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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.

Aim. To evaluate the potential utility of fibrin matrices containing 10, 20, and 25 mg/ml of fibrinogen (fibrin-10, fibrin-20, and fibrin-30, respectively) in vascular tissue engineering (VTE). Materials and Methods. Fibrinogen was isolated using the method of ethanol cryoprecipitation and polymerized using a solution of thrombin and CaCl2. The fibrin structure was studied in a scanning electron microscope, and the physical and mechanical properties of the material were tested on a Zwick/Roell test machine. The metabolic activity of endothelial cells (EC) on the fibrin surface was evaluated by the MTT assay, and the viability of fibroblasts in the thickness of fibrin and possibility for migration by in fluorescent and light microscopy. Percent of fibrin shrinkage was determined from the difference in the sample volumes before and after removal of moisture. Results. The fiber diameter did not differ among all fibrin samples, but the pore diameter in fibrin-30 was smaller than those in fibrin-10 and fibrin-20. A possibility for migration of fibroblasts into the depth of the fibrin matrix and preservation of 97-100% viability of cells at a depth 5 mm was confirmed. The metabolic activity of EC on the surface of fibrin-20 and fibrin-30 exceeded that on collagen, fibronectin, and fibrin-10. All fibrin samples shrank in volume to 95.5-99.5%, and the highest shrinkage was seen in fibrin-10. The physical and mechanical properties of fibrin were inferior to those of human A. mammaria by a factor of 10. Conclusion. Fibrin with fibrinogen concentrations of 20 and 30 mg/ml maintains a high metabolic and proliferative activity of EC on the surface and also a high viability of fibroblasts in the matrix. Its availability, ease of preparation, and a number of other favorable properties make fibrin a promising material for VTE. However, the problem of insufficient strength requires further investigations.

Objective. To study the dynamics of immunosuppressive cell populations in patients who underwent heart valve replacement surgery under artificial circulation. Materials and methods. We investigated the dynamics of MDSC, PD-1-positive cells among Th and Tcyt and PD-L1-positive monocytes in patients operated on for the heart under cardiopulmonary bypass in the volume of prosthetic heart valves, the study points were before surgery, immediately after surgery and after 1, 3, 7 days. The study was carried out on a CytoFlex laser flow cytometer. Results. In the group of patients without complications and in the group with complications outside the infection, an increase in all MDSC populations was observed 1 day after surgery, with a return to baseline values within a week. The dynamics of MDSC in a patients with sepsis was characterized by an increase within 3 days with the achievement of maximum figures in comparison with the previous groups. In patients without complications, an increase in PD-L1+, PD-1+ CD4+ and PD-1+CD8+ monocytes were observed immediately after surgery and one day later. In the case of the development of infectious complications in the postoperative period, a relatively moderate increase in the monocyte content was observed only by 3 days after the operation. The content of PD-1 positive T cells increased moderately up to 7 days among Th, and significantly by 7 days, followed by a decrease among Tcyt. Conclusions. A high initial content of Mon-MDSC is a risk factor for the development of postoperative infectious complications. A significant increase in immunosuppressive populations in the early postoperative period can be regarded as an unfavorable variant of the course of the compensatory anti-inflammatory syndrome.

This review looks at the use of fibrin in vascular tissue engineering (VTE). Autologous fibrin is one of the most affordable biopolymers because it can be obtained from peripheral blood by simple techniques. A description and comparative analysis of the methods and approaches for producing fibrin gel is provided. The ability of fibrin to promote cell attachment and migration, survival and angiogenesis, to accumulate growth factors and release them in a controlled manner, are unique and extremely useful in VTE. Fibrin gels can serve as a three-dimensional matrix molded in different sizes and shapes to be applied in a variety of ways, including as a scaffold, coating, or impregnation material. Fibrin’s high porosity and biodegradability allows controllable release of growth factors, yet fibrinolysis must be tightly regulated to avoid side effects. We discuss the main methods of regulating the rate of fibrinolysis, as well as possible side effects of such exposure. Low mechanical strength is the main limitation in using fibrin as a scaffold for vascular tissue engineering. Possible options for increasing the strength properties of fibrin matrix and evaluating their effectiveness are presented. We propose that unique biocompatibility and ideal biodegradation profile of fibrin justify its use as a scaffold material for developing an ideal fully autologous small-diameter tissue-engineered vascular graft.

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.

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.

Aim. To study adipokine-cytokine profile of epicardial adipocytes (EAT) and subcutaneous adipose tissue (SAT) in conjunction with the area of visceral adipose tissue (VAT), biochemical and clinical characteristics of patients with coronary heart disease. Materials and methods. Examined 84 patients (70 men and 14 women) with coronary artery disease. In fact the presence of visceral obesity (VO) the patients were divided into two groups. Patients VO the sampling of adipocytes of EAT and SAT, with subsequent cultivation and evaluation of adipokine and provospalitelna activity. Carried out the determination of carbohydrate and lipid metabolism, adipokine and pro-inflammatory status in the blood serum. Results and discussion. It was found that adipokine-cytokine profile of adipocytes of EAT and SAT differ. Adipocytes art of the disease on the background characterized by an increase IL-1, TNF-α, leptin-adiponectin relationships and a decrease in the content of protective factors: adiponectin and anti-inflammatory cytokine IL-10. While the SAT adipocytes was characterized by a decrease in the concentration of soluble receptor for leptin and the more pronounced leptinresistance, and the increase in proinflammatory cytokines was offset by the increase in the concentration of IL-10. The presence associated with multi-vessel coronary bed lesion, multifocal atherosclerosis, insulin resistance, atherogenic dyslipidemia, an imbalance of adipokines and markers of inflammation. So the value of the square VAT determined higher concentrations of leptin, TNF-α in adipocytes and serum, lipid and carbohydrate metabolism and a lower content of soluble receptor for leptin. Conclusion. Thus, the disease on the background of the status of the adipocytes of EAT characterized as a "metabolic inflammation", and may indicate the direct involvement of adipocytes in the pathogenesis of coronary artery disease, due to the formation of adipokine imbalance and the activation of proinflammatory reactions.

In the present work the production method influence (solution blow spinning and electrospinning) on the structure and properties of the ferroelectric nonwoven materials based on VDF-TeFE copolymer is investigated. It was shown that the nonwoven materials obtained by electrospinning have smooth cylindrical-shaped fibers with a narrow diameter distribution, whereas the nonwoven materials produced by solution blow spinning are characterized by multi-level spatial organization with the fibers having their own advanced morphology. By using DSC and XRD analysis it was found that the nonwoven materials obtained by electrospinning have higher content of the electrically active phases. Also these materials have higher strength owing to their morphological and structural features. It was shown that both types of nonwoven materials are non-toxic. A higher adhesion of stem cells and cells from EA-hy 926 cell line to nonwoven materials produced by solution blow spinning was observed.

Poly-e-caprolactone (PCL) biodegradable fibrous scaffolds were modified by plasma of magnetron discharge with titanium target sputtering. The influence of the plasma treatment time on the structure and properties of the electrospun scaffolds was investigated. It was shown that increasing the plasma treatment time increases hydrophilicity of scaffolds by increasing the content of titanium and oxygen, as well as increasing the size and number of pores on the fibers surface without changing the mean diameter and volume fraction of the scaffolds. In vitro studies demonstrated that the plasma treatment within the chosen time intervals increases the adhesion of cells to the scaffolds, but at the same time it causes the decline in cell viability when increased to 9 min.

Background. Commercially available synthetic and animal-derived vascular patches used in patch angioplasty during carotid endarterectomy have several disadvantages, such as postoperative thrombosis or occlusion and restenosis. This problem may be resolved by the development of biologically active materials that are biodegradable and can stimulate tissue regeneration.Aim. To evaluate the properties and efficacy of a biodegradable patch based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) into which vascular endothelial growth factor (VEGF) is incorporated, in comparison with unmodified PHBV/PCL and commercial vascular patches.Methods. Porous patches were fabricated by emulsion electrospinning from a mixture of PHBV and PCL, into which VEGF was incorporated. The morphological and mechanical properties of these patches were tested, and they were implanted into the wall of rat abdominal aortas for 1, 3, 6 and 12 months. Histological and immunofluorescence examinations were performed to evaluate endothelisation, cellular composition and calcification.Results. PHBV / PCL patches with VEGF had a highly porous structure and demonstrated tensile strength similar to that of the aorta in rats and the internal thoracic artery in humans. After 3 months of implantation, an endothelial monolayer was formed on the inner surface of these patches. The patches were populated by cells that secreted the extracellular matrix faster than did cells of patches from the xenopericardium. Remodelling with PHBV / PCL patches was not accompanied by chronic inflammation; in contrast, inflammation was observed with long-term implantation of unmodified PHBV / PCL samples.Conclusion. VEGF incorporated into biodegradable PHBV / PCL patches stimulated their endothelisation, increased their biocompatibility and promoted remodelling and formation of the components of the blood vessel. PHBV / PCL / VEGF patches thus have a high potential for use in tissue engineering of the vascular wall.Received 2 June 2020. Revised 27 June 2020. Accepted 16 July 2020.Funding: This study was supported by the Complex Program of Basic Research under the Siberian Branch of the Russian Academy of Sciences within the Basic Research Topic of Research Institute for Complex Issues of Cardiovascular Diseases № 0546-2019-0002 “Pathogenetic basis for the development of cardiovascular implants from biocompatible materials using patient-oriented approach, mathematical modeling, tissue engineering, and genomic predictors”.Conflict of interest: Authors declare no conflict of interest.Author contributionsConception and study design: V.V. Sevostianova, A.V. Mironov, L.V. Antonova, R.S. Tarasov, L.S. BarbarashData collection and analysis: V.V. Sevostianova, A.V. Mironov, L.V. Antonova, E.O. Krivkina, V.G. Matveeva, E.A. Velikanova, T.V. GlushkovaStatistical analysis: V.V. Sevostianova, T.V. GlushkovaDrafting the article: V.V. Sevostianova, A.V. Mironov Critical revision of the article: L.V. Antonova, R.S. Tarasov, L.S. BarbarashFinal approval of the version to be published: V.V. Sevostianova, A.V. Mironov, L.V. Antonova, E.O. Krivkina, V.G. Matveeva, E.A. Velikanova, R.S. Tarasov, T.V. Glushkova, L.S. Barbarash

In this study, we incorporated carbon nanotubes (CNTs) into poly(styrene-block-isobutylene-block-styrene) (SIBS) to investigate the physical characteristics of the resulting nanocomposite and its cytotoxicity to endothelial cells. CNTs were dispersed in chloroform using sonication following the addition of a SIBS solution at different ratios. The resultant nanocomposite films were analyzed by X-ray microtomography, optical and scanning electron microscopy, tensile strength was examined by uniaxial tension testing, hydrophobicity was evaluated using a sessile drop technique, for cytotoxicity analysis, human umbilical vein endothelial cells were cultured on SIBS&ndash, CNTs for 3 days. We observed an uneven distribution of CNTs in the polymer matrix with sporadic bundles of interwoven nanotubes. Increasing the CNT content from 0 wt% to 8 wt% led to an increase in the tensile strength of SIBS films from 4.69 to 16.48 MPa. The engineering normal strain significantly decreased in 1 wt% SIBS&ndash, CNT films in comparison with the unmodified samples, whereas a further increase in the CNT content did not significantly affect this parameter. The incorporation of CNT into the SIBS matrix resulted in increased hydrophilicity, whereas no cytotoxicity towards endothelial cells was noted. We suggest that SIBS&ndash, CNT may become a promising material for the manufacture of implantable devices, such as cardiovascular patches or cusps of the polymer heart valve.

Surface modification of polylactic acid (PLLA) by plasma of radio-frequency magnetron discharge with hydroxyapatite target sputtering was investigated. Increased biocompatibility was demonstrated using studies with bone marrow multipotent mesenchymal stromal cells. Atomic force microscopy demonstrates that the plasma treatment modifies the surface morphology of PLLA to produce rougher surface. Infrared spectroscopy and X-ray diffraction revealed that changes in the surface morphology are caused by the processes of PLLA crystallization. Fluorescent X-ray spectroscopy showed that the plasma treatment also changes the chemical composition of PLLA, enriching it with ions of the sputtered target: calcium, phosphorus and oxygen. It is hypothesized that these surface modifications increase biocompatibility of PLLA without increasing toxicity.

Background Cytokines play an significant role in regulating non-specific inflammatory response involved in many pathological processes. The current study tested the hypothesis that myocardial infarction in patients with obesity can lead to increased production of proinflammatory cytokines and unfavorable course of the pathological process. Methods The study recruited 232 male patients with ST-elevated myocardial infarction. The mean age of the patients was 58.7 (52.2-69.9) years. All the patients were assigned to two groups according to the computed tomography findings: 1 (n = 160) patients with visceral obesity (VO), and 2 (n = 72) patients without VO. Interleukins were measured in blood serum on days 1 and 12 after MI. Results All patients with MI demonstrated elevated levels of proinflammatory markers and reduced anti-inflammatory markers in the in-hospital period. The results suggested that among all studied inflammatory markers IL-6 (OR 1.9; 95% CI (1.6–2.8) and CRP (OR 1.3; 95% CI (1.1–1.8) were closely related to VO. One year after MI adverse cardiovascular outcome frequently occurred in patients with VO. There were two cardiac deaths (3.1%), 6 cases (9.3%) of recurrent MI, 19 cases (29.6%) of repeated hospitalizations for unstable angina, whereas only 2 patients without VO (6.6%) were hospitalized for unstable angina. The results of the logistic regression analysis demonstrated that IL-6, IL-12, and IL-10 had the highest predictive value for occurrence of adverse cardiovascular events in patients with VO. Conclusion Cytokine profile in MI patients with VO is characterized by an imbalance caused by elevated pro-inflammatory interleukins and decreased anti-inflammatory interleukins. Obesity in patients was associated with a marked increase in IL-6 and CRP levels.

The combination of a natural hydrophilic polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and a synthetic hydrophobic polymer poly(e-caprolactone) (PCL) is promising for the preparation of biodegradable and biocompatible small-diameter vascular grafts for bypass surgery. However, physico-mechanical properties and endothelialization rate of PHBV/PCL grafts are poor. We suggested that incorporation of vascular endothelial growth factor (VEGF) into PHBV/PCL grafts may improve their physico-mechanical properties and enhance endothelialization. Here we compared morphology, physico-mechanical properties, and in vivo performance of electrospun small-diameter vascular grafts prepared from PHBV/PCL with and without VEGF. Structure of the graft surface and physico-mechanical properties were examined by scanning electron microscopy and universal testing machine, respectively. Grafts were implanted into rat abdominal aorta for 1, 3, and 6 months with the further histological, immunohistochemical, and immunofluorescence examination. PHBV/PCL grafts with and without VEGF were highly porous and consisted mostly of nanoscale and microscale fibers, respectively. Mean pore diameter and mean pore area were significantly lower in PHBV/PCL/VEGF compared to PHBV/PCL grafts (1.47 µm and 10.05 µm2; 2.63 µm and 47.13 µm2, respectively). Durability, elasticity, and stiffness of PHBV/PCL grafts with VEGF were more similar to internal mammary artery compared to those without, particularly 6 months postimplantation. Both qualitative examination and quantitative image analysis showed that three-fourths of PHBV/PCL grafts with VEGF were patent and had many CD31-, CD34-, and vWF-positive cells at their inner surface. However, all PHBV/PCL grafts without VEGF were occluded and had no or a few CD31-positive cells at the inner surface. Therefore, VEGF enhanced endothelialization and improved graft patency at all the time points in a rat abdominal aorta replacement model. In conclusion, PHBV/PCL grafts with VEGF have better biocompatibility and physico-mechanical properties compared to those without. Incorporation of VEGF improves graft patency and accelerates formation of endothelial cell monolayer.

Calcium phosphate bions (CPB) are biomimetic mineralo-organic nanoparticles which represent a physiological mechanism regulating the function, transport and disposal of calcium and phosphorus in the human body. We hypothesised that CPB may be pathogenic entities and even a cause of cardiovascular calcification. Here we revealed that CPB isolated from calcified atherosclerotic plaques and artificially synthesised CPB are morphologically and chemically indistinguishable entities. Their formation is accelerated along with the increase in calcium salts-phosphates/serum concentration ratio. Experiments in vitro and in vivo showed that pathogenic effects of CPB are defined by apoptosis-mediated endothelial toxicity but not by direct tissue calcification or functional changes in anti-calcification proteins. Since the factors underlying the formation of CPB and their pathogenic mechanism closely resemble those responsible for atherosclerosis development, further research in this direction may help us to uncover triggers of this disease.

Small diameter arterial bypass grafts are considered as unmet clinical need since the current grafts have poor patency of 25% within 5 years. We have developed a 3D scaffold manufactured from natural and synthetic biodegradable polymers, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(𝜀-caprolactone) (PCL), respectively. Further to improve the biophysical properties as well as endothelialisation, the grafts were covalently conjugated with arginine-glycine-aspartic acid (RGD) bioactive peptides. The biophysical properties as well as endothelialisation of PHBV/PCL and PCL 2 mm diameter bypass grafts were assessed with and without biofunctionalisation with RGD peptides in vitro and in vivo. Morphology of the grafts was assessed by scanning electron microscopy, whereas physico-mechanical properties were evaluated using a physiological circulating system equipped with a state of art ultrasound vascular wall tracking system. Endothelialisation of the grafts in vitro and in vivo were assessed using a cell viability assay and rat abdominal aorta replacement model, respectively. The biofunctionalisation with RGD bioactive peptides decreased mean fiber diameter and mean pore area in PHBV/PCL grafts; however, this was not the case for PCL grafts. Both PHBV/PCL and PCL grafts with RGD peptides had lower durability compared to those without; these durability values were similar to those of internal mammary artery. Modification of PHBV/PCL and PCL grafts with RGD peptides increased endothelial cell viability in vitro by a factor of eight and enhanced the formation of an endothelial cell monolayer in vivo 1 month postimplantation. In conclusion, PHBV/PCL small-caliber graft can be a suitable 3D scaffold for the development of a tissue engineering arterial bypass graft.

Surface modification of bioresorbable polymer material (polycaprolactone, PCL) with abnormal glow discharge, initiated during radio-frequency magnetron sputtering of a hydroxyapatite target was investigated. Plasma treatment resulted in an increase of surface roughness of PCL, crystallite size, the surface free energy and hydrophilicity. Increased treatment time (30, 60, 150 seconds) provoked the polymer surface saturation with the sputtering target ions (calcium, phosphorus). The assessment of plasma exposure of PCL surface on bone marrow multipotent mesenchymal stromal cells behavior (BM MSCs) has been performed. Modification of the polymer surface with the abnormal glow discharge stimulated adhesion and subsequent proliferation of BM MSCs; thus, maximum values were achieved with the surface treatment for 60 s. This type of plasma modification did not affect cell viability (apoptosis, necrosis). Thus, the surface modification with abnormal glow discharge, initiated during radio-frequency magnetron sputtering of a hydroxyapatite target, appear to be a promising method of surface modification of bioresorbable polymer material (PCL) for tissue engineering.V rabote izuchena vozmozhnost' modifitsirovaniia poverkhnosti biorezorbiruemogo polimernogo materiala (polikaprolaktona, PCL) v plazme anomal'no tleiushchego razriada, voznikaiushchego pri vysokochastotnom magnetronnom raspylenii tverdotel'noĭ misheni, izgotovlennoĭ iz gidroksiapatita. Issledovano izmenenie fiziko-khimicheskikh svoĭstv poverkhnosti polikaprolaktona v zavisimosti ot dlitel'nosti vozdeĭstviia plazmy (30, 60, 150 s). Plazmennaia obrabotka privela k uvelicheniiu sherokhovatosti i razmerov kristallitov na poverkhnosti PCL, povysheniiu poverkhnostnoĭ svobodnoĭ énergii i gidrofil'nosti. Uvelichenie vremeni obrabotki sposobstvovalo nasyshcheniiu poverkhnosti polimernogo materiala ionami raspyliaemoĭ misheni (kal'tsiem, fosforom). Provedena otsenka vliianiia dlitel'nosti ékspozitsii plazmennoĭ obrabotki PCL na povedenie kul'tiviruemykh na ikh poverkhnosti mul'tipotentnykh mezenkhimal'nykh stromal'nykh kletok kostnogo mozga (MMSK KM). Poverkhnost' polimera, modifitsirovannogo v plazme anomal'no tleiushchego razriada, stimulirovala adgeziiu i posleduiushchuiu proliferatsiiu MMSK KM. Pri étom maksimal'nye pokazateli dostigalis' pri obrabotke poverkhnosti v techenie 60 s. Dannyĭ vid plazmennoĭ obrabotki ne snizhal kletochnuiu zhiznesposobnost'. Takim obrazom, obrabotka v plazme anomal'no tleiushchego razriada, voznikaiushchego pri vysokochastotnom magnetronnom raspylenii tverdotel'noĭ misheni, izgotovlennoĭ iz gidroksiapatita, sposobstvuet povysheniiu biosovmestimosti poverkhnosti biodegradiruemykh polimernykh materialov i potentsial'no mozhet byt' ispol'zovana v tkanevoĭ inzhenerii.

Modification with Arg-Gly-Asp (RGD) peptides is a promising approach to improve biocompatibility of small-calibre vascular grafts but it is unknown how different RGD sequence composition impacts graft performance. Here we manufactured 1.5 mm poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/poly(&epsilon, caprolactone) grafts modified by distinct linear or cyclic RGD peptides immobilized by short or long amine linker arms. Modified vascular prostheses were tested in vitro to assess their mechanical properties, hemocompatibility, thrombogenicity and endothelialisation. We also implanted these grafts into rat abdominal aortas with the following histological examination at 1 and 3 months to evaluate their primary patency, cellular composition and detect possible calcification. Our results demonstrated that all modes of RGD modification reduce ultimate tensile strength of the grafts. Modification of prostheses does not cause haemolysis upon the contact with modified grafts, yet all the RGD-treated grafts display a tendency to promote platelet aggregation in comparison with unmodified counterparts. In vivo findings identify that cyclic Arg-Gly-Asp-Phe-Lys peptide in combination with trioxa-1,13-tridecanediamine linker group substantially improve graft biocompatibility. To conclude, here we for the first time compared synthetic small-diameter vascular prostheses with different modes of RGD modification. We suggest our graft modification regimen as enhancing graft performance and thus recommend it for future use in tissue engineering.