Cold plasma: a technological leap for antisepsis and regeneration

Modern dentistry faces a dual challenge: the eradication of resistant polymicrobial biofilms and the management of healing in hostile environments, such as in aphthous stomatitis or diabetic wounds. Recent studies, notably those by Lee et al. (2019) on titanium surfaces or Kolenko and Sinko (2024) on mucosal lesions, address these deadlocks via a breakthrough technology: cold atmospheric plasma (CAP).

The objective of this research is to evaluate the ability of CAP to disinfect complex surfaces — such as sandblasted and acid-etched (SLA) implants — and to accelerate tissue repair. The challenge is to validate a non-thermal alternative capable of inactivating target pathogens such as Porphyromonas gingivalis or Streptococcus mutans while modulating the host's biological response.

The tested hypotheses are based on the direct action of reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by the plasma. These molecules would target bacterial membrane integrity and stimulate the expression of growth factors, thus offering a dual therapeutic potential: precision decontamination and local biostimulation, without damaging the surrounding peri-implant or mucosal tissues.

Methodological approaches and experimental protocols

The reported data synthesise several experimental protocols targeting the efficacy of cold atmospheric plasma (CAP) in various clinical and biological settings:

• Microbiological models: Bactericidal activity was tested on 78 genetically distinct strains of Staphylococcus aureus (including the mecA and luk-P genes). In dentistry, Porphyromonas gingivalis biofilms were isolated on SLA (sandblasted and acid-etched) titanium discs to simulate implant surfaces.
• Instrumentation and parameters: Studies primarily use argon-based plasma jets (APPJ) or dielectric barrier discharge (DBD) devices. A specific protocol evaluated an argon plasma brush on oral pathogens, while other tests compared the effect of "ozone-free" plasmas dependent or not on H2O2.
• In vivo models: Protocols include the use of Nc/Nga mice to treat dermatitis induced by 2,4-Dinitrochlorobenzene, as well as rats to evaluate sciatic nerve regeneration following transection.
• Analyses: The evaluation of results is based on the measurement of growth factor expression in chronic diabetic wounds, the viral and bacterial inactivation rate, and the molecular analysis of the mechanisms of action mediated by reactive oxygen species (ROS).

Results: From surface decontamination to tissue regeneration

Data from various experimental and clinical studies demonstrate that cold plasma (CAP) acts through a complex synergy of reactive oxygen and nitrogen species (RONS), electric fields and UV radiation, without deleterious thermal effects on healthy tissues.

1. Antimicrobial efficacy and biofilm management

The bactericidal action of CAP is documented against a wide range of oral pathogens, even within complex biofilm structures. For the practitioner, the challenge is the decontamination of implant surfaces and dentinal tubules.

A key observation concerns the mechanism of action: the inactivation of oral microbes by ozone-free cold plasma can occur via hydrogen peroxide (H2O2)-dependent or -independent pathways, offering therapeutic flexibility depending on the device used (Park et al., 2022).

2. Healing and biological modulation

Beyond antisepsis, CAP directly influences the host response. Molecular analyses show a modification in gene expression promoting tissue repair.

• Growth factors: In the treatment of chronic diabetic wounds, CAP increases the expression of growth factors (notably VEGF and TGF-β), accelerating re-epithelialisation (Hiller et al., 2022).
• Nerve regeneration: Tests on rat sciatic nerve transection models show that the application of non-thermal plasma significantly improves functional recovery (Lee et al., 2021).
• Anti-inflammatory effect: CAP inhibits cytokine-mediated inflammatory reactions in dermatitis models, suggesting a potential for controlling aggressive periodontitis (Choi et al., 2016).

3. Oral clinical observations

Local application of cold plasma has demonstrated clinical efficacy in the treatment of recurrent aphthous stomatitis, with pain reduction and accelerated lesion closure (Kolenko & Sinko, 2024). In oral oncology, the mechanisms of programmed cell death induced by CAP open up perspectives for the targeted treatment of malignant tissues without damaging adjacent healthy cells (Semmler et al., 2020).

The era of targeted biological decontamination

The analysis of these studies highlights a major transition: the shift from purely physical sterilisation to biological modulation by cold plasma (CAP). The results of Nicol et al. (2020) confirm that antibacterial efficacy relies on reactive oxygen species (ROS), acting directly on biofilms. In dentistry, the study by Lee et al. (2019) is crucial: it demonstrates a bactericidal action against Porphyromonas gingivalis specifically on sandblasted and acid-etched (SLA) titanium surfaces, without altering the topography of the material. This is a direct response to the limitations of curettes or lasers on implant threads.

Beyond asepsis: regeneration and inflammation

The potential of CAP extends beyond simple disinfection. Data from Hiller et al. (2022) show an increased expression of growth factors in chronic wounds, while the models of Choi et al. (2016) highlight a marked inhibition of inflammatory reactions. Even more surprisingly, the study by Lee et al. (2021) suggests an accelerated recovery of injured sciatic nerves in rats, opening up perspectives in oral surgery for the management of nerve trauma.

Limitations and perspectives

Despite the demonstrated efficacy against 78 strains of S. aureus (Matthes et al., 2016) and clinical successes on aphthous stomatitis (Kolenko, 2024), the heterogeneity of the devices — argon brushes vs plasma jets — complicates the standardisation of protocols. Most mechanisms, although identified as H2O2-dependent or independent (Park et al., 2022), still largely derive from in vitro or animal models.

Summary of results

Cold plasma (CAP) demonstrates major bactericidal efficacy against 78 strains of S. aureus and biofilms of P. gingivalis on SLA titanium. Beyond antisepsis, the activation of growth factors and nerve regeneration (p < 0.05) confirms its therapeutic potential in complex wound healing.

In practical terms, for the practitioner:

• Management of peri-implantitis: Use CAP to decontaminate implant surfaces without altering their topography, eliminating biofilms where conventional antiseptics fail.
• Difficult healing: Apply the plasma to chronic wounds or aphthous ulcers to accelerate mucosal closure via the modulation of local oxidative stress.
• Biological alternative: Favour this technology for targeted disinfection without tissue toxicity, replacing the extensive use of harsh chemical solutions during oral surgeries.

Technical glossary of plasma medicine

Cold atmospheric plasma (CAP): Partially ionised state of matter produced at atmospheric pressure, characterised by a macroscopic temperature close to ambient temperature (often between 30 and 45°C). This unique property allows interaction with living tissues without causing thermal denaturation of proteins.

Reactive Oxygen Species (ROS): Highly reactive molecules (such as singlet oxygen or the hydroxyl radical) generated within the plasma. They constitute the primary vector of bactericidal activity by causing irreversible oxidative damage to the cell membranes and DNA of pathogens.

Atmospheric pressure plasma jet (APPJ): Application device projecting a stream of ionised gas (typically argon or helium) through a nozzle. Its manoeuvrability enables precise treatment of complex anatomical areas, such as periodontal pockets or implant surfaces.

Dielectric Barrier Discharge (DBD): Method of plasma production using an insulating layer to limit electrical discharge. This technology ensures rigorous thermal stability, essential for safe clinical applications on the skin or mucous membranes.

Microbial inactivation: Process of neutralising microorganisms (including bacteria such as P. gingivalis, viruses and spores) by structural alteration of their cell walls and genetic material, without inducing any known antibiotic resistance.

Redox Biology: Field of study of cellular oxidation-reduction reactions. Cold plasma is used as a redox modulating agent, capable of stimulating cell proliferation and wound healing at low doses, or triggering apoptosis in cancer cells at higher doses.

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