The active components explained.
Active components (excerpt from position paper on risk potential and application perspectives of cold atmospheric pressure plasma in medicine, NZPM)
According to current international research, the main active components of cold atmospheric pressure plasma are reactive nitrogen and oxygen species (RNS, ROS), UV radiation and electric fields.
Reactive nitrogen and oxygen species (RNS, ROS) are formed locally and for a short time by coupling electrical energy into gases that are not biologically active per se (argon, helium, nitrogen, oxygen, air as well as mixtures thereof) and subsequent interacting with adjacent media (atmospheric air, liquids, surfaces). In principle, the same reactive species are sometimes produced in the human body as part of normal metabolism and in some cases have important functions in controlling and mediating physiological and pathological processes. Briefly elevated doses of these RNS and ROS can be effectively detoxified by endogenous systems.
UV radiation is used medically in phototherapy and photochemotherapy, among other applications. In this context, as well as from the point of view of general personal and occupational safety, also outside the medical environment, limit values have been established for UV exposure, which are significantly lower in cold atmospheric pressure plasma devices.
Two important findings of basic plasma medical research in recent years are:
1. biological plasma effects on cells and in tissues are mediated by changes in the fluid cell environment.
2. oxidizing species, so-called reactive oxygen and nitrogen species (ROS, RNS), put into the liquid or formed in the liquid play a dominant role in biological effects induced by plasma action.
The same reactive species (ROS, RNS) are also produced in the human body as part of normal metabolism and in some cases have important functions in controlling and mediating physiological and pathological processes. The most important ROS and RNS are hydroxyl radical (OH-), hydrogen peroxide (H2O2), superoxide or hyperoxide (O2–), nitric oxide (NO-), nitrogen dioxide (NO2-) and peroxy nitrite (ONOO-). They play an important role in wound healing processes, for example. This finding provides an essential scientific basis for the concept of plasma-assisted wound healing, in which, in addition to the well-known antibacterial/disinfectant plasma effect, stimulation of tissue regeneration is also to be achieved by plasma action. One mechanism of plasma action is thus based on the support of endogenous functions which – for example in the case of non-healing chronic wounds – cannot be sufficiently effective due to disease-related disorders. Furthermore, it is known that a certain basic concentration of RNS and ROS is always present in human cells. Due to the physiological occurrence of these species, short-term elevated concentrations can be effectively detoxified by endogenous systems [16-24]. Using transcriptome analyses of in vitro plasma-treated human cells, it has been shown that genes associated with the cellular stress response are increasingly upregulated and antioxidant active enzymes are produced as a result of plasma treatment . Since plasma treatments are localized and time-limited, under normal conditions, the risk of side effects associated with entry of these ROS and RNS into tissues is expected to be exceptionally low.
3. Ultraviolet Radiation (UV radiation).
UV-B radiation in particular is used in dermatology as part of phototherapy. According to the recommendations of the German Dermatological Society (DDG) on phototherapy and photochemotherapy, initial doses between 20 and 60 mJ/cm2 are recommended for broad-spectrum UV- B application (280-320 nm), depending on the skin type, and doses between 200 and 600 mJ/cm2 are recommended for narrow-spectrum UV-B treatment (311 nm) .
A comparison with solar radiation shows that the UV intensity emitted by the cold atmospheric pressure plasma sources used in clinical trials or approved as medical devices to date is far below that of sunlight [31-33].
For the plasma sources currently certified as medical devices, it has been shown that under the recommended conditions of use (working distance, treatment time), the maximum permissible daily UV dose is significantly undercut [34, 35].
4. Electric Fields
Electric fields can first be divided into direct and alternating fields. In addition, the pulsation of such signals as well as monophasic or biphasic modulation allows for a high parametric diversity. Technical frequencies are in the range of a few Hz up to the GHz range. Devices using only electric fields have been established for many years for application in and on the human body and can induce an electric current flow in biological tissue as a result of the electric fields. Regardless of the device, the use of electrical signals for electrostimulation offers a variety of proven applications in medical care. For example, cell movement of immune cells (macrophages and granulocytes) and migration of skin cells (keratinocytes) and corneal epithelium can be specifically influenced in response to an electric field, proliferation behavior of connective tissue cells (fibroblasts) is stimulated, and for new vessel formation (angiogenesis) and nerve growth, the electric field is also important. Finally, in vivo studies using electric fields have shown an antibacterial effect on both gram-negative and gram-positive bacteria [36-40].
In recent years, research in the field of bioelectricity has demonstrated significant links between endogenous electric fields and the wound healing process [41-43]. A meta-analysis by Gardner et al. was performed using data sets from 15 clinical trials with the aim of quantifying the effect of electrical stimulation (ES) on chronic wound healing. Treatments with ES achieved an average wound reduction of 22.2% per week, compared with only 9.1% in control groups . In the published partial results of Cochrane Review #077, the healing success (wound closure) using electrical stimulation was compared with placebo control. This question was investigated in 13 of the 20 studies. The analysis showed that twice as many (OR=2.12; 95% CI: 1.55 – 2.90) wounds were healed by treatment with electrostimulation (verum) compared to controls .