Applications and Perspectives of Cold Electric Discharge Plasmas in Biomedicine and Bioengineering

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

Deadline for manuscript submissions: 30 June 2025 | Viewed by 3091

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Guest Editor
Physics and Biophysics Education Research Laboratory (P&B-EduResLab), Biomedical Science Department, Faculty of Medical Bioengineering, "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Str. M. Kogalniceanu No. 9-13, 700454 Iasi, Romania
Interests: plasma sources; plasma diagnosis; plasma-cell interactions; atmospheric pressure plasmas; non-thermal plasmas; plasma-surface modification of polymers; plasma-surface interface; surface characterization; atomic force microscopy; surface energy-contact angle; thin film deposition; nanoparticles; nanomaterials
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Special Issue Information

Dear Colleagues,

Cold electric discharge plasmas have been of great interest for society since their discovery almost a century ago. The emerging interdisciplinary fields that include electric discharges are rapidly growing, opening new perspectives but also demanding new tools to monitor, investigate and control plasma parameters. The involvement of electric discharges in the bio-medicine path (e.g., plasma medicine, plasma pharmacology, plasma oncology, plasma bioengineering, plasma agronomy) is a broad new field that needs specific regulations in order to fulfill the needs/demands of the beneficiaries of these plasma technologies. Therefore, research on plasma technology is still challenging and requires many steps that must be regulated/standardized so that the results can be reproductible in a broad range of operational parameters. This Special Issue is intended to present results concerning new and innovative applications, as well as perspectives, of cold electric discharge plasma for the bio-medicine field. Here, we welcome the submission of results on plasma discharge diagnostics using electric to optic/spectroscopic methods, monitoring techniques, as well as new devices specially made for plasma diagnostics, plasma–surface interactions or even for surface investigation after plasma exposure.

Potential topics include, but are not limited to, the following:

  • Plasma technology;
  • Atmospheric–pressure plasmas;
  • Plasma medicine;
  • Plasma oncology;
  • Biological effects of plasmas;
  • Future perspectives for electrical discharges;
  • Role of cold plasmas in medicine.

Dr. Andrei Vasile Nastuta
Guest Editor

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Keywords

  • plasma medicine
  • plasma pharmacology
  • plasma oncology
  • plasma bioengineering
  • plasma agronomy

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Published Papers (4 papers)

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Research

23 pages, 5160 KiB  
Article
The Hormetic Adaptative Capacity and Resilience to Oxidative Stress Is Strengthened by Exposome Enrichment with Air Cold Atmospheric Plasma: A Metabolome Targeted Follow-Up Approach
by Lucía González-Llorente, Miguel Andrés-Gasco, Macarena Alba Gil Aranda, Rubén Rabadán-Ros, Rubén Zapata-Pérez, Estrella Núñez-Delicado, Nerea Menéndez-Coto, Claudia García-González, Francisco Javier Baena-Huerta, Ana Coto-Montes and Enrique Caso-Peláez
Biomedicines 2025, 13(4), 949; https://doi.org/10.3390/biomedicines13040949 - 12 Apr 2025
Viewed by 385
Abstract
Background/Objectives: The exposome, encompassing all environmental influences on health, plays a pivotal role in oxidative stress-related diseases. Negative air ions (NAIs), generated via cold atmospheric plasma (CAP), have been proposed as potential modulators of oxidative resilience. This study aims to investigate the [...] Read more.
Background/Objectives: The exposome, encompassing all environmental influences on health, plays a pivotal role in oxidative stress-related diseases. Negative air ions (NAIs), generated via cold atmospheric plasma (CAP), have been proposed as potential modulators of oxidative resilience. This study aims to investigate the metabolic adaptations induced by prolonged exposure to an NAI-enriched environment in mice, focusing on its effects in oxidative stress markers and energy metabolism in liver and blood. Methods: Twenty male C57BL/6J mice were divided into four groups: two experimental groups exposed to NAI-enriched air generated by an Air Cold Atmospheric Plasma–Nanoparticle Removal (aCAP-NR) device for either 18 days (short-term, ST) or 28 days (long-term, LT), and two control groups without exposure. Targeted metabolomics was performed in whole blood and liver using ultra-high-performance liquid chromatography–mass spectrometry (UHPLC-MS). Statistical and pathway analyses were conducted to assess metabolic alterations. Results: Metabolic profiling revealed significant shifts in oxidative stress-related pathways, including enhanced glutathione metabolism, reduced lipid peroxidation, and modulation of purine metabolism. Short-term exposure led to increased mitochondrial efficiency and energy homeostasis, while long-term exposure induced adaptive metabolic reprogramming, with higher inosine levels suggesting enhanced antioxidant and anti-inflammatory responses. No adverse effects on systemic or hepatic health markers were observed. Conclusions: NAI exposure via aCAP-NR elicits a hormetic response, enhancing metabolic efficiency and resilience to oxidative stress. These findings suggest that controlled environmental enrichment with NAIs may serve as a novel non-invasive strategy for mitigating oxidative damage and improving metabolic health, as hormetic adaptative capacity and resilience to oxidative stress, warranting further translational research. Full article
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15 pages, 3563 KiB  
Article
Anti-Tumor Effect of Non-Thermal Atmospheric Pressure Plasma-Activated Medium on Synovial Sarcoma: An In Vitro and In Vivo Study
by Hana Yao, Hiromitsu Toyoda, Naoki Takada, Naoto Oebisu, Kumi Orita, Yoshitaka Ban, Kosuke Saito, Katsumasa Nakazawa, Yuto Kobayashi, Hiroshi Taniwaki, Chinatsu Ohira, Jun-Seok Oh, Tatsuru Shirafuji, Hidetomi Terai and Hiroaki Nakamura
Biomedicines 2025, 13(3), 534; https://doi.org/10.3390/biomedicines13030534 - 20 Feb 2025
Viewed by 542
Abstract
Background/Objective: Anti-tumor effects of plasma-activated medium (PAM) were demonstrated using various malignant tumors. However, the anti-tumor effect of PAM on synovial sarcoma remains unclear. Therefore, we aimed to investigate the anti-tumor effects of PAM on synovial sarcoma and its underlying mechanisms, focusing [...] Read more.
Background/Objective: Anti-tumor effects of plasma-activated medium (PAM) were demonstrated using various malignant tumors. However, the anti-tumor effect of PAM on synovial sarcoma remains unclear. Therefore, we aimed to investigate the anti-tumor effects of PAM on synovial sarcoma and its underlying mechanisms, focusing on the quantitative analyses of both intracellular reactive oxygen species (ROS) and cell apoptosis. Methods: The human synovial sarcoma cell line HS-SY-II was used to investigate the cell viability after PAM treatment. We investigated the anti-tumor effects and side effects of local PAM injection in a synovial sarcoma xenograft murine model. Moreover, we observed PAM-induced intracellular ROS accumulation and cell apoptosis and assessed the involvement of intracellular ROS in the anti-tumor effects of PAM using an intracellular ROS scavenger. Results: PAM significantly decreased the viability of synovial sarcoma cells compared with untreated Dulbecco’s modified Eagle medium. Local PAM injection into a synovial sarcoma xenograft murine model significantly suppressed tumor growth, including tumor volume (p < 0.001) and weight (p = 0.031), without side effects. Regarding anti-tumor mechanisms, PAM induced significant cell apoptosis and intracellular ROS accumulation (p < 0.001). The intracellular ROS scavenger significantly inhibited the anti-tumor effect of PAM (p < 0.001). Conclusions: We confirmed the anti-tumor effects of PAM on synovial sarcoma in vitro and in vivo, as well as the absence of side effects. The underlying mechanism was suggested to involve cell apoptosis induced by intracellular ROS accumulation. Considering the various clinical issues associated with the existing treatments of synovial sarcoma, PAM is a promising new option. Full article
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15 pages, 3032 KiB  
Article
Antitumor Potential of Different Treatment Approaches Using Cold Atmospheric Pressure Plasma on Oral Squamous Cell Carcinoma Models: In Vitro Study
by Ognjan Pavlović, Miloš Lazarević, Aleksandar Jakovljević, Nikola Škoro, Nevena Puač, Slavko Mojsilović and Maja Miletić
Biomedicines 2025, 13(2), 443; https://doi.org/10.3390/biomedicines13020443 - 11 Feb 2025
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Abstract
Background/Objectives: Cold atmospheric plasma (CAP) has shown a strong anticancer effect on a variety of tumors, presenting a new approach for the effective treatment of oral squamous cell carcinoma (OSCC), one of the most prevalent malignant neoplasms with a high mortality rate. Here, [...] Read more.
Background/Objectives: Cold atmospheric plasma (CAP) has shown a strong anticancer effect on a variety of tumors, presenting a new approach for the effective treatment of oral squamous cell carcinoma (OSCC), one of the most prevalent malignant neoplasms with a high mortality rate. Here, we aimed to comprehensively investigate the antitumor potential of two approaches of CAP treatment on both two-dimensional and three-dimensional OSCC cell line models, as well as to analyze whether plasma treatment enhances the sensitivity of OSCC to chemotherapy. Methods: An in-house designed plasma needle, with helium as a working gas, was used to treat the SCC-25 cell line directly or indirectly via plasma-treated medium (PTM). The antitumor effect of CAP was assessed by measuring cell viability, apoptosis, adhesion, and migration. In addition, the combined effect of PTM and cisplatin was analyzed in SCC-25 tumor spheroids, as a more complex and reliable in vitro model. Results: Both plasma treatments showed time-dependent antitumor effects affecting their viability, adhesion, and migration. The rate of apoptosis was higher after incubation with PTM and is mediated by the intrinsic pathway. By utilizing the 3D spheroid carcinoma model, we confirmed the antitumor potential of CAP and additionally demonstrated an increased chemosensitivity of PTM-treated carcinoma cells. Conclusions: The results of our study illustrate a promising avenue for the application of CAP as a therapeutic option for OSCC, either as a standalone treatment or in combination with cisplatin. Full article
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23 pages, 4365 KiB  
Article
The Genetic Expression Difference of A2058 Cells Treated by Plasma Direct Exposure and Plasma-Treated Medium and the Appropriate Treatment Strategy
by Chao-Yu Chen, Chung-Hsien Chou and Yun-Chien Cheng
Biomedicines 2025, 13(1), 184; https://doi.org/10.3390/biomedicines13010184 - 13 Jan 2025
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Abstract
Background/Objectives: Cold atmospheric plasma (CAP) has been demonstrated as an adjustable device to generate various combinations of short-lived reactive oxygen and nitrogen species (RONS) and as a promising appliance for cancer therapy. This study investigated the effects of direct and indirect treatments [...] Read more.
Background/Objectives: Cold atmospheric plasma (CAP) has been demonstrated as an adjustable device to generate various combinations of short-lived reactive oxygen and nitrogen species (RONS) and as a promising appliance for cancer therapy. This study investigated the effects of direct and indirect treatments of Argon-based CAP to cancer cells (A2058, A549, U2OS and BCC) and fibroblasts (NIH3T3 and L929) on cell viability. We also aimed to understand whether plasma-generated RONS were involved in this process using genetic evidence. Methods: The intensity of reactive species in the plasma gas and the concentrations of RONS in phosphate-buffered saline (PBS) and cell culture medium were measured. A viability assay was performed after the cells were treated by plasma in PBS and medium with various volumes to realize the lethal effects of plasma under different conditions. Diverse cells were treated in the same solution to compare the sensitivities of different cells to plasma treatments. The gene expression profiles of A2058 cells after the direct and indirect treatments were analyzed by next generation gene sequencing. Accordingly, we discovered the advantages of sequential treatments on cancer therapy. Results: The cumulative concentration of hydroxyterephthalic acid (HTA) revealed that the pre-existing OH radical (•OH) in PBS increased with the treatment durations. However, there was no significant increase in the concentration of HTA in culture medium. HTA was detected in the treatment interface of PBS but not medium, showing the penetration of •OH through PBS. The concentrations of H2O2 and NO2 increased with the treatment durations, but that of NO3 was low. The direct treatments caused stronger lethal effects on cancer cells under certain conditions. The fibroblasts showed higher tolerance to plasma treatments. From gene expression analysis, the initial observations showed that both treatments influenced transcription-related pathways and exhibited shared or unique cellular stress responses. The pre-treatments, especially of direct exposure, revealed better cancer inhibition. Conclusions: The anti-cancer efficiency of plasma could be enhanced by pre-treatments and by adjusting the liquid interfaces to avoid the rapid consumption of short-lived RONS in the medium. To achieve better therapeutic effects and selectivity, more evidence is necessary to find optional plasma treatments. Full article
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