Healing with star power: Using plasma to treat skin wounds

New resistant bacteria strains and viruses are appearing all the time, making the treatment of infections increasingly difficult. Humanity is in dire need of new weapons to fight this worldwide war against emerging pathogens. Dr Eric Robert, Thierry Prazuck, and their teams at GREMI, CNRS/Université d’Orléans, and CHRO, Orléans, France, perform pioneering work using cold plasma to treat bacterial infections. They report the first wound decontamination and healing in patients suffering with severe skin wounds, using a plasma multi-jet device. Their work makes a significant contribution towards plasma use in a range of skin pathologies, from cancer to cosmetic treatments.

The skin is the largest organ of the human body, acting as the connection between the inside and the outside world. From the moment we are born, the latter is an unlimited source of pathogens, which can cause a variety of infections. Nowadays, with bacteria becoming more resistant to antibiotics, treatment for infections is becoming increasingly difficult. The solution might be a new, multidisciplinary technology that combines physics, biology, chemistry, and engineering. It’s called non-thermal plasma.

Treatment made of stars
The stars, the aurorae, the Sun, and lightning, might have something in common with future hospital treatments: so-called ‘plasma’. Plasma, quite often referred to as the fourth state, is generated when an electric or electromagnetic field is applied to a gas, and therefore ionises it. This ionised gas now contains several components including excited species, photons, and charged particles. It was first discovered in 1857 by Johann Heinrich Wilhelm Geissler, but it wasn’t until 1928 that Irving Langmuir described plasma as the state of a gas made of an equal mix of ions and electrons.

There are two types of plasma: hot (thermal) and cold (non-thermal). Thermal plasma, which is usually found naturally, possesses electrons and heavy particles at the same temperature. Today, it can be used as a hard cutting material and as a method for toxic waste destruction. In non-thermal plasma, the free electrons possess a higher temperature than ions and neutral gas molecules, which gives the whole plasma a relatively low temperature overall. As temperature is a key factor for the use of plasma in medicine – it needs to stay below 40˚C to be patient-friendly – research for medical purposes focuses on non-thermal plasma.

The stars, the aurorae, the Sun, and lightning, might have something in common with future hospital treatments.

Plasma in operation
Research has shown that species generated by plasma, such as reactive oxygen and nitrogen species, can influence many biological processes such as cell death, bactericidal action, vasodilation, oxygenation, and angiogenesis (the generation of new blood vessels). Applying plasma on a skin wound can therefore influence the above processes. In new work, Dr Eric Robert, Thierry Prazuck, and their teams at GREMI, CNRS/Université d’Orléans, and CHRO, Orléans, France, show that plasma can lead to the destruction of bacterial DNA, even if the strains are antibiotic resistant. Additionally, since it influences tissue oxygenation and angiogenesis, plasma can promote skin repair around wounds. Robert and Prazuck have used this understanding to focus their research on the treatment of chronic wounds that are ‘super infected’. In a recent paper, they address three main objectives: reducing (or even eradicating) even the most resistant pathogens in a wound; regenerating tissue to enable wounds to heal; and the oxygenation of healthy tissues to promote angiogenesis.

New tools developed
The application of non-thermal plasma to a patient is not a trivial process. The plasma can be applied to a patient wound using a small instrument called a plasma jet device, which can be used by a nurse or a medical doctor. To ensure safe use of plasma in the clinic, Robert, Prazuck and colleagues highlight a number of factors: the device needs to keep the temperature below 40˚C, must achieve the maximum surface covering over the minimum exposure time, and must be able to apply the plasma successfully on uneven surfaces to ensure the best performance on the patient’s skin. Taking these factors into consideration, the researchers designed a variety of plasma devices to achieve the best results.

Plasma can destroy bacterial DNA, even if the strains are antibiotic resistant, and can promote skin repair around wounds.

In vitro disinfection
The first step to evaluate the plasma devices was to inoculate different bacteria strains, including antibiotic resistant strains, and test the antibacterial properties of plasma in petri dishes in the laboratory. These bacteria include S. aureus, P. aeruginosa, and the drug-resistant S. aureus, P. aeruginosa, and E coli, while a mixture of these bacteria was also studied. Additionally, bacterial samples were collected from patient wounds from Orléans hospital. The team reported full decontamination for all the studied bacteria, even in bacterial-resistant samples, creating hope for future treatment plans. They also proved that plasma devices can act in a localised manner, leaving the surrounding areas unharmed – all of which is very encouraging for the transition of this treatment to clinical settings.

Step into the clinic
The impressive results from the in vitro experiments were followed by a successful pilot study using non-thermal technology to treat and even heal severe wounds in patients. This study included five patients bearing super-infected wounds with diameters of 3–15cm. A single plasma jet device of low voltage was used to deliver plasma for a duration of one minute on each half square-centimetre unit. The wound was treated for between 15 and 30 minutes and the overall process was found to be completely painless, without any skin injury reported and no inflammatory or other effects observed. Most importantly, the team reported outstanding tissue improvement in the areas treated with the plasma devices compared to untreated areas. Robert and Prazuck highlight that the treatment protocol can be highly personalised to account for the different characteristics of large surface wounds, such as humidity, depth, and bacterial load.

Beyond wound healing
These preliminary results are highly encouraging and promise a different future for wound treatment. The race is now on to translate successful laboratory results into the clinic. And wound healing does not seem to be the limit – plasma may prove to have multiple uses in the biomedical sector. It can be used in cancer therapy since it can increase tissue oxygenation and improve treatments like radiotherapy, which require oxygen to destroy cancer cells. Additionally, plasma can be used in drug delivery ranging from anticancer drugs to cosmetic treatments, since it has been demonstrated that plasma can accelerate chemical uptake in cells and tissue, as recently reported on human skin explants. This innovative technology opens new areas of research that should lead to new applications in wound healing, cancer therapy, and dermocosmetics.