Plasma medicine

Plasma medicine is an innovative and emerging field combining plasma physics, life sciences and clinical medicine to use physical plasma for therapeutic applications. Initial experiments confirm that plasma can be effective in in vivo antiseptics without affecting surrounding tissue and, moreover, stimulating tissue regeneration. Based on sophisticated basic research on plasma-tissue interaction, first therapeutic applications in wound healing, dermatology and dentistry will be opened.

Plasma, described as the fourth state of matter, comprises charged species, active molecules and atoms and is also a source of UV-photons. These plasma-generated active species are useful for several bio-medical applications such as sterilization of implants and surgical instruments as well as modifying biomaterial surface properties. Sensitive applications of plasma, like subjecting human body or internal organs to plasma treatment for medical purposes, are also possible. This possibility is profoundly^{[clarification needed]} being investigated by research groups worldwide under the highly-interdisciplinary research field called 'plasma medicine'.

Research fields

Progress in life sciences is increasingly caused by utilization of unrelated technologies and knowledge. In this spirit, microelectronics, optics, material sciences or nanotechnology became key technologies in modern medicine. A similar trend is expected now concerning plasma technology. Actually, plasma medicine is emerging worldwide as an independent medical field - comparable to the launch of laser technology into medicine years ago.

Plasma medicine can be subdivided into three main fields:

Non-thermal atmospheric-pressure direct plasma for medical therapy
Plasma-assisted modification of bio-relevant surfaces
Plasma-based bio-decontamination and sterilization

Non-thermal atmospheric-pressure plasma for medical therapy

Recently, one of challenges is the application of non-thermal plasmas directly on the surface of human body or on internal organs. Whereas for surface modification and biological decontamination both low-pressure and atmospheric pressure plasmas can be used, for direct therapeutic applications only atmospheric pressure plasma sources are applicable.

The high reactivity of plasma is a result of different plasma components: electromagnetic radiation (UV/VUV, visible light, IR, high-frequency electromagnetic fields, etc.) on the one hand and ions, electrons and reactive chemical species, primarily radicals, on the other. Besides surgical plasma application like argon plasma coagulation (APC),^[1] which is based on high-intensity lethal plasma effects, first and sporadic non-thermal therapeutic plasma applications are documented in literature.^[2] However, the basic understanding of mechanisms of plasma effects on different components of living systems is in the early beginning. Especially for the field of direct therapeutic plasma application, a fundamental knowledge of the mechanisms of plasma interaction with living cells and tissue is essential as a scientific basis.

Low-temperature plasmas at atmospheric pressure can in principle be classified into 3 types:

1) Direct plasmas- the tissue/skin itself serves as an electrode so that in this form current flows through the body. A common example of this is the “dielectric barrier discharge” device (DBD). A conventional DBD device comprises two planar electrodes with at least one of them covered with a dielectric material and the electrodes are separated by a small gap which is called the discharge gap. However, for medical application of DBD devices, the human body itself can serve as one of the two electrodes making it sufficient to devise plasma sources that consist of only one electrode covered with a dielectric such as alumina or quartz. DBD for medical applications^[3] such as for treatment of skin diseases and wounds, tumor treatment ^[4] and disinfection of skin surface are currently under investigation.

2) Indirect plasmas- are produced between two electrodes and then transported to the target area by a gas flow. The individual discharge can be markedly stronger here (there is no hindrance by a barrier), the transport of the charge carriers (and the pro- duced molecules) away from the dis- charge region results simply from the gas flow and from diffusion. Most devices of this type produce thin (mm diameter) plasma jets, larger surfaces can be treated simultaneously by joining many such jets or by multielectrode systems. Significantly larger surfaces can be treated than with direct plasmas. Further, the distance between the device and the skin is to a certain degree variable, as the skin is not needed as a plasma electrode, significantly simplifying use on the patient.

3) „Hybrid“ plasmas- also termed „barrier coronal discharges“, combine both techniques discussed above. They are produced just as direct plasmas, but due to a grounded mesh electrode no current flows through tissue anymore.

First therapeutic approaches of plasma medicine: dermatology and wound healing

Initial experiments confirm the fact that infectious agents can be killed without adverse reactions on surrounding healthy body cells. Furthermore, it is possible to stimulate physiological and biochemical processes in living tissues by plasma treatment under special conditions. This opens the possibility to use plasma to support wound healing as well as to treat several skin diseases. Therefore, application-oriented research is directed to develop an integrated concept of plasma-based wound treatment comprising both superficial wound cleaning and antiseptics and stimulation of tissue regeneration in deeper tissue layers. On a solid scientific basis, further therapeutic plasma applications e.g. in dentistry, or surgery, will be opened during the next years ^[5]

Plasma-assisted modification of bio-relevant surfaces

Plasma-assisted modification of bio-relevant materials is an established technique to optimize the biofunctionality of implants or to qualify polymer surfaces for cell culturing and tissue engineering. Plasma-based methods and processes for sterilization, decontamination or reprocessing of medical and diagnostic devices, pharmaceutical products or packaging materials are under development worldwide. Both fields are more or less indirect medical plasma applications.

Interdisciplinary basic research on plasma interaction with living matter

Based on knowledge about mechanisms of antimicrobial plasma activity, current research in plasma medicine is mainly focussed on the following fields:

Selective inactivation of infectious agents in the close presence of living tissue (in vivo antisepsis)
Direct interaction of active plasma components with biochemical and physiological processes influencing growth and vitality of cells and tissue
Indirect influencing of cells and tissue via changes of the vital environment (physiological liquids) of cells and tissue through physical plasma.

Combination of plasma technology and plasma diagnostics with cell biological, biochemical and chemical analytical techniques based on in vitro models using microorganisms as well as cell and tissue cultures, will facilitate a sophisticated evaluation of biological plasma effects.

To achieve sustained success of plasma medicine, for any potential therapeutic application optimal plasma composition (radicals, irradiation, temperature, etc.), useful application rate and acceptable relation between desired therapeutic effects and adverse reactions have to be found. This can be realized only in close collaboration between plasma physicists, life scientists and clinical physicians.

References

^ Zenker M, Argon plasma coagulation, GMS Krankenhaushyg Interdiszip 2008; 3(1):Doc15 (20080311)
^ Fridman G, Friedman G, Gutsol A, Shekter AB, Vasilets VN, Fridman A, Applied Plasma Medicine, Plasma Process Polym 5:503-533 (2008)
^ Kuchenbecker M, Bibinov N, Kaemlimg A, Wandke D, Awakowicz P, Viöl W, J. Phys. D: Appl. Phys. 42 (2009) 045212 (10pp)
^ Vandamme M., Robert E., Dozias S., Sobilo J., Lerondel S., Le Pape A., Pouvesle J.M., 2011. Response of human glioma U87 xenografted on mice to non thermal plasma treatment. Plasma Medicine 1:27-43.
^ Kramer A, Lindequist U, Weltmann K-D, Wilke C, von Woedtke Th, Plasma Medicine – its perspective for wound therapy, GMS Krankenhaushyg Interdiszip 2008; 3(1):Doc16 (20080311)

External links

plasmatis is the name of a Center of Innovation Competence in Greifswald (Germany) which aims at the basic research of the interactions of physical plasma with cells and tissue
Plasma research and life sciences work together in the new Campus PlasmaMed located in the farthest north-east of Germany. The main topics of Campus PlasmaMed are: Plasma Medicine, biofunctional surfaces and plasma decontamination
The Leibniz Institute for Plasma Science and Technology (INP Greifswald e.V.) is the largest non-university institute in the area of low temperature plasmas in Europe
International Society for Plasma Medicine (ISPM)
Plasma Health Care group at the Max Planck Institute for Extraterrestrial Physics

[1] Zenker M, Argon plasma coagulation, GMS Krankenhaushyg Interdiszip 2008; 3(1):Doc15 (20080311)

[2] Fridman G, Friedman G, Gutsol A, Shekter AB, Vasilets VN, Fridman A, Applied Plasma Medicine, Plasma Process Polym 5:503-533 (2008)

[3] Kuchenbecker M, Bibinov N, Kaemlimg A, Wandke D, Awakowicz P, Viöl W, J. Phys. D: Appl. Phys. 42 (2009) 045212 (10pp)

[4] Vandamme M., Robert E., Dozias S., Sobilo J., Lerondel S., Le Pape A., Pouvesle J.M., 2011. Response of human glioma U87 xenografted on mice to non thermal plasma treatment. Plasma Medicine 1:27-43.

[5] Kramer A, Lindequist U, Weltmann K-D, Wilke C, von Woedtke Th, Plasma Medicine – its perspective for wound therapy, GMS Krankenhaushyg Interdiszip 2008; 3(1):Doc16 (20080311)

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