Despite many treatment options and continuous innovation in the field of wound care, the treatment of chronic wounds is still a major challenge. Chronic wounds often persist for months to years, which is an immense burden for the affected patients and healthcare systems. In addition, tissue quality may slowly deteriorate because of increasing fibrosis. Given the high prevalence of chronic wounds and their difficult management, therapies to improve wound healing are of enormous clinical and social interest.
Cold atmospheric plasma has a proven beneficial impact on microcirculation.1 Further, it reduces microbial colonization, which can have a supportive effect on wound healing processes.2 Based on this knowledge, research on treatment of chronic wounds has been focused on cold plasma therapy in recent years.
In this article, the authors report on a case from their department that demonstrates the impressive results of treating a chronic wound with cold plasma. For the treatment, they used an innovative, active wound dressing (CPTpatch; Coldplasmatech GmbH), which attaches to the wound area with an atraumatic, self-adhesive border. This automated device generates a two-dimensional, cold atmospheric pressure plasma between the wound and the underside of the wound patch in the form of a purple glowing discharge. By virtue of being automatic, this wound dressing enables a user-friendly application of cold plasma therapy.
The patient was an 85-year-old man who presented to the clinic with a chronic wound over the right lateral malleolus after impact trauma. The probable cause for the stalled wound healing was peripheral arterial occlusive disease; an occlusion of the anterior tibial artery prevented any improvement in blood circulation. At the first clinic visit, the attending physicians performed a surgical debridement and subsequently covered the defect using a peroneal brevis flap and a split-thickness skin graft. The patient was discharged with completely closed wounds.
In the outpatient setting, the patient only sporadically wore compression stockings. Consequently, the wound condition worsened, resulting in a wound infection and an extensive loss of the skin graft. At the following inpatient stay approximately 2 weeks later, the attending team performed another surgical wound debridement, but it was not sufficient for complete wound healing.
To improve wound healing, the authors started cold plasma therapy during the inpatient stay, using an active wound dressing. The wound patch is used in combination with an energy supply unit. It attaches atraumatically to the wound area with a self-adhesive border, enabling the generation of cold, atmospheric plasma in a noninvasive, reproducible setting. It is approved as a class IIb medical device for the treatment of secondary healing wounds.
The first three treatments were performed during the inpatient stay, but with increasingly improved wound conditions, therapy was continued in an outpatient setting. During the first 4 weeks of treatment, therapy was performed 3 times per week by the wound manager in the outpatient department. Each treatment session had a duration of only 2 minutes. In the last 4 weeks of treatment, the frequency was reduced to two applications per week. After each plasma treatment, the wound was covered with gauze, polyhexanide, absorbent cotton, and elastic compression wrapping of the affected lower leg. Cold plasma therapy was well tolerated by the patient, and he showed no local or systemic adverse effects.
After only a few applications, providers noted a positive effect on wound healing. Starting from an initial wound size of 4 cm2, the defect had decreased in size to 0.75 cm2 after 4 weeks of treatment (Figure). After eight additional treatment sessions, the wound size had reduced to 0.08 cm2, and the residual defect appeared bland and dry (Figure).
In addition to the decreased wound size, the authors also registered a significant decrease in the fibrin coatings. Before the start of cold plasma application, a Staphylococcus aureus colonization was detected in the microbiological examination of the wound swab.
Because of the enormous improvement of the wound situation after cold plasma application, the attending physicians avoided another wound debridement and elaborate reconstruction of the soft tissue defect with a free flap. Despite exposed osseous structures, the wound showed good granulation and epithelialization following the completion of the cold plasma therapy (Figure).
The therapy principle of cold plasma is based on the ionization of the ambient air by electrical discharges. By adding energy to a neutral gas, the plasma state is generated.3 The result of ionization is a complex compound of biologically active agents such as reactive oxygen (ROS) and nitrogen (RNS) species. In addition to ROS/RNS, cold plasma also generates UV light, infrared radiation/heat, and electromagnetic fields.4 The different active components have a synergistic effect on the wound and initiate a cascade of actions that induces increased perfusion, tissue regeneration, and reduced contamination by microorganisms.3
Notably, these effects can be achieved with only a single treatment.5 However, a recent study by Jensen et al6 found that repeated applications of cold plasma increases tissue oxygen saturation and capillary blood flow in chronic wounds. Those authors concluded that multiple applications of this therapy method were superior to a single application.6
In addition to sufficient biocompatibility of the therapeutics used, supporting regeneration and having an antiseptic effect are also crucial. Besides reduced blood circulation, bacterial contamination is another major problem in the treatment of chronic wounds because it impedes healing. The challenge in developing new treatment options is the selective combating of microorganisms without simultaneous damaging the regenerative cells.3 The antimicrobial features of cold plasma show promising results.6,7
At the current state of clinical research, no clinically relevant adverse effects of cold plasma therapy are known. In the present case, the patient’s periwound skin was always intact. The authors did not observe any maceration or skin irritation during the cold plasma applications. The painless treatment and short therapy sessions encouraged high adherence by the patient during the treatment period. As a noninvasive and straightforward therapy, the application is simple and can be easily performed by nonmedical staff.
The CPTpatch is a special wound dressing. The plasma converts the air within the defined volume between the patch and the wound surface into an energetic active state. Thus, the various agents, such as RNS and ROS, UV radiation, and electric fields, affect the entire covered area.
Although the wound patch is a one-time-use material, which increases short-term costs, long-term treatment of therapy-resistant chronic wounds is much more cost-intensive and sometimes lasts for years. Therefore, the investment in short-term cold plasma treatment may be more profitable in the long run and is accompanied by savings for the healthcare system.
Cold plasma is a promising option for the efficient treatment of chronic wounds. Up until now, application has been the biggest hurdle in making this therapy reproducible and effective. The concept of the fully automatic wound dressing has almost completely resolved this problem. This case report provides promising results and could be the basis of further studies to confirm the effectiveness of active wound dressings with cold plasma in the treatment of chronic wounds.
1. Kisch T, Schleusser S, Helmke A, et al. The repetitive use of non-thermal dielectric barrier discharge plasma boosts cutaneous microcirculatory effects. Microvasc Res 2016;106:8–13.
2. Matzkeit N, Schulz L, Schleusser S, et al. Cold atmospheric plasma improves cutaneous microcirculation in standardized acute wounds: results of a controlled, prospective cohort study. Microvasc Res 2021;138:104211.
3. Emmert S, van Welzen A, Masur K, et al. Cold atmospheric pressure plasma for the treatment of acute and chronic wounds. Hautarzt 2020;71(11):855–62.
4. Metelmann HR, von Woedtke T, Weltmann KD. Plasmamedizin: Kaltplasma in der medizinischen Anwendung
. Heidelberg, Germany: Springer; 2016.
5. Tiede R, Helmke A, Wandke D, et al. PlasmaDerm®: kaltes Atmosphärendruckplasma als Spitzeninnovation. In: Spitzenforschung in der Dermatologie. Innovationen und Auszeichnungen
. Lampertheim, Germany: ALPHA Informations-GmbH; 2015:S70–80.
6. Jensen JO, Schulz L, Schleusser S, et al. The repetitive application of cold atmospheric plasma (CAP) improves microcirculation parameters in chronic wounds. Microvasc Res 2021;138:104220.
7. Brehmer F, Haenssle HA, Daeschlein G, et al. Alleviation of chronic venous leg ulcers with a hand-held dielectric barrier discharge plasma generator (PlasmaDerm((R)) VU-2010): results of a monocentric, two-armed, open, prospective, randomized and controlled trial (NCT01415622). J Eur Acad Dermatol Venereol 2015;29(1):148–55.