Argon Atmospheric Plasma Treatment Promotes Burn Healing by Stimulating Inflammation and Controlling the Redox State

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ORIGINAL ARTICLE

Argon Atmospheric Plasma Treatment Promotes Burn Healing by Stimulating Inflammation and Controlling the Redox State Lucas Buzeli de Souza ,1 Jennyffer Ione de Souza Silva ,1 Leonardo Bagne ,1 Amanda Tavares Pereira ,1 Maraiara Aparecida de Oliveira ,1 Bruno Bellotti Lopes,2 Maria Esméria Corezola do Amaral ,1 Andrea Aparecida de Aro ,1 Marcelo Augusto Marretto Esquisatto ,1 Gláucia Maria Tech dos Santos ,1 and Thiago Antônio Moretti de Andrade 1,3

Burns are a public health problem, with second-degree burns as one of the most common types. Although intense inflammation worsens burn healing, effective therapies are scarce. Thus, infections and hypertrophic scars may occur, which compromise patient quality of life and may delay healing. Argon atmospheric plasma (AP) has been shown to positively influence wound healing. In the context of identifying effective and alternative therapies for the treatment of second-degree burns, the present study evaluated AP in the treatment of second-degree burns in rats compared to that for sham treatment on the 2nd, 7th, 14th, and 21st days post-injury. Our results revealed proinflammatory effect for AP by recruiting predominantly neutrophils on the 7th day and macrophages on the 21st day compared to sham treatment, allowing a greater production of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-17, and also controlled the inflammation by IL-10 and transforming growth factor (TGF)-β1. AP also showed antioxidant activity important for controlling oxidative damage on the 2nd day. This favored the induction of angiogenesis from the 2nd day and induction fibroplasia and fibrillogenesis after the 14th day, which enhanced burn healing with the formation of a thinner burn eschar before the 21st day post-burn. Thus, AP effectively modulated the inflammatory phase of second-degree burn healing through the control of oxidative damage that favored the following phases. Therefore, AP is a relevant alternative in the treatment of second-degree burns. Abstract—

1

Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation – FHO, Dr. Maximiliano Baruto Avenue, 500. Jardim Universitario, Araras, SP 13607-339, Brazil 2 Surface - Engineering and Solutions by Plasma Ltda., Jose Rocha Bonfim Avenue, 214. Lot. Center Santa Genebra, Campinas, SP 13080-658, Brazil 3 To whom correspondence should be addressed at Graduate Program of Biomedical Sciences, University Center of Herminio Ometto Foundation – FHO, Dr. Maximiliano Baruto Avenue, 500. Jardim Universitario, Araras, SP 13607-339, Brazil. E-mail: [email protected]

0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature

de Souza, de Souza Silva, Bagne, Pereira, de Oliveira, Lopes, do Amaral, de Aro, Esquisatto, dos Santos, and de Andrade KEY WORDS: second-degree burn; argon atmospheric plasma; inflammation; antioxidant; angiogenesis; collagen type I.

INTRODUCTION Plasma is the fourth state of matter, after the solid, liquid, and gaseous states,