investigated. An in vitro approach is presented with rat liver epithelial WB-F344 cells grown and exposed...
Treatment of tumor progression and metastasis continues to be of major importance in the field of cancer medicine. It is reported that cancer cells often show a pronounced sensitivity towards oxidative stress. Cold plasma technology offers the ability to deliver a delicate mix of reactive oxygen and nitrogen species directly to cells and tissues. T...
Oxidative stress illustrates an imbalance between radical formation and removal. Frequent redox stress is critically involved in many human pathologies including cancer, psoriasis, and chronic wounds. However, reactive species pursue a dual role being involved in signaling on the one hand and oxidative damage on the other. Using a HaCaT keratinocyt...
Cold atmospheric pressure plasmas represent a favorable option for the treatment of heat sensitive materials and human or animal tissue. Beneficial effects have been documented in a variety of medical conditions, e.g., in the treatment of chronic wounds. It is assumed that the main mechanism of the plasma’s efficacy is mediated by a stimulating dis...
Supplementary Table: Differentially expressed genes present in all groups investigated (A)and their classification into protein functions and classes (B).
In plasma medicine, cold physical plasma delivers a delicate mixture of reactive components to cells and tissues. Recent studies suggested a beneficial role of cold plasma in wound healing. Yet, the biological processes related to the redox modulation via plasma are not fully understood. We here used the monocytic cell line THP-1 as a model to test...
Nanosecond pulsed electric fields can induce different biological effects in cells, depending on pulse length and field strength. Currently, they are investigated for medical applications such as cancer treatment and wound healing. Gap junctional intercellular communication (GJIC) is important to maintain the homeostasis in a tissue and plays a cru...
Plasma medicine has found first applications in hospitals. The presentation gives
an overview of pathways and mechanisms of reactive oxygen and nitrogen species from the
point of generation to the point where the biological effect is taking place. From these
effects, possible therapeutic applications are derived from pathogen inactivation over
woun...
Neural stem/progenitor cells (NSPCs) have the potential to self-renew and to generate all neural lineages as well as to repopulate damaged areas in the brain. Our previous targeting strategies have indicated precursor cell heterogeneity between different brain regions that warrants the development of NSPC-specific delivery vehicles. Here, we demons...
Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity to control redox-based processes, e.g. wound healing, cancer, or inflammatory diseases. By spatial and time resolved delivery of reactive oxygen- and nitrogen species, it allows to stimulate or inhibit cellular processes in biological systems. Our data show that both,...
Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity to control redox-based processes, e.g. wound healing, cancer, and inflammatory diseases. By spatial and time-resolved delivery of reactive oxygen and nitrogen species,
it allows stimulation or inhibition of cellular processes in biological systems. Our data show that b...
Der therapeutische Einsatz von kalten, nicht-thermischen Atmosphärendruckplasmen entwickelt sich immer mehr zu einem eigenständigen biomedizinischen Fachgebiet. Dabei stellt sich die Plasmamedizin als ein innovatives, hochgradig interdisziplinäres Forschungsfeld dar, in dem das Verständnis beider Fachdisziplinen - der Physik und der Biologie - unab...
Based on strong and sound results from basic research on plasma effects on living cells and tissue, plasma medicine now is starting its successful way into clinical practice. Currently, four cold atmospheric plasma (CAP) sources are CE-certified as medical devices. The main focus of plasma medical application is on wound healing as well as treatmen...
Plasma medicine is an exciting new scientific field due to recent developments
in nonthermal physical plasmas operating at atmospheric pressure. In the present study, the
effect of an argon-operated plasma jet (kINPen) using either humidified or dry argon as the
working gas was investigated on human keratinocytes with respect to changes in the cell...
Plasma medicine is an exciting new scientific field due to recent developments
in nonthermal physical plasmas operating at atmospheric pressure. In the present study, the
effect of an argon-operated plasma jet (kINPen) using either humidified or dry argon as the
working gas was investigated on human keratinocytes with respect to changes in the cell...
The application of physical plasma in medicine has great potential in wound
healing. Due to the generation of reactive oxygen and nitrogen species (ROS, RNS), emission
of UV radiation and the generated electric fields can be used to stimulate epithelial and
immune cells. To understand the processes on a molecular level the human keratinocyte cell
l...
A comprehensive gene expression profiling was done to explore cellular effects after non-thermal atmospheric pressure plasma treatment. We performed a high-content microarray comparison by assessing several categories of target probes in identical conditions of labeling, hybridization, and data analysis to compare specific gene expression profiles...
Cold plasma has become a promising application in the fields of biology and medicine. Its anti-microbial effects and stimulating properties on eukaryotic cells make plasma an encouraging option in treatment of chronic wounds. Apart from fibroblasts or keratinocytes, immune cells have a major contribution in wound healing. In this study, human perip...
Non thermal atmospheric pressure plasmas produce reactive oxygen and nitrogen species (ROS/RNS) which can influence cell physiology and trigger cellular signaling processes. This opens exiting new potentials e.g. in chronic wound care where encouraging results have been obtained in vivo by different research groups. Other data suggest the usability...
In the field of wound healing research non-thermal plasma (NTP) has attracted increasing attention over the last decades. NTP has a complex composition and consists of ions, exited atoms, electrons, ultraviolet (UV) light, visible and infrared radiation, neutral molecules, and free radicals e.g. reactive oxygen and nitrogen species (ROS/RNS)1. Next...
form only given. Non-thermal atmospheric pressure plasma consists of partially ionized gas and contains a range of reactive species including biological active ROS and RNS. There are numerous future applications planned in medicine, e.g. blood coagulation, disinfection and wound care. Recently it has been shown that plasma treatment can have lethal...
Abstract Non-thermal atmospheric pressure plasma has recently gained attention in the field of biomedical and clinical applications. In the area of plasma medicine research one promising approach is to promote wound healing by stimulation of cells involved. To understand basic molecular and cellular mechanisms triggered by plasma treatment we inves...
