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

Abstract

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.

Keywords: Low-Temperature Plasma (LTP); biomaterials; plasma medicine.

Figure 1

Two sources of LTP: dielectric barrier discharge (DBD) in argon driven by repetitive short duration (ns–µs) high-voltage pulses (left); a micro-jet using helium as operating gas, generating a cold plasma plume about 2.5 cm in length (right). Reproduced from Laroussi M, Cold plasma in medicine and healthcare: The new frontier in low temperature plasma applications. Front. Phys. 8:74. doi:10.3389/fphy.2020.00074 under the terms of the Creative Commons Attribution License (CC BY) [2].

Figure 2

Pathways for inhibition of glycolysis and tricarboxylic acid (TCA) cycle and electron transfer chain (ETC) by plasma-activated Ringer’s lactate solution (a). Extracellular H₂O₂ induces apoptosis and non-H₂O₂ PAL components induces non-apoptotic cell death (b) [76,85].

Figure 3

(a) Catalase (CAT) and superoxidase dismutase (SOD) catalyzed cell signaling pathways in normal (cancer) cells, (b) HOCl and ONOO⁻ pathway in plasma-treated cells, (c) representation of an extracellular matrix of normal (cancer) cells (d) plasma-treated ECM under oxidative stress, (e) components of extracellular matrix. Reproduced from Privat-Maldonado, et al., Modifying the tumor microenvironment: Challenges and future perspectives for anticancer plasma treatments. Cancers 2019, 11, 1920 [87] under the terms of the Creative Commons Attribution License (CC BY).

Figure 4

A schematic representation of the factors affecting the plasma gene transfection.

Figure 5

Types of orthopedic implants and plasma-induced properties for orthopedic implants.

Figure 6

Schematic representation of the LTP-based dental implant modification. Adapted and modified from Lata et al. Aurora Borealis in dentistry: The applications of cold plasma in biomedicine. Mater. Today Bio 2022, 13, 100200. [187] with copyright permission from Elsevier.