Researchers at the Eindhoven University of Technology in the Netherlands have recently introduced the unconventional concept of using cold plasmas for medical treatment, and they have invented and tested a simple device called a plasma needle. This generates a low-power atmospheric discharge by the radio-frequency excitation of a mixture of helium and air.1 The gas remains at room temperature and treatment with this device is non-contact and entirely painless (figure 1).
Ideally, any medical treatment should mimic the body's natural healing and renewal processes. After all, the body is designed to solve its own problems in its own manner, and only occasionally does it require external support. Plasma therapy may provide such gentle support, while inflicting far less tissue damage than conventional treatments.
The action of the plasma needle is not based on mechanical injury or thermal ablation, but on conveying chemical stimuli to the body's cells. These stimuli are provided by short-living species called radicals. Besides being highly chemically reactive, radicals have other useful properties. For example, they only affect a targeted area of tissue and do not remain there after treatment.
Radicals are abundant in a healthy organism, where they are actively involved in numerous physiological processes. Nitric oxide (NO), for example, regulates the functioning of blood vessels, while reactive oxygen species are produced by the body's inflammatory cells to fight infections.2 Impaired generation of these chemicals leads to serious disorders like atherosclerosis.
Of course, reactive oxygen species also have a negative image. This stems from the fact that they cause the cellular injury (via oxidative stress) that's responsible for tissue aging and degenerative diseases. It's therefore important to distinguish clearly between oxidative cell injury and plasma treatment. Oxidative injury is a reaction to a chronic excess of oxidants. It is usually a systemic problem, caused by poor nutrition and other detrimental lifestyle choices. Plasma therapy, by contrast, increases the radical concentration only in a very restricted area.
Reaction range
It appears that cold plasma can "mimic nature" by generating reactive oxygen species and nitric oxide.3 In vitro tests have been extremely encouraging. Cold plasma creates these radicals and topically delivers just the right amount: too low to cause oxidative stress but high enough to trigger cell responses.
Most remarkably, plasma doesn't cause accidental cell death (necrosis). Necrosis is a consequence of fatal injury to the cell, which results in membrane damage and cytoplasm leakage. It triggers an alarm reaction (inflammation) and one of its undesired consequences is scar formation. Such a reaction is inevitable in conventional, electro-, cryo- and laser surgery. Cold plasma, however, offers an attractive alternative: tissue treatment without necrosis, inflammation or scarring.
The action of plasma on living cells is versatile. Depending on the treatment conditions – such as the power, plasma composition and exposure time – several effects are achievable, as described below.
Bacterial inactivation Plasma can be bactericidal (killing bacteria) or bacteriostatic (suppressing bacteria).4 A significant feature is plasma's selectivity with respect to eukaryotic cells – it can remove microbial infections without causing serious damage to the tissue. The most important mechanism is reactive oxygen species-induced bacterial injury, which works in the same way as the organism's natural defence systems.
Cell detachment Plasma causes temporary interruption of cell adhesion, which leads to cell migration. The cells are unharmed and reattach within a few hours. This effect is limited to a single layer of exposed cells and is most likely due to electrostatic membrane charging by plasma electrons.
Cell activation This occurs only after long exposure of cells immersed in plenty of fluid (culture medium).5 Cells exhibit a temporary increase in motility, adhesion and proliferation rate – effects that may be of great value in tissue repair.
Apoptosis Plasma treatment induces apoptosis (programmed cell death) in various types of cell, including fibroblasts, smooth muscle, endothelium and epithelium.5 Apoptosis plays a crucial role in natural tissue renewal. In this way, old or damaged cells are disposed of without inflammation. The induction of apoptosis by exposure to plasma is an excellent way to "mimic nature". This method is of particular interest in non-inflammatory tissue removal as it can make tissue "disappear" without any complications.
Many possibilities
Currently, plasma's most important therapeutic functions appear to be disinfection and non-inflammatory tissue removal. The applicability of plasma disinfection to dermatology and wound care is obvious: it allows the non-contact treatment of painful inflamed sites and skin infections. Plasma may even become a true life-saving therapy when used to treat immunocompromised patients, for example. When successful in healing chronic wounds (e.g. diabetic foot ulcers) and large-area burns, plasma treatment could prevent life-threatening septicaemia and amputations of extremities.
Another vast area that may benefit from the use of plasma disinfection is dentistry. Here the specific advantage of plasma is its ability to treat irregular surfaces, and work round corners to reach fissures and cracks. This could provide a tissue-saving and pain-free way to cure dental caries and perform root-canal treatment. Gingival diseases, such as periodontal pockets and mucosal ulcerations, may also be healed.
Plasma can provide in vivo disinfection virtually anywhere and can be used even in the most delicate of sites. In the eye, for example, plasma could be used to treat bacterial conjunctivitis and keratitis. Somewhat more challenging, although a definite possibility, is the plasma treatment of internal infections in the respiratory, urinary and reproductive systems.
Plasma's other important function – non-inflammatory tissue removal – may prove equally powerful in non-contact disinfection. Again, the most obvious applications lie in dermatology for various cosmetic procedures, the removal of (benign) skin imperfections and the treatment of skin cancer. Other possibilities include the removal of arterial stenoses and malignant growths, and the extraction of embryonic cells, with potential applications in brain, cardiovascular and microsurgery.
Clearly the potential applications of cold plasma treatment are extensive, and the motivation to implement the technique in clinical practice is strong. At present, more in vitro tests are needed to assess the influence of the plasma on immune reactions. In vivo tests will commence thereafter. Many years may pass before plasma becomes a standard medical tool. In the meantime, it inspires fascinating fundamental research that will expand the frontiers of physics, chemistry, biology and medicine.