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Plasma Applications in Biomedicine

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 16714

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Prof. Dr. Christoph Viktor Suschek

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Department for Orthopedics and Trauma Surgery, Medical Faculty, Heinrich-Heine-University Dusseldorf, Düsseldorf, Germany
Interests: plasma medicine; cold atmospheric plasma; plasma activated liquid; nitric oxide; reactive oxygen species

Special Issue Information

Dear Colleagues,

Plasma medicine is a multidisciplinary research area focused on studying the interaction of cold atmospheric plasmas (CAPs) with biological cells and tissues, but more recently also investigating the therapeutic effects of plasma-activated liquids (PALs). It is a new, innovative research field at the interface between physics and life sciences and has gained significant international attention in recent years.

The current main area of application for CAPs and PALs is the treatment of chronic, infected wounds by stimulating tissue regeneration and pathogen-related skin diseases. CAPs and PALs can be used to inactivate many types of microorganisms including multi-resistant bacteria such as MRSA. The latest research results indicate a possible inactivation of tumor cells. However, many of the mechanisms by which plasma affects cells and tissues are still not well understood.

For this Special Issue, “Plasma Applications in Biomedicine”, researchers from all areas of plasma medicine are invited to submit their latest results. The Special Issue focuses primarily on basic scientific and application-related work. In particular, research articles, including reviews and experimental studies as well as clinical studies, in all medical fields such as wound treatment, cancer treatment, dermatology and dentistry are welcome. Moreover, in vitro studies on microorganisms and mammalian cells and tissues that investigate the biological effects of CAPs and PALs with regard to specific aspects are also welcome.

Prof. Dr. Christoph Viktor Suschek
Guest Editor

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Keywords

CAP
PAL
plasma biomedicine
microorganism
mammalian cells
mammalian tissue
tumor cells
reactive oxygen/nitrogen species

Published Papers (12 papers)

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Editorial

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4 pages, 175 KiB

Open AccessEditorial

Plasma Applications in Biomedicine: A Groundbreaking Intersection between Physics and Life Sciences

by Christoph V. Suschek

Biomedicines 2024, 12(5), 1029; https://doi.org/10.3390/biomedicines12051029 - 7 May 2024

Viewed by 390

Abstract

Plasma applications in biomedicine represent a groundbreaking intersection between physics and life sciences, unveiling novel approaches to disease treatment and tissue regeneration [...] Full article

(This article belongs to the Special Issue Plasma Applications in Biomedicine)

Research

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12 pages, 11697 KiB

Open AccessArticle

Cold Atmospheric Plasma Improves the Colonization of Titanium with Primary Human Osteoblasts: An In Vitro Study

by Madline P. Gund, Jusef Naim, Antje Lehmann, Matthias Hannig, Markus Lange, Axel Schindler and Stefan Rupf

Biomedicines 2024, 12(3), 673; https://doi.org/10.3390/biomedicines12030673 - 18 Mar 2024

Viewed by 785

Abstract

Several studies have shown that cold atmospheric plasma (CAP) treatment can favourably modify titanium surfaces to promote osteoblast colonization. The aim of this study was to investigate the initial attachment of primary human osteoblasts to plasma-treated titanium. Micro-structured titanium discs were treated with cold atmospheric plasma followed by the application of primary human osteoblasts. The microwave plasma source used in this study uses helium as a carrier gas and was developed at the Leibniz Institute for Surface Modification in Leipzig, Germany. Primary human osteoblasts were analyzed by fluorescence and cell biological tests (alkaline phosphatase activity and cell proliferation using WST-1 assay). The tests were performed after 4, 12, and 24 h and showed statistically significant increased levels of cell activity after plasma treatment. The results of this study indicate that plasma treatment improves the initial attachment of primary human osteoblasts to titanium. For the first time, the positive effect of cold atmospheric plasma treatment of micro-structured titanium on the initial colonization with primary human osteoblasts has been demonstrated. Overall, this study demonstrates the excellent biocompatibility of micro-structured titanium. The results of this study support efforts to use cold atmospheric plasmas in implantology, both for preimplantation conditioning and for regeneration of lost attachment due to peri-implantitis. Full article

(This article belongs to the Special Issue Plasma Applications in Biomedicine)

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16 pages, 11693 KiB

Open AccessArticle

Evaluating the Healing Potential of J-Plasma Scalpel-Created Surgical Incisions in Porcine and Rat Models

by Lilith Elmore, Nicholas J. Minissale, Lauren Israel, Zoe Katz, Jordan Safran, Adriana Barba, Luke Austin, Thomas P. Schaer and Theresa A. Freeman

Biomedicines 2024, 12(2), 277; https://doi.org/10.3390/biomedicines12020277 - 25 Jan 2024

Cited by 1 | Viewed by 1081

Abstract

Cold atmospheric plasma devices generate reactive oxygen and nitrogen species that can be anti-microbial but also promote cell migration, differentiation, and tissue wound healing. This report investigates the healing of surgical incisions created using cold plasma generated by the J-Plasma scalpel (Precise Open handpiece, Apyx Medical, Inc.) compared to a steel scalpel in in vivo porcine and rat models. The J-Plasma scalpel is currently FDA approved for the delivery of helium plasma to cut, coagulate, and ablate soft tissue during surgical procedures. To our knowledge, this device has not been studied in creating surgical incisions but only during deeper dissection and hemostasis. External macroscopic and histologic grading by blinded reviewers revealed no significant difference in wound healing appearance or physiology in incisions created using the plasma scalpel as compared with a steel blade scalpel. Incisions created with the plasma scalpel also had superior hemostasis and a reduction in tissue and blood carryover. Scanning electron microscopy (SEM) and histology showed collagen fibril fusion occurred as the plasma scalpel incised through the tissue, contributing to a sealing effect. In addition, when bacteria were injected into the dermis before incision, the plasma scalpel disrupted the bacterial membrane as visualized in SEM images. External macroscopic and histologic grading by blinded reviewers revealed no significant difference in wound healing appearance or physiology. Based on these results, we propose additional studies to clinically evaluate the use of cold plasma in applications requiring hemostasis or when an increased likelihood of subdermal pathogen leakage could cause surgical site infection (i.e., sites with increased hair follicles). Full article

(This article belongs to the Special Issue Plasma Applications in Biomedicine)

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13 pages, 2170 KiB

Open AccessArticle

Analyses of the Chemical Composition of Plasma-Activated Water and Its Potential Applications for Vaginal Health

by Hyun-Jin Kim, Hyun-A Shin, Woo-Kyung Chung, Ae-Son Om, Areum Jeon, Eun-Kyung Kang, Wen An and Ju-Seop Kang

Biomedicines 2023, 11(12), 3121; https://doi.org/10.3390/biomedicines11123121 - 23 Nov 2023

Cited by 1 | Viewed by 889

Abstract

This study aimed to elucidate the unique chemical compositions of plasma-activated water (PAW) and the potential antibacterial efficacy of PAW as a novel vaginal cleanser. We analyzed the ion compositions (four anions: F⁻, Cl⁻, NO₃⁻, SO₄²⁻; five cations: Na⁺, NH₄⁺, K⁺, Mg²⁺, Ca²⁺) of several formulations of PAW generated at different electrical powers (12 and 24 V) at various treatment time points (1, 10, and 20 min), and stay durations (immediate, 30, and 60 min). As treatment duration increased, hypochlorous acid (HOCl), Ca²⁺, and Mg²⁺ concentrations increased and Cl⁻ concentration decreased. Higher electrical power and longer treatment duration resulted in increased HOCl levels, which acts to prevent the growth of general microorganisms. Notably, PAW had no antibacterial effects against the probiotic, Lactobacillus reuteri, which produces lactic acid and is important for vaginal health. These findings indicate that PAW contains HOCl and some cations (Ca²⁺ and Mg²⁺), which should help protect against pathogens of the vaginal mucosa and have a cleansing effect within the vaginal environment while not harming beneficial bacteria. Full article

(This article belongs to the Special Issue Plasma Applications in Biomedicine)

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11 pages, 2697 KiB

Open AccessArticle

Synergistic Antimicrobial Effect of Cold Atmospheric Plasma and Redox-Active Nanoparticles

by Artem M. Ermakov, Vera A. Afanasyeva, Alexander V. Lazukin, Yuri M. Shlyapnikov, Elizaveta S. Zhdanova, Anastasia A. Kolotova, Artem S. Blagodatski, Olga N. Ermakova, Nikita N. Chukavin, Vladimir K. Ivanov and Anton L. Popov

Biomedicines 2023, 11(10), 2780; https://doi.org/10.3390/biomedicines11102780 - 13 Oct 2023

Cited by 2 | Viewed by 1151

Abstract

Cold argon plasma (CAP) and metal oxide nanoparticles are well known antimicrobial agents. In the current study, on an example of Escherichia coli, a series of analyses was performed to assess the antibacterial action of the combination of these agents and to evaluate the possibility of using cerium oxide and cerium fluoride nanoparticles for a combined treatment of bacterial diseases. The joint effect of the combination of cold argon plasma and several metal oxide and fluoride nanoparticles (CeO₂, CeF₃, WO₃) was investigated on a model of E. coli colony growth on agar plates. The mutagenic effect of different CAP and nanoparticle combinations on bacterial DNA was investigated, by means of a blue–white colony assay and RAPD-PCR. The effect on cell wall damage, using atomic force microscopy, was also studied. The results obtained demonstrate that the combination of CAP and redox-active metal oxide nanoparticles (RAMON) effectively inhibits bacterial growth, providing a synergistic antimicrobial effect exceeding that of any of the agents alone. The combination of CAP and CeF₃ was shown to be the most effective mutagen against plasmid DNA, and the combination of CAP and WO₃ was the most effective against bacterial genomic DNA. The analysis of direct cell wall damage by atomic force microscopy showed the combination of CAP and CeF₃ to be the most effective antimicrobial agent. The combination of CAP and redox-active metal oxide or metal fluoride nanoparticles has a strong synergistic antimicrobial effect on bacterial growth, resulting in plasmid and genomic DNA damage and cell wall damage. For the first time, a strong antimicrobial and DNA-damaging effect of CeF₃ nanoparticles has been demonstrated. Full article

(This article belongs to the Special Issue Plasma Applications in Biomedicine)

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16 pages, 2682 KiB

Open AccessArticle

Gas Flow-Dependent Modification of Plasma Chemistry in μAPP Jet-Generated Cold Atmospheric Plasma and Its Impact on Human Skin Fibroblasts

by Dennis Feibel, Judith Golda, Julian Held, Peter Awakowicz, Volker Schulz-von der Gathen, Christoph V. Suschek, Christian Opländer and Florian Jansen

Biomedicines 2023, 11(5), 1242; https://doi.org/10.3390/biomedicines11051242 - 22 Apr 2023

Cited by 4 | Viewed by 1907

Abstract

The micro-scaled Atmospheric Pressure Plasma Jet (µAPPJ) is operated with low carrier gas flows (0.25–1.4 slm), preventing excessive dehydration and osmotic effects in the exposed area. A higher yield of reactive oxygen or nitrogen species (ROS or RNS) in the µAAPJ-generated plasmas (CAP) was achieved, due to atmospheric impurities in the working gas. With CAPs generated at different gas flows, we characterized their impact on physical/chemical changes of buffers and on biological parameters of human skin fibroblasts (hsFB). CAP treatments of buffer at 0.25 slm led to increased concentrations of nitrate (~352 µM), hydrogen peroxide (H₂O₂; ~124 µM) and nitrite (~161 µM). With 1.40 slm, significantly lower concentrations of nitrate (~10 µM) and nitrite (~44 µM) but a strongly increased H₂O₂ concentration (~1265 µM) was achieved. CAP-induced toxicity of hsFB cultures correlated with the accumulated H₂O₂ concentrations (20% at 0.25 slm vs. ~49% at 1.40 slm). Adverse biological consequences of CAP exposure could be reversed by exogenously applied catalase. Due to the possibility of being able to influence the plasma chemistry solely by modulating the gas flow, the therapeutic use of the µAPPJ represents an interesting option for clinical use. Full article

(This article belongs to the Special Issue Plasma Applications in Biomedicine)

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13 pages, 1835 KiB

Open AccessArticle

Can Cold Atmospheric Plasma Be Used for Infection Control in Burns? A Preclinical Evaluation

by Mahsa Bagheri, Maria von Kohout, Andreas Zoric, Paul C. Fuchs, Jennifer L. Schiefer and Christian Opländer

Biomedicines 2023, 11(5), 1239; https://doi.org/10.3390/biomedicines11051239 - 22 Apr 2023

Cited by 3 | Viewed by 1567

Abstract

Wound infection with Pseudomonas aeruginosa (PA) is a serious complication and is responsible for higher rates of mortality in burn patients. Because of the resistance of PA to many antibiotics and antiseptics, an effective treatment is difficult. As a possible alternative, cold atmospheric plasma (CAP) can be considered for treatment, as antibacterial effects are known from some types of CAP. Hence, we preclinically tested the CAP device PlasmaOne and found that CAP was effective against PA in various test systems. CAP induced an accumulation of nitrite, nitrate, and hydrogen peroxide, combined with a decrease in pH in agar and solutions, which could be responsible for the antibacterial effects. In an ex vivo contamination wound model using human skin, a reduction in microbial load of about 1 log₁₀ level was observed after 5 min of CAP treatment as well as an inhibition of biofilm formation. However, the efficacy of CAP was significantly lower when compared with commonly used antibacterial wound irrigation solutions. Nevertheless, a clinical use of CAP in the treatment of burn wounds is conceivable on account of the potential resistance of PA to common wound irrigation solutions and the possible wound healing-promoting effects of CAP. Full article

(This article belongs to the Special Issue Plasma Applications in Biomedicine)

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14 pages, 5476 KiB

Open AccessArticle

Effects of Cold Atmospheric Plasma Pre-Treatment of Titanium on the Biological Activity of Primary Human Gingival Fibroblasts

by Madline P. Gund, Jusef Naim, Antje Lehmann, Matthias Hannig, Constanze Linsenmann, Axel Schindler and Stefan Rupf

Biomedicines 2023, 11(4), 1185; https://doi.org/10.3390/biomedicines11041185 - 16 Apr 2023

Cited by 2 | Viewed by 1382

Abstract

Cold atmospheric plasma treatment (CAP) enables the contactless modification of titanium. This study aimed to investigate the attachment of primary human gingival fibroblasts on titanium. Machined and microstructured titanium discs were exposed to cold atmospheric plasma, followed by the application of primary human gingival fibroblasts onto the disc. The fibroblast cultures were analyzed by fluorescence, scanning electron microscopy and cell-biological tests. The treated titanium displayed a more homogeneous and denser fibroblast coverage, while its biological behavior was not altered. This study demonstrated for the first time the beneficial effect of CAP treatment on the initial attachment of primary human gingival fibroblasts on titanium. The results support the application of CAP in the context of pre-implantation conditioning, as well as of peri-implant disease treatment. Full article

(This article belongs to the Special Issue Plasma Applications in Biomedicine)

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15 pages, 5081 KiB

Open AccessArticle

Selective Effects of Cold Atmospheric Plasma on Bone Sarcoma Cells and Human Osteoblasts

by Andreas Nitsch, Konrad F. Sieb, Sara Qarqash, Janosch Schoon, Axel Ekkernkamp, Georgi I. Wassilew, Maya Niethard and Lyubomir Haralambiev

Biomedicines 2023, 11(2), 601; https://doi.org/10.3390/biomedicines11020601 - 17 Feb 2023

Cited by 2 | Viewed by 1560

Abstract

Background: The use of cold atmospheric plasma (CAP) in oncology has been intensively investigated over the past 15 years as it inhibits the growth of many tumor cells. It is known that reactive oxidative species (ROS) produced in CAP are responsible for this effect. However, to translate the use of CAP into medical practice, it is essential to know how CAP treatment affects non-malignant cells. Thus, the current in vitro study deals with the effect of CAP on human bone cancer cells and human osteoblasts. Here, identical CAP treatment regimens were applied to the malignant and non-malignant bone cells and their impact was compared. Methods: Two different human bone cancer cell types, U2-OS (osteosarcoma) and A673 (Ewing’s sarcoma), and non-malignant primary osteoblasts (HOB) were used. The CAP treatment was performed with the clinically approved kINPen MED. After CAP treatment, growth kinetics and a viability assay were performed. For detecting apoptosis, a caspase-3/7 assay and a TUNEL assay were used. Accumulated ROS was measured in cell culture medium and intracellular. To investigate the influence of CAP on cell motility, a scratch assay was carried out. Results: The CAP treatment showed strong inhibition of cell growth and viability in bone cancer cells. Apoptotic processes were enhanced in the malignant cells. Osteoblasts showed a higher potential for ROS resistance in comparison to malignant cells. There was no difference in cell motility between benign and malignant cells following CAP treatment. Conclusions: Osteoblasts show better tolerance to CAP treatment, indicated by less affected viability compared to CAP-treated bone cancer cells. This points toward the selective effect of CAP on sarcoma cells and represents a further step toward the clinical application of CAP. Full article

(This article belongs to the Special Issue Plasma Applications in Biomedicine)

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19 pages, 2277 KiB

Open AccessArticle

Enrichment of Bone Tissue with Antibacterially Effective Amounts of Nitric Oxide Derivatives by Treatment with Dielectric Barrier Discharge Plasmas Optimized for Nitrogen Oxide Chemistry

by Dennis Feibel, Alexander Kwiatkowski, Christian Opländer, Gerrit Grieb, Joachim Windolf and Christoph V. Suschek

Biomedicines 2023, 11(2), 244; https://doi.org/10.3390/biomedicines11020244 - 17 Jan 2023

Cited by 2 | Viewed by 1178

Abstract

Cold atmospheric plasmas (CAPs) generated by dielectric barrier discharge (DBD), particularly those containing higher amounts of nitric oxide (NO) or NO derivates (NOD), are attracting increasing interest in medical fields. In the present study, we, for the first time, evaluated DBD-CAP-induced NOD accumulation and therapeutically relevant NO release in calcified bone tissue. This knowledge is of great importance for the development of new therapies against bacterial-infectious complications during bone healing, such as osteitis or osteomyelitis. We found that by modulating the power dissipation in the discharge, it is possible (1) to significantly increase the uptake of NODs in bone tissue, even into deeper regions, (2) to significantly decrease the pH in CAP-exposed bone tissue, (3) to induce a long-lasting and modulable NO production in the bone samples as well as (4) to significantly protect the treated bone tissue against bacterial contaminations, and to induce a strong bactericidal effect in bacterially infected bone samples. Our results strongly suggest that the current DBD technology opens up effective NO-based therapy options in the treatment of local bacterial infections of the bone tissue through the possibility of a targeted modulation of the NOD content in the generated CAPs. Full article

(This article belongs to the Special Issue Plasma Applications in Biomedicine)

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11 pages, 1517 KiB

Open AccessArticle

Healing of Recurrent Aphthous Stomatitis by Non-Thermal Plasma: Pilot Study

by Norma Guadalupe Ibáñez-Mancera, Régulo López-Callejas, Víctor Hugo Toral-Rizo, Benjamín Gonzalo Rodríguez-Méndez, Edith Lara-Carrillo, Rosendo Peña-Eguiluz, Regiane Cristina do Amaral, Antonio Mercado-Cabrera and Raúl Valencia-Alvarado

Biomedicines 2023, 11(1), 167; https://doi.org/10.3390/biomedicines11010167 - 9 Jan 2023

Cited by 4 | Viewed by 1783

Abstract

Recurrent aphthous stomatitis (RAS) is a common disease in the oral cavity characterized by recurrent ulcers (RU). Usually, these cause acute pain without definitive treatment. The present study determines the efficacy of non-thermal plasma (NTP) for treating RU. NTP is applied to the patient’s RU using a radiofrequency generator connected to a point reactor. The power density applied to the ulcer is 0.50 W/cm², less than 4 W/cm², which is the maximum value without biological risk. Each patient received two treatments of three minutes each and spaced 60 min apart at a distance of 5 mm from the RU. From a sample of 30 ulcers in patients treated for RU with an average age of 37 years, they stated that the pain decreased considerably and without the need for ingestion of analgesics and antibiotics. Regeneration took place in an average of three days. The NTP proved to be an excellent therapeutic alternative for the treatment of RU since it has a rapid effect of reducing pain and inflammation, as well as adequate tissue regeneration. Full article

(This article belongs to the Special Issue Plasma Applications in Biomedicine)

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Review

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13 pages, 298 KiB

Open AccessReview

Non-Thermal Atmospheric Pressure Plasma Application in Endodontics

by Ana Bessa Muniz, Mariana Raquel da Cruz Vegian, Lady Daiane Pereira Leite, Diego Morais da Silva, Noala Vicensoto Moreira Milhan, Konstantin Georgiev Kostov and Cristiane Yumi Koga-Ito

Biomedicines 2023, 11(5), 1401; https://doi.org/10.3390/biomedicines11051401 - 9 May 2023

Cited by 1 | Viewed by 1814

Abstract

The failure of endodontic treatment is frequently associated with the presence of remaining microorganisms, mainly due to the difficulty of eliminating the biofilm and the limitation of conventional irrigation solutions. Non-thermal atmospheric pressure plasma (NTPP) has been suggested for many applications in the medical field and can be applied directly to biological surfaces or indirectly through activated liquids. This literature review aims to evaluate the potential of NTPP application in Endodontics. A search in the databases Lilacs, Pubmed, and Ebsco was performed. Seventeen manuscripts published between 2007 and 2022 that followed our established inclusion criteria were found. The selected manuscripts evaluated the use of NTPP regarding its antimicrobial activity, in the direct exposure and indirect method, i.e., plasma-activated liquid. Of these, 15 used direct exposure. Different parameters, such as working gas and distance from the apparatus to the substrate, were evaluated in vitro and ex vivo. NTPP showed a disinfection property against important endodontic microorganisms, mainly Enterococcus faecalis and Candida albicans. The antimicrobial potential was dependent on plasma exposure time, with the highest antimicrobial effects over eight minutes of exposure. Interestingly, the association of NTPP and conventional antimicrobial solutions, in general, was shown to be more effective than both treatments separately. This association showed antimicrobial results with a short plasma exposure time, what could be interesting in clinical practice. However, considering the lack of standardization of the direct exposure parameters and few studies about plasma-activated liquids, more studies in the area for endodontic purposes are still required. Full article

(This article belongs to the Special Issue Plasma Applications in Biomedicine)

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