Role of mast cells in skin regeneration after thermal burn treated with melatonin-enriched dermal film

About authors

1 South-Ural State Medical University, Chelyabinsk, Russia

2 Chelyabinsk Regional Clinical Hospital, Chelyabinsk, Russia

3 Pirogov Russian National Research Medical University, Moscow, Russia

Correspondence should be addressed: Anna A. Ageeva
Vorovskogo, 64, Chelyabinsk, 454092; ur.xednay@r.aveega.enna

About paper

Funding: the study was supported by the Russian Foundation for Basic Research and the government of Chelyabinsk region (Project ID 20-415-740016).

Author contribution: Osikov MV — study concept and design; integral analysis of the obtained data; manuscript preparation and editing; Ageeva AA — data acquisition; statistical analysis; analysis of study results; manuscript preparation; Fedosov AA — analysis of study results; manuscript editing; Ushakova VA — synthesis of the dermal film; analysis of study results.

Compliance with ethical standards: the study was approved by the Ethics Committee of South-Ural State Medical University (Protocol № 10 dated November 15, 2019). The study was conducted at a standard vivarium in strict compliance with guidelines on the care and euthanasia of laboratory animals outlined in the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS № 123 , March 18, 1986, Strasburg), the EU Commission Recommendation 2007/526/EC on Guidelines for the Accommodation and Care of Animals used for Experimental and other Scientific Purposes (June 18, 2007), and the Directive 2010/63/EU of the European Parliament and of the Council on the Protection of Animals used for Scientific Purposes (September 22, 2010).

Received: 2021-06-28 Accepted: 2021-07-12 Published online: 2021-08-07

The development of novel local therapies for thermal burns (TB) and their pathogenetic rationale are a pressing challenge. Melatonin (MT) is an endogenous factor of hemostasis regulation with pleiotropic potential. The aim of this study was to assess some parameters of tissue regeneration, the functional state of mast cells and the levels of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the experimentally induced TB treated with the original MT-enriched dermal film (DF). A second-degree burn (3.5% of the total body surface area) was modelled by exposing a patch of skin to hot water. Applications of 12 cm2 DF enriched with 5 mg/g MT were performed every day for 5 days. The following parameters were calculated: the wound area, the rate of wound epithelization, the number of MC in the wound, the intensity of degranulation, and the levels of MMP-9 and VEGF expression.  Over the course of treatment, the absolute wound area shrank by 35%, its epithelization rate increased, the number of MC rose, their functional state changed, and the expression of ММР-9 and VEGF increased. A negative correlation was established between the wound area and the expression of ММР-9 and VEGF, as well as between the wound area and the degranulation coefficient. Applications of MT-enriched DF resulted in the reduction of the wound area, higher epithelization rate, an increase in the total MC count and degranulation intensity on days 5 and 10; it also led to a reduction in the total MC count and a loss in degranulation intensity on day 20 (166.87 (154.95; 178.78) un/mm2 vs. 464.84 (452.92; 476.76) un/mm2) in the group of intact animals), an increase in MMP-9 expression on day 5 (14.20 (11.30; 18.10) vs. 3.30 (2.20; 4.40) in the intact group), an increase in VEGF expression on days 5 and 10 (33.00 (30.20; 34.90) vs 25.40 (22.20; 29.30) in the intact group), and a reduction in MMP-9 expression on days 10 and 20 after thermal injury.

Keywords: mast cells, melatonin, dermal film, regeneration, thermal burn, VEGF, MMP-9