Application Of Cold Atmospheric Plasma Research Articles

Cold atmospheric plasma activation of human gingival fibroblasts for improved wound healing

Abstract Soft tissue regeneration plays a crucial role after oral surgery, as the successful healing of the soft tissue is a primary indicator of an efficacious intervention. Cold atmospheric plasma (CAP) has recently emerged as a promising therapeutic modality, exhibiting notable effects on cell migration and proliferation. Despite its potential, the dental application of CAP remains underexplored. This in vitro study aims to elucidate the impact of CAP activated medium on human gingival fibroblast responses, for future wound healing strategies. The study was divided into four parts: initial characterization of the plasma Jet, assessment of cell concentration, exploration of treatment distance effects, and treatment time dynamics. Human gingival fibroblasts were exposed to complete DMEM medium (without sodium pyruvate) activated with CAP at treatment distances of 2, 5, 7, and 9 mm, and treatment times of 15, 60, 120, 180, and 300 s for 1, 2 and 3 d of culture. The cell viability was evaluated using resazurin-based method, while wound healing dynamics was assessed via the scratch assay technique using phase-contrast microscopy. The cell morphology was characterised through fluorescence microscopy using propidium iodide and phalloidin staining, complemented by scanning electron microscopy. The results revealed that treatment distances and exposure times can influence the cell behaviour depending on the cell concentration. For the selected concentration of 1 × 104 cells ml−1, a treatment distance of 9 mm appeared to enhance human gingival fibroblast viability compared to a treatment distance of 2 mm and the control group. The images revealed adherent cells with a pattern typical of fibroblasts. However, no differences were observed for exposure times of 15 s and 180 s. The observed results further evidence that the exposure of the medium to the CAP device promoted an increase in cell viability, proliferation, and attachment in human gingival fibroblasts.

Effects of Pressure, Hypoxia, and Hyperoxia on Neutrophil Granulocytes

Background: The application of normo- and hyperbaric O2 is a common therapy option in various disease patterns. Thereby, the applied O2 affects the whole body, including the blood and its components. This study investigates influences of pressure and oxygen fraction on human blood plasma, nutrient media, and the functions of neutrophil granulocytes (PMNs). Methods: Neutrophil migration, reactive oxygen species (ROS) production, and NETosis were examined by live cell imaging. The treatment of various matrices (Roswell Park Memorial Institute 1640 medium, Dulbecco’s Modified Eagle’s Medium, H2O, human plasma, and isolated PMNs) with hyperbaric oxygen (HBO) was performed. In addition, the expression of different neutrophil surface epitopes (CD11b, CD62L, CD66b) and the oxidative burst were investigated by flow cytometry (FACS). The application of cold atmospheric plasma (CAP) to normoxic and normobaric culture media served as a positive control. Soluble reaction products such as H2O2, reactive nitrogen species (RNS: NO2− and NO3−), and ROS-dependent dihydrorhodamine oxidation were quantified by fluoro- and colorimetric assay kits. Results: Under normobaric normoxia, PMNs migrate slower and shorter in comparison with normobaric hyper- or hypoxic conditions and hyperbaric hyperoxia. The pressure component has less effect on the migration behavior of PMNs than the O2 concentration. Individual PMN cells produce prolonged ROS at normoxic conditions. PMNs showed increased expression of CD11b in normobaric normoxia, lower expression of CD62L in normobaric normoxia, and lower expression of CD66b after HBO and CAP treatment. Treatment with CAP increased the amount of ROS and RNS in common culture media. Conclusions: Hyperbaric and normobaric O2 influences neutrophil functionality and surface epitopes in a measurable way, which may have an impact on disorders with neutrophil involvement. In the context of hyperbaric experiments, especially high amounts of H2O2 in RPMI after hyperbaric oxygen should be taken into account. Therefore, our data support a critical indication for the use of normobaric and hyperbaric oxygen and conscientious and careful handling of oxygen in everyday clinical practice.

Anticancer transmission effects induced by hybrid plasma bubble-activated medium

As an indirect application of cold atmospheric plasma, the use of plasma-activated solutions has recently attracted significant attention for intracavity tumor perfusion therapy. Here, an underwater plasma-bubble reactor with three discharge modes was applied to activate a cell culture medium, with the aim of inhibiting the growth of bladder cancer T24 cells in vitro. The results showed that although the reactive species in cell culture medium generated by the underwater bubble plasma varied between the dielectric barrier discharge (DBD) mode, spark mode, and hybrid mode, the plasma-activated cell culture medium (PAM) corresponding to all three discharge modes effectively decreased the viability of T24 cells. However, after co-culturing the PAM-pretreated T24 cells with normal T24 cells, it was observed that normal T24 cells were not affected by either the DBD or spark mode; however, the hybrid mode PAM-pretreated T24 cells further induced inactivation and apoptosis of normal T24 cells. Further studies suggested that the aqueous reactive species generated by the underwater bubble plasma in hybrid mode not only induced the apoptosis of T24 cells directly but also triggered PAM-pretreated T24 cell-derived exosome-mediated anticancer activity toward cancer cells. These results may provide a strategy for enhancing the anticancer extent and effect of PAM as well as advancing its clinical application.

On-demand release of silver from composite hydrogel by cold atmospheric plasma jet for wound infection control

Silver is an antimicrobial commonly used within wound care chiefly in advanced dressings or in a topical cream form, such as silver sulfadiazine (SSD). Although silver is effective at controlling the growth of many common wound bacteria, it can be cytotoxic and can build up in tissue, stalling the healing process. Here, we demonstrate the development of an on-demand release system for delivery of silver from a composite hydrogel comprising sodium polyacrylate particles dispersed in a cryo-crosslinked polyvinyl alcohol carrier gel. Application of cold atmospheric plasma (CAP) jet to the silver loaded hydrogel resulted in controlled release of silver. This release is thought to occur due to the formation of nitrous acids in the hydrogel by the CAP, resulting in protonation of carboxylate groups in the hydrogel and subsequent gel de-swelling due to the reduction in interchain charge repulsion. The location of silver within the sodium polyacrylate particles was probed using scanning electron microscopy and EDX imaging. The released silver inhibited the growth of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus and significantly reduced the viable cell count of the P. aeruginosa biofilm.

The extended transmission of cold atmospheric plasma-induced anticancer effects between cells

The application of cold atmospheric plasma (CAP) in cancer therapy has recently received extensive attention. However, researchers have mainly studied the effects of CAP on plasma-irradiated cancer cells and have not determined whether CAP affects surrounding or distant non-irradiated cancer cells. Here, the viability and intracellular reactive oxygen species levels of plasma-irradiated and non-irradiated cancer cells were monitored in vitro. Our results showed that CAP may induce plasma-irradiated cancer cells (A549 cells, A375 cells, J82 cells and HT29 cells) to secrete soluble factors into the cell culture medium, which can transmit plasma-induced anticancer effects from plasma-irradiated cancer cells to non-irradiated cancer cells. Our research confirmed that plasma-induced anticancer effects can be transmitted between cancer cells.

Potential Applications of Cold Atmospheric Plasma (CAP) Technologies to Improve the Phytochemical Content of Fresh Fruits and Vegetables.

Potential Applications of Cold Atmospheric Plasma (CAP) Technologies to Improve the Phytochemical Content of Fresh Fruits and Vegetables.

Application of Cold Atmospheric Plasma to Decrease Biological Contamination on Surfaces of Equipment and Furniture for Indoor Sports Facilities

Application of Cold Atmospheric Plasma to Decrease Biological Contamination on Surfaces of Equipment and Furniture for Indoor Sports Facilities

Low-Temperature Plasma Techniques in Biomedical Applications and Therapeutics: An Overview.

Plasma, the fourth fundamental state of matter, comprises charged species and electrons, and it is a fascinating medium that is spread over the entire visible universe. In addition to that, plasma can be generated artificially under appropriate laboratory techniques. Artificially generated thermal or hot plasma has applications in heavy and electronic industries; however, the non-thermal (cold atmospheric or low temperature) plasma finds its applications mainly in biomedicals and therapeutics. One of the important characteristics of LTP is that the constituent particles in the plasma stream can often maintain an overall temperature of nearly room temperature, even though the thermal parameters of the free electrons go up to 1 to 10 keV. The presence of reactive chemical species at ambient temperature and atmospheric pressure makes LTP a bio-tolerant tool in biomedical applications with many advantages over conventional techniques. This review presents some of the important biomedical applications of cold-atmospheric plasma (CAP) or low-temperature plasma (LTP) in modern medicine, showcasing its effect in antimicrobial therapy, cancer treatment, drug/gene delivery, tissue engineering, implant modifications, interaction with biomolecules, etc., and overviews some present challenges in the field of plasma medicine.

Applications of cold atmospheric plasma in immune-mediated inflammatory diseases via redox homeostasis: evidence and prospects

As a representative technology in plasma medicine, cold atmospheric plasma (CAP) has beneficial outcomes in surface disinfection, wound repair, tissue regeneration, solid tumor therapy. Impact on immune response and inflammatory conditions was also observed in the process of CAP treatment. Relevant literatures were collected to assess efficacy and summarize possible mechanisms of the innovation. CAP mediates alteration in local immune microenvironment mainly through two ways. One is to down-regulate the expression level of several cytokines, impeding further conduction of immune or inflammatory signals. Intervening the functional phenotype of cells through different degree of oxidative stress is the other approach to manage the immune-mediated inflammatory disorders. A series of preclinical and clinical studies confirmed the therapeutic effect and side effects free of CAP. Moreover, several suggestions proposed in this manuscript might help to find directions for future investigation.

Understanding the mechanisms of action of atmospheric cold plasma towards the mitigation of the stress induced in molds: The case of Aspergillus chevalieri

Aspergillus chevalieri is a xerophilic/xerotolerant fungi affecting dried food products. In this study the ability of non-thermal cold atmospheric plasma (CAP) at high power density (NOx) to affect biological process inducing the stress responses of A. chevalieri species exposed for 5 min (5’CAP-NOx) and 30 min (30’CAP-NOx) were analysed at 0, 1, 6, 12 and 48-h post treatment (hpt). At 48 hpt with 30’CAP-NOx, 84% of fungal growth reduction was observed. The membrane integrity estimated by confocal investigation after carboxyfluorescein diacetate/propidium iodide staining showed the dead surface mycelium layers exposed to the treatments. Reverse transcription-quantitative real-time PCR revealed an early downregulation, at 0 hpt, followed by upregulation or recovery starting to 1 hpt, of selected key genes involved in fungal stress responses. The cellular response to stress was confirmed by mycelial glutathione accumulation in the early phase after both CAP-NOx treatments, at 0 and 1 hpt, followed by the strong glutathione reduction at 12 and 48 hpt using 30’CAP-NOx treatment. The ability of A. chevalieri to modulate metabolic profile according to treatments was underlined by volatilome investigation, which mainly involved lipid metabolism. This work highlighted the adaptative response mechanisms of A. chevalieri to overcome the CAP-NOx treatment. Industrial relevanceThe application of cold atmospheric plasma (CAP) technology to avoid microbial growth in foods is considered of high interest. Utilization of CAP technology, a nonthermal technique, is encouraged because of its efficiency in maintaining natural aroma and flavor and product shelf-life. Regarding the management of Aspergillus chevalieri, the developments in mechanistic insights indicated that cold plasma affected several targets in fungal cells and was a successful tactic when employed to stop the selection of resistant fungal strains.

Effects of Nitro-Oxidative Stress on Biomolecules: Part 1-Non-Reactive Molecular Dynamics Simulations.

Plasma medicine, or the biomedical application of cold atmospheric plasma (CAP), is an expanding field within plasma research. CAP has demonstrated remarkable versatility in diverse biological applications, including cancer treatment, wound healing, microorganism inactivation, and skin disease therapy. However, the precise mechanisms underlying the effects of CAP remain incompletely understood. The therapeutic effects of CAP are largely attributed to the generation of reactive oxygen and nitrogen species (RONS), which play a crucial role in the biological responses induced by CAP. Specifically, RONS produced during CAP treatment have the ability to chemically modify cell membranes and membrane proteins, causing nitro-oxidative stress, thereby leading to changes in membrane permeability and disruption of cellular processes. To gain atomic-level insights into these interactions, non-reactive molecular dynamics (MD) simulations have emerged as a valuable tool. These simulations facilitate the examination of larger-scale system dynamics, including protein-protein and protein-membrane interactions. In this comprehensive review, we focus on the applications of non-reactive MD simulations in studying the effects of CAP on cellular components and interactions at the atomic level, providing a detailed overview of the potential of CAP in medicine. We also review the results of other MD studies that are not related to plasma medicine but explore the effects of nitro-oxidative stress on cellular components and are therefore important for a broader understanding of the underlying processes.

Application of cold atmospheric plasma for mold inactivation

Mold growth in indoor interiors is an increasing problem that has adverse effects on both occupants and building materials. The aim of this study was to present the new environmentally friendly method (cold atmospheric plasma treatment) for decontamination of indoor environments contaminated by mold spores, with the potential to become an effective replacement for conventional methods, such as ultraviolet-C (UV-C) germicidal irradiation. The spores of Aspergillus species on malt extract agar plates were exposed to plasma produced by diffuse coplanar surface barrier discharge. The surface coverage of mold was evaluated using image analysis. Cold plasma treatment inactivated spores on the surface of the culture medium in 0.5 min, whereas a weak growth delay was observed after 30 minute exposure to UV-C irradiation. This study demonstrated that cold atmospheric plasma is a more effective method for reducing mold spores on agar compared with germicidal UV-C irradiation.

The applications of cold atmospheric plasma in dentistry

AbstractCold atmospheric plasma (CAP), as a noninvasive technology, has shown promise in dentistry as it might successfully treat various oral conditions. The antimicrobial capacity of CAP has been proven and it is effective in reducing the main microorganisms responsible for oral infections. Furthermore, CAP has also been explored in the field of tissue regeneration with a great response from both soft and hard tissue. The surface modification ability of CAP is another area of interest, revealing a potential improvement in the osseointegration of dental implants. Additionally, there are other areas within dentistry that have studied the use of CAP, such as surface disinfection, bleaching, and cavity preparation.

Studies on plasma‐activated perilla seed oil: Diagnosis, optimisation, and validation of reactive species

AbstractRecently, the applications of cold atmospheric plasma (CAP) in liquid treatment have attracted increasing attention owing to its excellent medical efficacy. It has been proved that CAP can effectively enhance the biological activity of vegetable oils due to the generation of reactive species. Optimising the reactor parameter is an important approach to regulate reactive species in plasma‐activated oil to obtain better biological effects. In this study, a self‐made jet array driven by a pulsed power supply was used to generate large‐area plasma to irradiate perilla seed oil (PSO), with the formation of plasma‐activated perilla seed oil (PAPSO). By means of laser‐induced fluorescence and chemical titration, the relative density of hydroxyl radical radical in plasma jet, as well as the activity of PAPSO were measured under different discharge parameters, and realised the control of the activity of PAPSO. In vitro experiments showed that PAPSO significantly enhanced its ability to inhibit cancer cells proliferation and induce apoptosis after plasma treatment, which provides a reference for cancer treatment. This study is helpful to further understand the influence of plasma dose effect on the activity of media and provide guidance for related plasma medical applications.

Novel applications of Cold Atmospheric Plasma for the treatment of Plaque Psoriasis

Plasma is the fourth state of matter other than solid, liquid and gases. About 99 percent of mixture of free positive negative charges, neutral particles and photons. The plasma exists in two forms: hot plasma and cold plasma. Hot plasma is used in metallurgical operations while cold plasma is used in medical, skin psoriasis treatment, food agricultural, preservation and waste water treatment. Many clinical studies prove the effectiveness of cold plasma in dermatological disease management. Recent researches have established that combined use of cold plasma and nano-formulations is helpful in delivery of poorly water-soluble drugs. Plaque psoriasis is an autoimmune disorder in which silvery, thick, dead layer of skin shades off and cause inflammation, sometimes bleeding. It occurs in 3-4 percent of total world population. Scientific studies have proved that nano-scale particles permeate easily and interact with immune cells like lnterleukin-16, cytokines and TNF-alfa during inflammation and autoimmune disorders. As a result of which, thick layer of keratinocytes is produced and formation of TNF-alfa and interleukin is inhibited which are the causes of Plaque psoriasis. Since conventional medication has only been helpful in managing it, researches have been carried out using various techniques like phototherapy, use of UVA, UVB, IPL (Intense Pulsed Light), PDL (Pulsed Dye Light), LASER and low-level LASER light etc. but their excess exposure causes risk of skin cancer. Other therapies like use of nanometric Liposomes, Niosomes and their combination therapy are some novel clinical techniques for combating symptoms but are still in clinical trial. Since, Plasma therapy is non irritating and stops the triggering mechanism of inflammation, hence the use of nanotechnological topical formulation in combination with plasma therapy has the potential to become possible treatment of Plaque Psoriasis in future.

Reactive molecular dynamics simulations on interaction mechanisms of cold atmospheric plasmas and peptides

Plasma medicine is a rapidly growing multidisciplinary field, which mainly focuses on the application of Cold Atmospheric Plasma (CAP) in bioengineering. Several experiments have suggested that amino acids in proteins are excellent targets for plasma-derived chemical species. To gain a deep insight into the oxidative modification of proteins induced by CAP, a ReaxFF-based reactive Molecular Dynamics simulations are performed to investigate the reaction mechanism of Reactive Oxygen Species produced in CAP and the model peptides. The simulation results show that sulfur-containing amino acids with high reactivity could be oxidized to sulfuric acid moiety through sulfonation, and only H-abstraction reaction can take place for aromatic amino acids. The oxidation of five-membered ring amino acids could be observed by yielding the ring-open products in the simulations. Additionally, the dehydrogenation and hydroxylation of carbon-chain amino acids were also found from the simulations, with the formation of the hydroxyl group. The polar amino acids with the electron-rich structure were oxidized to a variety of products, such as di-hydroxylated lysine and hydroxylated asparagine. This study provides a crucial step to understand the processes of oxidative modifications and inactivation of proteins induced by CAP, showing a deep insight on the mechanism of plasma medicine.

The therapeutic perspective of cold atmospheric plasma in periodontal disease.

Periodontal disease (PD) is one of the most common infectious diseases with complex inflammatory conditions, having irreversibly destructive impacts on the periodontal supporting tissues. The application of cold atmospheric plasma (CAP) is a promising adjuvant therapy modality for PD. However, the mechanism of CAP in PD treatment is still poorly understood. The review motivates to outline the latest researches concerning the applications of CAP in PD treatment. We searched CAP-related literature through utilizing the well-established databases of Pubmed, Scopus and Web of Science according to the following keywords related to periodontal disease (periodontal, gingival, gingivitis, gingiva, periodontium, periodontitis). A total of 18 concerning original studies were found. These studies could be classified according to three pathophysiological perspectives of PD. The therapeutic mechanisms of CAP may be attributed to the oxidative stress-related cell death of periodontal bacteria, the suppression of periodontal inflammation and pro-inflammatory cytokine secretion, as well as the acceleration of periodontal soft tissue wound healing and hard tissue reconstruction. Cold atmospheric plasma has potential therapeutic effects on PD through three mechanisms: antimicrobial effect, inflammation attenuation, and tissue remodeling. This review hopefully provides a comprehensive perspective into the potential of CAP in PD therapy.

A Review of Cold Atmospheric Plasma Applications in Dermatology and Aesthetics

Nowadays, there is a growing use of plasma technology, especially in medicine and aesthetics. Plasma medicine is an innovative, multidisciplinary science combining plasma physics and technology with medicine and life sciences. Billions of dollars are spent annually in the United States to rejuvenate and reduce signs of aging. For this reason, several methods have been created to perform such operations. Methods with different degrees of invasiveness, from cosmetic surgery, like forehead lifts and blepharoplasty, to noninvasive, such as high-intensity focused ultrasound and nonablative lasers, have been used in the field of aesthetics and skin rejuvenation. Plasma can also be used as a noninvasive, minimally invasive, or even invasive method in cosmetic applications such as removing wrinkles and strengthening the skin, that can somewhat replace cosmetic procedures such as blepharoplasty and rhytidectomy. By using various active species, plasma affects biological activities and increases the proliferation and transfer of skin cells. With local application of heat and an increase in proliferation and activity of fibroblasts, the production of type III collagen and elastin density in the skin increases. Plasma can be used to sublimate the skin and remove excess tissue. This article summarizes the most recent studies and clinical trials in dermatology and skin rejuvenation, in which different cold plasma sources (jet and spark) have been used, and examines their results.

Open Questions in Cold Atmospheric Plasma Treatment in Head and Neck Cancer: A Systematic Review.

Over the past decade, we witnessed a promising application of cold atmospheric plasma (CAP) in cancer therapy. The aim of this systematic review was to provide an exhaustive state of the art of CAP employed for the treatment of head and neck cancer (HNC), a tumor whose late diagnosis, local recurrence, distant metastases, and treatment failure are the main causes of patients’ death. Specifically, the characteristics and settings of the CAP devices and the in vitro and in vivo treatment protocols were summarized to meet the urgent need for standardization. Its molecular mechanisms of action, as well as the successes and pitfalls of current CAP applications in HNC, were discussed. Finally, the interesting emerging preclinical hypotheses that warrant further clinical investigation have risen. A total of 24 studies were included. Most studies used a plasma jet device (54.2%). Argon resulted as the mostly employed working gas (33.32%). Direct and indirect plasma application was reported in 87.5% and 20.8% of studies, respectively. In vitro investigations were 79.17%, most of them concerned with direct treatment (78.94%). Only eight (33.32%) in vivo studies were found; three were conducted in mice, and five on human beings. CAP showed pro-apoptotic effects more efficiently in tumor cells than in normal cells by altering redox balance in a way that oxidative distress leads to cell death. In preclinical studies, it exhibited efficacy and tolerability. Results from this systematic review pointed out the current limitations of translational application of CAP in the urge of standardization of the current protocols while highlighting promising effects as supporting treatment in HNC.

Cold Plasma Irradiation Attenuates Atopic Dermatitis via Enhancing HIF-1α-Induced MANF Transcription Expression.

Cold atmospheric plasma has been widely applied in medical treatment clinically, especially skin diseases. However, the mechanism of cold atmospheric plasma on the treatment of skin diseases is still undefined. In this study, dinitrofluorobenzene-induced atopic dermatitis mice model was constructed. Cold atmospheric plasma was able to decrease skin cells apoptosis, relieve skin inflammation, ER stress and oxidative stress caused by dinitrofluorobenzene stimulation, which was mediated by cold atmospheric plasma-induced MANF expression. In terms of mechanism, hypoxia-inducible factor-1α expression was increased intracellularly after cold atmospheric plasma treatment, which further bound to the promoter region of manf gene and enhanced MANF transcriptional expression. This study reveals that cold atmospheric plasma has a positive effect on atopic dermatitis treatment, also demonstrates the regulatory mechanism of cold atmospheric plasma on MANF expression via HIF-1α, which indicates the potential medical application of cold atmospheric plasma for atopic dermatitis treatment.