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A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: closed (31 July 2019) | Viewed by 54385

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Prof. Dr. Emilio Martines

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Department of Physics "G. Occhialini", University of Milano-Bicocca, 20126 Milan, Italy
Interests: plasma medicine; nuclear fusion; low temperature plasmas; plasma physics; plasma technology
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Special Issue Information

Dear Colleagues,

I invite you to contribute to a Special Issue of the journal Applied Sciences, “Plasma Technology for Biomedical Applications”, which aims to present recent developments in the field of the use of ionized gases in biology and medicine.

The use of plasmas for biomedical applications in encountering a growing interest, especially in the framework of so-called “plasma medicine”, which aims at exploiting the action of low-power, atmospheric pressure plasmas for therapeutic purposes. Several applications have already reached the stage of clinical trials, while others are on their way, a large set of different plasma sources able to work at atmospheric pressure with low dissipated power have been created, and some of them are already certified as medical devices. From the scientific viewpoint, action mechanisms for the interaction of plasmas with cells, tissues and pathogens are being elucidated, although this is a slower process which still requires great efforts. Furthermore, the indirect action through the use of plasma-treated liquids is also being explored, presenting promising possibilities. The use of plasmas for proper functionalization of materials to be used in medical practice is also a field where constant advances are being made. Finally, one should mention the possibility of plasma-cell interactions not directly related to a therapeutic action of the plasma, but of great importance for facilitating other therapeutic approaches, such as plasma-mediated gene transfection and drug penetration.

I thus invite you to submit your research on these topics, in the form of original research papers, mini-reviews and perspective articles.

Dr. Emilio Martines

Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Applied Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

plasma medicine
biomedical plasma applications
plasma sources for biomedical applications
plasma disinfection
plasma in cancer treatment
plasma-stimulated wound healing
plasma sterilization
plasma activated water
plasma activated medium

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Published Papers (12 papers)

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Editorial

Jump to: Research, Review

6 pages, 183 KiB

Open AccessEditorial

Special Issue “Plasma Technology for Biomedical Applications”

by Emilio Martines

Appl. Sci. 2020, 10(4), 1524; https://doi.org/10.3390/app10041524 - 24 Feb 2020

Cited by 6 | Viewed by 2868

Abstract

(This article belongs to the Special Issue Plasma Technology for Biomedical Applications)

Research

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11 pages, 10504 KiB

Open AccessArticle

The Role of Thermal Effects in Plasma Medical Applications: Biological and Calorimetric Analysis

by Luigi Cordaro, Gianluca De Masi, Alessandro Fassina, Clarice Gareri, Antonio Pimazzoni, Daniele Desideri, Ciro Indolfi and Emilio Martines

Appl. Sci. 2019, 9(24), 5560; https://doi.org/10.3390/app9245560 - 17 Dec 2019

Cited by 14 | Viewed by 2950

Abstract

Plasma Medicine tools exploit the therapeutic effects of the exposure of living matter to plasma produced at atmospheric pressure. Since these plasmas are usually characterized by a non-thermal equilibrium (highly energetic electrons, low temperature ions), thermal effects on the substrate are usually considered negligible. Conversely, reactive oxygen and nitrogen species (RONS), UV radiation and metastables are thought to play a major role. In this contribution, we compare the presence of thermal effects in different operational regimes (corresponding to different power levels) of the Plasma Coagulation Controller (PCC), a plasma source specifically designed for accelerating blood coagulation. In particular, we analyze the application of PCC on human blood samples (in vitro) and male Wistar rats tissues (in vivo). Histological analysis points out, for the highest applied power regime, the onset of detrimental thermal effects such as red cell lysis in blood samples and tissues damages in in-vivo experiments. Calorimetric bench tests performed on metallic targets show that the current coupled by the plasma on the substrate induces most of measured thermal loads through a resistive coupling. Furthermore, the distance between the PCC nozzle and the target is found to strongly affect the total power. Full article

(This article belongs to the Special Issue Plasma Technology for Biomedical Applications)

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15 pages, 2334 KiB

Open AccessFeature PaperArticle

Interaction of Cold Atmospheric Argon and Helium Plasma Jets with Bio-Target with Grounded Substrate Beneath

by Irina Schweigert, Dmitry Zakrevsky, Pavel Gugin, Elena Yelak, Ekaterina Golubitskaya, Olga Troitskaya and Olga Koval

Appl. Sci. 2019, 9(21), 4528; https://doi.org/10.3390/app9214528 - 25 Oct 2019

Cited by 40 | Viewed by 5669

Abstract

The cold atmospheric pressure plasma jet interaction with the bio-target is studied in the plasma experiment, 2D fluid model simulations, and with MTT and iCELLigence assays of the viability of cancer cells. It is shown, for the first time, that the use of the grounded substrate under the media with cells considerably amplifies the effect of plasma cancer cell treatment in vitro. Plasma devices with cylindrical and plane geometries generating cold atmospheric plasma jets are developed and tested. The sequence of the streamers which forms the plasma jet is initiated with a voltage of 2.5–6.5 kV applied with the frequency 40 kHz. We suggest using the grounded substrate under the bio-target during the plasma jet treatment of cancer cells. The analysis of the measured plasma spectra and comparison of OH-line intensity for different voltages and gas flow rates allows us to find a range of optimal plasma parameters for the enhanced OH generation. The time-dependent viability is measured for human cell lines, A431 (skin carcinoma), HEK 293 (kidney embryonic cells), and A549 (human lung adenocarcinoma cells) after the plasma jet treatment. The results with cell-based experiments (direct treatment) performed with various plasma jet parameters confirm the maximum efficiency of the treatment with the optimal plasma parameters. Full article

(This article belongs to the Special Issue Plasma Technology for Biomedical Applications)

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17 pages, 4449 KiB

Open AccessArticle

Direct Treatment of Liquids Using Low-Current Arc in Ambient Air for Biomedical Applications

by Vladislav Gamaleev, Naoyuki Iwata, Masaru Hori, Mineo Hiramatsu and Masafumi Ito

Appl. Sci. 2019, 9(17), 3505; https://doi.org/10.3390/app9173505 - 26 Aug 2019

Cited by 15 | Viewed by 4771

Abstract

In this work, we developed a portable device with low production and operation costs for generating an ambient air low-current arc (AALCA) that is transferred to the surface of a treated liquid. It was possible to generate a stable discharge, irrespective of the conductivity of the treated liquid, as a sequence of corona, repeating spark, and low-current arc discharges. The estimated concentration of reactive oxygen and nitrogen species (RONS) in plasma-treated water (PTW) produced using AALCA treatment was two orders of magnitude higher than that of PTW produced using conventional He nonequilibrium atmospheric pressure plasma jets or dielectric barrier discharges. The strong bactericidal effect of the treatment using AALCA and the water treated using AALCA was confirmed by survival tests of Escherichia coli. Further, the possibility of treating a continuous flow of liquid using AALCA was demonstrated. Full article

(This article belongs to the Special Issue Plasma Technology for Biomedical Applications)

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16 pages, 12723 KiB

Open AccessArticle

Modulation of Metamorphic and Regenerative Events by Cold Atmospheric Pressure Plasma Exposure in Tadpoles, Xenopus laevis

by Ma Veronica Holganza, Adonis Rivie, Kevin Martus and Jaishri Menon

Appl. Sci. 2019, 9(14), 2860; https://doi.org/10.3390/app9142860 - 18 Jul 2019

Cited by 1 | Viewed by 3167

Abstract

Atmospheric pressure plasma has found wide clinical applications including wound healing, tissue regeneration, sterilization, and cancer treatment. Here, we have investigated its effect on developmental processes like metamorphosis and tail regeneration in tadpoles. Plasma exposure hastens the process of tail regeneration but delays metamorphic development. The observed differences in these two developmental processes following plasma exposure are indicative of physiological costs associated with developmental plasticity for their survival. Ultrastructural changes in epidermis and mitochondria in response to the stress of tail amputation and plasma exposure show characteristics of cellular hypoxia and oxidative stress. Mitochondria show morphological changes such as swelling with wide and fewer cristae and seem to undergo processes such as fission and fusion. Complex interactions between calcium, peroxisomes, mitochondria and their pore transition pathways are responsible for changes in mitochondrial structure and function, suggesting the subcellular site of action of plasma in this system. Full article

(This article belongs to the Special Issue Plasma Technology for Biomedical Applications)

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12 pages, 1933 KiB

Open AccessFeature PaperArticle

Plasma-Activation of Larger Liquid Volumes by an Inductively-Limited Discharge for Antimicrobial Purposes

by Michael Schmidt, Veronika Hahn, Beke Altrock, Torsten Gerling, Ioana Cristina Gerber, Klaus-Dieter Weltmann and Thomas von Woedtke

Appl. Sci. 2019, 9(10), 2150; https://doi.org/10.3390/app9102150 - 27 May 2019

Cited by 37 | Viewed by 4286

Abstract

A new configuration of a discharge chamber and power source for the treatment of up to 1 L of liquid is presented. A leakage transformer, energizing two metal electrodes positioned above the liquid, limits the discharge current inductively by utilizing the weak magnetic coupling between the primary and secondary coils. No additional means to avoid arcing (electric short-circuiting), e.g., dielectric barriers or resistors, are needed. By using this technique, exceeding the breakdown voltage leads to the formation of transient spark discharges, producing non-thermal plasma (NTP). These discharges effected significant changes in the properties of the treated liquids (distilled water, physiological saline solution, and tap water). Considerable concentrations of nitrite and nitrate were detected after the plasma treatment. Furthermore, all tested liquids gained strong antibacterial efficacy which was shown by inactivating suspended Escherichia coli and Staphylococcus aureus. Plasma-treated tap water had the strongest effect, which is shown for the first time. Additionally, the pH-value of tap water did not decrease during the plasma treatment, and its conductivity increased less than for the other tested liquids. Full article

(This article belongs to the Special Issue Plasma Technology for Biomedical Applications)

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13 pages, 7031 KiB

Open AccessArticle

Dispersion of OH Radicals in Applications Related to Fear-Free Dentistry Using Cold Plasma

by Mehrdad Shahmohammadi Beni, Wei Han and K.N. Yu

Appl. Sci. 2019, 9(10), 2119; https://doi.org/10.3390/app9102119 - 24 May 2019

Cited by 9 | Viewed by 3749

Abstract

Cold atmospheric plasmas (CAPs) are being used in applications related to dentistry. Potential benefits include tooth whitening/bleaching, the sterilization of dental cavities, and root canal disinfection. Generated reactive species, such as hydroxyl (OH) radicals, play a critical role in the effectiveness of CAPs in dentistry. In the present work, the mandibular jaw and teeth were modeled. The propagation of CAP plume in ambient air was dynamically tracked using the level set method. The transport and dispersion OH radicals away from the nozzle and towards the teeth under treatment were also tracked. The distributions of concentration of OH radicals over the teeth were obtained for nozzle to tooth distances of 2 and 4 mm. The discharge of the OH radicals out of the nozzle was found to be asymmetrical. Interestingly, depending on the type of tooth treated, the dispersion of OH radicals out of the nozzle could be altered. The present model and obtained results could be useful for advancements towards a fear-free dentistry using CAPs. Full article

(This article belongs to the Special Issue Plasma Technology for Biomedical Applications)

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16 pages, 2917 KiB

Open AccessArticle

Cold Argon Plasma as Adjuvant Tumour Therapy on Progressive Head and Neck Cancer: A Preclinical Study

by Sybille Hasse, Christian Seebauer, Kristian Wende, Anke Schmidt, Hans-Robert Metelmann, Thomas von Woedtke and Sander Bekeschus

Appl. Sci. 2019, 9(10), 2061; https://doi.org/10.3390/app9102061 - 19 May 2019

Cited by 30 | Viewed by 4241

Abstract

Investigating cold argon plasma (CAP) for medical applications is a rapidly growing, innovative field of research. The controllable supply of reactive oxygen and nitrogen species through CAP has the potential for utilization in tumour treatment. Maxillofacial surgery is limited if tumours grow on vital structures such as the arteria carotis. Here CAP could be considered as an option for adjuvant intraoperative tumour therapy especially in the case of squamous cell carcinoma of the head and neck. Further preclinical research is necessary to investigate the efficacy of this technology for future clinical applications in cancer treatment. Initially, a variety of in vitro assays was performed on two cell lines that served as surrogate for the squamous cell carcinoma (SCC) and healthy tissue, respectively. Cell viability, motility and the activation of apoptosis in SCC cells (HNO97) was compared with those in normal HaCaT keratinocytes. In addition, induction of apoptosis in ex vivo CAP treated human tissue biopsies of patients with tumours of the head and neck was monitored and compared to healthy control tissue of the same patient. In response to CAP treatment, normal HaCaT keratinocytes differed significantly from their malignant counterpart HNO97 cells in cell motility only whereas cell viability remained similar. Moreover, CAP treatment of tumour tissue induced more apoptotic cells than in healthy tissue that was accompanied by elevated extracellular cytochrome c levels. This study promotes a future role of CAP as an adjuvant intraoperative tumour therapy option in the treatment of head and neck cancer. Moreover, patient-derived tissue explants complement in vitro examinations in a meaningful way to reflect an antitumoral role of CAP. Full article

(This article belongs to the Special Issue Plasma Technology for Biomedical Applications)

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10 pages, 3431 KiB

Open AccessArticle

Dry Bio-Decontamination Process in Reduced-Pressure O₂ Plasma

by Hongxia Liu, Xinxin Feng, Xin Ma, Jinzhuo Xie and Chi He

Appl. Sci. 2019, 9(9), 1933; https://doi.org/10.3390/app9091933 - 10 May 2019

Cited by 2 | Viewed by 2658

Abstract

The main objective of this work was to fully understand the bio-decontamination process in a reduced-pressure oxygen plasma. Gram-negative Escherichia coli species was chosen as the target microorganism in this test. The comparison of decontamination efficacy between plasma total and UV radiation individually under various treatment parameters and tests of DNA agarose electrophoresis were made to evaluate the inactivation effect of UV radiation. The quantity of protein leakage and the concentration of malondialdehyde (MDA), which are markers of the end products of lipid peroxidation, in bacterial suspension after treatment were determined to estimate the contribution of both charged particles and free radicals for bacterial death. In addition, a scanning electronic microscope was used to visualize the plasma effect on microorganisms. The results showed that the essential action of the oxygen plasma on Escherichia coli is believed to be attributed to the fast and intense etching on cell membrane by electrons and ions. Attacks on polyunsaturation fatty acid (PUFA) in the cell membrane by oxygen free radicals and the destruction of the DNA in the cell by UV radiation are accessorial during an effective decontamination process. Full article

(This article belongs to the Special Issue Plasma Technology for Biomedical Applications)

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10 pages, 2728 KiB

Open AccessArticle

Anticancer Efficacy of Long-Term Stored Plasma-Activated Medium

by Ngoc Hoan Nguyen, Hyung Jun Park, Soon Young Hwang, Jong-Soo Lee and Sang Sik Yang

Appl. Sci. 2019, 9(4), 801; https://doi.org/10.3390/app9040801 - 25 Feb 2019

Cited by 13 | Viewed by 4391

Abstract

The therapeutic potential of nonthermal atmospheric-pressure plasma for cancer treatment via generation of reactive species, induction of decreased mitochondrial membrane potential, and sequential apoptosis has been reported in our previous studies. Nonthermal atmospheric-pressure plasma-activated medium produced by jetting air plasma above a liquid surface shows advantages over direct plasma such as storage and delivery to tissues inside the body. In this study, we demonstrated that plasma-activated medium can be stored for up to 6 months in a freezer and that the stored plasma-activated medium has anticancer effects similar to those of direct plasma. Plasma-activated medium stored for 6 months showed cytocidal effects on human cervical cancer HeLa cells that were comparable to the effects of fresh plasma-activated medium or direct plasma. Furthermore, the levels of reactive species in plasma-activated medium persisted for up to 6 months. These results indicate that therapeutic application of plasma-activated medium is applicable in plasma medicine and is a promising anticancer strategy. Full article

(This article belongs to the Special Issue Plasma Technology for Biomedical Applications)

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17 pages, 2595 KiB

Open AccessArticle

Activation of Murine Immune Cells upon Co-culture with Plasma-treated B16F10 Melanoma Cells

by Katrin Rödder, Juliane Moritz, Vandana Miller, Klaus-Dieter Weltmann, Hans-Robert Metelmann, Rajesh Gandhirajan and Sander Bekeschus

Appl. Sci. 2019, 9(4), 660; https://doi.org/10.3390/app9040660 - 15 Feb 2019

Cited by 29 | Viewed by 6542

Abstract

Recent advances in melanoma therapy increased median survival in patients. However, death rates are still high, motivating the need of novel avenues in melanoma treatment. Cold physical plasma expels a cocktail of reactive species that have been suggested for cancer treatment. High species concentrations can be used to exploit apoptotic redox signaling pathways in tumor cells. Moreover, an immune-stimulatory role of plasma treatment, as well as plasma-killed tumor cells, was recently proposed, but studies using primary immune cells are scarce. To this end, we investigated the role of plasma-treated murine B16F10 melanoma cells in modulating murine immune cells’ activation and marker profile. Melanoma cells exposed to plasma showed reduced metabolic and migratory activity, and an increased release of danger signals (ATP, CXCL1). This led to an altered cytokine profile with interleukin-1β (IL-1β) and CCL4 being significantly increased in plasma-treated mono- and co-cultures with immune cells. In T cells, plasma-treated melanoma cells induced extracellular signal-regulated Kinase (ERK) phosphorylation and increased CD28 expression, suggesting their activation. In monocytes, CD115 expression was elevated as a marker for activation. In summary, here we provide proof of concept that plasma-killed tumor cells are recognized immunologically, and that plasma exerts stimulating effects on immune cells alone. Full article

(This article belongs to the Special Issue Plasma Technology for Biomedical Applications)

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Review

Jump to: Editorial, Research

20 pages, 2710 KiB

Open AccessReview

Application of Non-Thermal Plasma on Biofilm: A Review

by Tripti Thapa Gupta and Halim Ayan

Appl. Sci. 2019, 9(17), 3548; https://doi.org/10.3390/app9173548 - 29 Aug 2019

Cited by 63 | Viewed by 7227

Abstract

The formation of bacterial biofilm on implanted devices or damaged tissues leads to biomaterial-associated infections often resulting in life-threatening diseases and implant failure. It is a challenging process to eradicate biofilms as they are resistant to antimicrobial treatments. Conventional techniques, such as high heat and chemicals exposure, may not be suitable for biofilm removal in nosocomial settings. These techniques create surface degradation on the treated materials and lead to environmental pollution due to the use of toxic chemicals. A novel technique known as non-thermal plasma has a great potential to decontaminate or sterilize those nosocomial biofilms. This article aims to provide readers with an extensive review of non-thermal plasma and biofilms to facilitate further investigations. A brief introduction summarizes the problem caused by biofilms in hospital settings with current techniques used for biofilm inactivation followed by the literature review strategy. The remainder of the review discusses plasma and its generation, the role played by plasma reactive species, various factors affecting the antimicrobial efficacy of non-thermal plasma and summarizes many studies published in the field. Full article

(This article belongs to the Special Issue Plasma Technology for Biomedical Applications)

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