Cold Atmospheric Plasma Research Articles

Delivery Systems for Plasma-reactive Species and their Applications in the Field of Biomedicine.

Cold atmospheric plasma (CAP) is an ionized matter with potential applications in various medical fields, ranging from wound healing and disinfection to cancer treatment. CAP's clinical usefulness stems from its ability to act as an adjustable source of reactive oxygen and nitrogen species (RONS), which are known to function as pleiotropic signaling agents within cells. Plasma-activated species, such as RONS, have the potential to be consistently and precisely released by carriers, enabling their utilization in a wide array of biomedical applications. Furthermore, understanding the behavior of CAP in different environments, including water, salt solutions, culture medium, hydrogels, and nanoparticles, may lead to new opportunities for maximizing its therapeutic potential. This review article sought to provide a comprehensive and critical analysis of current biomaterial approaches for the targeted delivery of plasma-activated species in the hope to boost therapeutic response and clinical applicability.

Effectiveness of cold atmospheric plasma in decontaminating enterococcus faecalis colonized collagen and PTFE membranes used in guided bone regeneration: a comparative in vitro investigation.

Wound healing disorders caused by bacterial infections in dental surgery, especially where membranes are used, are a common issue in oral surgery. Cold atmospheric plasma (CAP) offers a non-invasive solution for surface decontamination, including dental implants. The aim of this study was to evaluate the antibacterial effectiveness of CAP on various clinically applied membranes made of collagen and polytetrafluoroethylene (PTFE). To assess the antibacterial properties of CAP, enterococcus faecalis were seeded on different membranes: Memlock (collagen), Memlock Pliable (collagen), Agronaut (collagen), and PermaPro (PTFE); n = 4. After in vitro cultivation for 6days, CAP using a kINPen® MED with an output of 5 W was applied 5min and 10min. Bacterial colony-forming units (CFU) were quantified to detect decontamination effectiveness. In addition, live and dead staining as well as scanning electron microscopy (SEM) of membranes was performed for validation and surface texture analysis. Bacterial colonization was highest on collagen-based membranes (CFU Memlock: 14.38 ± 8.91). The results showed that CAP significantly reduced bacterial colonization on all membrane types after 10min application of CAP; Memlock (CFU after 10min 0.22 ± 0.16^106; p = 0.0256), Argonaut (CFU after 10min 0.02 ± 0.01^106; p = 0.0129) and PermaPro (complete bacterial decontamination; p = 0.0058). This was paralleled by fluorescence and scanning electron microscopy. CAP was most effective on smooth membrane surfaces as SEM revealed. CAP thus offers a non-invasive, cost-effective method to reduce bacterial infections in guided bone regeneration using membranes.

Radical formation in skin and preclinical characterization of a novel medical plasma device for dermatology after single application.

Cold atmospheric plasma (CAP) enables painless tissue treatment by producing reactive species including excited molecules and charged particles and is of great interest for medical applications. Medical CAP sources work in contact with air at ambient pressure, resulting in the generation of substantial amounts of reactive oxygen and nitrogen radicals. These radicals have a significant influence on cellular biochemistry, are crucial components of the immune system, and play a central role in wound therapy. CAP has a variety of applications, with a particular emphasis on tissue treatment in dermatology. It eradicates microorganisms by preventing biofilm formation so that wounds can be effectively disinfected and treated antiseptically. Using both in vitro and ex vivo methods, a comprehensive preclinical assessment of a novel battery-operated cold plasma handheld device with a reusable, and autoclavable glass cylinder was performed. The objectives were to evaluate the potential impact of single CAP application on radical formation with and without wound dressing, by directly measuring radicals in skin, to investigate the influence of CAP application on antimicrobial activity and cytotoxicity in vitro, and to assess skin tolerance ex vivo. The direct effect of CAP on the formation of radicals in the skin after plasma application at different levels with and without wound dressing was demonstrated quantitatively for the first time using electron paramagnetic resonance spectroscopy. Free radicals were measured in the skin as a function of the duration of CAP treatment. Furthermore, it was found that an alginate or wound plaster dressing does not significantly inhibit radical formation in skin compared to application without a dressing. In vitro and ex vivo data showed no cytotoxic potential with simultaneous efficacy against bacteria strains and no risk of temperature rise, pH change, skin barrier or DNA damage. These results show a high potential for wound healing applications in vivo.

Evaluating the impact of Cold plasma on Seedling Growth properties, seed germination, and soybean antioxidant enzyme activity.

Cold atmospheric pressure plasma (CAP) has garnered significant attention in recent years for its potential applications in biomedical, environmental, and agricultural fields. Cold plasma treatment exhibits a variety of effects in agricultural applications, including impacts on seed germination and seedling growth; however, further research is required. Soybean serves as a fundamental source of nutrients for both animals and humans. Soybean seeds possess impermeable and thick testae, which results in prolonged germination times and suboptimal germination rates. The soybeans exhibit low uniformity. As a result, poor crop establishment and yield reduction are inevitable outcomes. Therefore, the purpose of this study was to examine the effects of Iranian soybean cultivars, such as Sari, Saba, Arian, Katoul, and Williams, on seedling growth properties, seed germination, and antioxidant enzyme activity, using argon at time intervals of 30, 60, 180, 300, and 420s. Cold plasma treatment significantly enhanced germination potential from 1.18 to 66.97%, germination index from 0.50 to 60.09%, germination rate from 1.78 to 32.17%, seedling length from 2.70cm to 78.13cm, root length from 2.87cm to 56.13cm, and seedling dry weight from 1.80g to 36.63g. Additionally, CAT activity increased from 0.88- to 4.40-fold, SOD activity from 0.86- to 5.89-fold, and APX activities from 0.40- to 4.01-fold compared to the control treatment. The findings indicated that the samples exhibited optimal results at treatment durations of 60 and 180s. The influence of plasma on the antioxidant responses of seedlings, seed germination, and growth characteristics was contingent upon the duration of treatment. Cold plasma, when applied for an appropriate duration, may enhance soybean seedling growth characteristics and seed germination.

Evaluating the clinical potential of bioceramic-rods for revascularization in osteonecrosis of the femoral head: a systematic review.

To evaluate the safety, reliability, and effectiveness of bioceramic rods (BR) in treating osteonecrosis of the femoral head (ONFH), compared with other treatments such as core decompression and autologous bone grafting. Systematic review and meta-analysis. Pubmed, Embase, and CNKI databases from January 2011 to July 2023. Included studies involved patients treated with bioceramic rods. Studies were required to have a follow-up time of more than six months and no statistically significant differences in baseline information between groups in controlled studies. Exclusions included literature reviews, case reports, conference abstracts, animal experiments, and studies without defined success criteria or lacking analysis on factors influencing efficacy. The primary outcome measure was the Harris Hip Score (HHS) improvement rate. Secondary outcomes included the femoral head stability and survival rate, alongside the hip replacement rate. The systematic review revealed significant improvements in symptom relief and functional recovery using BR for the treatment of ONFH. An average follow-up of 20.44 months showed an overall HHS improvement rate of 33.93%. Hip preservation efficacy with BR was superior to core decompression and autologous bone grafting. The overall femoral head survival rate was 84.42%, with results sustained for three years. The success rate of hip preservation was notably higher with early intervention, which showed better outcomes when the overall HHS improvement exceeded 27%, and rates of excellent and good outcomes approached 90%. Bioceramic rods offer a safe, minimally invasive, reliable, and effective treatment option for ONFH, ensuring substantial symptom relief and functional recovery. The technique's success in early disease stages suggests a strong potential for broader clinical adoption. Although additional benefits from combining BR with stem cells, platelet-rich plasma, and traditional Chinese medicine are noted, definitive conclusions on enhanced therapeutic effects remain inconclusive.

Cold Plasma for Enhanced Water Purification

Abstract Access to clean water remains a critical global challenge, with traditional water treatment methods often failing to eliminate complex pollutants such as pharmaceuticals, dyes, and antibiotics. Cold atmospheric plasma technology offers a promising solution by generating reactive oxygen and nitrogen species at room temperature, effectively degrading these contaminants and inactivating pathogens. Recent advancements in cold plasma have shown significant potential in water treatment applications. Cold plasma has demonstrated efficacy in disrupting bacterial biofilms, reducing antibiotic contaminants, and degrading complex organic pollutants, making it an innovative and eco-friendly alternative to conventional methods. This review examines the principles of plasma technology, evaluates its performance in water sanitation, and addresses the challenges of scalability and economic feasibility. By integrating cold plasma into existing water treatment systems and developing standardized protocols, this technology can significantly contribute to sustainable water management and public health, supporting the Sustainable Development Goals (SDGs).

Comparison of the effects of laser systems and cold atmospheric plasma on the surface roughness and shear bond strength of flexible hybrid ceramics.

The aim of this study was to compare the effects of laser systems and cold atmospheric plasma (CAP) on the surface roughness (Ra) and shear bond strength (SBS) of flexible hybrid ceramics (FHCs). Eighty FHC samples were divided into 5 groups to be subjected to surface treatments (hydrofluoric acid (HFA), HFA + 5W Er: YAG laser (HFA + 5WE), HFA + 3W Er: YAG laser (HFA + 3WE), HFA + ultrafast fiber laser (HFA + FL), and CAP). The Er: YAG laser (AT Fidelis Plus III, Fotona, Slovenia) was operated with a 0.9mm diameter tip, delivering 250mJ and 150mJ per pulse, with output powers of 5W and 3W, and fluences of 23,623J/cm² and 14,157J/cm², respectively, at a frequency of 20Hz and a pulse duration of 600 µs for 30s. The FL (FiberLAST Inc., Turkey) was applied with a 7mm spot size, 1mJ pulse energy, 20W output power, 100kHz repetition rate, ultrashort pulse length (100 ns), and the fluence of 1,820J/cm² for 7s. The CAP (PiezoBrush PZ3, Relyon Plasma, Germany) applied to the surfaces for 80s at a treatment speed of 5 cm2/s and 100% plasma power. After the Ra values were measured, each group was divided into 2 subgroups to be cemented with total-etch (TE) and self-adhesive (SA) resin cements. The SBS of all the samples was measured. One sample was randomly selected from each group, and the fractured surfaces were examined by SEM analysis. The significance level was at P < 0.05. HFA + FL had the highest Ra values, and there was no significant difference between HFA + FL and HFA + 5WE (P > 0.05). There was no difference in Ra between CAP and HFA (P > 0.05). The highest SBS values were observed for the samples cemented with TE after HFA + FL. The difference between the SBS values of the groups cemented with TE after CAP, HFA + 5WE, HFA + 3WE, and HFA + FL was not significant (P < 0.05). The use of FL may be a promising method to improve SBS without causing thermal damage when using TE or SA cements. CAP can be recommended as a practical and safe treatment with SA cement because it is suitable for chairside use with a handheld device and does not change the physical properties of the material.

SURG-58. COLD ATMOSPHERIC PLASMA (CAP) CAUSES SELECTIVE TUMOR CELL DEATH VIA APOPTOSIS AND FERROPTOSIS IN MALIGNANT GLIOMA CELLS

Abstract BACKGROUND High-grade gliomas (HGGs) are primary brain tumors associated with significant morbidity and mortality, and despite advances in neuro-oncology, the prognosis remains poor. Cold atmospheric plasma, a novel experimental anti-cancer therapeutic tool, is a near-room temperature ionized gas generated at atmospheric pressure. It has many promising results in vitro and in vivo with a variety of cancers. CAP cytotoxicity appears to be selective to cancer cells without significant damage to surrounding healthy tissues. We aim to evaluate the efficacy of CAP in generating tumor-selective cytotoxicity against high-grade glioma. METHODS B16, U87, GL261, patient derived high grade glioma, human neural stem cells (LM-NSC008) and astrocytes (NHA hTERT) were treated with CAP. Proliferation and propidium iodide (PI)/annexin V flow cytometry assays were employed to quantify cytotoxicity, cell cycle phases and apoptosis. Cells were pre-treated with ferroptosis inhibitors Ferrostatin-1 and Deferoxamine (DFO) in rescue assays. Cerebral organoids were transplanted with fluorescent tumor cell lines and stained with cleaved caspase-3, ki67 and transferrin receptor. RESULTS CAP induces dose dependent cell death in all glioma cell lines tested. CAP induces an accumulation of intracellular ROS, most prominent in glioma cells. CAP-mediated cell death involves apoptosis and ferroptosis. CAP selectively leads to apoptosis in tumor implanted organoids and leads to decreased proliferation in malignant and non-malignant cells. CAP leads to a shift into G0 phase of all treated cells, malignant and non-malignant. CONCLUSIONS CAP treatment induces dose-dependent increases in ROS and apoptosis in HGG lines tested more significantly than in NHAs and hNSCs. CAP induces decreased proliferation and G0 phase cell cycle arrest in all CAP-treated cells. CAP-mediated cytotoxicity was significantly mitigated with DFO pre-treatment in HGG cells, suggesting that ferroptosis plays a critical role in the mechanism of CAP treatment in HGG. CAP led to selective glioma cell death in tumor implanted cerebral organoids.

Transition from afterglow to streamer discharge in an atmospheric capacitively coupled micro-plasma jet

This Letter focuses on the discharge mechanisms of an atmospheric pressure micro-plasma jet optimized for endoscopic applications in biology and medicine. This capacitively coupled plasma (CCP) features a concentric double flow allowing for shielding the Helium or Neon plasma gas with carbon dioxide from the humid ambient air. High-resolution optical emission spectroscopy allows for the analyses of the Stark effect of the He I 492.19 nm and the Hydrogen Hβ lines to determine the electric field (EF) and the electron density spatially resolved along the discharge expansion outside the source. EF in Neon at atmospheric pressure was reliably determined with the Stark shift measurement of the weak Ne I line at 515.196 nm. In both gases, the EF diagnostic revealed a steep transition from CCP afterglow to streamer discharge with a magnitude up to 30 kV/cm. This research is a significant step forward in the field of plasma medicine with a plasma source capable of delivering a reactive chemistry with or without an intense EF to the target.

Determining plasma dose using equivalent total oxidation potential (ETOP): Concept to practical application via machine learning

Atmospheric pressure nonequilibrium plasma holds significant potential in biomedical applications due to its ability to generate reactive species at low temperatures. However, accurately quantifying and controlling plasma dosage remains challenging. Although equivalent total oxidation potential (ETOP) has been proposed for defining dosage, previous methods required measurement of various reactive oxygen and nitrogen species (RONS) densities, which are impractical in diverse plasma settings. Efficient ETOP prediction across variable conditions is thus essential. To address this, we propose a machine learning-based ETOP modeling method. This study collected RONS density data under various conditions using laser-induced fluorescence and trained an artificial neural network to predict ETOP values based on input parameters like voltage, gas flow rate, oxygen concentration, and humidity. This approach enables efficient ETOP prediction across variable conditions, supporting the standardization and clinical application of plasma medicine.

Non-Thermal Atmospheric Pressure Plasma as an Adjunct to Intestinal Anastomosis: A Pilot Study on Preventing Anastomotic Leaks

Anastomotic leaks remain a significant challenge in intestinal surgery, often leading to severe complications. This study investigated a novel approach to enhance anastomotic healing and reduce the risk of leaks by combining traditional suturing and stapling techniques with non-thermal atmospheric pressure plasma (NTAPP) application. NTAPP, a cold atmospheric plasma generated through the ionization of ambient air, has been shown to possess antimicrobial, hemostatic, and wound-healing properties. NTAPP promotes sterilization, coagulation, and tissue regeneration by generating reactive oxygen and nitrogen species, potentially strengthening anastomotic union. This pilot study evaluated the efficacy of NTAPP in three patients undergoing intestinal anastomosis. Following the standard surgical procedure, NTAPP was applied directly to the anastomotic site. Postoperative outcomes were monitored for six months, including anastomotic leaks and healing rates. Preliminary results demonstrated promising outcomes. All three patients exhibited successful sealing of the anastomosis, with no evidence of leakage during the follow-up period, providing reassurance and confidence in the potential of sutures, staples, and NTAPP. These findings suggest that NTAPP can significantly improve the safety and efficacy of intestinal surgeries by reducing the incidence of anastomotic leaks. While further research with a larger sample is necessary to confirm these initial findings, the results of this study provide a strong foundation for exploring the potential of NTAPP as a valuable adjunct to conventional surgical techniques for preventing anastomotic leaks. This innovative approach could reduce postoperative complications, improve patient outcomes, and enhance the overall quality of care in intestinal surgery.

The effect of cold atmospheric plasma on viability of osteoblasts and expression of RANKL and OPG genes in medium with bisphosphonates.

Medication-related osteonecrosis of the jaw is a rare but severe complication with challenging treatment protocols. Cold atmospheric plasma (CAP) has shown promising effects in wound healing, cell proliferation and viability. This study investigated the effect of CAP on osteoblasts in a culture medium containing bisphosphonates. Pilot study was designed to determine the optimal setting of CAP. MG-63 cells were exposed to zoledronic acid at a concentration of 10 micromolar for 72h. Study groups with the best MTT assay results, were chosen for assessing OPG and RANKL genes by RT-PCR. Cell viability was significantly higher in groups 9kV.1mm.90s, 10kV.1mm.60s, and 12kV.1mm.60s (P < 0.05). Expression of RANKL in these groups was significantly lower than the positive control group (medium culture without zoledronic and plasma treatment) and higher than the BP group (culture with zoledronic without plasma treatment), except for the 12kV.1mm.60s group, which did not differ significantly from the positive control group (P > 0.05). OPG decreased in all test groups compared to BP (p < 0.05), except for the 12kV.1mm.60s group, which did not significantly differ from BP (P > 0.05). RANKL/OPG ratio in groups 9kV.1mm.90s and 12kV.1mm.60s significantly increased compared to BP (P < 0.05).CAP treatment may enhance the viability of osteoblasts exposed to bisphosphonates, increase their activity levels, enhance osteoclast activity, and improve bone turnover rates.

Enhancing the discharge uniformity of atmospheric pressure DBD cold plasma for food efficient microbial inactivation

Identification and optimization of the discharge uniformity is worldwide problems in the plasma industry. In this study, a simple, practical, and economical alternative for quantitatively identifying discharge uniformity of DBD plasma was proposed using the gray-level histogram, discharge area curve, and gray level transformation characteristics of discharge images. The influences of discharge peak voltage, excitation frequency, dielectric material, and dielectric thickness on discharge uniformity on the time scale of seconds were discussed, and the intrinsic relationship and mechanism between discharge uniformity and microbial inactivation efficiency were revealed. Within a certain range, with the gradual increase of discharge peak voltage (13–17 kV), excitation frequency (9–11 kHz), relative dielectric constant (3.6–9.6), and the gradual decrease of dielectric thickness (1–5 mm), the discharge image corresponded to the relative discharge uniformity and the average inactivation of L. monocytogenes and S. typhimurium (0.12–1.40 log-reduction and 0.26–2.34 log-reduction) increased as a whole. Overall, the findings revealed disruption or improvement of the discharge uniformity was the main factor contributing to the inactivation of bacteria by cold plasma, facilitating the scaling-up of DBD reactors on an industrial scale.

Efficacy of Cold Atmospheric Plasma in Chronic Diabetic Foot Ulcer Management: A Case Report

Efficacy of Cold Atmospheric Plasma in Chronic Diabetic Foot Ulcer Management: A Case Report

Autofluorescence-guided Removal of Bacterial Biofilms from Tissues Using Cold Atmospheric Pressure Plasma (CAP).

Cold atmospheric pressure plasma (CAP) has the potential to completely remove biofilms from surfaces. The goal of this study is to employ the autofluorescence nature of bacterial biofilms to guide the removal of these biofilms using a CAP scalpel. Pseudomonas fluorescens biofilms, which produce a green fluorescence under 405 nm UV light, were grown on 12 chicken samples. The tissue model (chicken tissue) is placed on a motorized X-Y stage with the plasma discharge device directly above the sample. Fluorescent-guided CAP treatment of biofilm regions was carried out using a 1.37 lpm Ar/H2O plasma device with 39.5 × 54 mm2 dimension and a 1 * 0.6 mm2 plasma discharge outlet with discharge speed was 1 mm/s and sample distance of 4 mm. The discharge voltage and current were 3.24 kV and 1.2 mA respectively. Results based on analysis of the fluorescent images show that 97% biofilm removal; CFU analysis confirms that up to 99.98% of the bacteria are now absent from the tissue's surface. This is the first instance of two new applications: using cold atmospheric plasma (CAP) to remove bacterial biofilms from soft tissues and employing CAP in an image-guided procedure.

Application of Atmospheric Cold Plasma (ACP) for Processing of Raw Bovine Colostrum: Investigation of Antimicrobial Efficacy of Different ACP Treatments

As a rich source of bioactive components, bovine colostrum (BC)1 can be used to produce valuable nutraceuticals. Achieving this goal with common thermal pasteurization processes is challenging due to the heat-sensitive nature of raw BC. This research aimed to investigate the potential of atmospheric cold plasma (ACP) as a novel non-thermal process in inactivating the microbial population in BC. Raw BC was treated with different ACP treatments, including direct dielectric barrier discharge (DBD) in both static and continuous modes, indirect DBD, corona discharge, and gliding arc discharge. The occurrence of creaming and curdling of BC during the treatments was one of the challenges of this research, which was the most and least severe during static and continuous treatments, respectively. The continuous and the indirect DBD treatments were the most and least effective in terms of microbial inactivation. The inactivation of natural microflora with the continuous ACP at the voltage of 15 kV for 20 min was approximately 98%. The indirect DBD treatment led to an increase in the microbial population of BC. In addition, the initial microbial population significantly affected the antimicrobial efficacy of ACP. Treatment voltage and time had a significant effect on the creaming and curdling, natural microflora population, and the total coliform population of the treated samples. The voltage of 14.5 kV and the exposure time of 14.2 min were determined as optimal treatment conditions by response surface methodology (RSM) to achieve the maximum reduction of microbial population, without pH changing of ACP-treated BC. The optimal treatment conditions of ACP reduced the total plate count and total coliform count of raw BC by 1.41 and 3.55 log CFU/ml, respectively, with a minor change in pH. These results promise the potential of ACP technology for BC processing.

Physicochemical properties and antimicrobial efficacy of argon cold atmospheric pressure plasma jet activated liquids – a comparative study

Cold atmospheric pressure plasma jet activated liquids (CAPJALs) have attracted considerable scientific attention due to their peculiar antimicrobial characteristics. In the current context, there is a need to compare the bactericidal activity of CAPJALs and demonstrate the specific parameters necessary to obtain greater effectiveness. This in-vitro research examines the antimicrobial activity of liquids, such as deionized water (DI-W), drinking water (DW), tap water (TW), and normal saline (NS) activated by Ar cold atmospheric pressure plasma jet (CAPJ) against multidrug-resistant (MDR) E. coli and S. aureus. The computed D- value showed that CAPJALs' bacterial inactivation efficacy followed the trend – DI-W ≈ NS > DW > TW for both the isolates. To obtain greater bactericidal effectiveness, an optimum combination of liquid activation time by CAPJ and CAPJAL – bacteria interaction time was noticed. In addition, the rate at which the physicochemical parameters (pH, electrical conductivity (EC), total dissolved solids (TDS), and concentration of reactive species (H2O2, NO3-, and NO2-)) changed within the liquid varied in different ways. It was observed that the identified gas-phase species (Ar I, Ar+, N2, N2+, O I, OH•, OH+, NO+, O2+, N2O3-, NO3-, N2O2-, etc.) would contribute to modification of liquid physicochemical property by generating liquid phase reactive species (NO3-, NO2-, H+, H2O2, ONOOH, Cl2, HOCl, etc.) via reaction cascades. These reactive species in the liquid phase, together with other physicochemical characteristics, were found to play a part in the process of bacterial inactivation. This study into the underlying mechanism of CAPJ – liquid and CAPJAL – bacteria interaction would help to determine its potential use as a disinfectant in healthcare settings. List of microorganismsE. coli: Escherichia coli; S. aureus: Staphylococcus aureus

Cold atmospheric plasma as an alternative decontaminant to control healthcare-associated infections and antimicrobial resistance. Significant potential that can be realised globally

Cold atmospheric plasma as an alternative decontaminant to control healthcare-associated infections and antimicrobial resistance. Significant potential that can be realised globally

Cold atmospheric plasma degradation of deoxynivalenol in solid and liquid phases and its effect on whole wheat flour quality

Cold atmospheric plasma degradation of deoxynivalenol in solid and liquid phases and its effect on whole wheat flour quality

Effects of cold atmospheric plasma on patulin degradation, polyphenol oxidase inactivation and other physicochemical properties of fresh-cut apple slices during storage

Effects of cold atmospheric plasma on patulin degradation, polyphenol oxidase inactivation and other physicochemical properties of fresh-cut apple slices during storage