New Technology on the Horizon: Nonthermal Plasma

In this exclusive interview with The Dermatologist, Dr Peter Friedman introduces nonthermal plasma and shares insights into how this new technology is being reviewed and implemented in practice.

Peter Friedman, MD, PhD, FAAD, is a diplomate of the American Academy of Dermatology and an instructor of clinical dermatology in the department of dermatology at NewYork-Presbyterian Columbia University Irving Medical Center in New York, NY. He is also the author of more than 40 research and clinical articles, and currently runs his own private practice.

The Dermatologist: What is nonthermal plasma?

First, it is not blood plasma. It is an ionized gas resulting from a high temperature electric discharge. In nonthermal plasma, or it is also called cold plasma or nonthermal atmospheric pressure plasma, we knock off some of the electrons from the molecules. When this ionized gas reaches a steady, consistent temperature, it is called equilibrium. The core of the molecules in a lower energy state is kind of cold and the electrons are just freezing in a higher energy state, but because of the mass difference, the total temperature of the gas can be room temperature or a little bit higher.

The Dermatologist: You mentioned cold plasma, can these terms be used interchangeably?

Yes, different labs and research groups use variations in terminology. One of the commonly used terms to describe this ionized gas is nonthermal atmospheric plasma and the other is cold atmospheric plasma. It is important to note that it is not a very uniform material. The composition of cold plasma depends on what gas is being used. A lot of experiments and studies use gas presence, whether argon or helium, where they get ionized gas mixed with air. The characteristics of the electric field that is used to ionize the gas can really make a difference in the composition.

The Dermatologist: How can nonthermal plasma be used in dermatology?

This is a quickly evolving field. It started when it was realized that there is a large field of in vitro and animal studies for cold plasma. The earliest experiments were based on using cold plasma to inhibit bacterial growth primarily, in addition to fungal growth. The initial devices were used to treat chronic ulcers, and the main pattern mechanism was just sterilizing the wounds or reducing bacterial contamination. Later studies showed that cold plasma can have an effect of inducing wound healing and tissue regeneration. This is where it becomes interesting. Depending on the circumstances, such as how long it is applied and the amount of plasma, cold plasma can do a lot of different things. However, currently the well-established and licensed medical use for cold plasma is treating leg ulcers due to the decontamination of the ulcers, which partially induces wound healing.

It has been shown that cold plasma induces stem cell differentiation and proliferation in wound healing. There are also pilots looking into whether it helps with tissue regeneration such as rejuvenation treatments. It has also been shown in various types of cell culture experiments that cold plasma is able to induce apoptosis or cell senescence selectively in malignant cell lines. We had ongoing experiments and publications treating actinic keratosis on the face or other areas with cold plasma, and similar studies were published later. Another thing that we are very happy about is using cold plasma to treat warts and moles in children. This is because the main advantage of cold plasma is that it is a painless treatment. There were a couple of pilots published looking first in adults and then in children that showcased a great response because it was not only an effective treatment but was also well tolerated. Currently, we have an ongoing open enrolled trial with a pediatric dermatology department in South Carolina. At the last meeting, more children were enrolled in larger numbers, and it seems to be a very effective treatment.

We also have some preliminary results for in situ squamous cell carcinoma in addition to treating inflammatory disorders based on the possibility of cold plasma changing immune cell activity. Additionally, there was a very small study looking at the utilization of the stem cell triggering effects of cold plasma to induce hair growth. There was also a small study looking at indirect plasma treatment where plasma-treated liquid was created and patients used it as a topical medication for 6 months, with the results showing that it was well tolerated with some improvement. A reminder, these are very sporadic, typically single case studies, so it is hard to tell what will work out and what will not.

All this to say that there is a wide range of usage, with the main avenues focused on bacterial and fungal disinfection. Another is fighting microorganisms or even cutaneous parasites, in addition to targeting cancerous, precancerous, or otherwise rapidly multiplying cells, such as actinic keratosis, skin cancers, and warts. Another use is to trigger the cell proliferation phase of healing, whether in hair loss or potentially cosmetic treatments to regenerate collagen.

The Dermatologist: Is there anything else you would like to share with your colleagues about nonthermal plasma?

This is an exciting new technology. What we do not have at this point is an available device that physicians can just go and buy. It is important to keep in mind that there are many ways of generating cold plasma and they are not all the same. Some ways are going to be more effective for certain applications. For example, jet plasma vs barrier discharge plasma where both technologies were tried for a certain condition. One may work better than the other, partially because the plasma concentration and its composition can be very different. However, sometimes this can become a practical issue. Some conditions are just not really feasible to treat with one device vs the other. The instinct would be to have a plasma device that can work for all reported uses, but it might not be that simple. It is important to use the right device in the right setting for the right condition.

Aside from that, there is currently a lot of basic research needed in terms of figuring out the biologic and even chemical effects of plasma while looking at what exactly triggers those changes. It is a very complex entity, so there is not a straightforward answer. There are different ways of studying it, and the work from basic science research groups and more of the dermatology groups aims to see what really drives the effect of cold plasma. This is being done kind of backward, starting with a hypothesis per disease and then reverse engineering. It is important to try and figure out how exactly the mechanism works so it can help physicians make the treatment more effective.