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Background. Due to the constant increase in the number of surgeries to restore blood flow in the affected vessels, the development of synthetic prostheses is relevant. One of the key success factors is an increase in the adhesive properties of the inner surface, since the rapid endothelialization of vascular prostheses is considered a factor necessary to prevent thrombosis and neointimal hypertrophy.Aim: To determine the effect of surface modification of polymer matrices with fibrin, fibronectin, or type I collagen on the adhesion and viability of endothelial cells.Material and Methods. Polymer matrices prepared by electrospinning from a mixture of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly(ε-caprolactone) were studied. Matrix samples were coated with type I collagen or fibronectin or fibrin. Then, human umbilical vein endothelial cells (HUVEC) were colonized on the matrices and cultured for 3 days. Unmodified matrices and culture plate wells were used as controls. Cell viability was assessed by combined staining with Hoechst 33342 and ethidium bromide. The metabolic activity of the cells was studied using the MTT test. Cell adhesion was analyzed by staining for F-actin. Statistical analysis of the results was performed using the GraphPrism 7.0 program.Results. It was found that the number of adherent cells and their metabolic activity of matrices with collagen did not differ from unmodified ones. Coating with fibronectin demonstrated higher rates of cell adhesion to the surface. However, a rather high level of cell death in this group indicates that such a modification cannot fully ensure the normal functioning of cells. Finally, we observed the best results when using a fibrin coating, which was comparable to culture plastic in terms of adhesion and viability of endothelial cells.Conclusion. Modification of the surface of polymer matrices with fibrin can significantly improve their adhesive properties and can be used in the development of polymer prostheses for small-diameter vessels.

Tissue-engineered vascular prostheses developed for prosthesis of small-diameter arteries have high biocompatibility and coverage of their patency after implantation into the vascular bed, and should also show a high probability of forming on their basis a newly formed tissue that is largely susceptible to native vascular tissue.Aim: To evaluate the expected patency of biodegradable vascular prostheses with athrombogenic drug coating in large laboratory animal models.Material and Methods. Vascular prostheses Ø 4 mm were fabricated by electrospinning from a polymer composition of 5% polyhydrosibutyrate/valeriate (PHBV) and 10% polycaprolactone (PCL) and a complex of proangiogenic tissues (GFmix): vascular endothelial growth (VEGF), rare fibroblast growth (bFGF) and chemoattractant molecule (SDF-1α). To induce thromboresistant properties of grafts, an athrombogenic modification of the surface of parts of the fabricated prostheses with heparin and iloprost was carried out. Modified prostheses were implanted in the carotid artery for a period of 12 months. The group with autoarterial implantation acted as a control.Results. In 12 months after implantation, the patency of auto-arterial grafts was 87.5%. The patency of PHBV/PCL/GFmix with heparin and iloprost reached 50% at the time of implantation. The biodegradable frame made of reinforced prostheses was almost completely resorbed with the formation of aneurysms throughout. In the modified prostheses, the main elements of the newly formed vascular tissue are present. There is no formation in the walls of the prostheses.Conclusion. The results showed that biodegradable vascular prostheses PHBV/PCL/GFmixHep/Ilo have a high final patency, which allows us to consider them suitable for the formation of newly formed vascular tissue on their basis. However, due to the aneurysm formation, a long-term execution of the bone tissue of the prosthesis and the thrombogenic properties of the inner surface are required.

Highlights. It is assumed that pre-colonization by endothelial cells of the inner surface of tissue-engineered vessels of small diameter can serve as an effective way to prevent thrombosis. The question of choosing the optimal source of endothelial cells for use in tissue engineering remains debatable. The paper considers the features of the culture of colony-forming endothelial cells obtained from the peripheral blood of patients with coronary heart disease, in comparison with mature endothelial cells from the coronary artery.Aim. To study the effect of laminar flow on the morphological and functional characteristics of mature endothelial cells and peripheral blood-derived endothelial colony-forming cells.Methods. Coronary artery endothelial cells were purchased from the Cell Applications, Inc. Colony-forming endothelial cells were obtained from the peripheral blood of patients with coronary artery disease who underwent percutaneous coronary intervention. The cells were isolated using a Ficoll gradient and cultured in EGM-2MV culture medium containing 5% fetal bovine serum. The cells of the experimental group were cultured in µ-Luer plates in a perfusion system with a shear stress of 3 dyn/cm2 . The cultivation time was 2 days. The cells of the control group were cultured under static conditions. At the end of the cultivation we performed immunofluorescent staining for CD31, KDR/CD309, CD144, vWF, type IV collagen, F-actin.Results. Colony-forming endothelial cells and coronary artery endothelial cells retained high density and viability both under static and laminar flow conditions. Shear stress stimulated a change in the phenotype of colony-forming endothelial cells towards a mature endothelial cells, in particular, a significant increased the expression of KDR/CD309 and CD31. The action of laminar flow reduced the synthesis of von Willebrand factor, stimulated the synthesis of type IV collagen. Shear stress promoted the development of structural rearrangements in cells in response to transduction, which manifested in a change in F-actin fibrils orientation on the flow direction.Conclusion. Colony-forming endothelial cells showed a characteristic response to the action of shear stress, consisting in a change in morphology, phenotype, and secretory activity of cells, comparable to that of coronary artery endothelial cells.

Highlights. The use of vascular smooth muscle cell markers, e.g. smooth muscle myosin heavy chain (SM-MHC) and alpha smooth muscle actin (α-SMA) for immunodetection of adventitial and perivascular microvessels (vasa vasorum) is preferrable over endothelial markers (CD31 and VE-cadherin) as it allows to define vascular geometry regardless of sectioning artifacts and provides ideal signal-to-noise ratio.Aside from elastic laminae which discriminate arterioles from venules and capillaries, we were unable to confirm any specific markers of arterial, venous, and capillary differentiation, although KLF2 and PROX1 transcription factors indicated venous specification and HEY1 suggested capillary identity in rat aortas.Aim. To develop an optimal approach to detection of microvessels and to evaluate the techniques for the differential immunostaining of arterioles, venules, and capillaries in human saphenous veins and rat aortas.Methods. Saphenous veins excised during the coronary artery bypass graft surgery were used for the study. Serial cryosections were analyzed by means of haematoxylin and eosin and Russell-Movat’s pentachrome stainings and by immunofluorescent staining for endothelial cell markers (CD31 and VE-cadherin), vascular smooth muscle cell markers (SM-MHC and α-SMA), mechanosensitive transcription factors (KLF2 and KLF4), transcription factors of arterial specification (HES1, HEY1, ERG), transcription factors and markers of venous identity (NR2F2, NRP2), and transcription factors and markers of lymphatic lineage (PROX1, LYVE1, VEGFR3). Samples were visualized by light and confocal microscopy.Results. In comparison with endothelial cell markers (CD31 and VE-cadherin), vascular smooth muscle cell markers (SM-MHC and α-SMA) permitted objective evaluation of vascular geometry and maximized signal-to-noise ratio irrespective of specific marker, microvessel specification or antibody used. Autofluorescence and specific histological pattern of elastic membranes at Russell-Movat’s pentachrome staining allowed to discriminate arterioles from venules and capillaries. Albeit immunostaining of rat aortas found specific markers of venous endothelial cells (KLF2 and PROX1) and capillary endothelial cells (HEY1), these findings have not been confirmed in saphenous veins. We were unable to find specific markers of human venules and capillaries among the saphenous vein vasa vasorum despite an extensive screening of multiple markers.Conclusion. Immunodetection of microvessels (e.g., vasa vasorum) should be performed by using vascular smooth muscle cell markers (SM-MHC and α-SMA) rather than endothelial cell markers (CD31 and VE-cadherin). Lack of specific markers to discern microvessels of different lineages suggests Russell-Movat’s pentachrome staining as an optimal option for the machine learning of neural networks to analyse the microvessels including vasa vasorum.

Highlights. Spontaneous endothelial-to-mesenchymal transition of primary human umbilical vein endothelial cells (HUVEC) is characterized by an acquired expression of SNAI2 and TWIST1 genes, loss of endothelial markers and transcription factors (CD31/PECAM1, VE-cadherin, and ERG transcription factor), pronounced expression of S100A4 and ACTA2 genes, and active production of type I collagen, a major component of the extracellular matrix.An optimal algorithm to detect endothelial-to-mesenchymal transition includes gene expression profiling of endothelial lineage markers (PECAM1, CDH5, VWF, ERG), SNAI2 and TWIST1 transcription factors, mesenchymal specification markers (FAP, S100A4, ACTA2) and markers of extracellular matrix synthesis (COL1A1, COL1A2) along with the subsequent negative staining for CD31/PECAM1, VE-cadherin, or ERG and positive staining for intracellular type I collagen.Aim. To develop an algorithm and tools to determine endothelial-to-mesenchymal transition (EndoMT) in vitro.Methods. We examined two batches of human umbilical vein endothelial cells (HUVEC) where the first cell batch had a conventional endothelial morphology and the second cell batch underwent a spontaneous EndoMT. Human coronary artery endothelial cells (HCAEC) and human internal thoracic artery endothelial cells (HITAEC) were used as the negative control for EndoMT. Molecular profile was assessed by means of reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunofluorescence staining with the further confocal microscopy.Results. In contrast to HUVEC with the physiological profile and arterial ECs, HUVEC undergoing EndoMT lost the expression of endothelial lineage markers (PECAM1, CDH5, VWF, ERG) and acquired the expression of EndoMT transcription factors (SNAI2, TWIST1), mesenchymal markers (FAP, S100A4, ACTA2), and extracellular matrix components (COL1A1, COL1A2) while retaining expression of the common vascular markers (HES1, NRP1). Western blotting analysis confirmed the loss of endothelial markers (CD31/PECAM1, VE-cadherin/CDH5, ERG) and demonstrated retained expression of abovementioned vascular markers. Negligible expression of MYH11 and SMTN genes encoding specific contractile markers (smooth muscle myosin heavy chain and smoothelin) in combination with the acquired expression of ACTA2 gene encoding less specific contractile marker alpha smooth muscle actin indicated the phenotypic identity of EndoMT-transformed HUVEC to myofibroblasts but not contractile vascular smooth muscle cells. Loss of immunofluorescence staining of endothelial markers (CD31/PECAM-1, VE-cadherin, and ERG transcription factor) and pronounced intracellular staining of type I collagen testified to the ongoing EndoMT.Conclusion. An algorithm to assess EndoMT implies measurement of the expression of PECAM1, CDH5, VWF, ERG, SNAI2, TWIST1, FAP, S100A4, ACTA2, COL1A1, and COL1A2 genes in combination with the respective immunofluorescence staining for CD31/PECAM-1, VE-cadherin, or ERG transcription factor and type I collagen.

Aim. To create a personalized cell-populated small-diameter vascular prosthesis in a pulsating bioreactor.Methods. Tubular grafts were made by electrospinning from mixtures of biodegradable polymers, poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(εcaprolactone) (PCL). The inner surface is modified with fibrin. Tubular scaffolds were colonized with cultured colony-forming endothelial cells and grown under static conditions for 2 days. Then, the cell-populated prostheses continued to be cultivated for 5 days in a pulsating bioreactor system with a final shear stress of 2.85 dynes/cm².Results. The advantages of the cultivation of cell-populated vascular prostheses in a pulsating bioreactor have been revealed. The selected mode of cultivation of cellpopulated vascular prostheses under conditions of a pulsating flow with a shear stress of 2.85 dynes/cm² did not have a damaging effect on the integrity of the endothelial monolayer. Moving unidirectional mechanical stimuli of chaotic orientation fibers of F-actin changed to a predominant orientation in the direction of flow, and also increased the expression of F-actin, Talin focal adhesion protein, and specific endothelial markers CD309, CD31, vWF.Conclusion. The creation of a personalized cell-populated small-diameter vascular prosthesis with a functional endothelial monolayer is possible due to the use of autologous endothelial cells, autologous fibrin, and cultivation under conditions of a pulsating flow.

Актуальность. Коммерческие сосудистые заплаты на основе синтетических материалов и тканей животного происхождения для реконструкции сонной артерии при каротидной эндартерэктомии обладают рядом недостатков, связанных с возникновением послеоперационных осложнений: тромбоза и рестеноза. Решением данной проблемы может стать разработка биологически активных материалов, способных к деградации и стимулирующих регенерацию тканей.Цель. Оценить свойства и эффективность биодеградируемой заплаты на основе полигидроксибутирата / валерата и поликапролактона с инкорпорированным фактором роста эндотелия сосудов в сравнении с немодифицированным полигидроксибутиратом / валератом и поликапролактоном и коммерческой сосудистой заплатой.Методы. Пористые заплаты из смеси полигидроксибутирата / валерата и поликапролактона с введенным фактором роста эндотелия сосудов изготавливали методом эмульсионного электроспиннинга. Далее изучали морфологию и механические свойства модифицированных заплат, а также имплантировали их в стенку брюшной аорты крыс на 1, 3, 6 и 12 мес. с последующим гистологическим и иммунофлуорисцентным анализом для оценки эндотелизации, заселения клетками и кальцификации.Результаты. Заплаты из полигидроксибутирата / валерата и поликапролактона c фактором роста эндотелия сосудов обладали высокопористой структурой и прочностью, не отличающейся от прочности аорты крысы и внутренней грудной артерии человека. На внутренней поверхности данных заплат через 3 мес. имплантации формировался эндотелиальный монослой. Заплаты из полигидроксибутирата / валерата и поликапролактона с фактором роста эндотелия сосудов быстрее заселялись клетками с формированием межклеточного матрикса относительно заплат из ксеноперикарда, и их ремоделирование не сопровождалось персистирующим воспалением, которое провоцировали немодифицированные образцы полигидроксибутирата / валерата и поликапролактона при долгосрочной имплантации.Выводы. Фактор роста эндотелия сосудов в составе биодеградируемых заплат из полигидроксибутирата / валерата и поликапролактона стимулировал их эндотелизацию и увеличивал биосовместимость, способствовал ремоделированию с образованием элементов стенки кровеносного сосуда. Таким образом, заплаты из полигидроксибутирата / валерата и поликапролактона с фактором роста эндотелия сосудов имеют высокий потенциал применения в тканевой инженерии сосудистой стенки.Поступила в редакцию 2 июня 2020 г. Исправлена 27 июня 2020 г. Принята 16 июля к печати 2020 г.Конфликт интересовАвторы заявляют об отсутствии конфликта интересов.ФинансированиеРабота выполнена при поддержке комплексной программы фундаментальных научных исследований СО РАН в рамках фундаментальной темы НИИ КПССЗ № 0546-2019-0002 «Патогенетическое обоснование разработки имплантатов для сердечно-сосудистой хирургии на основе биосовместимых материалов, с реализацией пациент-ориентированного подхода с использованием математического моделирования, тканевой инженерии и геномных предикторов».Вклад авторовКонцепция и дизайн работы: В.В. Севостьянова, А.В. Миронов, Л.В. Антонова, Р.С. Тарасов, Л.С. БарбарашСбор и анализ данных: В.В. Севостьянова, А.В. Миронов, Л.В. Антонова, Е.О. Кривкина, В.Г. Матвеева, Е.А. Великанова, Т.В. Глушкова Статистическая обработка данных: В.В. Севостьянова, Глушкова Т.В.Написание статьи: В.В. Севостьянова, А.В. МироновИсправление статьи: Л.В. Антонова, Р.С. Тарасов, Л.С. БарбарашУтверждение окончательной версии: все авторы

Here, we discuss pathophysiological approaches to the defining of endothelial dysfunction criteria (i.e., endothelial activation, impaired endothelial mechanotransduction, endothelial-to-mesenchymal transition, reduced nitric oxide release, compromised endothelial integrity, and loss of anti-thrombogenic properties) in different in vitro and in vivo models. The canonical definition of endothelial dysfunction includes insufficient production of vasodilators, pro-thrombotic and pro-inflammatory activation of endothelial cells, and pathologically increased endothelial permeability. Among the clinical consequences of endothelial dysfunction are arterial hypertension, macro- and microangiopathy, and microalbuminuria. We propose to extend the definition of endothelial dysfunction by adding altered endothelial mechanotransduction and endothelial-to-mesenchymal transition to its criteria. Albeit interleukin-6, interleukin-8, and MCP-1/CCL2 dictate the pathogenic paracrine effects of dysfunctional endothelial cells and are therefore reliable endothelial dysfunction biomarkers in vitro, they are non-specific for endothelial cells and cannot be used for the diagnostics of endothelial dysfunction in vivo. Conceptual improvements in the existing methods to model endothelial dysfunction, specifically, in relation to the blood-brain barrier, include endothelial cell culturing under pulsatile flow, collagen IV coating of flow chambers, and endothelial lysate collection from the blood vessels of laboratory animals in situ for the subsequent gene and protein expression profiling. Combined with the simulation of paracrine effects by using conditioned medium from dysfunctional endothelial cells, these flow-sensitive models have a high physiological relevance, bringing the experimental conditions to the physiological scenario.

The article presents the results of determining the expiry date of Grushevaya food supplement obtained from the secondary resources of the processing of «Conference» pears. The use of secondary resources to obtain finished products in the form of food additives and the assessment of their consumer properties is an urgent task. One of the important consumer properties of food products is its storability along with organoleptic, physical and chemical and functional properties, as well as safety and nutritional value, which determines its shelf life,The aim of the research is to determine the shelf life of Grushevaya supplement. Changes in microbiological safety indicators during storage of Grushevaya food supplement, namely, the number of mesophilic aerobic and facultative anaerobic microorganisms (QMAFAnM), the number of molds, bacteria of Escherichia coli group (coliforms) and pathogenic microorganisms have been studied, and 18 months period has been established as its shelf life. It has been found that during the shelf life the loss of vitamin C and polyphenolic compounds in its composition is 5.5 % and 4.8 %, respectively. It has been revealed that the antioxidant activity, determined in experiments in vitro and in vivo of the food supplement after 18 months of storage differs slightly compared with those for a freshly prepared supplement.The same pattern has been established in in vivo experiments on manifestation of hepatoprotective properties in freshly prepared supplement after 18 months of storage.

Secondary apple processing resources – apple pomace formed during the production of direct-squeezed juice, serve as a valuable source of a complex of antioxidants such as phenolic compounds, contain dietary fiber, including pectin, cellulose and hemicelluloses, B vitamins, macro and trace elements. The article overviews modern research in the field of obtaining food ingredients from the secondary resources of apple processing.So, apple pomace has been studied by many researchers as a promising source of biologically active phenolic compounds, which are used in the food, pharmaceutical and cosmetic industries due to their high antioxidant and antimicrobial activity. Apple pomace is used as raw material for pectins due to the widespread use of pectin in the food industry (production of marshmallows, marmalade, confiture, jams, sausages, juices, yogurts, bakery products and other products), medicine and pharmaceuticals (production of baby granules, suspensions, gels, for imparting viscosity to emulsions, binding of heavy metal ions, healing of wounds, development of nutrient media), the cosmetics industry (production of certain types of face masks and gels).As a result of bioconversion of apple pomace, a number of edible organic acids of the L form can be obtained: acetic, citric and lactic acids. A review of modern foreign studies in the field of obtaining food ingredients from apple pomace showed the promise of their use as a valuable raw material, as well as the relevance and need for the development of domestic highly effective innovative technologies for the production of phenolic compounds, pectin and food organic acids to solve the problems of import substitution.

Modification by Arg-Gly-Asp (RGD) peptides is a promising approach to improve the biocompatibility of biodegradable vascular patches for arteriotomy. In this study, we evaluated the performance of vascular patches electrospun using a blend of polycaprolactone (PCL) and polyhydroxybutyrate/valerate (PHBV) and additionally modified with RGDK, AhRGD, and c[RGDFK] peptides using 1,6-hexamethylenediamine or 4,7,10-trioxa-1,13-tridecanediamine (TTDDA) linkers. We examined mechanical properties and hemocompatibility of resulting patches before implanting them in rat abdominal aortas to assess their performance in vivo. Patches were explanted 1, 3, 6, and 12 months postoperation followed by histological and immunofluorescence analyses. Patches manufactured from the human internal mammary artery or commercially available KemPeriplas-Neo xenopericardial patches were used as a control. The tensile strength and Fmax of KemPeriplas-Neo patches were 4- and 16.7-times higher than those made of human internal mammary artery, respectively. Both RGD-modified and unmodified PHBV/PCL patches demonstrated properties similar to a human internal mammary artery patch. Regardless of RGD modification, experimental PHBV/PCL patches displayed fewer lysed red blood cells and resulted in milder platelet aggregation than KemPeriplas-Neo patches. Xenopericardial patches failed to form an endothelial layer in vivo and were prone to calcification. By contrast, TTDDA/RGDK-modified biodegradable patches demonstrated a resistance to calcification. Modification by TTDDA/RGDK and TTDDA/c[RGDFK] facilitated the formation of neovasculature upon the implantation in vivo.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

Tissue-engineered vascular graft for the reconstruction of small arteries is still an unmet clinical need, despite the fact that a number of promising prototypes have entered preclinical development. Here we test Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)Poly(ε-caprolactone) 4-mm-diameter vascular grafts equipped with vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and stromal cell-derived factor 1α (SDF-1α) and surface coated with heparin and iloprost (PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo, n = 8) in a sheep carotid artery interposition model, using biostable vascular prostheses of expanded poly(tetrafluoroethylene) (ePTFE, n = 5) as a control. Primary patency of PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts was 62.5% (5/8) at 24 h postimplantation and 50% (4/8) at 18 months postimplantation, while all (5/5) ePTFE conduits were occluded within the 24 h after the surgery. At 18 months postimplantation, PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts were completely resorbed and replaced by the vascular tissue. Regenerated arteries displayed a hierarchical three-layer structure similar to the native blood vessels, being fully endothelialised, highly vascularised and populated by vascular smooth muscle cells and macrophages. The most (4/5, 80%) of the regenerated arteries were free of calcifications but suffered from the aneurysmatic dilation. Therefore, biodegradable PHBV/PCL[VEGF-bFGF-SDF]Hep/Ilo grafts showed better short- and long-term results than bio-stable ePTFE analogues, although these scaffolds must be reinforced for the efficient prevention of aneurysms.

Tissue-engineered vascular grafts are widely tested as a promising substitute for both arterial bypass and replacement surgery. We previously demonstrated that incorporation of VEGF into electrospun tubular scaffolds from poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(ε-caprolactone) enhances formation of an endothelial cell monolayer. However, an overdose of VEGF can induce tumor-like vasculature, thereby, other bioactive factors are needed to support VEGF-driven endothelialization and successful recruitment of smooth muscle cells. Utilizing emulsion electrospinning, we fabricated one-layer vascular grafts with either VEGF, bFGF, or SDF-1α, and two-layer vascular grafts with VEGF incorporated into the inner layer and bFGF and SDF-1α incorporated into the outer layer with the following structural evaluation, tensile testing, and in vivo testing using a rat abdominal aorta replacement model. The latter graft prototype showed higher primary patency rate. We found that the two-layer structure improved surface topography and mechanical properties of the grafts. Further, the combination of bFGF, SDF-1α, and VEGF improved endothelialization compared with VEGF alone, while bFGF induced a rapid formation of a smooth muscle cell layer. Taken together, these findings show that the two-layer structure and incorporation of bFGF and SDF-1α into the vascular grafts in combination with VEGF provide a higher primary patency and therefore improved in vivo performance.

Wound healing is a complex process and an ongoing challenge for modern medicine. Herein, we present the results of study of structure and properties of ferroelectric composite polymer membranes for wound healing. Membranes were fabricated by electrospinning from a solution of vinylidene fluoride/tetrafluoroethylene copolymer (VDF&ndash, TeFE) and polyvinylpyrrolidone (PVP) in dimethylformamide (DMF). The effects of the PVP content on the viscosity and conductivity of the spinning solution, DMF concentration, chemical composition, crystal structure, and conformation of VDF&ndash, TeFE macromolecules in the fabricated materials were studied. It was found that as PVP amount increased, the viscosity and conductivity of the spinning solutions decreased, resulting in thinner fibers. Using FTIR and XRD methods, it was shown that if the PVP content was lower than 50 wt %, the VDF&ndash, TeFE copolymer adopted a flat zigzag conformation (TTT conformation) and crystalline phases with ferroelectric properties were formed. Gas chromatography results indicated that an increase in the PVP concentration led to a higher residual amount of DMF in the material, causing cytotoxic effects on 3T3L1 fibroblasts. In vivo studies demonstrated that compared to classical gauze dressings impregnated with a solution of an antibacterial agent, ferroelectric composite membranes with 15 wt % PVP provided better conditions for the healing of purulent wounds.

Herein, we report results of the study of the composite ferroelectric scaffolds based on vinylidene fluoride-tetrafluoroethylene copolymer (VDF-TeFE) and polyvinylpyrrolidone (PVP) produced by electrospinning and their application as a wound-healing material. The physicochemical properties of ferroelectric composite polymer scaffolds depending on the content of PVP (in the range from 0 to 50 wt %) including morphology, composition and crystalline structure were studied. The cytotoxicity of materials and the proliferative activity of cells during their cultivation on the surface of formed scaffolds are reported. It has been found that the optimal PVP content in the VDF-TeFE composite scaffolds is 15 wt%. On a model of a full-thickness contaminated wound in vivo, it was shown that piezoelectric scaffolds based on VDF-TeFE copolymer containing 15 wt% PVP provide better wound healing results in comparison with standard gauze dressings impregnated with a solution of an antibacterial agent.

Endothelial colony-forming cells (ECFC) are currently considered as a promising cell population for the pre-endothelialization or pre-vascularization of tissue-engineered constructs, including small-diameter biodegradable vascular grafts. However, the extent of heterogeneity between ECFC and mature vascular endothelial cells (EC) is unclear. Here, we performed a transcriptome-wide study to compare gene expression profiles of ECFC, human coronary artery endothelial cells (HCAEC), and human umbilical vein endothelial cells (HUVEC). Characterization of the abovementioned cell populations was carried out by immunophenotyping, tube formation assay, and evaluation of proliferation capability while global gene expression profiling was conducted by means of RNA-seq. ECFC were similar to HUVEC in terms of immunophenotype (CD31+vWF+KDR+CD146+CD34-CD133-CD45-CD90-) and tube formation activity yet had expectedly higher proliferative potential. HCAEC and HUVEC were generally similar to ECFC with regards to their global gene expression profile, nevertheless, ECFC overexpressed specific markers of all endothelial lineages (NRP2, NOTCH4, LYVE1), in particular lymphatic EC (LYVE1), and had upregulated extracellular matrix and basement membrane genes (COL1A1, COL1A2, COL4A1, COL4A2). Proteomic profiling for endothelial lineage markers and angiogenic molecules generally confirmed RNA-seq results, indicating ECFC as an intermediate population between HCAEC and HUVEC. Therefore, gene expression profile and behavior of ECFC suggest their potential to be applied for a pre-endothelialization of bioartificial vascular grafts, whereas in terms of endothelial hierarchy they differ from HCAEC and HUVEC, having a transitional phenotype.

Polymeric heart valves seem to be an attractive alternative to mechanical and biological prostheses as they are more durable, due to the superior properties of novel polymers, and have the biocompatibility and hemodynamics comparable to tissue substitutes. This study reports a comprehensive assessment of a nanocomposite based on the functionalised graphene oxide and poly(carbonate-urea)urethane with the trade name “Hastalex” in comparison with GORE-TEX, a commercial polymer routinely used for cardiovascular medical devices. Experimental data have proved that GORE-TEX has a 2.5-fold (longitudinal direction) and 3.5-fold (transverse direction) lower ultimate tensile strength in comparison with Hastalex (p

Background Currently, the search for the bioactive molecules capable of promoting formation of the vascular tissue is still ongoing. We have previously demonstrated that incorporation of the growth factors and chemoattractant molecules into the biodegradable tubular scaffolds can increase their primary patency upon the implantation into rat abdominal aorta. However, further studies are required to investigate tissue remodeling using functionalized vascular grafts with the same diameter as a replaced native vessel. Aim To investigate the specific aspects of de novo vascular tissue formation and calcification employing rat abdominal aorta interposition model and vascular grafts with 1.5 mm diameter with incorporated vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and stromal cell-derived factor (SDF)-1α. Methods Tubular grafts with a diameter of 1.5 mm were blended of poly(3-hydroxybutyrateco-3-hydroxyvalerate) and poly(ε-caprolactone) (PHBV/PCL). Grafts without growth factors were fabricated using standard electrospinning technique whilst grafts with incorporated growth factors were prepared utilizing emulsion electrospinning. VEGF was incorporated into the inner third, whereas bFGF and SDF-1α were incorporated into the outer two-thirds of the graft. Grafts were implanted into the abdominal aortas of Wistar rats for 1, 3, 6, and 12 months following scanning electron microscopy along with histological and immunofluorescent examination. Results Primary patency of the grafts with VEGF, bFGF, and SDF-1α reached 93% indicative of structural integrity of the vascular tissue. Neither signs of inflammation nor severe calcification was detected. Conclusion As in 2 mm diameter vascular grafts, incorporation of bioactive factors into 1.5 mm diameter grafts increased their long-term primary patency and improved vascular tissue formation in comparison with non-modified grafts.

The results of the research on the effect of “Pear Powder” food additive on the quality and properties of first grade wheat flour are presented. It’s been determined that adding of the investigated food additive to the first grade wheat flour has a strengthening effect on gluten flour, which converts the gluten flour from quality group II to quality group I. It is shown that adding food additive to wheat flour provides an increase in its gas-forming ability, that is due to the presence of sugars, minerals and organic acids in the additive, that contribute to the intensification of the gassing process.

The article presents the results of the investigation of NMR characteristics of protons contained in sunflower lecithins. The basic requirements for creating NMR simulant samples of proton characteristics contained in sunflower lecithins are formulated. The results of the investigation of NMR characteristics of organosilicon fluids of various brands are presented in order to select the most effective simulant samples. The composition of simulant samples of NMR proton characteristics contained in sunflower lecithins is developed, the application of which will significantly simplify the process of calibration and verification of NMR analyzers.

The article presents the results of the study of the effect of "Pear powder" food additive on baking pressed yeast activation. It is established that the use of the studied food additive in the process of activating baking pressed yeast has a positive effect on their lifting power. It is revealed that the introduction of the studied "Pear powder" food additive in the amount of 1.5% to the mass of flour at the stage of activation of baking pressed yeast reduces the duration of the activation process by 1 hour.

The deposition of thin titanium coatings using magnetron spattering on the surface of bioresorbable fibrous scaffolds produced by electrospinning was investigated. Parameters that allow the surface modification without damaging the “macro” structure of scaffolds were determined. Physicochemical properties of the modified scaffolds were described using SEM, EDS, DSC, optical goniometry, and mechanical testing. It was shown that plasma treatment has a significant influence on the scaffolds’ fiber surface relief. The modification process leads to a slight decrease of the scaffold mechanical performance mainly caused by polymer crystallization. Increasing the deposition time increases the amount of titanium on the surface. The biocompatibility of the modified scaffolds was studied using hybridoma of the endothelial cells of human umbilical vein and human lung carcinoma (EA.hy 926 cell line). Cell adhesion, viability, and secretion of interleukin-6 (IL6), interleukin-8 (IL8), and vascular endothelial growth factor (VEGF) were investigated. It was demonstrated that the deposition of thin titanium coatings on the fibrous scaffolds’ surface enhances cell adhesion. Additionally, it was determined that modified scaffolds have proangiogenic activity.

The article tells about the most common bacterial infection in the world - pneumococcal disease, in particular, pneumococcal meningitis, which is the second most common purulent meningitis and the most common cause of mortality and severe neurological deficits in recovered patients. A clinical case of severe pneumococcal meningitis in infant is described in detail.

Calcium phosphate bions (CPBs) are formed under blood supersaturation with calcium and phosphate owing to the mineral chaperone fetuin-A and representing mineralo-organic particles consisting of bioapatite and multiple serum proteins. While protecting the arteries from a rapid medial calcification, CPBs cause endothelial injury and aggravate intimal hyperplasia in balloon-injured rat aortas. Here, we asked whether CPBs induce intimal hyperplasia in intact rat arteries in the absence of cardiovascular risk factors. Normolipidemic Wistar rats were subjected to regular (once/thrice per week over 5 weeks) tail vein injections of either spherical (CPB-S) or needle-shaped CPBs (CPB-N), magnesium phosphate bions (MPBs), or physiological saline (n = 5 per group). Neointima was revealed in 3/10 and 4/10 rats which received CPB-S or CPB-N, respectively, regardless of the injection regimen or blood flow pattern in the aortic segments. In contrast, none of the rats treated with MPBs or physiological saline had intimal hyperplasia. The animals also did not display signs of liver or spleen injury as well as extraskeletal calcium deposits. Serum alanine/aspartate transaminases, interleukin-1&beta, MCP-1/CCL2, C-reactive protein, and ceruloplasmin levels did not differ among the groups. Hence, CPBs may provoke intimal hyperplasia via direct endothelial injury regardless of their shape or type of blood flow.

Carotid endarterectomy using vascular patches is associated with a large number of complications, thereby necessitating the development of novel biocompatible materials suitable for the reconstruction of the vascular wall. A promising approach to overcome this problem is to use a combination of a biodegradable polymer and bioactive molecules that stimulate the regeneration of vascular tissue. In this study, porous vascular patches were made from polycaprolactone (PCL) with incorporated vascular endothelial growth factor (VEGF) molecules using emulsion electrospinning. Their morphology, mechanical properties, and ability to regenerate in vivo were assessed and compared with original PCL patches and commercially available xenopericardial patches. PCL/VEGF patches had a highly porous structure and strength similar to that of the native artery. After the implantation into the rat aortic wall, these patches were populated faster by cells with the formation of the inner endothelial layer and the extracellular matrix compared to xenopericardial and original PCL patches. PCL/VEGF patches maintained their integrity and were less susceptible to calcification in the long-term period.

An important area of tissue engineering is the development of small-dimeter vascular grafts. In our study we assessed whether an electrospun polymer scaffold is beneficial for developing a tissue-engineered graft. The polymeric grafts were made from a blend of polyhydroxybutyrate/valerate and polycaprolactone (PHBV/PCL) and added type I collagen. Additionally, the grafts were treated with fibronectin. Cells were isolated from the peripheral blood of patients with coronary artery disease (CAD) and then seeded on the luminal graft surface. Then, the grafts with cells were cultured in a pulsatile flow bioreactor. We confirmed that separate feeding of PHBV/PCL and type I collagen during electrospinning allows developing a scaffold for a vascular graft suitable for maintaining the viability of the endothelial layer on the luminal surface.

Developed for bypass surgery, tissue-engineered vascular grafts should remain passable after implantation and have high rate of endothelialization to ensure long-term patency, atrombogenicity and biocompatibility. This study was aimed at assessing the long-term patency of polyhydroxybutyrate/valerate (PHBV)/polycaprolactone (PCL) vascular grafts modified by pro-angiogenic factors and athrombogenic drug coating in a large laboratory animal model.