Introduction

Wound healing is important physiological process that requires the coordination of many immune and biochemical processes and prevents excessive penetration of pathogens into the subcutaneous layers and deeper structures. This process requires the nutrients expenditure on collagen synthesis, recycling and removal of damaged tissues [1].

One of the ways to speed up the healing process is to provide the body with additional nutrients, especially amino acids involved in the collagen synthesis. According to Albaugh V. L., et al., 2017, this delivery is possible orally — by increasing the amino acids content in the diet. However, this approach has a number of disadvantages associated with the metabolism of amino acids (according to the authors, an increase in the proline or hydroxyproline content involved in the collagen synthesis did not affect the wound crust strength, the speed and quality of wound healing, unlike, for example, glutamine) [2].

An alternative approach is to stimulate directly the cells that produce collagen. In particular, stimulation of fibroblasts — connective tissue cells that secrete collagen [3, 4]. This can be achieved by including certain substances in the wound coating or by providing the body with such substances in a complex way [5]. According to Teplicki E., et al., 2018, the aloe vera extract inclusion in the wound coating composition promotes migration to the lesion with following fibroblasts and keratinocytes proliferation in it [6]. Similar data were obtained in the desJardins-Park H. E., et al., 2018 study regarding the inclusion of interleukins in the wound coating, since they also stimulate the fibroblasts migration to the lesion site and the collagen secretion activation [7]. On the other hand, it is possible to stimulate fibroblasts in vitro, followed by their in vivo colonization. A study by Mahmoudi S., et al., 2019, describes a method for stimulating and reprogramming fibroblasts, which will accelerate wound healing in individuals with immune system insufficiency, as well as in the elderly [8]. In a similar study, Hesketh M., et al., 2017, it was shown that selective stimulation of the M2 fraction of macrophages can mitigate the course of the healing process (by reducing the severity of the inflammatory phase) [9].

Another way to accelerate the healing process is the collagen inclusion in the wound coatings [10, 11]. One of the primary and effective solutions was described by Chattopadhyay S., Raines R. T., 2014 — the collagen powder using [12]. However, various hydrogel coatings have become more widespread due to the their application simplicity and convenience [13]. In the Amaral R. J. F. C., et al., 2019 study, the optimal collagen-containing wound coating "loading" with platelet-rich plasma is shown, which accelerates healing and expands the range of applications of this type of coating [14].

Today, the active study of collagen-containing wound coating composition and effectiveness continues [15-17]. In the Min J. G., et al., 2020, study was shown that the additional introduction of antibiotics into the collagen-containing hydrogel wound coating also accelerates the healing process and reduces the severity of its course, due to preventing microbial contamination of the wound [18]. However, there were no reliable data on the treatment of burn wounds at various stages using collagen-containing hydrogels. In this regard, as well as the current trend to accelerate the healing process without loss of quality, this study was conducted.

Materials and methods

In the period November 2019 — July 2020, the patients care quality who applied for the treatment of burn wounds of various localization was retrospectively evaluated. The study involved 100 people with second-degree skin burn injuries with a total area of damage not exceeding 6 cm2. The distribution of participants was: 43 men (43%), 67 women (67%). All participants in the study signed an informed consent. Burn wound treatment was performed by using a biodegradable hydrogel based on collagen hydrolysate, sodium alginate, glycerol, poviargol, benzalkonium chloride, dioxydine, methylparaben, propylbaraben, DMSO (dimethyl sulfoxide), sodium hypochlorite (Drug 1), with proven in studies Afinogenov G. E., et al., 2014 , Trezubov V. N., et al., 2010, Neizberg D. M., et al., 2017, efficiency in the various reasons mucosal and flesh wounds treatment [19-21]. The comparison group included patients treated with dioxomethyltetrahydropyrimidine-based ointment with chloramphenicol (Drug 2) with proven efficacy in the treatment of flesh wounds of various genesis (in the first stage of inflammation) in the works of Sameva E. V., 2016, Midlenko V. I., et al., 2016 [22, 23].

Drug 1 is the biodegradable hydrogel that forms an elastic air — and water-permeable film on the wound surface, easily removed with normal saline or water. This gel has a high bactericidal activity against the main wound infection pathogens, which is due to the presence in its composition of antiseptics with different action mechanisms. The "drug 1" composition includes collagen hydrolysate, sodium salt of alginic acid, antiseptics with various mechanisms of action, sodium hypochlorite, glycerin and preservatives-nipagin, nipazol.

Certain advantages are: the use at all treatment stages, starting with prehospital both on the skin and on the mucous membranes, including intra-cavity interventions. This gel forms on the skin a gas-permeable film that is similar to the skin.

Patients who signed informed consent were divided into three groups: patients treated with drug 1 (group 1), treated with drug 2 (group 2) and voluntarily refused from the therapy (group 3). The distribution by groups was: 35, 32, 23 patients, respectively. The wound area was measured using a flexible centimeter and a centimeter pallet on days 1, 3, 5, 7, 9 of the study. In the case of intermediate wound healing between the days of pacification, the post — burn scar was measured. In the case of more than 9 days of wound healing, the patient was eliminated from the study with the treatment of drug 1 or drug 2 of the patient's choice. A clinical example of treatment of a patient with drug 1 with temperature reduction for 1, 3, 5, 7, 9 days is given.

The wound and wound area temperature was assessed using a portable thermal imager HT-A1 (Figure 1).

Fig. 1. Portable thermal imager HT-A1 (a) and thermal image obtained from the thermal camera HT-A1 (b).

Criteria for inclusion in the study:

The presence of a second-degree burn wound with an area of no more than 6 cm2, the presence of a signed informed consent.

Criteria for exclusion from the study:

The presence of any autoimmune diseases, the presence of lesions of the liver, bone marrow, spleen, the presence of oncological pathologies, the presence of immunodeficiency conditions.

Results

In the study course, a comparative effectiveness evaluation of the "drug 1" and "drug 2" using for the second-degree burn wounds treatment was carried out.

For patients in group 1, the obtained results are shown in Figure 2 and Table 1, 2.

Fig. 2. Change in the area of the wound (a) and the temperature of the wound area (b) during treatment with the Preparation 1.

Table 1. Changes in the area of the wound with treatment with Preparation 1 and Preparation 2 and without treatment

Days	Drug 1	Drug 2	Without treatment
1	4.542±0.174	4.51±0.202	4.317±0.235
3	4.452±0.178	4.376±0.21	4.317±0.235
5	3.947±0.165	4.221±0.217	4.154±0.24
7	3.019±0.157	3.504±0.22	3.896±0.269
9	1.897±0.113	2.5±0.231	2.875±0.291

Table 2. Change in the temperature of the wound area during treatment with Preparation 1 and Preparation 2 and without treatment

Days	Drug 1	Drug 2	Without treatment
1	29.4±0.501	29.5±1.05	30.0±1.05
3	30.8±1.01	30.0±0.8	30.3±0.604
5	31.5±0.804	30.8±1.03	30.8±0.301
7	31.8±1.01	31.3±1.08	31.0±0.304
9	32.0±0.6	31.8±1.01	31.3±1.06

For patients in group 2, the obtained results are shown in Figure 3 and Table 1, 2.

Fig. 3. Change in the area of the wound (a) and the temperature of the wound area (b) during the treatment with the Preparation 2.

For patients in group 3, the obtained results are shown in Figure 4 and Table 1, 2.

Fig. 4. Change in the area of the wound (a) and the temperature of the wound area (b) without treatment.

A clinical example is given. On Figure 5 changes in the temperature and area of the patient's wounds (20 years old, second-degree burn in the area of the little finger metacarpal joint) are shown.

Fig. 5. Changes in the area of the wound (a) and the temperature of the wound area (b) of a patient with a second-degree burn in the area of the little finger metacarpal-toe joint.

Healthy limb temperature: 32.3 °C.

Discussion

From the above data, it can be seen that both the biodegradable collagen-containing hydrogel (Drug 1) and the ointment (Drug 2) have a proven therapeutic effect for the second-degree burn wounds treatment. However, drug 1 has a slightly more pronounced effect, since the wound area in group 1 decreases faster than that in group 2 (Figure 6a). So, as a result of the difference between the initial and final values: for drug 1, it was 58.23%, for drug 2 — 44.57%, in the absence of treatment — 33.4%. Perhaps this is due to the difference in the composition of the funds, as part of the drug 2 is dioxotetrahydrofuran — stimulator of regeneration of tissues, while the drug 1 composition is such that is a more gradual increase in temperature. The collagen in drug 1 may not accelerate as much as it promotes a smoother flow of the natural healing process, which gives a more complete wound healing.

Fig. 6. Comparative graph of the reduction in the area of the wound (a) and changes in the temperature of the wound area (b) during the treatment with Preparation 1 and Preparation 2.

Also, during the study, the wound temperature was measured, which makes it possible to assume that there is a relationship between the wound temperature and the nonspecific activation of macrophage cells. Thus, from the above data, it can be seen that when using both drugs (1 and 2), the temperature of the wound area significantly decreases (Figure 6b) (and soon the wound area decreases), which may indicate the activation of macrophage cells, which is consistent with the results of studies Gu L. J., et al., 2014, Balbino B., et al., 2017, Prindeze NJ et al., 2014, but contradicts the study of Silva A. B., et al.., 2014 [24, 25, 26, 27]. The method of non-contact thermography, given in this study, allows you to diagnose various both primary and postoperative pathologies, due to the primary finding of the" healthy " temperature of the patient. This statement is consistent with the conclusions of Anisimov A. Yu ., Abbaszade T. N., 2015 and Sollai S., et al., 2016 [28, 29].

Conclusions

The use of biodegradable collagen-containing hydrogels in the small burn wounds treatment has a pronounced qualitative therapeutic effect, and the use of the method of non-contact thermometry allows to diagnose the disorder and determine its stage (if the patient "healthy" temperature is known).

The participation of the authors:

Concept and design of the study — A.D. Kashtanov, Yu.L. Vasiliev

Data collection and processing —A.D. Kashtanov, R.D. Meilanova

Statistical processing of the data —R.D. Meilanova

Text writing —A.D. Kashtanov

Editing — Yu.L. Vasiliev

The authors declare no conflicts of interest.