Aim: To perform a quantitative analysis of the effectiveness of three concepts of heart valve prosthesis support frames from the perspective of their safety under the most critical loads, conducted through numerical modeling.Materials and Methods. The study utilized three computer-generated concepts of stent-like support frames, created based on the analysis of similar balloon-expandable prostheses. The modeling was conducted using Abaqus/CAE software and included the analysis of two key loads characteristic for this element: compression and implantation phases. A linear description of cobalt-chromium was used as the material model. The feasibility of the concepts was quantitatively assessed using von Mises stress and its qualitative distribution on the surface of the models as stress contours.Results. The analysis revealed that two of the three proposed models experienced stresses exceeding the strength limit (933 MPa) – 999.6 and 954.0 MPa during the compression phase and reaching 1022.4 and 1044.7 MPa, respectively, during the implantation phase. Concept 3 had significantly lower stresses during loading; however, in the working state, the indicators approached the threshold, reaching 924.2 MPa.Conclusion. Numerical modeling identified the inefficacy of concepts 1 and 2 and directions for optimizing concept 3 – reducing amplitudes to form a “strength reserve” for stress. The analysis emphasized the importance of numerical modeling in the early assessment and optimization of medical devices.

The physical and mechanical characteristics of the component materials of bioprosthetic heart valves presented in clinical practice in Russia were obtained and generalized for subsequent adaptation of the properties for numerical modeling problems. It was shown that all materials studied have pronounced nonlinearity and can be represented only in the form of polynomial models. A comparison of the results of computer modeling based on the obtained material coefficients did not demonstrate any differences with the data of full-scale bench tests, which made it possible to verify the computer models.

Background. Using numerical modeling to study biomechanics of implantable devices for cardiovascular healthcare can help specialists understand underlying mechanisms of clinical complications caused by these devices.Aim: To describe the results of numerical modeling of aneurysm formation in vascular grafts based on the simulation of degradation of their mechanical properties.Material and Methods. The simulation was carried out using a three-dimensional computer model obtained by high-resolution computed tomography of the vascular graft “KemAngioProtez” (CJSC “NeoKor”, Russia). Using the 3D model obtained with a specialized script in the Abaqus/CAE environment (Dassault systems, USA), we have simulated the decrease in the elastic modulus (from 100 to 10%) with post-threshold stresses in the material and the accumulation of plastic strain.Results. Undergoing 150 loading cycles, the vascular wall in the model swelled up to 0.7 mm in the radial direction, and its mechanical properties degraded significantly (by 90% compared to baseline) due to prolonged pressure exposure. The value of maximum plastic deformation was 0.55%.Conclusion. Numerical modeling of graft mechanical properties degradation can assist in qualitative and quantitative assessment of the areas of aneurysm formation. The method makes it possible to visualize the swelling areas and can be used as a valuable tool to complement the existing approaches to studying vascular grafts, and biografts in particular.

Background. The average lifespan of a bioprosthetic heart valves (BHVs) is limited to 10–15 years due to structural valve degeneration (SVD). One of the causes of SVD is the infiltration of immune cells. Inflammation like this usually develops several years after valve replacement, the cause of it remains unknown. Presumably, the main stimulus of the immune response is an asymptomatic colonization by bacterial agents.Aim: To study bacterial invasion of BHVs explanted due to SVD, and to identify patterns in microorganism and cellular infiltrate localization.Material and Methods. 23 BHVs excised during replacement due to SVD were included in the study. The identification of bacteria in the samples was carried out by Gram staining and PCR analysis. Immunohistochemical staining with antibodies to markers CD45 (pan-leukocyte marker), CD68 (macrophage marker), CD3 (T-lymphocyte marker) and neutrophil elastase (ELA2) were used for phenotyping of immune cells. The composition of BHVs tissues was studied using Russell-Movat pentachrome staining.Results. All BHVs showed traditional signs of SVD (perforations and large calcifications at the base and dome of the leaflets, ruptures in the commissural zone), but had no signs of prosthetic valve endocarditis (no vegetation, blood culture and swab results were negative). Using the histological method, we detected bacterial cells in 19 of the 23 studied valves (82.6%), whereas PCR data indicated the presence of bacteria in 11 (47,8%) valves (Streptococcus ssp. and Staphylococcus ssp. without species identification). Moreover, we identified the co-localization of colonies of microorganisms and inflammatory infiltrates composed of macrophages (CD45+, CD68+) and neutrophils (CD45+, ELA2+).Conclusion. Bacteria commonly cause asymptomatic colonization of BHVs which is strongly associated with inflammatory cell infiltration.

Aim. To evaluate the cytotoxicity of poly(ε-caprolactone) and polyurethane scaffolds in vitro. Materials and Methods. Polymer scaffolds were made by electrospinning from a 12% solution of poly(ε-caprolactone) or a 12% solution of polyurethane. Surface structure was examined by scanning electron microscopy, whilst cytotoxicity was evaluated by seeding EA.hy 926 endothelial cells on scaffold surface for 72 hours. Cell culture viability and proliferation was assessed by MTT assay and by quantifying cell culture density. On the xCELLigence device, cells were cultured in the presence of the studied matrix samples, and the dynamics of cell culture growth was evaluated in real time. Results. Poly(ε-caprolactone) scaffolds were characterised by a higher variability in the filament thickness and by a significantly larger pore size. Polyurethane filaments formed a dense web with a smoother surface. Poly(ε-caprolactone) scaffolds had significantly higher biocompatibility in comparison with polyurethane. Adhesion of cells to poly(ε-caprolactone) scaffolds did not differ from the cell culture plastic, and poly(ε-caprolactone) supported cell proliferation in the MTT test. Poly(ε-caprolactone) and polyurethane did not differ significantly in terms of inducing cell proliferation. Both poly(ε-caprolactone) and polyurethane scaffolds did not pose considerable cytotoxicity. Conclusion. Poly(ε-caprolactone) and polyurethane scaffolds did not exhibit cytotoxic effects and can be used for manufacturing polymer scaffolds of vascular grafts.

The aim of the study was to compare scenarios of numerical modeling of the operation of a heart valve bioprosthesis, identifying their advantages and limitations. Material and methods. Numerical modeling was conducted in the Abaqus/ CAE (Dassault Systèmes, France) engineering analysis environment, simulating two cycles of the valve apparatus’s operation. In total, three different computer models were studied, each providing different levels of detail and complexity of the “UniLine” bioprosthesis. Model No.1 was the most simplified and considered only the geometry of the flap; Model No. 2 incorporated elastic connectors with variable stiffness; Model No. 3 included a composite support frame. Qualitative validation of the modeling results was conducted by comparing with the bench tests data obtained on the hydrodynamic stand (ViVitro Labs, Canada) during tests of the corresponding clinical model of the “UniLine” bioprosthesis. Results. One of the setups, Model No. 2, displayed an artificial stress concentration according to Von Mises in the connector attachment area, reaching 2.695 MPa, which is close to the material’s strength limit. Other setups showed a more moderate stress distribution – up to 0.803 and 0.529 MPa. Moreover, it was demonstrated that only Model No. 2 and Model No. 3 reproduce the key effect of the bioprosthesis operation, the mobility of the commissural posts, ensuring a qualitative match with the work in bench conditions. Conclusions. A methodology is proposed that may be useful for conducting further in silico studies of heart valve bioprostheses. Boundary conditions, methods for linking prosthetic components, and opportunities for large-scale “exploratory” studies based on using simplified models are described. The study results confirm the necessity of including all prosthesis components in the numerical model for a more comprehensive and realistic representation of its biomechanics. Such detail contributes to a more accurate safety and effectiveness assessment of the device and can also serve as a foundation for its further optimization.

Postoperative complications in surgery, including thrombosis, are often associated with the suture material. The search for new types of suture materials that reduce the risk of vascular anastomotic complications remains an urgent task. The aim of the study was to compare and evaluate the effectiveness of two types of suture materials modified with heparin in terms of the hemocompatibility. Material and methods. The study involved a thread based on the Prolene 3.0 Polypropylene Suture (Ethicon, USA) that had undergone subsequent modification. The suture was modified with either heparin with polydimethylsiloxane or heparin with polyhydroxybutyrate/oxyvalerate. The consistency and hemocompatibility of the modifying layer were evaluated by scanning electron microscopy, diffuse scattering spectroscopy, hemolysis, platelet adhesion and aggregation. Results and discussion. The modifying layer based on heparin and polydimethylsiloxane was nonhomogeneous, with either thick or completely absent coating layer. The modifying layer based on heparin and polyhydroxybutyrate/oxyvalerate was homogeneous, without signs of thickening. Diffuse reflectance spectroscopy confirmed its presence on the thread surface. Evaluation of the hemocompatibility of the modified thread revealed the absence of hemolysis in all the studied groups. The modifying layer based on heparin and polyhydroxybutyrate/ oxyvalerate significantly reduced the maximum platelet aggregation (46.28 %) compared with the unmodified thread (82.64 %), the thread modification with heparin and polydimethylsiloxane did not influence on the indicator (77.72 %). The number of platelets adhered on the surface of the thread modified with heparin and polyhydroxybutyrate/oxyvalerate was insignificant, consisting of single inactivated platelets, in contrast to a thread modified with polydimethylsiloxane rubber and heparin, on the surface of which a large number of adherent activated platelets were found. Conclusions. The results obtained indicate the promising approach for the prevention of postoperative thrombosis by layer-by-layer modification of thread with heparin and polyhydroxybutyrate/oxyvalerate.

There is a growing need for synthetic small-diameter vascular grafts (<6 mm) for bypass surgery since the majority of currently developed products have demonstrated unacceptable high frequency of thrombosis in preclinical studies. The proprietary composite vascular graft based on a nonwoven polymer with anti-thrombogenic and anti-aneurysm effect and functional activity is aimed at stimulating the formation of vascular neotissue at the implantation site. The aim of the investigation is to study the surface morphology, physical and mechanical properties of the polycaprolactone/ polyurethane (PCL/PU) small-diameter tissue-engineered vascular graft with growth factors and an anti-thrombogenic surface coating. Materials and Methods. PCL/PU vascular grafts with growth factor mix (GFmix) were manufactured using the electrospinning method. The hydrogel coating containing iloprost (Ilo) and heparin (Hep) was formed by complexation with polyvinylpyrrolidone. The controls were multilayer vascular grafts of similar composition and nonwoven matrices based on 12% PCL and 12% PU. The surface structure was analyzed with the S-3400N scanning electron microscope (Hitachi, Japan). The physical properties of the surface were determined by the wetting angle method. The mechanical properties were evaluated on a Z series universal testing machine (Zwick/ Roell, Germany). Statistical processing of the data was performed using the GraphPad Prism 8 software. Results. Our new manufacturing technique for the composite PU/PCL/GFmix/Ilo/Hep graft has eliminated the problem of graft delamination. The inner surface of the graft consisted of interwined microfibers (1.34 [1.15; 2.28] mu m thick), nanofibers (790.0 [604.0; 853.5] nm thick), and interpenetrating pores of different diameters (5.4 [3.8; 8.4] mu m). The process of coating formation did not affect the fibers and did not seal the pores, the surface retained its hydrophilic properties (theta=68.61 +/- 11.85 degrees). The tensile strength (3.45 [3.17; 4.03] & Mcy;P & acy;) and Young's modulus (4.88 [3.95; 5.80] MPa) of PU/PCL/GFmix/Ilo/Hep grafts were almost similar to the human internal thoracic artery compared to the multilayer analogs. The PU/PCL/GFmix/Ilo/Hep grafts were superior to the multilayer PCL/PU/GFmix/Ilo/Hep grafts in terms of reduced excessive elasticity (to 118.0 [111.0; 125.0]%; & rcy;=0.043). Conclusion. The composite functionalized vascular PU/PCL/GFmix/Ilo/Hep grafts have enhanced characteristics and compliance, which, in turn, increases the probability of their high patency in future preclinical studies.

Objective: to conduct a pilot study of the effect of bioprosthetic heart valve leaflet calcification on biomechanics and to identify the «stress in the material – dysfunction» relationship. Materials and methods. The study’s focus was on two commercially available UniLine bioprosthetic mitral valves sized 26 and 30 (NeoCor, Russia). The samples were subjected to microcomputer tomographic scanning in order to reconstruct calcium volumes. The resulting 3D models were correlated with prostheses of corresponding sizes and projected to the volume of the locking element in the Abaqus/CAE engineering analysis software (Dassault Systemes, France).Results. According to numerical modeling, the maximum principal stresses increased significantly to 90.8 MPa in the samples, the opening decreased qualitatively, and impact on the prosthetic frame increased. Comparison of stress diagrams of numerical simulation with samples demonstrates the relationship between peak amplitude and rupture and thinning localizations in the flap apparatus.Conclusion. The work presented demonstrated the findings of a pilot study of the connection between biomechanics in a patient-specific calcified mitral prosthetic heart valve UniLine and macroscopic characterization of explanted samples. The comparative stage showed that stress values correlate with localization of leaflet dysfunction.

The aim of the study is to assess protective capabilities of the polymer coating made of polyvinyl alcohol to prevent leukocyte adhesion to epoxy-treated bovine pericardium, which is used in production of bioprosthetic heart valves. Materials and Methods:Fragments of unmodified (control) and modified with polyvinyl alcohol epoxy-treated bovine pericardium were incubated in the dedicated chambers connected to a pulsatile flow system (Ibidi GmbH, Germany). During 48 h incubation was conducted in whole donor plasma containing 3·106 of mononuclear fraction cells. To simulate plasma flow, the shear stress on the inflow and outflow sides of of bioprosthetic heart valve in the aortic position was set to 50 and 20 dynes/cm2, respectively. After the experiment was completed, the surface of the studied samples was subjected to scanning electron microscopy and immunofluorescence using antibodies to the pan-leukocyte marker CD45. Results:Adhesion of leukocytes (CD45+) was seen for both the serous (outflow side) and fibrous (inflow side) surfaces of the control epoxy-treated bovine pericardium, whereas both surfaces of the material modified with polyvinyl alcohol were clear of immune cells. Scanning electron microscopy confirmed the adhesion of leukocytes to intact biological tissue: the cells on the surface of the control xenopericardium were of an irregular shape and formed numerous pseudopodia. Conclusion:The suggested modification of epoxy-treated bovine pericardium with polyvinyl alcohol prevents the adhesion of immune cells to the implant surface and can potentially protect bioprosthetic heart valves from immune rejection.

Highlights. We have proposed and patented a method for obtaining fully autologous fibrin without the use of exogenous thrombin, which can be implemented within the framework of a personalized approach in tissue engineering. Such fibrin, in addition to lower risk of infection and inflammation, possesses greater strength and resistance to degradation, as well as better hemocompatibility compared to fibrin polymerized with exogenous thrombin, which is an undoubted advantage when used as a coating for small-diameter vascular grafts.Background. Autologous fibrin can be used as a coating to impart biomimetic properties to various polymers used in vascular tissue engineering. Traditionally, fibrinogen polymerization is performed with the addition of exogenous thrombin and calcium chloride. Our patented method of obtaining fibrin without the use of exogenous thrombin allows us to obtain a completely autologous material that does not have the risk of infection. The differences in methods polymerization can change the fibrin properties.Aim. To compare the most important properties of vascular tissue engineering of fibrin obtained by various methods: using endogenous thrombin and exogenous thrombin in vitro.Methods. The fibrinogen precipitate was obtained with ethanol precipitation method using low concentration of ethanol. The content of fibrinogen in the precipitate was normalized to a final concentration in fibrin of 30 mg/mL. Polymerization of fibrin polymerized with exogenous thrombin was performed by adding 50 U/ mL and 0.2% calcium chloride to the thrombin precipitate, fibrin polymerized by activation of endogenous thrombin only by adding 0.2% calcium chloride. The strength properties of the samples were tested on a Z tensile tester (Zwick/ Roell). The structure of fibrin was studied using scanning electron microscopy, a quantitative analysis of the size of pores and fibers, the density of branching points was carried out. The quantitative content of FXIII in plasma and the resulting precipitate was determined by ELISA. FXIII activity was studied by the formation of γ-γ crosslinks by SDS-PAGE, the resistance of samples to proteolytic and fibrinolytic degradation. The ability of fibrin polymerized by activation of endogenous thrombin and fibrin polymerized with exogenous thrombin to activate contact coagulation and platelet aggregation was evaluated.Results. Thinner fibers predominated in the structure of the fibrin polymerized by activation of endogenous thrombin samples, while the samples were distinguished by greater strength and stiffness. The described features may be associated with a more efficient activation of FXIII, which is confirmed by the formation of a larger number of γ-γ dimers in fibrin polymerized by activation of endogenous thrombin samples, as well as resistance to proteolytic degradation compared to fibrin polymerized with exogenous thrombin. Moreover, fibrin polymerized by activation of endogenous thrombin samples in vitro activated platelets less than fibrin polymerized with exogenous thrombin.Conclusion. The method for obtaining and polymerizing fibrin using endogenous thrombin makes it possible to obtain a completely autologous material that has better physical and mechanical properties, resistance to proteolytic degradation and lower thrombogenicity compared to traditional fibrin polymerization.

The aim of the study was to make a vascular patch based on regenerated silk fibroin (SF) and study its physical and mechanical characteristics, biocompatibility and matrix properties in comparison with polyhydroxybutyrate/valerate/polycaprolactone with incorporated vascular endothelial growth factor (PHBV/PCL/VEGF) and commercial bovine xenopericardium (XP) flap in experiments in vitro.Materials and Methods.Tissue-engineered matrices were produced by electrospinning.The surface structure, physical and mechanical characteristics, hemocompatibility (erythrocyte hemolysis, aggregation, adhesion and activation of platelets after contact with the material) and matrix properties of vascular patches (adhesion, viability, metabolic activity of EA.hy926 cells on the material) were studied.Results.The surface of SF-based matrices and PHBV/PCL/VEGF-based tissue engineered patches had a porous and fibrous structure compared to a denser and more uniform XP flap.The physical and mechanical characteristics of SF matrices were close to those of native vessels.Along with this, tissue-engineered patches demonstrated high hemocompatible properties, which do not differ from those for commercial XP flap.Adhesion, viability, and metabolic activity of EA.hy926 endothelial cells also corresponded to the previously developed PHBV/PCL/VEGF matrix and XP flap, which indicates the nontoxicity and biocompatibility of SF matrices. Conclusion.Matrices produced from regenerated SF demonstrated satisfactory results, comparable to those for PHBV/PCL/VEGF and commercial XP flap, and in the case of platelet adhesion and activation, they outperformed these patches.In total, SF can be defined as material having sufficient biological compatibility, which makes it possible to consider a tissue-engineered matrix made from it as promising for implantation into the vascular wall.

Background. Around half of bioprosthetic heart valves become dysfunctional 15 years postimplantation because of structural valve deterioration notable for the degradation and calcification of the prosthetic tissue. Protection of bioprosthetic heart valves from structural valve deterioration requires innovative materials, science approaches including enveloping of the bioprosthetic heart valves into the polymer sheath.Aim. To develop a polyvinyl alcohol sheath for improving resistance of bioprosthetic heart valves to calcification.Material and methods. Bovine pericardium fixed with ethylene glycol diglycidyl ether was incubated with distinct concentrations of polyvinyl alcohol (5, 10, 12, or 15%) with the following freezing and thawing to perform cryotropic gelation. Surface and structure of unmodified and polyvinyl alcohol-modified bovine pericardium have been investigated by fluorescence microscopy and scanning electron microscopy, whilst tensile testing was carried out by uniaxial tension test. Haemocompatibility was assessed through the measurements of haemolysis and platelet aggregation/adhesion upon the contact of donor blood with the samples. Resistance to calcification was tested by incubation of the samples in calcium and phosphate supersaturated (10 µmol/L) cell culture medium for 3 and 6 weeks with the following tissue lysis and colorimetric measurement of Ca2+ ions.Results. Using cryotropic gelation, we obtained a polyvinyl alcohol-coated and filled bovine pericardium matrix. Out of all polyvinyl alcohol concentrations, 12% polyvinyl alcohol solution sealed pores and hollows within the bovine pericardium (what was not achieved using 5% or 10% polyvinyl alcohol solutions) and demonstrated the best processability as compared to 15% polyvinyl alcohol solution. Cryotropic gelation did not deteriorate durability, elasticity, or haemocompatibility of bovine pericardium. After 3 and 6 weeks of the incubation in calcium-supersaturated solution, polyvinyl alcoholmodified bovine pericardium contained 5- and 3-fold reduced amount of calcium compared to unmodified bovine pericardium.Conclusions. Enveloping of bovine pericardium into polyvinyl alcohol increases its calcification resistance, retains its tensile properties and haemocompatibility, and can be considered as a promising approach for the modification of bovine pericardium during the manufacturing of bioprosthetic heart valves.

Background. Bioprosthetic heart valves (BHVs) are prone to the proteolytic degradation, eventually resulting in their degeneration and failure. Previously, we found cysteine cathepsins with a collagenase and elastase activity in bioprosthetic tissue but it remained unclear whether they precipitated from the circulating blood or have been produced by the infiltrating host cells. Aim: To study the distribution of cathepsin B, cathepsin K, cathepsin L, cathepsin S, cathepsin V, and cathepsin Z in bioprosthetic heart valves and to identify their source. Material and Methods. We examined five BHVs excised from the mitral position during the repeated heart valve replacement. Average duration of BHV functioning was 169 ± 31 months. Consecutive sections from the degenerated BHV segments were investigated by Russell-Movat’s pentachrome staining and immunohistochemistry, employing antibodies to leukocyte markers (pan-leukocyte marker CD45, macrophage marker CD68, neutrophil marker myeloperoxidase, T cell marker CD3, and B cell marker CD19) and cathepsins (B, K, L, S, V, and Z). Results. Macrocalcification and tears were the most frequent degenerative alterations found in BHV leaflets. Further, BHVs were notable for the fragmentation of collagen fibers at and beneath the surface, and were devoid of elastic fibers and mucopolysaccharides. Macrophages were co-localised with the degraded extracellular matrix foci. Cathepsin B was detected only in macrophages whilst other cathepsins (K, L, S, V, and Z) were expressed both in the immune cells and extracellular matrix. Conclusion. Macrophages are capable of producing all cysteine cathepsins in BHV leaflets. Localisation of cathepsins K, L, S, V, and Z in the extracellular matrix also indicated blood as their major source.

Background: Interpenetrating polymer network (IPN) hybrid hydrogels enable regulating their properties by varying the composition and concentration of their components. Fibrin is an available natural polymer with ideal biological properties but low strength and tendency to retraction. Polyvinyl alcohol hydrogels are stable, comparable in strength to biological tissues but bioinert. Fibrin/polyvinyl alcohol (F/PVA) IPN can overcome the shortcomings of each component and create an improved material for tissue engineering.Objective: To assess the possibility of and conditions for obtaining a homogeneous IPN by subsequent fibrin polymerization and polyvinyl alcohol cryostructuring while preserving as much as possible mechanical and biological properties beneficial for tissue engineering.Methods: F/PVA IPN was obtained by subsequent fibrin polymerization (30 mg/mL) and polyvinyl alcohol cryostructuring (15, 30, and 60 mg/mL). We studied the structure using a scanning electron microscope, histology, infrared spectroscopy, and X-ray diffraction analysis. We tested mechanical properties and shrinkage of the samples. Biological features were assessed in vitro in terms of viability, cell count, proliferative and metabolic activity of EA.hy926 endothelial cell culture.Results: Our study found the maximum amount of fibrin on the surface of F30PVA15 IPN and its minimum amount on the surface of F30PVA60. These results were supported by the high biological appeal of F30PVA15 compared with F30PVA30 and F30PVA60. F30PVA60 hydrogels demonstrated shrinkage resistance compared to the template; F30PVA30 and F30PVA15 samples decreased by 1.4 and 2.5 times, respectively. Although the mechanical strength of all monocomponent hydrogels and IPN samples did not compare to that of the internal thoracic vein, F30PVA30 and F30PVA60 demonstrated better results than F30PVA15 and fibrin alone.Conclusion: Our method allows obtaining shrink-resistant IPN hydrogels with improved mechanical and tolerable biological properties at polyvinyl alcohol concentrations of > 15 mg/mL and < 60 mg/mL. However, the insufficient strength of this material limits its use in vascular engineering to a modifying coating. Received 25 January 2023. Revised 17 March 2023. Accepted 29 March 2023. Funding: This research was funded 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 No. 0419-2022-0001 “Molecular, cellular and biomechanical mechanisms of the pathogenesis of cardiovascular diseases in the development of new treatment methods based on personalized pharmacotherapy, minimally invasive medical devices, biomaterials and tissue-engineered implants”. Conflict of interest: The authors declare no conflict of interest. Contribution of the authorsConception and study design: V.G. Matveeva, M.A. RezvovaData collection and analysis: V.G. Matveeva, M.A. Rezvova, T.V. Glushkova, E.O. Krivkina, A.V. SergeevaStatistical analysis: V.G. Matveeva, M.A. Rezvova, T.V. Glushkova, A.V. SergeevaDrafting the article: V.G. MatveevaCritical revision of the article: V.G. Matveeva, M.A. Rezvova, L.V. Antonova, L.S. BarbarashFinal approval of the version to be published: V.G. Matveeva, M.A. Rezvova, T.V. Glushkova, A.V. Sergeeva, E.O. Krivkina, L.V. Antonova, L.S. Barbarash

Five commercial patches and one unchanged native bovine xenopericardium are studied on a test setup to supplement the existing data on the physical and mechanical properties of commercial patches used for reconstructive interventions on the heart and blood vessels and to adapt the corresponding models for applications in computer simulation environment. The models are verified under conditions for numerical simulation of the uniaxial tension experiment using the finite element method. The full-scale study of physical and mechanical properties shows that all materials exhibit developed nonlinearity, which is manifested as an initial low-slope fragment of stress with a subsequent increase in rigidity. The results of numerical verification of the coefficients for models of hyperelastic materials show high convergence with the results of field tests. The results of evaluation of the physical and mechanical properties of patches for reconstructive surgery of the heart and blood vessels used in the Russian Federation are presented. The resulting coefficients of the models for these materials can be used in the environment of engineering analysis for the problems of numerical simulation using the finite element method.

Aim. The aim of this review was to analyze publications describing studies focusing on the pathophysiological mechanisms of calcification of bioprosthetic heart valves, and to substantiate new and promising methods of calcification prevention for the implantable medical devices.Material and methods. Databases and electronic libraries such as PubMed, Google Scholar and eLibrary were used for searching relevant articles. Search queries included the following word combinations: “bioprosthetic heart valves”, “structural valve degeneration”, “calcification”, “cyclic loading”, “inflammation”, “proteolysis”, “proteolytic enzymes”, “decellularization”, “anticalcification treatment”. The references in relevant articles were used for the search as well. Preference was given to works published from January 2013 to January 2023.Results. We have considered the key aspects of bioprosthetic heart valves calcification and the main strategies of calcification prevention. Calcification of bioprosthetic heart valves incorporates a complex set of mechanisms that includes, but is not limited to: 1) binding of calcium in chemically stabilized biomaterial by free groups of the preservative; 2) precipitation of calcium on residual donor cells and cell debris; 3) pro-calcifying changes in biological material due to proteolysis, mechanical and oxidative stress; 4) cell-mediated biomineralization. Despite modern advances in biopreservation, such as treatment with chemical agents that prevent the deposition of calcium, the problem of bioprosthetic heart valves calcification still prevails. The cause of it lies in the heterogeneity of the pathophysiological mechanisms behind the mineralization of biomaterial: the currently developed methods of calcification prevention cannot block all ways of bioprosthetic heart valves calcification.Conclusion. Calcification of bioprosthetic heart valves leaflets is a complex process that underlies the main cause of dysfunction of the medical devices. Supposedly, a new innovative approach that involves polymer hydrogel filler in biomaterials can completely prevent its calcification.

This study uses computer modeling to assess the potential of using certain biocompatible polymer materials in coronary stent-grafts. Numerical experiments were carried out to assess mechanical properties of samples of polymer materials: hydrogels based on polyvinyl alcohol or polylactide–polycaprolactone copolymer. The studies showed that when the stent-graft membrane was free to move, all the materials showed similar shortening, with changes in diameter of 7.21-7.63 mm from the initial 20 mm (36.05-36.6%). This was accompanied by thinning of the component by 34-37%. When the membrane was fully fixed to prevent shortening, the decrease in thickness was greater – by 53-61% – and was accompanied by a significant increase in stress (for one polylactide–polycaprolactone copolymer it reached 44.37 MPa, which is close to the tensile strength of the material, 47.07 MPa). These results show that three of the studied materials have potential for use in coronary stent-grafts: two modified hydrogels based on polyvinyl alcohol and a polylactide–polycaprolactone copolymer.

A full-scale study of the physical and mechanical properties of a number of samples of commercial biomaterials-patches was carried out. It is shown that all materials have a pronounced non-linearity of behavior, manifested in the presence of an initial gentle stress section with a subsequent increase in stiffness, however, there are quantitative differences in the length of these sections and, accordingly, in the final characteristics: tensile strength, elongation at break, elasticity. The results of numerical verification of the obtained coefficients of hyperelastic materials models showed high convergence with the results of field tests. Keywords: numerical modeling, physical and mechanical tests, hyperelastic material model, polynomial approximation.. Keywords: numerical simulation, physical and mechanical testing, hyperelastic material model, polynomial approximation.