Cold Atmospheric Plasma

thermal plasma; CAP; cold atmospheric plasma; non-thermal plasma, NTP;

The term “cold plasma” refers to a partially ionized gas (plasma) that is generated at atmospheric pressure and whose gas temperature, when the equipment is properly adjusted, remains approximately within the “physiologically tolerable” (usually < 40 °C at the treated surface). Cold plasma is generated by supplying energy—usually via high-frequency electrical discharge—to ambient air or specific gases such as argon or helium.

Unlike thermal plasma, whose temperatures can reach several thousand degrees Celsius, cold plasma contains high-energy electrons, while the temperature of the heavy gas particles remains comparatively low.

The effect of cold plasma is dose-dependent and biphasic: Low exposures can promote regenerative cell functions, while higher oxidative stress levels can have a cytotoxic effect. Selective damage to tumor cells as opposed to healthy cells has been described experimentally, but has not been generally confirmed clinically (oncological therapies are currently still considered experimental). 

The biological effect of cold plasma is based on a complex interaction of several components:

• Reactive oxygen species (ROS): superoxide, hydroxyl radicals, hydrogen peroxide, and singlet oxygen.
• Reactive nitrogen species (RNS): nitric oxide, nitrogen dioxide, and other reactive nitrogen compounds.
• Electric fields and charged particles: Influence on cell membranes and signal transduction processes.
• UV radiation: Varies depending on the plasma source; usually not the dominant factor.

Cold plasmas have the following effects:

• Antimicrobial: Oxidative damage to microbial membranes, proteins, and nucleic acids. They impair biofilms and, consequently, microbial survival mechanisms.
• Promotes wound healing: Modulation of keratinocytes, fibroblasts, and growth factors. Comment: The most convincing evidence currently available pertains to chronic wounds. A 2025 meta-analysis of twelve studies involving a total of 448 patients demonstrated a significantly greater reduction in wound area and microbial load compared to control treatments. A randomized, placebo-controlled multicenter study by Strohal et al. (2025) involving 70 patients demonstrated a significant acceleration of wound healing with supplemental cold plasma therapy (p < 0.0001). The German AWMF S2k guideline “Rational Therapeutic Use of Cold Physical Plasma,” registration number 007-107, was published in 2022 and, following an extension, remains valid through February 2027. In particular, it supports the adjunctive treatment of chronic and infected wounds as well as selected palliative ulcerated tumor nodules.
• Immunomodulatory: Modulation of inflammatory signaling pathways and cytokine expression
• Angiogenic: Modulation of NO signaling pathways and endothelial processes
• Antitumor (plasma oncology): Induction of oxidative stress, cell cycle arrest, and apoptosis in experimental models. The mechanisms observed experimentally include ROS/RNS-induced mitochondrial dysfunction, DNA damage, activation of apoptotic signaling pathways, and immunogenic cell death mechanisms. Studies have included melanomas, squamous cell carcinomas, and other solid tumors. Cold plasma is not currently an established curative tumor therapy. This should be distinguished from the palliative treatment of ulcerated, contaminated tumor wounds (see above), for which there is a consensus-based guideline recommendation.

Claplasma is being studied and used as a physical therapy method, particularly in dermatology—especially for chronic wounds—as well as in infectious diseases and experimental oncology.

Clinical evidence for various indications:

• Chronic wounds (venous leg ulcers, diabetic foot ulcers, pressure ulcers); reduction of microbial load, promotion of granulation and epithelialization. Relatively good; randomized studies available.
• Infected, poorly healing wounds: Antimicrobial effect, biofilm reduction. Clinical observations
• Acne: Reduction of Cutibacterium acnes, anti-inflammatory effect. Small clinical studies
• Onychomycosis: Inactivation of dermatophytes: Experimental, limited clinical data
• Bacterial and fungal skin infections: Local reduction of microorganisms, early-stage clinical research
• Atopic dermatitis: Modulation of the skin microbiome and inflammation. Experimental data.
• Psoriasis: Modulation of inflammatory signaling pathways. Experimental data! 
• Oncology:
  • Direct tumor cell damage caused by oxidative stress. Primarily preclinical data.

  • Ulcerated tumor metastases: Palliative microbial reduction (guideline-supported option, limited evidence)

     

Summary from a dermatological perspective: Cold plasma is an innovative physical therapy method with antimicrobial, redox-modulating, and tissue-regenerative properties. Its most important clinical application at present is the adjunctive treatment of chronic, slow-healing wounds. From a dermatological perspective, it is particularly noteworthy that cold plasma not only has an antiseptic effect but can also influence cellular repair mechanisms. This fundamentally distinguishes it from purely disinfecting methods. The expansion of cold plasma applications to inflammatory dermatoses, infectious diseases, and malignant skin tumors is scientifically interesting but requires further controlled clinical trials.

1. Bekeschus S et al. (2026) Cold plasma technology for the treatment of patients with chronic wounds. J Dtsch Dermatol Ges 24:216–228.
2. Strohal R et al. (2025) Treatment of chronic wounds with cold plasma: a randomized, single-blind, placebo-controlled clinical study. J Wound Care 34:542–554.
3. AWMF S2k Guideline (2022): Rational therapeutic use of cold physical plasma.
4. Werra UEM et al. (2025) Cold plasma in wound healing. Urology 64:52–58.