Dual effects of atmospheric pressure plasma jet on skin wound healing of mice

Abstract

Cold plasma has become an attractive tool for promoting wound healing and treating skin diseases. This article presents an atmospheric pressure plasma jet (APPJ) generated in argon gas through dielectric barrier discharge, which was applied to superficial skin wounds in BALB/c mice. The mice (n = 50) were assigned randomly into five groups (named A, B, C, D, E) with 10 animals in each group. Natural wound healing was compared with stimulated wound healing treated daily with APPJ for different time spans (10, 20, 30, 40, and 50 seconds) on 14 consecutive days. APPJ emission spectra, morphological changes in animal wounds, and tissue histological parameters were analyzed. Statistical results revealed that wound size changed over the duration of the experimental period and there was a significant interaction between experimental day and group. Differences between group C and other groups at day 7 were statistically significant (p < 0.05). All groups had nearly achieved closure of the untreated control wounds at day 14. The wounds treated with APPJ for 10, 20, 30, and 40 seconds showed significantly enhanced daily improvement compared with the control and almost complete closure at day 12, 10, 7, and 13, respectively. The optimal results of epidermal cell regeneration, granulation tissue hyperplasia, and collagen deposition in histological aspect were observed at day 7. However, the wounds treated for 50 seconds were less well healed at day 14 than those of the control. It was concluded that appropriate doses of cold plasma could inactivate bacteria around the wound, activate fibroblast proliferation in wound tissue, and eventually promote wound healing. Whereas, over doses of plasma suppressed wound healing due to causing cell death by apoptosis or necrosis. Both positive and negative effects may be related to the existence of reactive oxygen and nitrogen species (ROS and RNS) in APPJ.

Skin Wound Healing: An Update on the Current Knowledge and Concepts

“…Keratinocytes mainly regenerate the epidermis and play an important role in wound closure. Daily short plasma applications (up to 40 s) to murine superficial skin wounds showed significantly increased epidermal cell regeneration, granulation tissue hyperplasia, and collagen deposition [93]. This was also confirmed by plasma application on human skin biopsies where short CAP exposure (1-3 min) was already able to induce the proliferation of keratinocytes [94].…”

“…This was also confirmed by plasma application on human skin biopsies where short CAP exposure (1-3 min) was already able to induce the proliferation of keratinocytes [94]. Concomitantly, longer exposures might lead to overdosing of the plasma application inducing apoptotic cell death with a further disturbed wound healing process [93,94]. Chernets et al [95] examined appendage regeneration stimulated by NTP dependent on reactive oxidative species.…”

High throughput image cytometry micronucleus assay to investigate the presence or absence of mutagenic effects of cold physical plasma

“…All mentioned components can be tailored by the operating parameters such as voltage, current, gas, and geometry. Cold plasmaderived ROS/RNS are hypothesized to play a major role in these processes [Arndt et al, 2013a;Ngo Thi et al, 2014;Xu et al, 2015]. Three plasma devices have received accreditation as medical device based on clinical observations with chronic wounds.…”

Non-thermal air plasma promotes the healing of acute skin wounds in rats

“…Indeed, a positive effect of NTPs on wound healing without adverse reactions to the surrounding healthy tissue has been reported in animal studies16171819. Furthermore, randomised clinical trials have proven that NTPs can reduce bacteria load as well as promote the healing of chronic wounds, while no side-effects and good treatment tolerability were reported20212223.…”