N₂ non‐thermal atmospheric pressure plasma promotes wound healing in vitro and in vivo: Potential modulation of adhesion molecules and matrix metalloproteinase‐9

Abstract

Advances in physics and biology have made it possible to apply non-thermal atmospheric pressure plasma (NTP) in the biomedical field. Although accumulating evidence suggests that NTP has various medicinal effects, such as facilitating skin wound healing on exposed tissue while minimizing undesirable tissue damage, the underlying molecular mechanisms are not fully understood. In this study, NTP generated from N optimized wound healing in the scratch wound healing assay. In addition, matrix metalloproteinase (MMP)-9 expression and enzyme activity increased and the urokinase-type plasminogen activator (uPA) system was activated after NTP treatment. We also showed that NTP treatment increased Slug and TCF8/ZEB1 expression and decreased that of E-cadherin, suggesting induction of the epithelial-to-mesenchymal transition (EMT). The effect of N NTP was verified on rat wound model. Taken together, these results suggest that N NTP promotes wound healing by inducing the EMT and activating the MMP-9/uPA system. These findings show the therapeutic potential of NTP for skin wound healing.

Plasma Medicine: A Field of Applied Redox Biology

“…These clinical experiences confirm a very early hypothesis in plasma medicine research, that plasma effects on wound healing may be a result of a two-step activity: antiseptics on wound surface in combination with stimulation of tissue regeneration (67) in several in vivo animal experiments (69,(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90) and in human volunteers or patients with reasonably defined wounds (91)(92)(93). It has to be pointed out that these lastmentioned wound healing effects in vivo were demonstrated in acute wounds without any interfering microbial contamination.…”

“…. Several experimental in vitro studies could demonstrate a direct impact of CAP on cell proliferation and migration as well as on angiogenesis(68)(69)(70)(71)(72)(73)(74)(75)(76). The stimulating effect on skin tissue regeneration was confirmed in vivo 33: 1011-1026 (2019) Schematic of interactions between the kINPen plasma effluent with aqueous liquid.…”

Formation of reactive oxygen species by irradiation of cold atmospheric pressure plasma jet to water depends on the irradiation distance

“…(1) CAP can be applied to biological samples because it is produced at room temperature and normal atmospheric pressure. (2) Therefore, CAP has potential for biomedical applications such as wound healing, (3)(4)(5)(6) infection control, (7)(8)(9)(10) and cancer therapy. (11)(12)(13)(14) There are at least three types of CAP used for biological samples: 1) plasma jets, 2) corona discharge plasma sources, and 3) dielectric barrier discharge plasma sources.…”

Diffusion Criteria of O₃ Gas Emitted From Non-Thermal Atmospheric-Pressure Biocompatible Plasma Sterilizer for Safety Environment

“…Non-thermal atmospheric-pressure biocompatible plasma (NBP) has been shown to effectively sterilize viruses and bacteria by the reactive oxygen species (ROS) and reactive nitrogen species (RNS) [6,7]. NBP is also applicable to treatment of wounds [8] and cancers [9], making it a growth engine for the 21st century. Recently, permeation models for various reactions of plasma in skin and living cells have been proposed [10].…”