PLASMA Wundzirkel – Plasmamedizin in Mecklenburg-Vorpommern

Herzlich willkommen beim PLASMA Wundzirkel!

Mit Ihrer Hilfe bauen wir ein landesweites Netzwerk zum Erfahrungsaustausch zwischen medizinischen Leistungserbringern (u.a. mit Dermatologen, Allgemeinmedizinern, Medizinischen Versorgungszentren, Kliniken, medizinischem Fachpersonal), Wissenschaftlern aus dem Bereich der Plasmamedizin, Herstellern der Plasmageräte, Kostenträgern sowie Patienten(verbänden) auf.

Sie finden hier umfassende Informationen zur Plasmamedizin und deren Einsatz bei der Behandlung von chronischen Wunden, können Kontakt zu Experten der Plasmamedizin aufnehmen und Ihre Erfahrungen teilen. Hier werden Sie zentral über Veranstaltungen in Ihrer Region informiert und neue Erkenntnisse aus der plasmamedizinischen Forschung und Produktentwicklung vorgestellt.

 

Als Medizinerinnen und Mediziner können Sie sich gerne über unsere Kontaktformular an uns wenden.

 

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  • Kontakt mit anderen Mediziner*innen zum fachlichen Austausch unter Kolleginnen und Kollegen
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  • Bereitstellung aktueller Informationen zur Plasmamedizin
  • Einladungen zu Veranstaltungen des PLASMA Wundzirkels

 

Medizinische Anwendung von kaltem Atmosphärendruckplasma

 

Plasmamedizin ist ein neues Forschungsgebiet an der Schnittstelle von Physik, Lebenswissenschaften und Medizin,
das gegenwärtig einen immensen internationalen Aufschwung erfährt. Im Zentrum des Interesses steht dabei
die Anwendung von kalten Atmosphärendruckplasmen in der medizinischen Therapie. Die plasmamedizinische
Grundlagenforschung konzentriert sich auf die Aufklärung von Mechanismen der Plasmawirkung auf lebende
Zellen und Gewebe, wobei in die flüssigeZellumgebung eingetragene oder dort gebildete reaktive Sauerstoff- und Stickstoffspezies eine zentrale Rolle spielen.
Der Fokus klinischer Forschung liegt derzeit auf der Plasmaanwendung zur Unterstützung von Wundheilungsprozessen sowie zur Behandlung infektiöser und entzündlicher Hauterkrankungen. Weitere Anwendungsmöglichkeiten in der Zahnmedizin und der Onkologie sind abzusehen.

Etablierte Anwendungen von Plasma in der Medizin

 

Eine Verbindung zwischen physikalischem Plasma und Biologie oder Medizin scheint schwer vorstellbar zu sein, obwohl diese bereits in den Anfängen der Plasmaphysik, nämlich bei der Namensgebung, bestanden haben soll. Der Versuch einer Systematisierung biomedizinischer Anwendungen von physikalischem Plasma führt zur Einteilung in drei Anwendungsfelder, die nicht scharf voneinander zu trennen sind: Oberflächenmodifikationen, Therapeutische Anwendungen und Biologische Dekontamination.
Die beiden medizinischen Anwendungsfelder Oberflächenmodifikationen und Biologische Dekontamination können auch als indirekte Plasmaanwendungen klassifiziert werden, da hierbei Materialien oder Produkte durch Plasmabehandlung mit Eigenschaften bzw. Qualitäten versehen werden, die ihre anschließende medizinische Anwendung unterstützen oder überhaupt erst ermöglichen. Für diese Anwendungsfelder können auch sogenannte Niederdruckplasmen eingesetzt werden, wobei die Plasmaerzeugung in abgeschlossenen Kammern bei extrem niedrigem Druck in der Nähe des Vakuums und damit unter sehr kontrollierten Bedingungen erfolgt.
Das zentrale und neue medizinische Anwendungsfeld, die Plasmamedizin im eigentlichen oder engeren Sinne, zielt auf die direkte Anwendung physikalischer Plasmen am oder im menschlichen (oder tierischen) Organismus zum Zweck der Erzielung oder Unterstützung therapeutischer Effekte ab.

Plasmamedizin: Kaltplasma in der medizinischen Anwendung (Lehrbuch)

 

Herausgeber: Metelmann, Hans-Robert; von Woedtke, Thomas; Weltmann, Klaus-Dieter.

Was ist Plasmamedizin? Wie lässt sich Plasma in Dermatologie und Chirurgie einsetzen? Welche Risiken gibt es? Dieses Buch beschreibt die Einsatzmöglichkeiten von modernen Plasmageräten in der Chirurgie und der Dermatologie. Grundlagen der Methode und die Technologie unterschiedlicher Geräte werden erläutert und klinische Anwendungen dargestellt. Aktuelle Forschungsergebnisse bieten einen Ausblick auf den Anwendungshorizont für unterschiedliche Fachgebiete.

Springer-Verlag Berlin Heidelberg (2016), DOI 10.1007/978-3-662-52645-3

 

Publikationen

 

Die Ergebnisse der Forschung zur Plasmamedizin werden regelmäßig in referierten Fachzeitschriften im peer-review-Verfahren sowie in nicht-referierten Fachmagazinen publiziert. Hier finden Sie eine Auswahl der grundlegenden und aktuellen Veröffentlichungen.

Eine vollständige Publikationsübersicht zur plasmamedizinischen Forschung für Ihr Fachgebiet stellen wir Ihnen auf Anfrage zur Verfügung. Bitte nutzen Sie unser Kontaktformular.

 

Studien und Paper in 2017

 

Cold atmospheric plasma: a new tool for the treatment of superficial driveline infections,

Hilker, L.; von Woedtke, Th.; Weltmann, K.-D.; Wollert, H.-G.

Percutaneous driveline infections (DI) are leading factors for morbidity and mortality in ventricular assist device (VAD) patients. In recent years, cold atmospheric plasma (CAP) has been safely and effectively used in clinical settings to treat topical infections. We describe the first use of CAP to treat a superficial DI. CAP was applied with the kinPen® MED plasma jet device (neoplas tools GmbH, Greifswald, Germany), in the treatment of a DI in a 66-year-old VAD patient in Klinikum Karlsburg, Germany. The patient received a daily application of CAP of 1 min for 12 days. One CAP application was administered each week for 4 weeks in our outpatient clinic after patient discharge. Laboratory tests were conducted and photographs of the driveline exit site were taken. After CAP treatment, the local infection was completely regressed without any signs of exudation or recurrence of the infection. There were no adverse side effects observed, and the HVAD logfile data did not show any abnormalities during treatment. Here, we demonstrate a successful resolution of a VAD DI with the kinPen plasma jet device. We believe that CAP has the potential to be a simple and effective tool in the treatment of superficial DIs.

DOI: 10.1093/ejcts/ezw212, Eur. J. Cardio-Thorac. Surg. 51 (2017) 186-187.

 

A cold plasma jet accelerates wound healing in a murine model of full-thickness skin wounds,

Schmidt, A.; Bekeschus, S.; Wende, K.; Vollmar, B.; von Woedtke, Th.:

Cold plasma has been successfully applied in several fields of medicine that require, for example, 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 cells and tissues. To investigate the wound healing activity of an atmospheric pressure plasma jet in vivo, we examined the cold plasma's efficacy on dermal regeneration in a murine model of dermal full-thickness ear wound. Over 14 days, female mice received daily plasma treatment. Quantitative analysis by transmitted light microscopy demonstrated a significantly accelerated wound re-epithelialization at days 3-9 in comparison with untreated controls. In vitro, cold plasma altered keratinocyte and fibroblast migration, while both cell types showed significant stimulation resulting in accelerated closure of gaps in scratch assays. This plasma effect correlated with the downregulation of the gap junctional protein connexin 43 which is thought to be important in the regulation of wound healing. In addition, plasma induced profound changes in adherence junctions and cytoskeletal dynamics as shown by downregulation of E-cadherin and several integrins as well as actin reorganization. Our results theorize cold plasma to be a beneficial treatment option supplementing existing wound therapies.

DOI: 10.1111/exd.13156. Exp. Dermatol. 26 (2017) 156-162.

 

One Year Follow-Up Risk Assessment in SKH-1 Mice and Wounds Treated with an Argon Plasma Jet,

Schmidt, A.; von Woedtke, Th.; Stenzel, J.; Lindner, T.; Polei, S.; Vollmar, B.; Bekeschus, S.:

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 longterm side effects of repetitive plasma treatment over 14 consecutive days in a rodent full-thickness ear wound model. Subsequently, animals were housed for 350 days and sacrificed thereafter. In blood, systemic changes of the proinflammatory cytokines interleukin 1β and tumor necrosis factor α were absent. Similarly, tumor marker levels of α-fetoprotein and calcitonin remained unchanged. Using quantitative PCR, the expression levels of several cytokines and tumor markers in liver, lung, and skin were found to be similar in the control and treatment group as well. Likewise, histological and immunohistochemical analysis failed to detect abnormal morphological changes and the presence of tumor markers such as carcinoembryonic antigen, α-fetoprotein, or the neighbor of Punc11. Absence of neoplastic lesions was confirmed by non-invasive imaging methods such as anatomical magnetic resonance imaging and positron emission tomography-computed tomography. Our results suggest that the beneficial effects of cold plasma in wound healing come without apparent side effects including tumor formation or chronic inflammation.

DOI: 10.3390/ijms18040868 Int. J. Mol. Sci. 18 (2017) 868.

 

Kaltes Atmosphärendruck-Plasma - eine zusätzliche Therapieoption in der Krebsbehandlung? Metelmann, P.; Weltmann, K.-D.; von Woedtke, Th. Spitzenforschung in der Dermatologie 2017/18

 

Plasma medicine - current state of research and medical application,

Weltmann, K.-D.; von Woedtke, Th.

Plasma medicine means the direct application of cold atmospheric plasma (CAP) on or in the human body for therapeutic purposes. Further, the field interacts strongly with results gained for biological decontamination. Experimental research as well as first practical application is realized using two basic principles of CAP sources: dielectric barrier discharges (DBD) and atmospheric pressure plasma jets (APPJ). Originating from the fundamental insights that the biological effects of CAP are most probably caused by changes of the liquid environment of cells, and are dominated by reactive oxygen and nitrogen species (ROS, RNS), basic mechanisms of biological plasma activity are identified. It was demonstrated that there is no increased risk of cold plasma application and, above all, there are no indications for genotoxic effects. The most important biological effects of cold atmospheric pressure plasma were identified: (1) inactivation of a broad spectrum of microorganisms including multidrug resistant ones; (2) stimulation of cell proliferation and tissue regeneration with lower plasma treatment intensity (treatment time); (3) inactivation of cells by initialization of programmed cell death (apoptosis) with higher plasma treatment intensity (treatment time). In recent years, the main focus of clinical applications was in the field of wound healing and treatment of infective skin diseases. First CAP sources are CE-certified as medical devices now which is the main precondition to start the introduction of plasma medicine into clinical reality. Plasma application in dentistry and, above all, CAP use for cancer treatment are becoming more and more important research fields in plasma medicine. A further in-depth knowledge of control and adaptation of plasma parameters and plasma geometries is needed to obtain suitable and reliable plasma sources for the different therapeutic indications and to open up new fields of medical application.

DOI: 10.1088/0741-3335/59/1/014031. Plasma Phys. Control. Fusion 59 (2017) 14031. Open Access.

 

Studien und Paper in 2016

 

Grundlagen der Plasmamedizin.

von Woedtke, Th.; Weltmann, K.-D.,

Hintergrund: Das neue Gebiet der Plasmamedizin beschäftigt sich mit der medizinischen Anwendung physikalischer, kalter Atmosphärendruckplasmen („cold atmospheric plasma“, CAP). Fragestellung: Darstellung der wissenschaftlichen Grundlagen der Plasmamedizin und gegenwärtiger sowie potenzieller medizinischer Anwendungsmöglichkeiten. Material und Methode: Zusammenfassung des aktuellen Stands der präklinischen und der klinischen Forschung unter besonderer Berücksichtigung der CAP-Plasmajet-Quelle kINPen®. Ergebnisse: Physikalisches Plasma wird auch als 4. Aggregatzustand der Materie bezeichnet. Mit CAP ist es möglich, ein breites Spektrum an Mikroorganismen, einschließlich multiresistenter Bakterien, sehr effektiv zu inaktivieren, sowie die Regeneration verletzten Gewebes zu stimulieren. Darüber hinaus wurde die Möglichkeit der Induktion des programmierten Zelltods (Apoptose) auch und v. a. in Krebszellen experimentell nachgewiesen. Kalte Atmosphärendruckplasmen beeinflussen insbesondere über temporär und lokal erhöhte Konzentrationen von reaktiven Sauerstoff- und Stickstoffspezies in der flüssigen Zellumgebung die zelluläre Redoxbalance. Die Anwendung von CAP am oder im menschlichen Körper birgt bei bestimmungsgemäßer Anwendung keine erhöhten Risiken. Gegenwärtiger Anwendungsschwerpunkt von CAP sind v. a. die Wundheilung und die Behandlung infektiöser Hauterkrankungen. An Einsatzmöglichkeiten in der Krebsbehandlung wird intensiv geforscht. Schlussfolgerungen: Die Plasmamedizin steht am Anfang eines sehr erfolgversprechenden Wegs in die klinische Anwendung. Das Besondere und Einzigartige der CAP liegt darin, dass die Wirkkomponenten lokal am Ort und nur für die erforderliche Zeit der Anwendung primär durch einen physikalischen Prozess generiert werden.

DOI: 10.1007/s12285-016-0075-0. MKG-Chirurg 9 (2016) 246-254.

 

Low Temperature Plasma Applications in Medicine.

Weltmann, K.-D.; Metelmann, H.-R.; von Woedtke, Th.,

The main field of plasma medicine is the direct application of cold atmospheric plasma (CAP) on or in the human body for therapeutic purposes. CAP is effective both to inactivate a broad spectrum of microorganisms including multiple drug resistant ones and to stimulate proliferation of mammalian cells. Clinical application has started in the field of wound healing and treatment of infective skin diseases.

DOI: 10.1051/epn/2016507. Europhys. News 47 (2016) 39-42.

 

Risk assessment of a cold argon plasma jet in respect to its mutagenicity.

Wende, K.; Bekeschus, S.; Schmidt, A.; Jatsch, L.; Hasse, S.; Weltmann, K.-D.; Masur, K.; von Woedtke, Th.,

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 dissipation of energy via radiation and/or chemical energy. Although no evidence on undesired side effects of a plasma treatment has yet been presented, skepticism toward the safety of the exposure to plasma is present. However, only little data regarding the mutagenic potential of this new treatment option is available. Accordingly, we investigated the mutagenic potential of an argon plasma jet (kinpen) using different testing systems in accordance with ISO norms and multiple cell lines: a HPRT1 mutation assay, a micronucleus formation assay, and a colony formation assay. Moderate plasma treatment up to 180 s did not increase genotoxicity in any assay or cell type investigated. We conclude that treatment with the argon plasma jet kinpen did not display a mutagenic potential under the test conditions applied and may from this perspective be regarded as safe for the use in biomedical applications.

DOI: 10.1016/j.mrgentox.2016.02.003. Mutat. Res.-Gen. Tox. En. 798 (2016) 48-54.

Studien und Paper in 2015

 

Head and neck cancer treatment and physical plasma

Metelmann, H.-R.; Nedrelow, D.S.; Seebauer, C.; Schuster, M.; von Woedtke, Th.; Weltmann, K.-D.; Kindler, S.; Metelmann, P.H.; Finkelstein, S.E.; von Hoff, D.D.; Podmelle, F.

This study is a retrospective review of representing clinical follow-up of 12 patients afflicted with advanced squamous cell carcinoma of the head and neck. Herein, we have used novel physical cold atmospheric pressure plasma (CAP) to decontaminate infected cancer ulcerations and evaluated anti-cancer effects. With use of CAP in this cohort, the data suggests: (1) decreased request for pain medication and (2) reduction of typical fetid odor related to (3) reduction of microbial load. In some cases there is (4) superficial partial remission of tumor and even (5) wound healing of infected ulcerations has been observed following CAP exposure. As a result, CAP treatment appears of benefit for select head and neck cancer patients and future work to optimize CAP in the therapeutic armamentarium advances.

DOI: 10.1016/j.cpme.2015.02.001. Clin. Plasma Med. 3 (2015) 17-23.

Studien und Paper in 2014

 

In vitro susceptibility of multidrug resistant skin and wound pathogens against low temperature atmospheric pressure plasma jet (APPJ) and dielectric barrier discharge plasma (DBD).

Daeschlein G., Napp M., von Podewils S., Lutze S., Emmert S., Lange A., Klare I., Haase H., Gümbel D., von Woedtke Th., Jünger M.:

Plasma medicine has become an emerging field in medical sciences since cold plasma has demonstrated important antimicrobial properties. As microbial plasma susceptibility data yet are not available, the susceptibility of 194 wound isolates exhibiting multiple antibiotic resistance was tested in vitro to CP and correlated with inhibition zones. Inhibition zones increased in parallel with the number of antibiotic classes to which the tested strain exhibit resistance. CP exhibited strong antimicrobial efficacy against most important clinical skin and wound pathogens in vitro irrespective of multidrug resistance.

DOI: 10.1002/ppap.201300070. Plasma Process. Polym. 11 (2014), p. 175-183. Open Access.

 

Cold plasma - a new antimicrobial treatment tool against multidrug resistant pathogens. In: Worldwide Research Efforts in the Fighting against Microbial Pathogens: From Basic Research to Technological Developments.

Daeschlein G., Scholz S., von Podewils S., Arnold A., Klare I., Haase H., Emmert S., von Woedtke Th., Jünger M.

In Worldwide Research Efforts in the Fighting Against Microbial Pathogens from Basic Research to Technological Developments, p. 110-113. A. Mendez-Vilas (ed.), Pub. BrownWalker Press, 2014. ISBN-13: 978-1-61233-636-7.

 

Non-thermal atmospheric-pressure plasma possible application in wound healing.

Haertel B., von Woedtke Th., Weltmann K.-D., Lindequist U.:

Non-thermal atmospheric-pressure plasma, also named cold plasma, is defined as a partly ionized gas. Therefore, it cannot be equated with plasma from blood; it is not biological in nature. Non-thermal atmospheric-pressure plasma is a new innovative approach in medicine not only for the treatment of wounds, but with a wide-range of other applications, as e.g. topical treatment of other skin diseases with microbial involvement or treatment of cancer diseases. This review emphasizes plasma effects on wound healing. Non-thermal atmospheric-pressure plasma can support wound healing by its antiseptic effects, by stimulation of proliferation and migration of wound relating skin cells, by activation or inhibition of integrin receptors on the cell surface or by its pro-angiogenic effect. We summarize the effects of plasma on eukaryotic cells, especially on keratinocytes in terms of viability, proliferation, DNA, adhesion molecules and angiogenesis together with the role of reactive oxygen species and other components of plasma. The outcome of first clinical trials regarding wound healing is pointed out.

DOI: 10.4062/biomolther.2014.105. Biomol. Ther. 22 (2014), p. 477-490. Open Access.

 

Physikalische Plasmen für die Wundheilung. Rechtsdepesche für das Gesundheitswesen. Mann, M.; von Woedtke, Th., Sonderausgabe 2/2014 (2014) 52-54.

 

Plasma Applications: A Dermatological View.

Tiede R., Hirschberg J., Daeschlein G., von Woedtke Th., Vioel W., Emmert S.

The ability to produce cold plasma at atmospheric pressure conditions was the basis for the rapid growth of plasma related application areas in biomedicine. Plasma comprises a multitude of active components such as charged particles, electric current, UV radiation, and reactive species which can act synergistically. The antiitch, antimicrobial, and anti-inflammatory effect was already demonstrated in in vivo and in vitro experiments and until now no resistance of pathogens against plasma treatment was observed. The combination of the different active agents and their broad range of positive effects on various diseases, especially easily accessible skin diseases, render plasma quite attractive for applications in medicine. Hence, plasma medicine as an independent and promising medical field has been emerged recently.

For medical applications two different types of cold plasma are suitable; indirect (plasma jet, plasma torch) and direct plasma sources (dielectric barrier discharge - DBD). So far, no standards and norms are defined for any of these plasma sources. Also, no convenient criteria for standardization of the quality rating of plasma in the view of dermatological applications exist. Although various cold plasma studies have been performed the results are hardly comparable, as physical parameters of the plasma devices, experimental conditions, and organisms used vary greatly. Therefore, standardized risk analyses are necessary for the assessment of different plasma sources. In this review two plasma sources are described and possible risk factors are discussed to estimate the safety of plasma used as a therapeutic tool in dermatology. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

DOI: 10.1002/ctpp.201310061. Contributions to Plasma Physics 54 (2014), p. 118-130. Open Access.

 

Plasmamedizin in der Dermatologie.

Tiede R., Mann M., Viöl W., Daeschlein G., Welz C., Wolff H.A., von Woedtke Th., Lademann J., Emmert S.

Das interdisziplinäre Gebiet der Plasmamedizin beschäftigt sich mit der Möglichkeit therapeutischer Anwendungen kalter physikalischer Plasmen. Insbesondere in der Dermatologie finden sich zahlreiche Therapiemöglichkeiten für kalte Plasmen, wie zum Beispiel zur Behandlung von Wunden und diversen entzündlichen Hauterkrankungen (z. B. Psoriasis oder Neurodermitis), zur Hautantiseptik oder auch zur Hautregeneration. Dies liegt zum einen an den zahlreichen und zum Teil auch synergistisch wirkenden Plasmakomponenten, die durch Justierung der physikalischen Parameter eingestellt werden können. Zum anderen besteht mittlerweile eine hohe Diversität von verfügbaren Plasmaquellen, die angepasst auf die
jeweils gewünschten Anwendungsbereiche und Therapiemodalitäten entwickelt wurden. Durch die rasche Entwicklung der Plasmamedizin werden immer mehr Geräte auf dem medizinischen Markt angeboten, wodurch die Frage nach überprüfbarer und damit vergleichbarer Anwendungssicherheit immer dringlicher wird. Eine erste DIN-Spezifikation für medizinische Plasmaquellen, DIN-SPEC 91315 „Allgemeine Anforderungen an medizinische Plasmaquellen“, als erster Schritt zur spezifischen Evaluierung von Plasmageräten insbesondere im Hinblick auf deren Sicherheit wurde kürzlich veröffentlicht.
Dieser Artikel soll basierend auf der aktuellen Literatur sowie eigenen Arbeiten der Autoren eine Zusammenfassung der potenziellen Wirkungen und Nebenwirkungen von kaltem Atmosphärendruck-Plasma in der Dermatologie bieten.

HAUT 6 (2014), 228 – 233.

 

Clinical Plasma Medicine: State and Perspectives of in Vivo Application of Cold Atmospheric Plasma.

von Woedtke Th., Metelmann H.-R., Weltmann K.-D.

Driven by extensive basic research on plasma effects on living cells and microorganisms, plasma medicine has been developed as innovative medical research field during the last years. Besides partially established applications of plasma to treat materials or devices to allow effective medical applications with respect to biocompatibility or microbiological safety, respectively, the primary focus of plasma-medical research is the direct application of plasma as part of therapeutic concepts. Even if a huge number of atmospheric pressure plasma sources for biomedical applications are described in the literature and characterized by in vitro microbiology and cell biology, there is only a limited number of in vivo experience with animals or human beings up to now. Research in plasma medicine has been mainly focused on applications in dermatology and aesthetic surgery with the aim to support tissue regeneration to improve healing of infected and/or chronic wounds as well as to treat infective and inflamed skin diseases. In general, there are four cold atmospheric plasma sources which were tested comprehensively in animals as well as human beings with respect both to its therapeutic potential and the safety of its application.

Three clinical trials with cold atmospheric pressure plasma sources have been carried out yet. All three studies realized in Germany are focused on ulcer treatment. Two cold atmospheric pressure plasma sources got a CE marking as medical device in 2013. This marks a very important step to bring plasma medicine into the clinical daily routine!

In future, it will become a general practical requirement to adapt special plasma sources to specific medical applications. Consequently, it is one of the main requirements for the physical and technical field of research and development in plasma medicine to find solutions for modular and flexible plasma devices which are adaptive to some extent e.g. to variable target areas. Based on this as well as together with comprehensive basic research to get much more insight into detailed mechanisms of plasma-induced effects on living structures and the particular role of single plasma components, further fields of plasma application in vivo will be opened or extended, respectively, with both new targets like cancer treatment or new application sites like teeth, lung, eyes, nasal cavity or gastrointestinal tract. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

DOI: 10.1002/ctpp.201310068. Contrib. Plasma Phys. 54 (2014), p. 104-117. Open Access.

Studien und Paper in 2013

 

Clinical Plasma Medicine Core Group (Emmert S., Isbary G., Kluschke F., Lademann J., Podmelle F., Metelmann H.-R., Daeschlein G., Masur K., von Woedtke Th., Weltmann K.-D.): Clinical plasma medicine – position and perspectives in 2012. Paper of consent, result of the workshop "Clinical Concepts in Plasma Medicine", Greifswald April 28th, 2012. DOI: 10.1016/j.cpme.2012.11.003. Clinical Plasma Medicine 1 (2013) 3-4.

 

Plasmamedizin in der Zahnmedizin.

Jablonowski L., Koban I., Kocher T.

Cold atmospheric pressure plasma is still comparatively unknown in dentistry. Plasma medicine is a young and interdisciplinary field that examines the possibilities of cold atmospheric pressure plasmas for medical applications. Plasma provides a broad range of properties that could offer new treatment alternatives in numerous diseases. Many diseases in medicine and dentistry are associated with bacteria, which are organized in biofilms, where they are protected from external influences, such as drugs or treatments. The good antimicrobial activity of plasma on biofims was already demonstrated. Plasma opens up new possibilities in the treatment of dental caries, periodontal disease or peri-implantitis which is still untreatable. Furthermore plasma has the ability to modify surfaces, which could be interesting for new filling techniques or implant materials. On the basis of current knowledge about the application of cold atmospheric pressure plasmas we discuss the possibilities and prospects of plasma medicine in the field of dentistry.

Hyg. Med. 38 (2013) 206-211(Schwerpunktheft Plasmamedizin).

 

Physikalisches kaltes Atmosphärendruckplasma als aussichtsreiche Option zur Behandlung chronischer Wunden

Kramer A., Bender C., Assadian O., Ekkernkamp A., Hartmann B., Heidecke C.D., Hinz P., Koban I., Masur K., Matthes R., Metelmann H.-R., Partecke I., Reuter S., Sckell A., Weltmann K.-D., Lademann J.

Cold atmospheric pressure plasma was investigated by means of a graded test hierarchy regarding its suitability for the treatment of chronic wounds. The working hypothesis is underlined by the following reasons. I. Every healing process involves energy. II. A wound cannot heal as long as it is infected. III. Necrotic tissue must be removed for healing. IV. The chronic wound should be transferred from its stagnation to an acute healing state by inflammatory and proliferation-supporting stimuli. Initially, the effectiveness against bacterial biofilms in vitro and the antiseptic efficacy on the skin were established. In parallel, the compatibility of the monolayer and the 3-D cell culture were determined. Using bioassays like the chorioallantois membrane of the hen’s egg, porcine eye tissue and also on the human skin the wound tolerance of the plasma treatment could be confirmed. Thereby, the analysis of a mild activity of inflammation processes in the chorioallantois membrane of the hen’s egg presented an important finding regarding the assessment of the prospects of success in the treatment of chronic wounds. The first successful treatment by atmospheric pressure plasma of ineffective conventionally treated chronic wounds in domestic animals and, for the first time, in patients, allows the conclusion that physical cold plasma – also termed as “tissue tolerable plasma” – presents an innovative option in the treatment of chronic wounds.

Hyg. Med. 38 (2013) 186-191 (Schwerpunktheft Plasmamedizin).

 

Suitability of tissue tolerable plasmas (TTP) for the management of chronic wounds.

Kramer A., Lademann J., Bender C., Sckell A., Hartmann B., Münch S., Hinz P., Ekkernkamp A., Matthes R., Koban I., Partecke I., Heidecke C.D., Masur K., Reuter S., Weltmann K.-D., Koch S., Assadian O.

This review considers qualifying standards of wound management, explains the hypothesis for the applicability of tissue tolerable plasma (TTP) and lists the TTP effects relevant for wound healing. TTP fulfils these requirements in-vitro and in-vivo together with its demonstrated good tissue tolerability. Cases of treatment of chronic wounds in pets are presented which healed by TTP in combination with polihexanide or octenidine within 3 to 24 weeks. It may be concluded that TTP is a new option for the treatment of chronic wounds.

DOI: 10.1016/j.cpme.2013.03.002. Clinical Plasma Medicine 1 (2013) 11-18.

 

Risk assessment of the application of tissue-tolerable plasma on human skin.

Lademann J. , Ulrich C., Patzelt A., Richter H., Kluschke F., Klebes M., Lademann O., Kramer A., Weltmann K.-D., Lange-Asschenfeldt B.:

The results of the risk assessment of the tissue-tolerable plasma (TTP) jet kINPen med® and first results of pilot clinical studies are presented. Producing an atmospheric pressure plasma, this plasma jet entails no risk for humans in terms of temperature increase, UV radiation or free radical formation by the plasma. The antiseptic efficacy in vitro on porcine skin and in vivo on human skin was compared to that of octenidine. TTP could significantly reduce the bacterial load in comparison to untreated skin. However, the slightly reduced antiseptic properties of TTP are attributed to the current parameter set-up and technical limitations.

DOI: 10.1016/j.cpme.2013.01.001. Clinical Plasma Medicine 1 (2013) 5–10.

 

Scar formation of laser skin lesions after cold atmospheric pressure plasma (CAP) treatment: A clinical long term observation.

Metelmann H.-R., Vu T.T., Do H.T., Le T.N. B., Hoang T.H.A., Phi T.T.T., Luong T.M.L., Doan V.T., Nguyen T.T.H., Nguyen T.H.M., Le D.Q., Le T.K.X., von Woedtke Th., Bussiahn R., Weltmann K.-D., Khalili R., Podmelle F.

CAP treatment is likely to be of benefit in wound healing. In a clinical study, 20 laser lesions in five individuals have been treated with argon plasma 10, 30 or three times for 10 s, with untreated as control. The scar formation was followed for 10 days, six and 12 months. In early stages of wound healing, plasma treatment seems to support the inflammation needed for tissue recovery. In later stages, plasma treatment shows better results in terms of avoiding post-traumatic skin disorders. Plasma treatment shows superior aesthetics during scar formation. No precancerous skin features occurred up to 12 months.

DOI: 10.1016/j.cpme.2012.12.001. Clinical Plasma Medicine 1 (2013) 30-35.

 

Plasmas for medicine.

von Woedtke Th., Reuter S., Masur K., Weltmann K.-D.

Plasma medicine is an innovative and emerging field combining plasma physics, life science and clinical medicine. In a more general perspective, medical application of physical plasma can be subdivided into two principal approaches. (i) “Indirect” use of plasma-based or plasma-supplemented techniques to treat surfaces, materials or devices to realize specific qualities for subsequent special medical applications, and (ii) application of physical plasma on or in the human (or animal) body to realize therapeutic effects based on direct interaction of plasma with living tissue. The field of plasma applications for the treatment of medical materials or devices is intensively researched and partially well established for several years. However, plasma medicine in the sense of its actual definition as a new field of research focuses on the use of plasma technology in the treatment of living cells, tissues, and organs. Therefore, the aim of the new research field of plasma medicine is the exploitation of a much more differentiated interaction of specific plasma components with specific structural as well as functional elements or functionalities of living cells. This interaction can possibly lead either to stimulation or inhibition of cellular function and be finally used for therapeutic purposes. During recent years a broad spectrum of different plasma sources with various names dedicated for biomedical applications has been reported. So far, research activities were mainly focused on barrier discharges and plasma jets working at atmospheric pressure.

Most efforts to realize plasma application directly on or in the human (or animal) body for medical purposes is concentrated on the broad field of dermatology including wound healing, but also includes cancer treatment, endoscopy, or dentistry.

Despite the fact that the field of plasma medicine is very young and until now mostly in an empirical stage of development yet, there are first indicators of its enormous economic potential. This ambivalent situation fundamentally requires a responsible use of plasma sources, which are specifically designated for biomedical applications. To enable physicians as well as life scientists to decide whether a given plasma source is really suitable for medical applications or biological experiments, a meaningful and mandatory spectrum of indicators has to be compiled to allow for a basic estimation of the potential of this plasma source.

DOI: 10.1016/j.physrep.2013.05.005. Phys. Rep. 530 (2013), p. 291-320.

 

Plasmamedizin - Medizinische Anwendung von physikalischem Plasma.

von Woedtke Th., Weltmann K.-D.

Plasma medicine is a new research field at the interface between physics, life sciences and medicine with a present huge international upward movement. In the centre of attention is the application of cold atmospheric plasmas for medical therapy. Basic research in plasma medicine is concentrated on mechanisms of plasma effects on living cells and tissue in which reactive oxygen and nitrogen species generated in or transferred into the liquid cell environment play a key role. Clinical research is focused on plasma applications to support wound healing processes as well as to treat infective and inflammative skin diseases. Further applications in dentistry or oncology are to be expected.

Hyg. Med. 38 (2013) 180-185 (Schwerpunktheft Plasmamedizin).

Studien und Paper in 2012

 

Cold plasma is well-tolerated and does not disturb skin barrier or reduce skin moisture.

Daeschlein G., Scholz S., Ahmed R., A, Majumdar, von Woedtke Th., Haase H., Niggemeier M., Kindel E., Brandenburg R., Weltmann K.-D., Jünger M.

Background: Cold plasma, a new treatment principle in dermatology based on ionic discharge delivering reactive molecular species and UV-light, exhibits strong antimicrobial efficacy in vitro and in vivo. Before implementing plasma as new medical treatment tool, its safety must be proven, as well as assessing skin tolerance and patient acceptance. Patients and Methods: We investigated the plasma effects of three different plasma sources (pulsed, non-pulsed atmospheric pressure plasma jet (APPJ) and a dielectric barrier discharge (DBD)) on the transepidermal water loss (TEWL) and skin moisture after treating the fingertips of four healthy male volunteers. Results: TEWL values were reduced by pulsed APPJ and DBD by about 20% but increased after non-pulsed APPJ by 5–20%. TEWL values normalized 30 min after all forms of plasma treatment. Skin moisture was increased immediately and 30 min after treatment with pulsed APPJ but was not affected by non-pulsed APPJ and DBD. Conclusions: All plasma treatments were well-tolerated and did not damage the skin barrier nor cause skin dryness. Cold plasma fulfils basic recommendations for safe use on human skin and as future option may serve as the first physical skin antiseptic.

DOI: 10.1111/j.1610-0387.2012.07857.x. JDDG 10 (2012) 509-515. Open Access.

 

Skin decontamination by low-temperature atmospheric pressure plasma jet and dielectric barrier discharge plasma.

Daeschlein G., Scholz S., Ahmed R., von Woedtke Th., Haase H., Niggemeier M., Kindel E., Brandenburg R., Weltmann K.-D., Jünger M.:

Background: Over the past few years, plasma medicine has become an important field in medical science. Cold plasma has proven anti-inflammatory, antimicrobial and antineoplastic effects. Aim: To test the decontamination power of two cold plasma sources [low-temperature atmospheric pressure plasma jet (APPJ) and dielectric barrier discharge plasma (DBD)] in vivo on human fingertips. Methods: After 3, 15, 30, 60, 90, 120, 150, 180, 210 and 240 s of spot treatment with the APPJ and DBD, the log reduction factors (RFs) of physiological (PF) and artificially (AF) contaminated flora (Staphylococcus epidermidis and Micrococcus luteus) were calculated. The bacterial load was determined after counting. Tolerance (paresthesia, pain and heat) was measured using a numerical rating scale. Findings: Both plasma devices led to a significant reduction in PF and AF. The maximum log reduction factors for PF were 1.3 for the DBD at 210 s and 0.8 for the APPJ at 60 s. For AF, the maximum log reduction factors were 1.7 for the DBD at 90 s and 1.4 for the APPJ at 120 s. Treatment with both devices was well tolerated. Conclusion: 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.

DOI: 10.1016/j.jhin.2012.02.012. J. Hosp. Infect. 81 (2012) 177-183.

 

In vitro susceptibility of important skin and wound pathogens against low temperature atmospheric pressure plasma jet (APPJ) and dielectric barrier discharge plasma (DBD).

Daeschlein G., Scholz S., Arnold A., S. von Podewils, Haase H., Emmert S., von Woedtke Th., Weltmann K.-D., Jünger M.

Plasma medicine has become an emerging field in medical sciences since cold plasma has demonstrated anti-inflammatory, anti-tumor as well as antimicrobial effects. In the light of increasing resistance of many pathogens like methicillin-resistant Staphylococcus aureus (MRSA) to a multitude of antimicrobial therapies cold plasma therapy with complete different modes of action could constitute an alternative to conventional external antibiotic and antiseptic therapies. As plasma susceptibility data of human skin and wound pathogens are not available, the susceptibility of 105 typical isolates from dermatologic patients' wounds to low temperature atmospheric pressure plasma (APPJ device) and dielectric barrier discharge plasma device are tested in vitro. Plasma treatment proved to be highly effective in eradicating all (n = 105) strains including Escherichia coli, Pseudomonas aeruginosa, Klebsiella group (K. pneumoniae ssp. pneumoniae, K. oxytoca), S. aureus, hemolysing Lancefield Streptococci (group A and B), Proteus group (P. mirabilis, P. vulgaris), Acinetobacter spp., Stenotrophomonas spp., Enterococcus faecalis, Candida albicans and Staphylococcus epidermidis. In conclusion, cold plasma treatment exhibited strong and rapid antimicrobial effects against clinical most relevant skin and wound pathogens in vitro. Cold plasma may constitute an effective alternative to antiseptics in the attempt to eradicate skin and wound pathogens.

DOI: 10.1002/ppap.201100160. Plasma Process. Polym. 9 (2012) 380-389. Open Access.

 

Plasma Medicine in Dermatology: Basic antimicrobial efficacy testing as prerequisite to clinical plasma therapy.

Daeschlein G., Scholz S., Emmert S., von Podewils S., Haase H., von Woedtke T., Weltmann K.-D., Jünger M.:

Plasma medicine has become an emerging field in medical sciences since cold plasma has demonstrated significant antibacterial properties in vitro and in vivo. However, systematic antimicrobial plasma testing against bacteria, fungi, and parasites is still lacking. Chronic wounds, fungal skin and nail infections, and colonization with multidrug-resistant pathogens like Staphylococcus aureus (MRSA) often pose significant therapeutic and economical problems and new therapeutic concepts are strongly warranted. The challenge of worldwide increasing resistance problems including different pathogens like methicillin-resistant MRSA, vancomycin-resistant enterococci, and gram-negative species producing beta-lactam hydrolysing enzymes (extended spectrum β-lactamases) constitute the need for alternative antimicrobial treatments. Cold plasma therapy with a completely different mode of action compared to conventional antimicrobials may offer an alternative to conventional external antibiotic and antiseptic therapies. In order to estimate the possible role as physical antiseptic, basic susceptibility data from plasma are needed. To provide such data, the plasma susceptibility of representative skin and wound pathogens against low-temperature atmospheric pressure plasma jet (APPJ device) and dielectric barrier discharge plasma treatment was tested in vitro on agar. The same plasma sources were used to test clinical fungal isolates in vitro and isolates of the parasite demodex folliculorum ex vivo. Plasma treatment proved to be highly effective in eradicating all treated strains and species including Escherichia coli, Pseudomonas aeruginosa, Klebsiella group (K. pneumoniae ssp. pneumoniae, K. oxytoca), Staphylococcus aureus, hemolysing Lancefield Streptococci (group A and B), Proteus group (P. mirabilis, P. vulgaris), Acinetobacter spp, Stenotrophomonas spp., Enterococcus faecalis, Candida albicans, and Staphylococcus epidermidis. Plasma irradiation of Trichophyton rubrum, Trichophyton interdigitale, Microsporon canis, and the yeast Candida albicans was able to kill >90% of the organisms during 30 s in vitro with no isolate exhibiting resistance. The APPJ-plasma killed Demodex folliculorum after exposure time of 2 s. Our data suggest plasma as a possible new option in the treatment of microbial, fungal, and parasitic dermal infections.

DOI: 10.1615/PlasmaMed.2014006217. Plasma Medicine 2 (2012) 33-69.

 

Experimental Recovery of CO2-Laser Skin Lesions by Plasma Stimulation.

Metelmann H.-R., von Woedtke Th., Bussiahn R., Weltmann K.-D.,Rieck M., Khalili R., Podmelle F., Waite P.D.

Highly purified betuline as a triterpene dry extract from birch cork stimulates wound healing via induction of basal cell proliferation and promotion of keratinocyte differentiation. A multicenter, prospective, randomized, controlled, clinical trial compared, intra-individually, betuline to a state-of-the-art moist wound healing dressing. As a wound model, split thickness skin was grafted in 16 patients due to plastic surgery. The donor site area at the upper leg was divided into equal halves. By randomization one site was treated with betuline oleogel and the other with moist dressing alone. Treatment continued for 14 days after surgery. Photographs were taken 1 year after treatment and sent to distant experts in a blinded version. The main objective was to compare the 2 areas with different treatment in terms of superior normal skin appearance. After 1 year and with 14 patients in control, superior healing by betuline was evident in 12 of 14 cases, and 9 of 14 patients had obvious esthetic benefit due to betuline, whereas no one performed perfectly by moist dressing alone.

DOI: 10.5992/AJCS-D-11-00046.1. Am J. Cosmetic Surg. 29 (2012) 52-56.