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Keywords Summary
• plasma medicine As a result of both the better understanding of complex plasma phenomena
• plasma and the development of new plasma sources in the past few years, plasma
• cold atmospheric plasma medicine has developed into an innovative field of research showing high
• microbiology potential. While thermal plasmas have long been used in various medical fields
• chronic wounds (for instance for cauterization and sterilization of medical instruments), current
• sterilization research mainly focuses on application of non-thermal plasmas.
• disinfection Experiments show that cold atmospheric plasmas (CAPs) allow efficient, con-
tact-free and painless disinfection, even in microscopic openings, without dam-
aging healthy tissue. Plasmas influence biochemical processes and offer new
possibilities for the selective application of individually designable medically
active substances. In dermatology, new horizons are being opened for wound
healing, tissue regeneration, therapy of skin infections, and probably many
more diseases. First clinical trials show the efficacy and tolerability of plasma in
treating infected chronic wounds. A major task will be the introduction of plas-
ma into clinical medicine and, simultaneously, the further investigation of the
mechanisms of action of plasma at the cellular level.
Introduction devices and in packaging of food stuffs. cell membranes, DNA, lipids and pro-
In physics plasma is considered the The development of diverse, usually teins up to studies on plant, animal and
fourth state of matter next to solids, liq- non-thermal atmospheric-pressure plasma human tissue and finally on patients.
uids and gases. In 1879 the British sources makes its use also in the Without damaging surrounding healthy
chemist and physicist William Crookes (bio)medical field possible. While in the tissue, cold atmospheric-pressure plas-
first described it as “radiant matter “ [1]. past only the thermal properties of plas- mas at room temperature lead to diverse
The term “plasma” itself comes from mas (> 80 °C) were utilized – cauteriza- reactions in tissue. Numerous compo-
Greek (“something molded”) and was in- tion, sterilization of heat-resistant instru- nents of plasma such as e. g reactive oxy-
troduced in 1928 by Irving Langmuir, as ments or for cosmetic, reconstructive gen or nitrogen species, charged parti-
the multicomponent mixture of highly procedures – current research is directed cles, electric fields and even UV light
ionized gases reminded him of blood primarily at the non-thermal effects of (Figure 1) are involved in these effects.
plasma. In technology plasmas have been plasma. Research ranges from investiga- Possible uses include – among others –
established for a very long time – for ex- tion of the fundamental physics, study of very rapid and gentle tissue disinfection
ample in the manufacture of television the optimal, individual plasma composi- via inactivation of diverse pathogens
screens or fluorescent tubes. On the basis tion over the interaction of plasmas with (gram-positive and –negative bacteria,
of their high bactericidal effectiveness prokaryotic and eukaryotic cells, viruses, fungi, viruses, spores and parasites), pre-
plasmas are also used to sterilize medical spores and fungi, cell structures such as cise tissue removal and stimulation of
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Plasma medicine Review Article 969
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970 Review Article Plasma medicine
but due to a grounded mesh elec- and the plasma composition and can ria with plasma was reported [12]. In
trode no current flows through tissue therefore vary greatly. For bacterial steril- contrast to conventional methods which
anymore [10]. In contrast to DBD ization, for example, with suitable pa- usually require high temperatures or
systems no air space exists between rameters a short application time of a high concentrations of chemical sub-
the barrier and the opposite electrode few seconds is sufficient. stances such as ethylene oxide, ozone or
(in which the micro-discharges oc- In medical use on patients safety comes chlorine, cold plasma can also be used on
cur) and the opposite electrode must first, so that a risk evaluation of the re- heat-sensitive and chemically reactive
be structured (e. g. mesh). The micro spective plasma device must take place. surfaces. Plasma acts rapidly and very
discharges then occur parallel to the Potential risk factors such as electric cur- effectively and penetrates the smallest
surface of the dielectric barrier, which rent, thermal damage of tissue and the openings and hollow spaces. How
is why these electrodes are also intensity of UV emission as well as opti- plasma actually achieves disinfection or
termed surface micro discharge mal duration and intensity of application sterilization is not yet fully understood.
(SMD)” electrodes. These SMD sys- and gas composition must be checked According to current knowledge both
tems are also independent of the dis- exactly. Lademann et al. [11] in studies physical mechanisms (caused by reactive
tance from the surface to be treated on pig’s ears and tape stripping of volun- species, free radicals, UV photons) and
(within certain limits). teers demonstrated that in treatment biological mechanisms (cellular processes
Universal requirements for the composi- with a CE-certified plasma jet with ar- such as DNA and cell membrane dam-
tion of plasmas do not exist. Most cold gon as carrier gas and optimal treatment age) appear to be responsible for the in-
plasmas at atmospheric pressure are pro- parameters practically no UV light activation of bacteria [13]. UV radiation
duced using helium or argon gas, but reached living skin cells (< 1 % at via energy absorption directly damages
production of plasma e. g. from air or 200 µm skin thickness, maximum UV cellular macromolecules on the one
other mixtures is possible. Limits exist emission in this case at 310 nm, small hand, on the other, DNA proteins and
with regard to electric current, UV radi- bands between 325 and 450 nm), as each lipids are irreparably harmed by oxida-
ation (maximum allowed dose individual of the 15 to 25 corneocyte tive stress.
30 µW/cm², for details see SCCP Euro- layers in human skin absorbs about 25 % Numerous studies using varying treat-
pean Commission Report 0949/05) and of the radiation. Temperature effects also ment parameters prove in vitro the effi-
the production of reactive species (limit were negligible, so that no risk potential cacy of low-temperature plasmas towards
for ozone 50 ppb, see CPSC Consumer is expected for this device in vivo. gram-negative and gram-positive bacte-
Products Safety Commission – report of ria, spores, biofilm-producing bacteria,
09/26/2006, for NO2 2 or 5 ppm and Disinfection and sterilization viruses and fungi. In a phase I study
25 ppm for NO over a time period of of inert materials and vital tissue performed by our working group [7, 14]
8 hours, US National Institute for Occu- It has been known for a long time that in which low-temperature plasma at
pational Safety and Health, NIOH). The ionized gases have biocidal effects, but atmospheric pressure was employed
application time depends on the purpose only in 1996 successful killing of bacte- (MicroPlaSter®, a plasma torch with
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972 Review Article Plasma medicine
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Plasma medicine Review Article 973
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974 Review Article Plasma medicine
for several minutes and irritate the skin, MRSA: methicillin-resistant Staphylococ- 5 Fridman G, Friedman G, Gutsol A,
while at the same time remaining dis- cus aureus Shekhter AB, Vasilets VN, Fridman A.
tinctly below WHO limits for UV, toxic PSR: plasma skin regeneration Applied Plasma Medicine. Plasma Pro-
gases and electric current [10]. Naturally, SMD: surface micro discharge cess Polym 2008; 5: 503–33.
not only clinics but also public establish- SSCP: Scientific Committee on Consumer 6 Fridman G, Brooks AD, Balasubramanian
ments, nursing homes etc. could profit. Products M, Fridman A, Gutsol A, Vasilets VN,
Cold plasmas may also find applications Ayan H, Friedman G. Comparison of
in dentistry in the future. Due to the direct and indirect effects of non-ther-
ability to enter microscopically small mal atmospheric-pressure plasma on
openings, theoretically therapeutic meas- bacteria. Plasma Process Polym 2007;
ures against periodontitis, chronic gin- 4: 370–5.
givitis and in the treatment of infected 7 Shimizu T, Steffes B, Pompl R,
root canals are possible. Clinical evidence Jamitzky F, Bunk W, Ramrath K,
for this must still be gathered. Further, in Georgi M, Stolz W, Schmidt HU,
vivo the combination with H2O2 showed Urayama T, Fujii S, Morfill GE. Cha-
an increase in the bleaching effect as well racterization of microwave plasma
as protein removal on the surface of torch for decontamination. Plasma
plasma-treated teeth [52, 53]. Process Polym 2008; 5: 577–82.
Julia Heinlin 8 Sladek RE, Stoffels E. Deactivation of
Conclusions Escherichia coli by the plasma needle.
Thanks to interdisciplinary cooperation J Phys D: Applied Physics 2005; 38:
in medicine, physics, chemistry, biology 1716–21.
Correspondence to 9 Cao Z, Walsh JL, Kong MG. Atmos-
and microbiology plasma medicine has
developed into an innovative and dy- pheric plasma jet array in parallel elec-
namic field of research in recent years. tric and gas flow fields for three-dimen-
Even if many questions remain unan- sional surface treatment. Appl Phys
swered – especially the mechanism of in- Lett 2009; 94: 021501.
teraction between plasma and living 10 Morfill GE, Shimizu T, Steffes B,
cells/ tissues and the optimization of Schmidt HU. Nosocomial infections –
plasma composition depending on the a new approach towards preventive me-
desired effect – studies to date illustrate dicine using plasmas. New Journal of
the great potential of plasma medicine. Physics 2009; 11: 115019.
Cold plasmas will surely be available in 11 Lademann J, Richter H, Alborova A,
the near future to an increasing extent Humme D, Patzelt A, Kramer A, Weltmann
both for therapy and prevention of Prof. Dr. Sigrid Karrer KD, Hartmann B, Ottomann C, Fluhr
diverse, particularly infectious diseases. Department of Dermatology JW, Hinz P, Hubner G, Lademann O.
There does exist a vision of a break- University of Regensburg Risk assessment of the application of a
through in medicine comparable to the Franz-Josef-Strauß-Allee 11 plasma jet in dermatology. J Biomed
introduction of antibiotics. The superi- D-93053 Regensburg, Germany Opt 2009; 14: 054025.
ority of plasmas in comparison to previ- Tel.: +49-941-944-9656 12 Laroussi M. Sterilization of Contami-
ous medical standards remains to be Fax: +49-941-944-9657 nated Matter with an Atmospheric
clarified, especially in economic terms. E-mail: Pressure Plasma. IEEE Trans Plasma Sci
sigrid.karrer@klinik.uni-regensburg.de 1996; 24: 1188–91.
13 Kong MG, Kroesen J, Morfill G,
Conflicts of interest References Nosenko T, Shimizu T, van Dijk J,
Some members of our working group 1 Crookes W. On Radiant Matter Spec- Zimmermann JL. Plasma medicine: an
hold patents on diverse plasma devices troscopy: A New Method of Spectrum introductory review. New Journal of
and techniques. A phase II study on the Analysis. Proc Roy Soc 1883; 35: Physics 2009; 11: 115012.
treatment of infected wounds with cold 262–71. 14 Pompl R, Shimizu T, Schmidt HU,
atmospheric plasma (MicroPlaSter®) is 2 Morfill G, Kong MG, Zimmermann Bunk W, Jamitzky F, Steffes B, Ramrath
being financed by the Max Planck Insti- JL. Focus on Plasma Medicine. New K, Peters B, Stolz W, Urayama T,
tute for Extraterrestrial Physics, Munich, Journal of Physics 2009; 11: 115011. Ramasamy R, Fujii S, Morfill GE.
Germany. <<< 3 Fridman A, Chirokov A, Gutsol A. Efficiency and medical compatibility of
Non-thermal atmospheric pressure di- low-temperature plasma sterilization.
Abbreviations scharges. J Phys D: Applied Physics 6th International Conference on
APC: argon plasma coagulator 2005; 38: R1–R24. Reactive Plasmas. Matsushima, Japan,
CAP: cold atmospheric plasma 4 Nosenko T, Shimizu T, Morfill GE. 2006.
DBD: dielectric barrier discharge Designing plasmas for chronic wound 15 Kamgang-Youbi G, Herry JM,
FE-DBD: floating-electrode dielectric disinfection. New Journal of Physics Meylheuc T, Brisset JL, Bellon-
barrier discharge 2009; 11: 115013. Fontaine MN, Doubla A, Naitali M.
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Plasma medicine Review Article 975
Microbial inactivation using plasma- 25 Kim D, Gweon B, Kim DB, Choe W, oxide. Bulletin of Experimental Biology
activated water obtained by gliding el- Shin JH. A feasibility study for the and Medicine 1998; 126: 829–34.
ectric discharges. Lett Appl Microbiol. cancer therapy using cold plasma. 13th 36 Lipatov KV, Sopromadze MA, Shekhter
2009; 48: 13–8. International Conference on Biomedi- AB, Emel’ianov A, Grachev SV. [Use of
16 Deng X, Shi JJ, Kong MG. Protein cal Engineering. Singapore: ICBME, gas flow with nitrogen oxide (NO-
destruction by a helium atmospheric 2008: 355–57. therapy) in combined treatment of pu-
pressure glow discharge: Capability and 26 Kim G, Lee H, Shon C. The effect of a rulent wounds]. Khirurgiia (Mosk)
mechanisms. J Appl Phys 2007; 101: micro plasma on melanoma (G361) 2002: 41–3.
074701. cancer cells. J Korean Physical Society 37 Shulutko AM, Antropova NV, Kriuger
17 Lee MH, Park BJ, Jin SC, Kim D, Han 2009; 54: 628–32. Iu A. [NO-therapy in the treatment of
I, Kim J, Hyun SO, Chung KH, Park 27 Zang X, Li M, Zhou R, Feng K, Yang purulent and necrotic lesions of lower
JC. Removal and sterilization of S. Ablation of liver cancer cells in vitro extremities in diabetic patients]. Khir-
biofilms and planktonic bacteria by by a plasma needle. Appl Phys Lett urgiia (Mosk) 2004: 43-6.
microwave-induced argon plasma at at- 2008; 93: 021502. 38 Daeschlein G, Darm K, Niggemeier M,
mospheric pressure. New Journal of 28 Robson MC, Heggers JP. Delayed Majunke S, von Woedtke T, Kindel E,
Physics 2009; 11: 115022. wound closure based on bacterial counts. Weltmann KD, Juenger M. Selective
18 Shashurin A, Keidar M, Bronnikov S, J Surg Oncol 1970; 2: 379–83. antistaphylococcal activity of atmos-
Jurjus RA, Stepp MA. Living tissue un- 29 Trengove NJ, Stacey MC, McGechie pheric pressure plasma jet (APPJ) on
der treatment of cold plasma atmos- DF, Mata S. Qualitative bacteriology human skin. Second International
pheric jet. Appl Phys Lett 2008; 93: and leg ulcer healing. J Wound Care Conference on Plasma Medicine. San
181501. 1996; 5: 277–80. Antonio, Texas, USA, 2009.
19 Kalghatgi S, Fridman A, Friedman G, 30 Grundmann H, Aires-de-Sousa M, 39 Mertens N, Helmke A, Goppold A,
Clyne AM. Non-thermal plasma Boyce J, Tiemersma E. Emergence and Emmert S, Kaemling A, Wandke D,
treatment enhances proliferation of resurgence of meticillin-resistant Sta- Vioel W. Low temperature plasma tre-
endothelial cells. Second International phylococcus aureus as a public-health atment of human tissue. Second Inter-
Conference on Plasma Medicine. San threat. Lancet 2006; 368: 874–85. national Conference on Plasma Medi-
Antonio, Texas, USA, 2009. 31 Klein E, Smith DL, Laxminarayan R. cine. San Antonio, Texas, USA, 2009.
20 Sosnin EA, Stoffels E, Erofeev MV, Hospitalizations and deaths caused 40 Bogle MA, Arndt KA, Dover JS. Eva-
Kieft IE, Kunts SE. The effects of UV by methicillin-resistant Staphylococcus luation of plasma skin regeneration
irradiation and gas plasma treatment on aureus, United States, 1999–2005. technology in low-energy full-facial
living mammalian cells and bacteria: a Emerg Infect Dis 2007; 13: 1840–6. rejuvenation. Arch Dermatol 2007;
comparative approach. IEEE Transact 32 Wende K, Landsberg K, Lindequist U, 143: 168-74.
Plasma Sci 2004; 32: 1544–50. Weltmann KD, v. Woedtke T. Microor- 41 Fitzpatrick R, Bernstein E, Iyer S,
21 Daeschlein G, Darm K, Majunke S, ganisms, human cells and cold atmos- Brown D, Andrews P, Penny K. A
Kindel E, Weltmann KD, Juenger M. pheric plasma – looking for an intersec- histopathologic evaluation of the
In vivo monitoring of atmospheric tion. 2nd International Workshop on Plasma Skin Regeneration System
pressure plasma jet (APPJ) skin therapy Plasma-Tissue Interactions. Greifswald, (PSR) versus a standard carbon dioxide
by confocal laserscan microscopy Germany, 2009. resurfacing laser in an animal model.
(CLSM). Second International Confe- 33 Isbary G, Morfill G, Schmidt HU, Lasers Surg Med 2008; 40: 93–9.
rence on Plasma Medicine. San Antonio, Georgi M, Ramrath K, Heinlin J, 42 Foster KW, Moy RL, Fincher EF.
Texas, USA, 2009. Karrer S, Landthaler M, Shimizu T, Advances in plasma skin regeneration.
22 Dobrynin D, Fridman G, Friedman G, Steffes B, Bunk W, Monetti R, J Cosmet Dermatol 2008; 7: 169–79.
Fridman A. Physical and biological me- Zimmermann JL, Pompl R, Stolz W. A 43 Kilmer S, Semchyshyn N, Shah G,
chanisms of direct plasma interaction first prospective randomized controlled Fitzpatrick R. A pilot study on the use
with living tissue. New Journal of Phy- trial to decrease bacterial load using of a plasma skin regeneration device
sics 2009; 11: 115020. cold atmospheric argon plasma on (Portrait PSR3) in full facial rejuvena-
23 Lee HJ, Shon CH, Kim YS, Kim S, chronic wounds in patients. Br J Der- tion procedures. Lasers Med Sci 2007;
Kim GC, Kong MG. Degradation of matol 2010 Mar 5. [Epub ahead of 22: 101–9.
adhesion molecules of G361 melanoma print]. 44 Kilmer S, Fitzpatrick R, Bernstein E,
cells by a non-thermal atmospheric 34 Fetykov AI, Avdeeva EA, Fulton J, Brown D. Long term follow-up on the
pressure microplasma. New Journal of Ferrel J, Gotsev VA, Galov AA. The use of plasma skin regeneration (PSR)
Physics. 2009; 11: 115026. effectiveness of cold plasma treatment in full facial rejuvenation procedures.
24 Fridman G, Shereshevsky A, Jost M, of diabetic feet syndrome, complicated Lasers Surg Med 2005; 36: 22.
Brooks A, Fridman A, Gutsol A, by purulonecrotic process. Second In- 45 Morrison JCF. Electrosurgical method
Vasilets V, Friedman G. Floating elec- ternational Conference on Plasma. San and apparatus for initiating an electrical
trode dielectric barrier discharge Antonio, Texas, USA, 2009. discharge in an inert gas flow. US
plasma in air promoting apoptotic 35 Shekhter AB, Kabisov RK, Pekshev AV, Patent. 1977; 4,040,426.
behavior in melanoma skin cancer cell Kozlov NP, Perov YL. Experimental 46 Ginsberg GG, Barkun AN, Bosco JJ,
lines. Plasma Chem Plasma Process and clinical validation of plasmadyna- Burdick JS, Isenberg GA, Nakao NL,
2007; 27: 163–76. mic therapy of wounds with nitric Petersen BT, Silverman WB, Slivka A,
© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin • JDDG • 1610-0379/2010/0812 JDDG | 12˙2010 (Band 8)
976 Review Article Plasma medicine
Kelsey PB. The argon plasma coagula- 49 Fridman G, Peddinghaus M, Ayan H, non-thermal atmospheric pressure
tor: February 2002. Gastrointest En- Fridman A, Balasubramanian M, plasma. 37th AIAA Plasmadynamics
dosc 2002; 55: 807–10. Gutsol A, Brooks A, Friedman G. Blood and Lasers Conference. San Francisco,
47 Katsch J, Müller RPA, Mailänder W. coagulation and living tissue sterilization California, USA, 2006.
Argon-Plasma-Koagulation (APC) in by floating-electrode dielectric barrier 52 Sun P, Wang R, Tong G, Zhang J, Fang
der Dermatologie – Eine Standortbe- discharge in air. Plasma Chem Plasma J. Teeth whitening with dental gel assi-
stimmung. VOD Dialog Beilage in Der Process 2006; 26: 425–42. sted by an atmospheric pressure non-
Deutsche Dermatologe 1997; 45: 2–6. 50 Fridman A. Non-thermal plasma assi- thermal plasma. Second International
48 Manner H, Enderle MD, Pech O, May sted blood coagulation. Cambridge Conference on Plasma Medicine. San
A, Plum N, Riemann JF, Ell C, University Press, New York, 2008. Antonio, Texas, USA, 2009.
Eickhoff A. Second-generation argon 51 Fridman G, Shereshevsky A, Pedding- 53 Lee HW, Kim GJ, Kim JM, Park JK,
plasma coagulation: two-center experi- haus M, Gutsol A, Vasilets V, Brooks A, Lee JK, Kim GC. Tooth bleaching
ence with 600 patients. J Gastroenterol Balasubramanian M, Friedman G, with nonthermal atmospheric pressure
Hepatol 2008; 23: 872–8. Fridman A. Bio-medical applications of plasma. J Endod 2009; 35: 587–91.
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