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Biomedicines
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The Advances of Cold Plasma in the Biomedicines
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The Advances of Cold Plasma in the Biomedicines

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: closed (15 March 2022) | Viewed by 37015

Special Issue Editor

Prof. Dr. Gyoocheon Kim

E-Mail Website
Guest Editor
Department of Oral Anatomy, School of Dentistry, Pusan National University, Yangsan 50612, Korea
Interests: tissue regeneration; cancer treatment; detal treatment; plasma medical device
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Plasma used in industrial fields requires a vacuum state and has a characteristic of generating high heat. When the temperature of the plasma is less than 250 degrees Celsius, it is called low-temperature plasma. In order to be treated on human tissues, the temperature of the plasma must be less than 40 degrees Celsius. In that respect, it has recently been referred to as Cold Plasma. The definition of plasma used in the biomedical field seems to be more appropriate for cold plasma than for low-temperature atmospheric pressure plasma or non-thermal plasma. Therefore, in this Special Issue, I look forward to the unified usage of the term “cold plasma”.

Plasma medicine, which started when cold plasma was applied to bacteria and cells, has made much progress for nearly 20 years. The scope of plasma research is expanding from just killing pathogens and cancer cells to tissue regeneration and selective cancer cell death. Among the numerous constituents of plasma, studies on which ones have medical functions and the mechanisms by which plasma-induced biomedical phenomena depend on are being actively conducted. Plasma medical devices are being developed based on these studies, and it is expected that various plasma medical devices will be introduced to the medical market in the near future.

In the current research climate, this Special Issue calls for advanced plasma medicine research results by explaining not only various life phenomena induced by plasma, but also cellular or histologic mechanisms. The scope of the research subject is limited to bacteria living in animals, animal cells and tissues, and biomaterials that can be inserted into the human body. Experimental as well as review papers consistent with this research topic are welcome.

You may choose our Joint Special Issue in Plasma.

Prof. Dr. Gyoocheon Kim
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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cold plasma (non-thermal plasma, low temperature plasma)
  • pathogen sterilization
  • regeneration
  • disease treatment
  • medical device
  • biomaterial

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Published Papers (11 papers)

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Editorial

Jump to: Research, Review

4 pages, 167 KiB  
Editorial
Editorials for ‘Advances in Cold Plasma in Biomedicines’
by Gyoo-Cheon Kim
Biomedicines 2022, 10(11), 2731; https://doi.org/10.3390/biomedicines10112731 - 28 Oct 2022
Cited by 1 | Viewed by 1240
Abstract
Research in the field of plasma medicine has provided many explanations for various phenomena, as well as the involvement of the chemical elements of plasma; however, it still lacks in biological mechanism analyses [...] Full article
(This article belongs to the Special Issue The Advances of Cold Plasma in the Biomedicines)

Research

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16 pages, 3017 KiB  
Article
Anti-Cancer Activity of the Combinational Treatment of Noozone Cold Plasma with p-FAK Antibody-Conjugated Gold Nanoparticles in OSCC Xenograft Mice
by Jeong-Hae Choi, Hee-Jin Gu, Kwang-Ha Park, Dae-Seok Hwang and Gyoo-Cheon Kim
Biomedicines 2022, 10(9), 2259; https://doi.org/10.3390/biomedicines10092259 - 12 Sep 2022
Cited by 5 | Viewed by 2135
Abstract
Oral squamous cell cancer (OSCC) is the most common type of oral cancer (about 80–90% of cases) and various research is being done to cure the disease. This paper aims to verify whether treatment with no-ozone cold plasma (NCP), which is designed for [...] Read more.
Oral squamous cell cancer (OSCC) is the most common type of oral cancer (about 80–90% of cases) and various research is being done to cure the disease. This paper aims to verify whether treatment with no-ozone cold plasma (NCP), which is designed for safe usage of the plasma on oral cavities, in combination with gold nanoparticles conjugated with p-FAK antibody (p-FAK/GNP) can trigger the selective and instant killing of SCC-25 cells both in vitro and in vivo. When SCC25 and HaCaT cells are exposed to p-FAK/GNP+NCP, the instant cell death was observed only in SCC25 cells. Such p-FAK/GNP+NCP-mediated cell death was observed only when NCP was directly treated on SCC25 harboring p-FAK/GNP. During NCP treatment, the removal of charged particles from NCP using grounded electric mesh radically decreased the p-FAK/GNP+NCP-mediated cell death. This p-FAK/GNP+NCP-mediated selective cell death of OSCC was also observed in mice xenograft models using SCC25 cells. The mere treatment of p-FAK/GNP and NCP on the xenograft tumor slowly decreased the size of the tumor, and only about 50% of the tumor remained at the end of the experiment. On the other hand, 1 week of p-FAK/GNP+NCP treatment was enough to reduce half of the tumor size, and most of tumor tissue had vanished at the end. An analysis of isolated tissues showed that in the case of individual treatment with p-FAK/GNP or NCP, the cancer cell population was reduced due to apoptotic cell death. However, in the case of p-FAK/GNP+NCP, apoptotic cell death was unobserved, and most tissues were composed of collagen. Thus, this paper suggests the possibility of p-FAK/GNP+NCP as a new method for treating OSCC. Full article
(This article belongs to the Special Issue The Advances of Cold Plasma in the Biomedicines)
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16 pages, 9344 KiB  
Article
Non-Invasive Physical Plasma Generated by a Medical Argon Plasma Device Induces the Expression of Regenerative Factors in Human Gingival Keratinocytes, Fibroblasts, and Tissue Biopsies
by Benedikt Eggers, Matthias Bernhard Stope, Jana Marciniak, Werner Götz, Alexander Mustea, James Deschner, Marjan Nokhbehsaim and Franz-Josef Kramer
Biomedicines 2022, 10(4), 889; https://doi.org/10.3390/biomedicines10040889 - 13 Apr 2022
Cited by 9 | Viewed by 3257
Abstract
After oral surgery, intraoral wound healing and tissue regeneration is an important factor for the success of the entire therapy. In recent years, non-invasive medical plasma (NIPP) has been shown to accelerate wound healing, which would be particularly beneficial for patients with wound [...] Read more.
After oral surgery, intraoral wound healing and tissue regeneration is an important factor for the success of the entire therapy. In recent years, non-invasive medical plasma (NIPP) has been shown to accelerate wound healing, which would be particularly beneficial for patients with wound healing disorders. Since the application of NIPP in dentistry has not been sufficiently understood, the aim of the present study was to investigate the effect of a medical argon plasma device on gingival cells. Human gingival fibroblasts, keratinocytes, and tissue biopsies were treated with NIPP for different durations. Crucial markers associated with wound healing were examined at the mRNA and protein levels by real-time PCR, ELISA and immunohistochemistry. NIPP treatment led to an increase in Ki67 and MMP1 at mRNA and protein levels. NIPP application lasting longer than 60 s resulted in an increase in apoptotic genes at mRNA level and superficial damage to the epithelium in the tissue biopsies. Overall, our experimental setup demonstrated that NIPP application times of 30 s were most suitable for the treatment of gingival cells and tissue biopsies. Our study provides evidence for potential use of NIPP in dentistry, which would be a promising treatment option for oral surgery. Full article
(This article belongs to the Special Issue The Advances of Cold Plasma in the Biomedicines)
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13 pages, 4678 KiB  
Article
New Approach against Chondrosoma Cells—Cold Plasma Treatment Inhibits Cell Motility and Metabolism, and Leads to Apoptosis
by Andreas Nitsch, Silas Strakeljahn, Josephine M. Jacoby, Konrad F. Sieb, Alexander Mustea, Sander Bekeschus, Axel Ekkernkamp, Matthias B. Stope and Lyubomir Haralambiev
Biomedicines 2022, 10(3), 688; https://doi.org/10.3390/biomedicines10030688 - 17 Mar 2022
Cited by 15 | Viewed by 2643
Abstract
(1) Background: Chondrosarcoma (CS) is a malignant primary bone tumor with a cartilaginous origin. Its slow cell division and severely restricted vascularization are responsible for its poor responsiveness to chemotherapy and radiotherapy. The decisive factor for the prognosis of CS patients is the [...] Read more.
(1) Background: Chondrosarcoma (CS) is a malignant primary bone tumor with a cartilaginous origin. Its slow cell division and severely restricted vascularization are responsible for its poor responsiveness to chemotherapy and radiotherapy. The decisive factor for the prognosis of CS patients is the only adequate therapy—surgical resection. Cold atmospheric pressure plasma (CAP) is emerging as a new option in anti-cancer therapy. Its effect on chondrosarcomas has been poorly investigated. (2) Methods: Two CS cell lines—SW 1353 and CAL 78—were used. Various assays, such as cell growth kinetics, glucose uptake, and metabolic activity assay, along with two different apoptosis assays were performed after CAP treatment. A radius cell migration assay was used to examine cell motility. (3) Results: Both cell lines showed different growth behavior, which was taken into account when using the assays. After CAP treatment, a reduction in metabolic activity was observed in both cell lines. The immediate effect of CAP showed a reduction in cell numbers and in influence on this cell line’s growth rate. The measurement of the glucose concentration in the cell culture medium showed an increase after CAP treatment. Live-dead cell imaging shows an increase in the proportion of dead cells over the incubation time for both cell lines. There was a significant increase in apoptotic signals after 48 h and 72 h for both cell lines in both assays. The migration assay showed that CAP treatment inhibited the motility of chondrosarcoma cells. The effects in all experiments were related to the duration of CAP exposure. (4) Conclusions: The CAP treatment of CS cells inhibits their growth, motility, and metabolism by initiating apoptotic processes. Full article
(This article belongs to the Special Issue The Advances of Cold Plasma in the Biomedicines)
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18 pages, 2563 KiB  
Article
In Vivo Metabolic Analysis of the Anticancer Effects of Plasma-Activated Saline in Three Tumor Animal Models
by Miao Qi, Dehui Xu, Shuai Wang, Bing Li, Sansan Peng, Qiaosong Li, Hao Zhang, Runze Fan, Hailan Chen and Michael G. Kong
Biomedicines 2022, 10(3), 528; https://doi.org/10.3390/biomedicines10030528 - 23 Feb 2022
Cited by 12 | Viewed by 2534
Abstract
In recent years, the emerging technology of cold atmospheric pressure plasma (CAP) has grown rapidly along with the many medical applications of cold plasma (e.g., cancer, skin disease, tissue repair, etc.). Plasma-activated liquids (e.g., culture media, water, or normal saline, previously exposed to [...] Read more.
In recent years, the emerging technology of cold atmospheric pressure plasma (CAP) has grown rapidly along with the many medical applications of cold plasma (e.g., cancer, skin disease, tissue repair, etc.). Plasma-activated liquids (e.g., culture media, water, or normal saline, previously exposed to plasma) are being studied as cancer treatments, and due to their advantages, many researchers prefer plasma-activated liquids as an alternative to CAP in the treatment of cancer. In this study, we showed that plasma-activated-saline (PAS) treatment significantly inhibited tumor growth, as compared with saline, in melanoma, and a low-pH environment had little effect on tumor growth in vivo. In addition, based on an ultra-high-performance liquid tandem chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) analysis of tumor cell metabolism, the glycerophospholipid metabolic pathway was the most susceptible metabolic pathway to PAS treatment in melanoma in vitro and in vivo. Furthermore, PAS also inhibited cell proliferation in vivo in oral tongue squamous-cell cancer and non-small-cell lung cancer. There were few toxic side effects in the three animal models, and the treatment was deemed safe to use. In the future, plasma-activated liquids may serve as a potential therapeutic approach in the treatment of cancer. Full article
(This article belongs to the Special Issue The Advances of Cold Plasma in the Biomedicines)
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15 pages, 4626 KiB  
Article
Treatment of Fungal-Infected Diabetic Wounds with Low Temperature Plasma
by Kyu Young Choi, Md. Tipu Sultan, Olatunji Ajiteru, Heesun Hong, Young Jin Lee, Ji Seung Lee, Hanna Lee, Ok Joo Lee, Soon Hee Kim, Joong Seob Lee, Sung-Jin Park, James Gary Eden and Chan Hum Park
Biomedicines 2022, 10(1), 27; https://doi.org/10.3390/biomedicines10010027 - 23 Dec 2021
Cited by 11 | Viewed by 4317
Abstract
Diabetes mellitus renders patients susceptible to chronic wounds and various infections. Regarding the latter, fungal infections are of particular concern since, although they are the source of significant morbidity and mortality in immunocompromised patients, they are generally resistant to conventional treatment and a [...] Read more.
Diabetes mellitus renders patients susceptible to chronic wounds and various infections. Regarding the latter, fungal infections are of particular concern since, although they are the source of significant morbidity and mortality in immunocompromised patients, they are generally resistant to conventional treatment and a definite treatment strategy has not yet been established. Herein, we report the treatment of skin wounds in a diabetic rat model, infected by Candida albicans, with low temperature helium plasma generated in a hand-held atmospheric jet device. A fungal infection was induced on two dorsal skin wounds of the diabetic rats, and one wound was treated with the plasma jet whereas the other served as a control. Histological analysis revealed accelerated skin wound healing and decreased evidence of fungal infection in the plasma-treated group, as compared to the control group. Regeneration of the epidermis and dermis, collagen deposition, and neovascularization were all observed as a result of plasma treatment, but without wound contraction, scar formation or any evidence of thermal damage to the tissue. These findings demonstrate that the He plasma jet is remarkably effective in diabetic skin wounds infected by Candida albicans, thereby providing a promising medical treatment option for diabetes mellitus patients with skin wound and fungal infections. Full article
(This article belongs to the Special Issue The Advances of Cold Plasma in the Biomedicines)
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19 pages, 3004 KiB  
Article
The Anti-Fibrotic Effect of Cold Atmospheric Plasma on Localized Scleroderma In Vitro and In Vivo
by Stephanie Arndt, Petra Unger, Anja-Katrin Bosserhoff, Mark Berneburg and Sigrid Karrer
Biomedicines 2021, 9(11), 1545; https://doi.org/10.3390/biomedicines9111545 - 26 Oct 2021
Cited by 11 | Viewed by 3365
Abstract
Cold Atmospheric Plasma (CAP) has shown promising results in the treatment of various skin diseases. The therapeutic effect of CAP on localized scleroderma (LS), however, has not yet been evaluated. We investigated the effects of CAP on LS by comparing human normal fibroblasts [...] Read more.
Cold Atmospheric Plasma (CAP) has shown promising results in the treatment of various skin diseases. The therapeutic effect of CAP on localized scleroderma (LS), however, has not yet been evaluated. We investigated the effects of CAP on LS by comparing human normal fibroblasts (hNF), human TGF-β-activated fibroblasts (hAF), and human localized scleroderma-derived fibroblasts (hLSF) after direct CAP treatment, co-cultured with plasma-treated human epidermal keratinocytes (hEK) and with an experimental murine model of scleroderma. In hAF and hLSF, 2 min CAP treatment with the MicroPlaSterβ® plasma torch did not affect pro-fibrotic gene expression of alpha smooth muscle actin, fibroblast activating protein, and collagen type I, however, it promoted re-expression of matrix metalloproteinase 1. Functionally, CAP treatment reduced cell migration and stress fiber formation in hAF and hLSF. The relevance of CAP treatment was confirmed in an in vivo model of bleomycin-induced dermal fibrosis. In this model, CAP-treated mice showed significantly reduced dermal thickness and collagen deposition as well as a decrease in both alpha smooth muscle actin-positive myofibroblasts and CD68-positive macrophages in the affected skin in comparison to untreated fibrotic tissue. In conclusion, this study provides the first evidence for the successful use of CAP for treating LS and may be the basis for clinical trials including patients with LS. Full article
(This article belongs to the Special Issue The Advances of Cold Plasma in the Biomedicines)
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13 pages, 1971 KiB  
Article
Enhancement of Osteoblast Differentiation Using No-Ozone Cold Plasma on Human Periodontal Ligament Cells
by Byul-Bora Choi, Jeong-Hae Choi, Tae-Hyung Kang, Seok-Jun Lee and Gyoo-Cheon Kim
Biomedicines 2021, 9(11), 1542; https://doi.org/10.3390/biomedicines9111542 - 26 Oct 2021
Cited by 10 | Viewed by 2284
Abstract
Periodontitis is an inflammatory disease that leads to periodontal tissue destruction and bone resorption. Proliferation and differentiation of cells capable of differentiating into osteoblasts is important for reconstructing periodontal tissues destroyed by periodontitis. In this study, the effects of the nozone (no-ozone) cold [...] Read more.
Periodontitis is an inflammatory disease that leads to periodontal tissue destruction and bone resorption. Proliferation and differentiation of cells capable of differentiating into osteoblasts is important for reconstructing periodontal tissues destroyed by periodontitis. In this study, the effects of the nozone (no-ozone) cold plasma (NCP) treatment on osteoblastic differentiation in periodontal ligament (PDL) cells were investigated. To test the toxicity of NCP on PDL cells, various NCP treatment methods and durations were tested, and time-dependent cell proliferation was analyzed using a water-soluble tetrazolium salts-1 assay. To determine the effect of NCP on PDL cell differentiation, the cells were provided with osteogenic media immediately after an NCP treatment to induce differentiation; the cells were then analyzed using alkaline phosphatase (ALP) staining, an ALP activity assay, real time PCR, and Alizarin Red S staining. The NCP treatment without toxicity on PDL cells was the condition of 1-min NCP treatment immediately followed by the replacement with fresh media. NCP increased ALP, osteocalcin, osteonectin, and osteopontin expression, as well as mineralization nodule formation. NCP treatment promotes osteoblastic differentiation of PDL cells; therefore, it may be beneficial for treating periodontitis. Full article
(This article belongs to the Special Issue The Advances of Cold Plasma in the Biomedicines)
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Graphical abstract

13 pages, 1915 KiB  
Article
The Anticancer Efficacy of Plasma-Oxidized Saline (POS) in the Ehrlich Ascites Carcinoma Model In Vitro and In Vivo
by Walison Augusto Silva Brito, Eric Freund, Thiago Daniel Henrique do Nascimento, Gabriella Pasqual-Melo, Larissa Juliani Sanches, Joyce Hellen Ribeiro Dionísio, William Capellari Fumegali, Lea Miebach, Alessandra Lourenço Cecchini and Sander Bekeschus
Biomedicines 2021, 9(8), 932; https://doi.org/10.3390/biomedicines9080932 - 31 Jul 2021
Cited by 6 | Viewed by 2422
Abstract
Cold physical plasma, a partially ionized gas rich in reactive oxygen species (ROS), is receiving increasing interest as a novel anticancer agent via two modes. The first involves its application to cells and tissues directly, while the second uses physical plasma-derived ROS to [...] Read more.
Cold physical plasma, a partially ionized gas rich in reactive oxygen species (ROS), is receiving increasing interest as a novel anticancer agent via two modes. The first involves its application to cells and tissues directly, while the second uses physical plasma-derived ROS to oxidize liquids. Saline is a clinically accepted liquid, and here we explored the suitability of plasma-oxidized saline (POS) as anticancer agent technology in vitro and in vivo using the Ehrlich Ascites Carcinoma (EAC) model. EAC mainly grows as a suspension in the peritoneal cavity of mice, making this model ideally suited to test POS as a putative agent against peritoneal carcinomatosis frequently observed with colon, pancreas, and ovarium metastasis. Five POS injections led to a reduction of the tumor burden in vivo as well as in a decline of EAC cell growth and an arrest in metabolic activity ex vivo. The treatment was accompanied by a decreased antioxidant capacity of Ehrlich tumor cells and increased lipid oxidation in the ascites supernatants, while no other side effects were observed. Oxaliplatin and hydrogen peroxide were used as controls and mediated better and worse outcomes, respectively, with the former but not the latter inducing profound changes in the inflammatory milieu among 13 different cytokines investigated in ascites fluid. Modulation of inflammation in the POS group was modest but significant. These results promote POS as a promising candidate for targeting peritoneal carcinomatosis and malignant ascites and suggest EAC to be a suitable and convenient model for analyzing innovative POS approaches and combination therapies. Full article
(This article belongs to the Special Issue The Advances of Cold Plasma in the Biomedicines)
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Review

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14 pages, 683 KiB  
Review
Applications of Plasma-Activated Liquid in the Medical Field
by Sungryeal Kim and Chul-Ho Kim
Biomedicines 2021, 9(11), 1700; https://doi.org/10.3390/biomedicines9111700 - 16 Nov 2021
Cited by 30 | Viewed by 5906
Abstract
Much progress has been made since plasma was discovered in the early 1900s. The first form of plasma was thermal type, which was limited for medical use due to potential thermal damage on living cells. In the late 1900s, with the development of [...] Read more.
Much progress has been made since plasma was discovered in the early 1900s. The first form of plasma was thermal type, which was limited for medical use due to potential thermal damage on living cells. In the late 1900s, with the development of a nonthermal atmospheric plasma called cold plasma, profound clinical research began and ‘plasma medicine’ became a new area in the academic field. Plasma began to be used mainly for environmental problems, such as water purification and wastewater treatment, and subsequent research on plasma and liquid interaction led to the birth of ‘plasma-activated liquid’ (PAL). PAL is currently used in the fields of environment, food, agriculture, nanoparticle synthesis, analytical chemistry, and sterilization. In the medical field, PAL usage can be expanded for accessing places where direct application of plasma is difficult. In this review, recent studies with PAL will be introduced to inform researchers of the application plan and possibility of PAL in the medical field. Full article
(This article belongs to the Special Issue The Advances of Cold Plasma in the Biomedicines)
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21 pages, 4407 KiB  
Review
Multi-Modal Biological Destruction by Cold Atmospheric Plasma: Capability and Mechanism
by Dayun Yan, Alisa Malyavko, Qihui Wang, Kostya (Ken) Ostrikov, Jonathan H. Sherman and Michael Keidar
Biomedicines 2021, 9(9), 1259; https://doi.org/10.3390/biomedicines9091259 - 18 Sep 2021
Cited by 26 | Viewed by 5073
Abstract
Cold atmospheric plasma (CAP) is a near-room-temperature, partially ionized gas composed of reactive neutral and charged species. CAP also generates physical factors, including ultraviolet (UV) radiation and thermal and electromagnetic (EM) effects. Studies over the past decade demonstrated that CAP could effectively induce [...] Read more.
Cold atmospheric plasma (CAP) is a near-room-temperature, partially ionized gas composed of reactive neutral and charged species. CAP also generates physical factors, including ultraviolet (UV) radiation and thermal and electromagnetic (EM) effects. Studies over the past decade demonstrated that CAP could effectively induce death in a wide range of cell types, from mammalian to bacterial cells. Viruses can also be inactivated by a CAP treatment. The CAP-triggered cell-death types mainly include apoptosis, necrosis, and autophagy-associated cell death. Cell death and virus inactivation triggered by CAP are the foundation of the emerging medical applications of CAP, including cancer therapy, sterilization, and wound healing. Here, we systematically analyze the entire picture of multi-modal biological destruction by CAP treatment and their underlying mechanisms based on the latest discoveries particularly the physical effects on cancer cells. Full article
(This article belongs to the Special Issue The Advances of Cold Plasma in the Biomedicines)
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