Non-Thermal Atmospheric-Pressure Plasma Possible Application in Wound Healing

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.

[1]  H. Machens,et al.  Innovations in wound medicine , 2014 .

[2]  A. Elvis,et al.  Ozone therapy: A clinical review , 2011, Journal of natural science, biology, and medicine.

[3]  Gary Friedman,et al.  Gas Plasma: Medical Uses and Developments in Wound Care , 2010 .

[4]  M. Oh,et al.  Nationwide Surveillance for Staphylococcus aureus with Reduced Susceptibility to Vancomycin in Korea , 2003, Journal of Clinical Microbiology.

[5]  K. Song,et al.  Non-Thermal Atmospheric Pressure Plasma Preferentially Induces Apoptosis in p53-Mutated Cancer Cells by Activating ROS Stress-Response Pathways , 2014, PloS one.

[6]  A. Yousef,et al.  Ozone and its current and future application in the food industry. , 2003, Advances in food and nutrition research.

[7]  M. Keidar,et al.  Integrin activation by a cold atmospheric plasma jet , 2012 .

[8]  K. Weltmann,et al.  Influence of the Air Humidity on the Reduction of Bacillus Spores in a Defined Environment at Atmospheric Pressure Using a Dielectric Barrier Surface Discharge , 2010 .

[9]  G Daeschlein,et al.  Alleviation of chronic venous leg ulcers with a hand‐held dielectric barrier discharge plasma generator (PlasmaDerm® VU‐2010): results of a monocentric, two‐armed, open, prospective, randomized and controlled trial (NCT01415622) , 2015, Journal of the European Academy of Dermatology and Venereology : JEADV.

[10]  Gheorghe Popa,et al.  Stimulation of wound healing by helium atmospheric pressure plasma treatment , 2011 .

[11]  Ya-ting Tu 涂亚庭,et al.  Non-thermal plasma suppresses bacterial colonization on skin wound and promotes wound healing in mice , 2011, Journal of Huazhong University of Science and Technology [Medical Sciences].

[12]  Michael Landthaler,et al.  Randomized placebo‐controlled human pilot study of cold atmospheric argon plasma on skin graft donor sites , 2013, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[13]  Chul Hee Choi,et al.  Prevalence of the ST239 Clone of Methicillin-Resistant Staphylococcus aureus and Differences in Antimicrobial Susceptibilities of ST239 and ST5 Clones Identified in a Korean Hospital , 2005, Journal of Clinical Microbiology.

[14]  T. von Woedtke,et al.  Non‐thermal atmospheric‐pressure plasma can influence cell adhesion molecules on HaCaT‐keratinocytes , 2011, Experimental dermatology.

[15]  Seungok Lee,et al.  Emergence of Community-Associated Methicillin-Resistant Staphylococcus aureus Strains as a Cause of Healthcare-Associated Bloodstream Infections in Korea , 2009, Infection Control & Hospital Epidemiology.

[16]  Jung-Bo Huh,et al.  Sterilization effect of atmospheric pressure non-thermal air plasma on dental instruments , 2013, The journal of advanced prosthodontics.

[17]  A. Bosserhoff,et al.  Cold atmospheric plasma, a new strategy to induce senescence in melanoma cells , 2013, Experimental dermatology.

[18]  J. Hornung,et al.  Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line , 1988, The Journal of cell biology.

[19]  T. von Woedtke,et al.  Differential sensitivity of lymphocyte subpopulations to non-thermal atmospheric-pressure plasma. , 2012, Immunobiology.

[20]  Petr Sáha,et al.  Cell Proliferation of HaCaT Keratinocytes on Collagen Films Modified by Argon Plasma Treatment , 2010, Molecules.

[21]  Arnaud Duval,et al.  Cell Death Induced on Cell Cultures and Nude Mouse Skin by Non-Thermal, Nanosecond-Pulsed Generated Plasma , 2013, PloS one.

[22]  N. Khardori Control of methicillin-resistant Staphylococcus aureus in planktonic form and biofilms: A biocidal efficacy study of nonthermal dielectric-barrier discharge plasma , 2010 .

[23]  A. Kramer,et al.  Effects of tissue-tolerable plasma on psoriasis vulgaris treatment compared to conventional local treatment: A pilot study , 2014 .

[24]  Mingli Chen,et al.  Dielectric barrier discharge non-thermal micro-plasma for the excitation and emission spectrometric detection of ammonia. , 2011, The Analyst.

[25]  D W Slaaf,et al.  Electric discharge plasmas influence attachment of cultured CHO K1 cells , 2004, Bioelectromagnetics.

[26]  I Langmuir,et al.  Oscillations in Ionized Gases. , 1928, Proceedings of the National Academy of Sciences of the United States of America.

[27]  M. Keidar,et al.  Targeting the cancer cell cycle by cold atmospheric plasma , 2012, Scientific Reports.

[28]  K. Weltmann,et al.  Controlling the NO production of an atmospheric pressure plasma jet , 2012 .

[29]  M Landthaler,et al.  Successful and safe use of 2 min cold atmospheric argon plasma in chronic wounds: results of a randomized controlled trial , 2012, The British journal of dermatology.

[30]  V. Travagli,et al.  The Ozone Paradox: Ozone Is a Strong Oxidant as Well as a Medical Drug , 2009 .

[31]  G. Collins,et al.  Bacterial Inactivation of Wound Infection in a Human Skin Model by Liquid-Phase Discharge Plasma , 2011, PloS one.

[32]  T. von Woedtke,et al.  Influence of non-thermal atmospheric pressure plasma on cellular structures and processes in human keratinocytes (HaCaT). , 2013, Journal of dermatological science.

[33]  A. Kramer,et al.  Risk assessment of the application of tissue-tolerable plasma on human skin , 2013 .

[34]  Alisa Morss Clyne,et al.  Non-thermal dielectric barrier discharge plasma induces angiogenesis through reactive oxygen species , 2011, 2011 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[35]  W. Dröge Free radicals in the physiological control of cell function. , 2002, Physiological reviews.

[36]  T. von Woedtke,et al.  Skin decontamination by low-temperature atmospheric pressure plasma jet and dielectric barrier discharge plasma. , 2012, The Journal of hospital infection.

[37]  M. Keidar,et al.  Influence of Cold Plasma Atmospheric Jet on Surface Integrin Expression of Living Cells , 2010 .

[38]  C. Kieda,et al.  ROS implication in a new antitumor strategy based on non‐thermal plasma , 2012, International journal of cancer.

[39]  K. Weltmann,et al.  Tracking plasma generated H2O2 from gas into liquid phase and revealing its dominant impact on human skin cells , 2014 .

[40]  R. Nicosia,et al.  The Mouse Aorta Model: Influence of Genetic Background and Aging on bFGF- and VEGF-Induced Angiogenic Sprouting , 2004, Angiogenesis.

[41]  W. Stolz,et al.  A randomized two‐sided placebo‐controlled study on the efficacy and safety of atmospheric non‐thermal argon plasma for pruritus , 2013, Journal of the European Academy of Dermatology and Venereology : JEADV.

[42]  U. Lindequist,et al.  Comparison of Biological Effects on Human Keratinocytes Using Different Plasma Treatment Regimes , 2013 .

[43]  Jörg Ehlbeck,et al.  Antimicrobial treatment of heat sensitive products by miniaturized atmospheric pressure plasma jets (APPJs) , 2008 .

[44]  A. Clyne,et al.  Endothelial Cell Proliferation is Enhanced by Low Dose Non-Thermal Plasma Through Fibroblast Growth Factor-2 Release , 2010, Annals of Biomedical Engineering.

[45]  W. Stolz,et al.  Ex vivo human skin experiments for the evaluation of safety of new cold atmospheric plasma devices , 2013 .

[46]  G. Kim,et al.  Nonthermal-plasma-mediated animal cell death , 2011 .

[47]  A. Kramer,et al.  Pilot-study on the influence of carrier gas and plasma application (open resp. delimited) modifications on physical plasma and its antimicrobial effect against Pseudomonas aeruginosa and Staphylococcus aureus , 2012, GMS Krankenhaushygiene interdisziplinar.

[48]  M. Jünger,et al.  Cold plasma is well‐tolerated and does not disturb skin barrier or reduce skin moisture , 2012, Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG.

[49]  T. von Woedtke,et al.  Clinical Plasma Medicine: State and Perspectives of in Vivo Application of Cold Atmospheric Plasma , 2014 .

[50]  H. Uhm,et al.  Sterilization effect of atmospheric plasma on Escherichia coli and Bacillus subtilis endospores , 2009, Letters in applied microbiology.

[51]  M. Kowalewski,et al.  Superficially, longer, intermittent ozone theraphy in the treatment of the chronic, infected wounds. , 2003, Ortopedia, traumatologia, rehabilitacja.

[52]  U. Lindequist,et al.  Differential effect of non-thermal atmospheric-pressure plasma on angiogenesis , 2014 .

[53]  G. Collet,et al.  Perspectives of endoscopic plasma applications , 2013 .

[54]  A. Fridman,et al.  DNA damage in mammalian cells by non-thermal atmospheric pressure microsecond pulsed dielectric barrier discharge plasma is not mediated by ozone , 2010, 2010 Abstracts IEEE International Conference on Plasma Science.

[55]  B. Nebe,et al.  Persistent Effectivity of Gas Plasma-Treated, Long Time-Stored Liquid on Epithelial Cell Adhesion Capacity and Membrane Morphology , 2014, PloS one.

[56]  Hans-Oliver Rennekampff,et al.  Evidence-based Management Strategies for Treatment of Chronic Wounds , 2009, Eplasty.

[57]  R. Leask,et al.  Effects of Non‐thermal Plasmas on DNA and Mammalian Cells , 2010 .

[58]  W. Stolz,et al.  Non-thermal plasma—More than five years of clinical experience , 2013 .

[59]  R. Sensenig,et al.  Live Pig Skin Tissue and Wound Toxicity of Cold Plasma Treatment , 2011 .

[60]  M. Steinbeck,et al.  Skeletal Cell Differentiation Is Enhanced by Atmospheric Dielectric Barrier Discharge Plasma Treatment , 2013, PloS one.

[61]  A. Fridman,et al.  Effects of Non-Thermal Plasma on Mammalian Cells , 2011, PloS one.

[62]  K. Weltmann,et al.  Atomic oxygen in a cold argon plasma jet: TALIF spectroscopy in ambient air with modelling and measurements of ambient species diffusion , 2012 .

[63]  J. Liao,et al.  Increased Fibroblast Cell Proliferation and Migration Using Atmospheric N2/Ar Micro‐Plasma for the Stimulated Release of Fibroblast Growth Factor‐7 , 2014 .

[64]  Sean P. Gorman,et al.  Eradication of Pseudomonas aeruginosa Biofilms by Atmospheric Pressure Non-Thermal Plasma , 2012, PloS one.

[65]  M Landthaler,et al.  A first prospective randomized controlled trial to decrease bacterial load using cold atmospheric argon plasma on chronic wounds in patients , 2010, The British journal of dermatology.

[66]  K. Weltmann,et al.  Non-thermal plasma treatment is associated with changes in transcriptome of human epithelial skin cells , 2013, Free radical research.

[67]  K. Weltmann,et al.  Identification of the Molecular Basis of Non-thermal Plasma-Induced Changes in Human Keratinocytes , 2013 .

[68]  Gregor E. Morfill,et al.  Bactericidal effects of non-thermal argon plasma in vitro, in biofilms and in the animal model of infected wounds. , 2011, Journal of medical microbiology.

[69]  G. Zhang,et al.  Effects of Low‐Temperature Atmospheric Air Plasmas on the Activity and Function of Human Lymphocytes , 2008 .

[70]  Nasruddin,et al.  Cold plasma on full-thickness cutaneous wound accelerates healing through promoting inflammation, re-epithelialization and wound contraction , 2014 .

[71]  A. Kramer,et al.  Differential Viability of Eight Human Blood Mononuclear Cell Subpopulations After Plasma Treatment , 2013 .

[72]  K. Fidelis,et al.  Functional characterization of Ape1 variants identified in the human population. , 2000, Nucleic acids research.

[73]  T. von Woedtke,et al.  Time-dependent effects of low-temperature atmospheric-pressure argon plasma on epithelial cell attachment, viability and tight junction formation in vitro , 2012 .

[74]  J. Azizkhan-Clifford,et al.  DNA Damage in Mammalian Cells by Atmospheric Pressure Microsecond-Pulsed Dielectric Barrier Discharge Plasma Is Not Mediated Via Lipid Peroxidation , 2011 .

[75]  J. Zimmermann,et al.  Decolonisation of MRSA, S. aureus and E. coli by Cold-Atmospheric Plasma Using a Porcine Skin Model In Vitro , 2012, PloS one.

[76]  W. Stolz,et al.  Cold atmospheric argon plasma treatment may accelerate wound healing in chronic wounds: Results of an open retrospective randomized controlled study in vivo , 2013 .

[77]  U. Lindequist,et al.  Viability of Human Blood Leukocytes Compared with Their Respective Cell Lines after Plasma Treatment , 2013 .

[78]  J. Zimmermann,et al.  In vivo skin treatment using two portable plasma devices: Comparison of a direct and an indirect cold atmospheric plasma treatment , 2013 .

[79]  A. Luch,et al.  Reactive species: a cell damaging rout assisting to chemical carcinogens. , 2008, Cancer letters.

[80]  U. Lindequist,et al.  Impact of non-thermal plasma treatment on MAPK signaling pathways of human immune cell lines. , 2013, Immunobiology.

[81]  Gary Friedman,et al.  Control of methicillin-resistant Staphylococcus aureus in planktonic form and biofilms: a biocidal efficacy study of nonthermal dielectric-barrier discharge plasma. , 2010, American journal of infection control.

[82]  K. Weltmann,et al.  Detection of ozone in a MHz argon plasma bullet jet , 2012 .

[83]  J. Zimmermann,et al.  Restoration of Sensitivity in Chemo — Resistant Glioma Cells by Cold Atmospheric Plasma , 2013, PloS one.

[84]  R. Tice,et al.  A simple technique for quantitation of low levels of DNA damage in individual cells. , 1988, Experimental cell research.

[85]  P. Dedon,et al.  Quantification of DNA damage products resulting from deamination, oxidation and reaction with products of lipid peroxidation by liquid chromatography isotope dilution tandem mass spectrometry , 2008, Nature Protocols.

[86]  T. von Woedtke,et al.  Atmospheric pressure plasma jet treatment evokes transient oxidative stress in HaCaT keratinocytes and influences cell physiology , 2014, Cell biology international.

[87]  M. Jünger,et al.  In Vitro Susceptibility of Multidrug Resistant Skin and Wound Pathogens Against Low Temperature Atmospheric Pressure Plasma Jet (APPJ) and Dielectric Barrier Discharge Plasma (DBD): In Vitro Susceptibility of Multidrug Resistant Skin and Wound Pathogens… , 2014 .

[88]  K. Weltmann,et al.  Innovative Plasma Generation in Flexible Biopsy Channels for Inner‐Tube Decontamination and Medical Applications , 2012 .

[89]  Wilhelm Stolz,et al.  Cold atmospheric plasma: a successful treatment of lesions in Hailey-Hailey disease. , 2011, Archives of dermatology.

[90]  Karsten Schröder,et al.  Atmospheric Pressure Plasma: A High-Performance Tool for the Efficient Removal of Biofilms , 2012, PloS one.

[91]  S. Gorman,et al.  Potential cellular targets and antibacterial efficacy of atmospheric pressure non-thermal plasma. , 2014, International journal of antimicrobial agents.

[92]  A. Kramer,et al.  In vivo skin treatment with tissue‐tolerable plasma influences skin physiology and antioxidant profile in human stratum corneum , 2012, Experimental dermatology.

[93]  A. Kramer,et al.  Hydrogen peroxide: A central player in physical plasma-induced oxidative stress in human blood cells , 2014, Free radical research.

[94]  S. Reuter,et al.  The dynamics of radio-frequency driven atmospheric pressure plasma jets , 2009 .

[95]  A. Sckell,et al.  Suitability of tissue tolerable plasmas (TTP) for the management of chronic wounds , 2013 .

[96]  Eva Stoffels,et al.  Superficial treatment of mammalian cells using plasma needle , 2003 .

[97]  Alisa Morss Clyne,et al.  Non-thermal dielectric barrier discharge plasma induces angiogenesis through reactive oxygen species , 2012, Journal of The Royal Society Interface.

[98]  M. Schön,et al.  Atmospheric pressure plasma in dermatology: Ulcus treatment and much more , 2013 .

[99]  Martin Polak,et al.  Low temperature atmospheric pressure plasma sources for microbial decontamination , 2011 .

[100]  P. Brun,et al.  Disinfection of Ocular Cells and Tissues by Atmospheric-Pressure Cold Plasma , 2012, PloS one.

[101]  Stephan Reuter,et al.  Plasmas for medicine , 2013 .

[102]  A. Kramer,et al.  Human Mononuclear Cell Survival and Proliferation is Modulated by Cold Atmospheric Plasma Jet , 2013 .

[103]  G. Daeschlein Antimicrobial and antiseptic strategies in wound management , 2013, International wound journal.

[104]  A. Clyne,et al.  Hydroxyl Radical and Hydrogen Peroxide are Primarily Responsible for Dielectric Barrier Discharge Plasma-Induced Angiogenesis , 2011 .

[105]  V. Scholtz,et al.  Decontamination of human skin by low-temperature plasma produced by cometary discharge , 2013 .

[106]  A. Widgerow Chronic wounds – is cellular ‘reception’ at fault? Examining integrins and intracellular signalling , 2013, International wound journal.

[107]  R. López-Callejas,et al.  Assessing Cellular DNA Damage from A Helium Plasma Needle , 2012, Radiation research.

[108]  J. Zimmermann,et al.  Effects of cold atmospheric plasmas on adenoviruses in solution , 2011, ICOPS 2012.

[109]  Linda J. Kuo,et al.  γ-H2AX - A Novel Biomarker for DNA Double-strand Breaks , 2008 .

[110]  A. Kramer,et al.  Antimicrobial Efficacy of Two Surface Barrier Discharges with Air Plasma against In Vitro Biofilms , 2013, PloS one.

[111]  F. Batista,et al.  The Interactions between Non-thermal Atmospheric Pressure Plasma and Ex-vivo Dermal Fibroblasts , 2013 .

[112]  T. von Woedtke,et al.  Differential Influence of Components Resulting from Atmospheric-Pressure Plasma on Integrin Expression of Human HaCaT Keratinocytes , 2013, BioMed research international.

[113]  Je Chul Lee,et al.  Emergence of vancomycin-intermediate Staphylococcus aureus from predominant methicillin-resistant S. aureus clones in a Korean hospital , 2010, The Journal of Microbiology.

[114]  A. Clyne,et al.  A Nitric Oxide Producing Pin-to-Hole Spark Discharge Plasma Enhances Endothelial Cell Proliferation and Migration , 2011 .

[115]  K. Weltmann,et al.  Reactive species output of a plasma jet with a shielding gas device—combination of FTIR absorption spectroscopy and gas phase modelling , 2014 .

[116]  D. Lauffenburger,et al.  Cell Migration: A Physically Integrated Molecular Process , 1996, Cell.

[117]  U. Lindequist,et al.  Surface molecules on HaCaT keratinocytes after interaction with non‐thermal atmospheric pressure plasma , 2012, Cell biology international.

[118]  Rosendo Peña-Eguiluz,et al.  Accelerated mice skin acute wound healing in vivo by combined treatment of argon and helium plasma needle. , 2013, Archives of medical research.

[119]  C. Franceschi,et al.  JC‐1, but not DiOC6(3) or rhodamine 123, is a reliable fluorescent probe to assess ΔΨ changes in intact cells: implications for studies on mitochondrial functionality during apoptosis , 1997, FEBS letters.