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There is growing interest in the use of physical plasmas (ionized gases) for biomedical applications, especially in the framework of so-called “plasma medicine”, which exploits the action of low-power, atmospheric pressure plasmas for therapeutic purposes. Such plasmas are “cold plasmas”, in the sense that only electrons have a high temperature, whereas ions and the neutral gas particles are at or near room temperature. As a consequence, the “plasma flame” can be directly applied to living matter without appreciable thermal load. Reactive chemical species, charged particles, visible and UV radiation, and electric fields are interaction channels of the plasma with pathogens, cells, and tissues, which can trigger a variety of different responses. Possible applications include disinfection, wound healing, cancer treatment, non-thermal blood coagulation, just to mention some. The understanding of the mechanisms of plasma action on living matter requires a strongly interdisciplinary approach, with competencies ranging from plasma physics and technology to chemistry, to biology and finally to medicine. This book is a collection of work that explores recent advances in this field.
Current breakthrough research on cold atmospheric plasma (CAP) demonstrates that CAP has great potential in various areas, including medicine and biology, thus providing a new tool for living tissue treatment. Depending on the configuration the cold plasma sources can be used in the following areas: wound healing, skin diseases, hospital hygiene, sterilization, antifungal treatments, dental care, cosmetics targeted cell/tissue removal, and cancer treatments. This dissertation is focused on the studies of biomedical applications of cold atmospheric plasma jet based on helium flow and resultant cell responses to the cold plasma treatment. The studies were carried out on extra-cellular and intra-cellular levels in vitro. The main practical applications are wound healing and alternative to existing cancer therapy methods, areas of great interest and significant challenges. The CAP jet was built in the Micropropulsion and Nanotechnology Laboratory of Dr. Michael Keidar, as a part of multidisciplinary collaboration with the GW Medical School (Dr. M.A. Stepp) concerned with plasma medicine and bioengineering studies. Normal and cancer cells have two fundamental behavioral properties, proliferation and motility, which can be evaluated through cell migration rates and cell cycle progression. Various microscopic, spectroscopic and flow cytometry techniques were used to characterize cell responses to the cold plasma treatment. It was found that CAP effect on the cells is localized within the area of the treatment (of around [approximately] 5mm in diameter). The migration rates of the normal skin cells can be reduced up to [approximately] 40%. However, depending on the cell type the required treatment time is different, thus differential treatment of various cells presented in tissue is possible. The CAP effect on the migration was explained through the changes of the cell surface proteins/integrins. It was also found that normal and cancer cells respond differently to the CAP treatment under the same experimental conditions. CAP is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. It was shown that the increased sensitivity of cancer cells to CAP treatment is caused by differences in the distribution of cancer cells and normal cells within the cell cycle. It was also shown that the expression of [Upsilon]H2A.X (pSer139), an oxidative stress reporter indicating S-phase damage, is enhanced specifically within CAP treated cells in the S phase of the cell cycle together with significant decrease in EdU-signal of DNA-replicating cells. Thus, newly developed CAP technology was proven to be of a great interest for practical applications in the areas of wound healing and cancer treatment. The identification and explanation of the mechanisms by which CAP affects the cells was presented.
Non-equilibrium plasma (or low-temperature plasma, LTP) offers a chemically rich medium without the need for high power and elevated temperatures. This unique characteristic has made LTP very useful for various industrial and biomedical applications where thermal effects are not desirable. In addition, the relative simplicity of the design of sources capable of generating non-equilibrium plasma at atmospheric pressure makes LTP a very attractive technology that can accomplish the same or better results than much more complex and expensive approaches. This book describes various low-temperature plasma sources and some of their environmental and biomedical applications. The plasma sources covered in this book include low-temperature plasma jets which are novel devices that can launch low-power, low-temperature plasma plumes in ambient air. These plasma plumes can accurately and reliably be aimed at a surface to be treated or at a biological target such as cells and tissues. The application of these plasma jets in medicine, including in cancer therapy, are thoroughly discussed in this book. The contents of this book will appeal to engineers, medical experts, academics, and students who work with plasma technology.
Low-temperature plasmas (LTP) at atmospheric gas pressure play an increasing role in biomedical applications. The experimentally observed benefits of LTP for these applications are attributed to the controllable fluxes of chemically active species that can be produced in air at near room temperatures and delivered to bio-matter to induce desired effects. Recent research on the biomedical applications of LTP has generated new scientific knowledge regarding the interaction of plasma with soft matter including cells, tissues, seeds, and plants. The observed effects of LTP on biological cells are mediated by the plasma-produced reactive oxygen species (ROS) and reactive nitrogen species (RNS). These include hydroxyl, OH, atomic oxygen, O, singlet delta oxygen, O2(1Δ), superoxide, O2-, hydrogen peroxide, H2O2, and nitric oxide, NO. Some of these species are known to play important roles in biology serving as signaling molecules in living organisms. When they come in contact with biological cells these species interact with the lipids and proteins of the cell membrane, enter the cell and increase the intracellular ROS concentrations, which can lead to DNA damage and may compromise the integrity of other cell organelles. ROS and RNS can also trigger cell signaling pathways, which can lead to cellular death by apoptosis or necrosis. Other plasma-generated agents that could play biological roles are charged particles (electrons and ions), UV photons, and electric fields.
Cold plasma generated in an open environment with a temperature nearly around room temperature has recently been a topic of great importance. It has unlocked the door of plasma application in a new direction: biomedical applications. Cold atmospheric pressure (CAP) plasma comprises various neutral and charged reactive species, UV radiations, electric current/fields etc., which have several impactful effects on biological matter. Some of the significant biological effects of CAP plasma are inactivation of microorganism, stimulation of cell proliferation and tissue regeneration, destruction of cells by initializing apoptosis etc. Although the detailed mechanism of action of plasma on biomaterials is still not completely understood, some basic principles are known. Studies have indicated that the reactive oxygen species and nitrogen species (ROS, RNS) play a crucial role in the observed biological effects. In this perspective, this chapter first provides a brief discussion on the fundamentals of CAP plasma and its generation methods. Then a discussion on the optical diagnostics methods to characterize the plasma is provided. Optical emission spectroscopy (OES) is used to identify the reactive species and to measure their relative concentration. Other important plasma parameters such as gas temperature, electron/excitation temperature and electron density measurement methods using OES have also been discussed. Then a discussion on the application of CAP plasma in biomedical field is provided. A thorough understanding of biochemical reaction mechanisms involving highly reactive plasma species will further improve and extend CAP plasma technology in biomedical applications.
Cold atmospheric plasma (CAP) generators have been actively developed as a new device for medical treatment. The applications of plasma treatment include 1) disinfection, sterilization, and decontamination, which inactivates or kills bacteria, fungi, viruses and spores; 2) bleeding control, which coagulates blood swiftly; 3) wound healing, which shortens the healing period and benefits the regeneration of the epithelization of tissue to avoid scar formation; etc.Biomedical applications of CAPs are explored via either in-vitro assays, or in-vivo tests using pigs as animal models; tests include sterilization of oral pathogens and biofilm, decontamination of biological warfare agent, blood clotting and rapid control of active life-threatening hemorrhage, and post-operative observation of wound healing after plasma treatment. The conventional approaches in each application are first introduced, then the advantages of plasma treatments are discussed and demonstrated by the test results. The mechanisms of CAPs' biocidal effect, blood clotting effect, and wound healing effect are presented and discussed.
Cold atmospheric plasma (CAP) emerges as a possible new modality for cancer treatment. This book provides a comprehensive introduction into fundamentals of the CAP and plasma devices used in plasma medicine. An analysis of the mechanisms of plasma interaction with cancer and normal cells including description of possible mechanisms of plasma selectivity is included. Recent advances in the field, the primary challenges and future directions are presented.
This book presents the state of the art in clinical plasma medicine and outlines translational research strategies. Written by an international group of authors, it is divided into four parts. Part I is a detailed introduction and includes basic and recent research information on plasma sciences, plasma devices and mechanisms of biological plasma effects. Parts II and III provide valuable clinical insights f.e. into the treatment of superficial contaminations, ulcerations, wounds, treatment of cells in cancer, special indications like in heart surgery, dentistry, palliative treatment in head and neck cancer or the use of plasma in hygiene. Part IV offers information on how and where to qualify in plasma medicine and which companies produce and supply medical devices and is thus of particular interest to medical practitioners. This comprehensive book offers a sciences based practical to the clinical use of plasma and includes an extended selection of scientific medical data and translational literature.
Plasma can be defined as the extracellular matrix of blood cells. Plasma components, their role in human health risk evaluation, and their functional and clinical analyses are covered in this book. Furthermore, physical plasma-ionized gas is one of the four fundamental states of matter. This homonym has begun to emerge because it can interact with living systems. The physical plasma biomedical applications are reviewed in drug delivery and wound healing medical applications. This approach revolutionizes the therapeutic approaches in medicine and may open up new concepts and clinical applications. The book is an essential source for researchers in the field and provides a platform for different professions.
This comprehensive text is suitable for researchers and graduate students of a ‘hot’ new topic in medical physics. Written by the world’s leading experts, this book aims to present recent developments in plasma medicine, both technological and scientific, reviewed in a fashion accessible to the highly interdisciplinary audience consisting of doctors, physicists, biologists, chemists and other scientists, university students and professors, engineers and medical practitioners. The book focuses on major topics and covers the physics required to develop novel plasma discharges relevant for medical applications, the medicine to apply the technology not only in-vitro but also in-vivo testing and the biology to understand complicated bio-chemical processes involved in plasma interaction with living tissues.