Introduction

From a cut on the hand to a scrape on the knee – it’s easy for an everyday wound to become infected if not treated properly. Antibiotics have long been our best defence against bacterial infection, but the rise in antibiotic-resistant superbugs are making these treatments less and less effective.¹ This is where cold plasma technology comes in. This exciting new therapy offers a safe, targeted, drug-free approach to wound disinfection that could revolutionise first-line care for many wound types, from diabetic foot ulcers to burns.²

In this article, we will cover what cold plasma technology is and how it can be used to disinfect wounds. We will also discuss its advantages over traditional wound disinfection methods, current limitations of the technology, and what needs to happen for it to become a readily available treatment option in the future.

What exactly is cold plasma technology?

Understanding cold plasma

You may have been taught in school that there are three states of matter: solid, liquid and gas. But this is not strictly true – there are actually four. This fourth state of matter is called plasma, and it is less talked about because it is much less common in everyday.² Some examples of plasma you are likely familiar with include lightning, stars, and the Aurora Borealis.³ Importantly, this plasma is different from blood plasma, which forms the liquid part of your blood.⁴

Plasma forms when energy is added to a gas (usually argon, helium, or air) which causes some of its atoms to become electrically charged.^2,5 There are two types of plasma: thermal and non-thermal. In thermal plasma, all parts of the atom – the heavy nucleus at the centre and the surrounding electrons - gain lots of energy.⁶ This makes the plasma dangerously hot, like the plasma that makes up lightning and the sun. In non-thermal or “cold” plasma, only the electrons gain high amounts of energy, while the heavier parts at the centre of the atom stay near room temperature.⁶ This makes cold plasma a low enough temperature (<40°C) to be safe to use on human skin.⁴

How the technology works

In cold plasma therapy, cold plasma is applied directly to the surface of the wound. Once the wound is cleaned and prepared, the damaged skin is exposed to cold plasma for a short time, usually two to five minutes.⁷ The number of times the treatment is required depends on the severity of the wound and infection.⁵ There are two main types of devices used to deliver cold plasma therapy: a dielectric barrier discharge (DBD) device, or an atmospheric pressure plasma jet (APPJ). A DBD device has a larger surface area, making it ideal for treating bigger wounds.⁵ Meanwhile, APPJs produce a narrow, concentrated beam of plasma - a bit like a cool, gentle blowtorch - allowing clinicians to target small or hard-to-reach wounds more precisely.⁵

How cold plasma fights infection

So how does cold plasma actually fight off infection? Its powerful antimicrobial effects come from the mixture of chemicals it contains, which allow it to kill bacteria and other germs in several clever ways. Importantly, it does this without damaging healthy human tissue.⁸

Reactive oxygen and nitrogen species (RONS)

First and foremost, cold plasma contains plenty of highly reactive oxygen and nitrogen species, or RONS. These RONS break down the outer fatty layer (membrane) of bacteria, causing leakage of chemicals the bacteria need to survive, which accelerates their death. Furthermore, these holes in the bacterial membrane make it easier for RONS and other harmful chemicals to enter the bacteria. Once inside, these chemicals can wreak havoc, causing catastrophic damage to proteins, sugars, DNA and more, which makes it impossible for the bacteria to survive.

Breaking the biofilm

Many bacteria live in biofilms - as a community with other microbes under a slimy, self-produced shield to keep themselves safe.⁹ A specific type of RONS called nitric oxide (NO) found in cold plasma can help to break down these biofilms by disrupting communication between the bacteria underneath.¹⁰ Breaking this shield exposes the bacteria, which reduces bacterial growth and allows the cold plasma to target the remaining bacteria more directly.²

Ultraviolet radiation

Cold plasma also contains a small amount of ultraviolet (UV) radiation, which can damage the genetic material or DNA inside bacteria.² Damage to their DNA can stop bacteria from making key proteins essential for their survival and prevent them from replicating properly. This will slow the growth of the bacteria and cause them to die.⁹  

Cold plasma versus antibiotics and antiseptics

The main advantage of cold plasma therapy over traditional wound disinfection methods, like antibiotics and antiseptics, is that it does not promote antibiotic resistance.⁵

Just as our bodies fight off illnesses more easily if we have had them before, bacteria can become more resistant to a specific antibiotic when exposed to it multiple times.¹¹ So, if a wound is colonised by antibiotic-resistant bacteria, a simple course of antibiotics is unlikely to resolve the infection. This is a major problem for chronic wounds, where long-term antibiotic use can increase resistance,¹² causing infections to recur, requiring even more antibiotics - creating a cycle that is hard to break.

Meanwhile, the brief and highly destructive nature of cold plasma therapy makes it harder for bacteria to learn how to resist its effects. As a result, cold plasma can reduce the amount of antibiotic-resistant bacteria in wounds by 60-70%.¹³ This reduces the risk of complications from prolonged, untreated infection and gives wounds a better chance to heal.²

Another benefit of cold plasma therapy is that it can treat infected burns. The blood vessels of burned skin are often damaged, making it impossible for oral antibiotics absorbed into the bloodstream to reach the wound site.¹⁴ Cold plasma therapy does not face this challenge as it is applied directly to the wound surface. While topical antibiotics applied directly to the skin (like silver sulfadiazine cream) can reach burned tissue, they are less effective than cold plasma at killing all types of bacteria, especially antibiotic-resistant ones.¹⁴

Current challenges in cold plasma technology

Clearly, cold plasma technology has advantages over antibiotics and antiseptics - but several limitations prevent it from being the current first choice for wound disinfection in clinical practice.

Standardising technique

Cold plasma technology is an emerging field. While the research shows promising results, it is unclear which procedure will be best for wider clinical use.² Which gas should be used: argon, helium, or air? Is a DBD or APPJ more effective for this type of wound? How should the correct dosage be calculated? These are questions that we cannot confidently answer yet. More large-scale studies are needed to generate standardised protocols for clinicians to follow to safely integrate cold plasma therapy for wound disinfection into everyday practice.⁵

Gram-positive infections

Some studies show that cold plasma is more effective at killing some types of infection over others. For example, gram-negative bacteria, a type of bacteria which have a thinner cell wall and therefore weaker defences, are more easily killed by cold plasma than gram-positive bacteria.² Therefore, more research is needed to understand how we can modify cold plasma technology to target infections of all kinds.

Cost and access

Two of the biggest challenges when it comes to making cold plasma therapy more mainstream are the high cost and low availability. With the research into cold plasma technology being so recent, the number of cold-plasma delivery devices available in healthcare settings at this moment is few.⁸ Making cold plasma therapy as accessible to patients as antibiotics are for wound disinfection will require significant funding.¹⁰

Future directions for cold plasma technology

One of the most exciting future directions for cold plasma therapy is the development of smaller, portable cold plasma-delivery devices.⁵ These devices will make it easier for clinicians to provide care for patients in a variety of settings. One day, this could even allow patients to disinfect wounds in the comfort of their own home, which may be especially useful for patients with chronic wounds who cannot travel to multiple appointments per week.¹⁰

Furthermore, cold plasma-activated liquids (PALs) are being investigated as an alternative method of disinfecting wounds using cold plasma. When saline or water is exposed to cold plasma, it causes the RONS and other chemicals to dissolve into the liquid, creating a solution charged with the plasma’s healing potential.¹⁵ PALs have been used as disinfectants against COVID-19 and other germs even after weeks of storage,¹⁶ suggesting they can be made in bulk, which would be more cost-effective and reduce the need for numerous cold-plasma devices in hospital settings.

Summary

• Cold plasma: A type of energised, room-temperature gas - can be applied directly to the surface of wounds to disinfect them
• Cold plasma kills bacteria in wounds: It does this by producing RONS to puncture holes in their defences, break down the biofilm that protects them, and damage their DNA to stop them from replicating
• Key advantages of cold plasma technology: Over other wound disinfection methods, like antibiotics and antiseptics, include its ability to destroy antibiotic-resistant bacteria and treat infected burns
• Widespread use of cold plasma technology: Currently limited by unstandardised treatment protocols, its varying effectiveness against different bacteria types, and low availability in clinical settings
• Future directions for research: Include the development of portable cold-plasma delivery devices and PALs to improve the efficacy and accessibility of wound disinfection

Ultimately, cold plasma technology presents an effective, safe, and gentle alternative to traditional methods for wound disinfection and holds massive potential to become a mainstream tool in wound care.