Christian FABRICIUS, M.D., Ph.D

GTC Life Science

Gamlestadsvägen 2-4

S-415 02 Göteborg, Sweden

Irem TEZER, M.D.

Hiperox Wound and Hyperbaric Center

Demirci Kara Mah. Avni Tolunay Cad. No: 46/1 07100 Antalya, Turkey

CHRONIC NON-HEALING WOUND MANAGEMENT WITH PLASMA TECHNOLOGY

• High temperature, low density

argon plasma

• Thermal energy – for coagulation

& vaporization

• Kinetic energy – for cutting &

fluid dispersal

• Controllable, visible effect

• Proprietary technology for rapid

generation of high energy Argon

Plasma

• High temperature

• Low thermal density

CHRONIC NON-HEALING WOUND MANAGEMENT WITH PLASMA TECHNOLOGY

Thermal and non-thermal plasma

Introduction • Chronic wounds demand an aggressive,

multifactorial approach. Repetitive surgical debridement, revascularization, when necessary, antibiotics and dressings form the foundation of therapy. However, once the wound is clean and well vascularized, they still may not progress to healing. Several adjuvant treatment methods have been developed to further stimulate healing and non-thermal plasma seems to be one of them.

Thermal and Non-thermal plasma • Plasmas have been used for a long time for

sterilization of medical equipment, packaging in the food industry, implants, blood coagulation, etc. This is partly due to their high bactericidal effectiveness and partly due to their easy access into narrow and confined spaces. Thermal and non-thermal (i.e. cold) plasmas – both already widely established in medicine – are used for various therapeutic applications. Particularly in dermatology, plasma applications hold big potential, for example, in wound healing, such as efficient disinfection or sterilization, therapy of various skin infections or tissue regeneration. It has recently been demonstrated that non-thermal atmospheric pressure plasma (less than 40 ◦C at the point of application) can be applied directly to living cells and tissues, killing bacteria and inducing blood coagulation without significant heating. Non-thermal plasma treatment has also been shown to promote cell proliferation, enhance cell transfection, sterilize root canals and possibly increase wound healing. The simplicity and flexibility of devices required to generate non-thermal plasma and apply it to tissues is particularly appealing. However, an understanding of mechanisms by which non-thermal plasma interacts with living cells and tissues is required to fully develop its clinical applications.

Medical plasma for wound healing • It is reported that direct plasma in contact with

tissue leads to a significantly faster bacteria inactivation on this tissue due to the presence of charges. Direct plasma treatment are able to sterilize and also responsible for many interesting biological effects; e.g. effect of NO in tissue regeneration. Optimal NO activity is required for the full expression and receptor upregulation of VEGF and PDGF. A deficiency in NO bioactivity is associated with diabetes-impaired wound healing . Experimentally and clinically it is validated that plasmadynamic therapy increases nitric oxide on wounds and sterilizing the bacteria that helps wound healing.

CHRONIC NON-HEALING WOUND MANAGEMENT WITH PLASMA TECHNOLOGY

Continuous and distance effects

Vaporization

Energy is focused more than with coagulation

• Smaller area = higher energy density

• Vaporization of Rapid Dry Layer

• Progression of thermal diffusion

Cutting with Coagulation

• Energy is tightly focused

• Rapid vaporization takes place over small area

• Lateral Coagulation occurs with latent thermal diffusion

The argon plasma is short-lived, and gives up its energy readily in three useful forms: • As UV light – in the visible and near ultraviolet parts of the spectrum, which helpfully illuminates the field, but is not sufficiently intense to cause damage or require any eye-protection, antibacterial wave lenght • As thermal energy – sufficient to heat the tissue to a very limited depth and cause coagulation of the surface bleeding • In the form of kinetic energy – that clears any biofilm layer of the bacterias from the surface of the tissue

CHRONIC NON-HEALING WOUND MANAGEMENT WITH PLASMA TECHNOLOGY

Clinical test

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Kalghatgi S, Kelly CM, Cerchar E, Torabi B, Alekseev O, et al. (2011) Effects of Non-Thermal Plasma on Mammalian Cells. PLoS ONE 6(1): e16270. doi:10.1371/journal.pone.0016270

Plasma applications in medicine with a special focus on dermatology. J Heinlin1,†, G Isbary2,†, W Stolz2, G Morfill3, M Landthaler1, T Shimizu3, B Steffes3, T Nosenko3, JL Zimmermann3 andS Karrer1,* Journal of the European Academy of Dermatology and Venereology Volume 25, Issue 1, pages 1–11, January 2011

Physical and biological mechanisms of direct plasma interaction with living tissue. Danil Dobrynin et al 2009 New J. Phys. 11 115020

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Shekhter A B, Serezhenkov V A, Rudenko T G, Pekshev A V and Vanin A F 2005 Beneficial effect of gaseousnitric oxide on the healing of skin wounds Nitric Oxide-Biol. Chem. 12 210–9

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Schaffer MR, Tantry U, Efron PA, Ahrendt GM, Thornton FJ, Barbul A. Diabetes-impaired healing and reduced nitric oxide synthesis: a possible pathophysiologic correlation. Surgery. 1997;121:513–9

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Thermal plasma is a surgically proven new technique for cutting, ablating, coagulating and drying. In a comparison with traditional wound care it can be used to: - illuminate the wound area - coagulate - clear the wound area from fluids - create a flexible sealing layer in the wound area It is thus suitable for infection control as well as debridement. Any side effects of this new technology is expected to be minimal since the thermal spread is minimized, thus ensuring delicated precision, still preserving the underlying tissues.

CHRONIC NON-HEALING WOUND MANAGEMENT WITH PLASMA TECHNOLOGY

Summary