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Cold-atmospheric plasma improves burn injury repair via modulation of angiogenesis, extracellular matrix formation and antibacterial effect

Abstract : Thermal injuries affect millions of adults and children worldwide. In the last 30 years little progress has been made in the management of major burns and despite improved rates of survival, patients continue to suffer debilitating consequences such as infections, hypertrophic scars, contractures, post-traumatic stress disorder and immunometabolic dysfunctions.Cold-atmospheric plasmas (CAP) are partially ionized gases which showed ability to promote wound closure and possess bactericidal properties. They safely deliver to the wounds a therapeutic mixture of reactive oxygen and nitrogen species at body temperature.This PhD study aimed to assess the therapeutic potential of CAP to improve healing of burn wounds under aseptic and septic conditions.First, we designed a plasma source that could be used for in vitro and in vivo studies. Although the first in vitro experiments showed that CAP treatment can improve cellular migration, we couldn’t see any beneficial of CAP on the healing of full-thickness excisional wounds in mice. Second, using a model of third degree burn reconstructed with an allogeneic graft, we assessed both effectiveness and mechanism of action of CAP compared to a placebo control (helium). Indeed, it was shown that through the promotion of pro-angiogenic activities as well as stimulation of the extracellular matrix formation, CAP improved engraftment and healing of the burn wounds. These effects are at least partly mediated by the TGF-β signaling pathway and eNOS modulation. Third, the bactericidal activity of CAP was evaluated in vitro using S. aureus strains and macrophages and in vivo using an infected burn wound model. We showed that CAP had the ability to significantly inactivate S. aureus compared to the helium control. Capacities of CAP treatment to activate macrophages were also evident.This proof-of-concept study demonstrated the therapeutic potential of CAP on tissue repair and burn wound healing. Given that mouse skin does not perfectly mimic wound healing patterns observed in human skin, further investigations are warranted using large animal models with greater similarity to human skin.
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https://hal-polytechnique.archives-ouvertes.fr/tel-03014527
Contributor : Aurélien Arnoux <>
Submitted on : Thursday, November 19, 2020 - 2:35:50 PM
Last modification on : Saturday, November 21, 2020 - 3:29:25 AM

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  • HAL Id : tel-03014527, version 1

Citation

Constance Duchesne. Cold-atmospheric plasma improves burn injury repair via modulation of angiogenesis, extracellular matrix formation and antibacterial effect. Cellular Biology. Université Paris-Saclay, 2019. English. ⟨NNT : 2019SACLX038⟩. ⟨tel-03014527⟩

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