Background: There is a need for better strategies to promote burn wound healing and prevent infection. The aim of our study was to develop an easy-to-use placental multipotent mesenchymal stromal cell (MMSC) secretome-based chitosan hydrogel (MSC-Ch-gel) and estimate its antimicrobial and regenerative activity in Staphylococcus aureus-infected burn wounds in rats. Methods: Proteomic studies of the MMSC secretome revealed proteins involved in regeneration, angiogenesis, and defence responses. The MMSC secretome was collected from cultured cells and mixed with water-soluble chitosan to prepare the placental MSC-Ch-gel, which was stored in liquid phase at 4 °C. The wounds of rats with established II-IIIa-degree burns were then infected with S. aureus and externally covered with the MSC-Ch-gel. Three additional rat groups were treated with medical Vaseline oil, the antiseptic drug Miramistin®, or the drug Bepanthen® Plus. Skin wound samples were collected 4 and 8 days after burning for further microbiological and histological analysis. Blood samples were also collected for biochemical analysis. Results: Application of the MSC-Ch-gel cleared the wound of microorganisms (S. aureus wasn’t detected in the washings from the burned areas), decreased inflammation, enhanced re-epithelialisation, and promoted the formation of well-vascularised granulation tissue. Conclusions: MSC-Ch-gel effectively promotes infected wound healing in rats with third-degree burns. Gel preparation can be easily implemented into clinical practice.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is a common clinical problem, leading to significant morbidity and mortality, and no effective pharmacotherapy exists. The problem of ARDS causing mortality became more apparent during the COVID-19 pandemic. Biotherapeutic products containing multipotent mesenchymal stromal cell (MMSC) secretome may provide a new therapeutic paradigm for human healthcare due to their immunomodulating and regenerative abilities. The content and regenerative capacity of the secretome depends on cell origin and type of cultivation (two- or three-dimensional (2D/3D)). In this study, we investigated the proteomic profile of the secretome from 2D- and 3D-cultured placental MMSC and lung fibroblasts (LFBs) and the effect of inhalation of freeze-dried secretome on survival, lung inflammation, lung tissue regeneration, fibrin deposition in a lethal ALI model in mice. We found that three inhaled administrations of freeze-dried secretome from 2D- and 3D-cultured placental MMSC and LFB protected mice from death, restored the histological structure of damaged lungs, and decreased fibrin deposition. At the same time, 3D MMSC secretome exhibited a more pronounced trend in lung recovery than 2D MMSC and LFB-derived secretome in some measures. Taking together, these studies show that inhalation of cell secretome may also be considered as a potential therapy for the management of ARDS in patients suffering from severe pneumonia, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, their effectiveness requires further investigation.

The aim of the investigation is to assess the influence of salt load on atrial (ANP) and brain (BNP) natriuretic peptide production in granules of secretory cardiomyocytes in rats.Materials and Methods. The experiments were carried out on 14 white out-bred male Wistar rats weighing 280-300 g. During the experiment all the animals were treated with standard-feed diet and had unlimited access to food and water. NaCl solution was introduced per os in the dose of 1 g per 1 kg of body mass during 14 days. Arterial pressure (AP) was measured noninvasively using a tail-cuff method. ANP and BNP production of atrial cardiomyocytes was studied by means of immunohistochemistry, transmission electron microscopy, immunocytochemistry. There was performed a morphometric analysis of granules containing peptides (A-type -"mature, storing" and B-type -"dissolving").Results. Increase in the number of granules with ANP and decrease in those with BNP accompanied by elevated AP was revealed 14 days after NaCl intake as compared to intact animals.Conclusion. Natriuretic peptides metabolism is regulated by various mechanisms. Early BNP release does not promote AP reduction due to compensatory mechanism disturbance in salt-induced arterial hypertension. Increase in ANP production occurs under the influence of renin-angiotensin-aldosterone system and elevated AP. The present data can indicate adaptive reaction in response to salt loading.

The aim of the investigation was to assess the possibilities of application of the polymer matrix made from Reperen material for closing open wound surface on the mucous membrane of the oral cavity.Materials and Methods. Experimental investigation was carried out on 15 Chinchilla rabbits. Half of the created defect on the hard palate mucous membrane healed under the Reperen polymer matrix, and the other half healed by secondary intention. The results of the histological and cytological examination were assessed on day 3, 5, and 7.Results. The area of granulation and connective tissue in the specimens of mucosa, healing without the Reperen matrix on day 5 amounted to 25.0±1.2 and 15.0±1.1%, and on day 7 -15.0±1.2 and 25.0±1.7%, respectively. Meanwhile, in the specimens of mucous membrane, healing under the Reperen polymer matrix, their values have essentially changed: they were 25.0±1.2 and 20.0±1.1% on day 3, and 10.0±1.3 and 40.0±1.7% on day 7.Conclusion. The Reperen polymer matrix promotes intensification of the local regenerative processes in the wound and can be used for closing large open wound surfaces on the mucous membrane of the oral cavity.

The aim of the investigation was to study toxic properties (chronic toxicity, local irritant and sensitizing effects) of medical products Hydrogel RS and Microgel RS, intended for use in regenerative medicine as implants for replacing defects of soft and bone tissues, treatment of deep burns and for in vitro cell culturing when testing medications.Materials and Methods. The work was carried out on outbred Wistar rats, Chinchilla rabbits, guinea pigs. There was investigated chronic toxicity, local irritant and sensitizing effects of medical products Hydrogel RS and Microgel RS (GosNIIGenetika, Russia) based on recombinant spidroin (with cutaneous and intramuscular routes of administration). While investigating chronic toxicity, there were recorded integral, hematological, biochemical indices. Local irritation was studied by pathomorphological examination of the areas of medical product introduction. Sensitization was studied using maximization method and closed epicutaneous applications.Results. Medical products Hydrogel RS and Microgel RS were found to be relatively safe when used during 90 days, they have no irritant effect when introduced epicutaneously and intramuscularly, no sensitizing properties and can be recommended for clinical testing.Conclusion. Medical products Hydrogel RS and Microgel RS can be recommended for clinical testing as implants for replacing defects of soft and bone tissues, treatment of deep burns and for in vitro cell culturing in testing medicines.