IntroductionCurrently, chronic immune rejection of bioprosthetic heart valves (BHVs) is considered among the key players in the development of structural valve degeneration (SVD). However, the relative contribution of leukocyte infiltration and cyclic mechanical loading into the SVD in bioprosthetic mitral valves (BMVs) and bioprosthetic tricuspid valves (BTVs, experiencing lower hemodynamic load due to the right heart’s pressure environment) remains unclear.MethodsHere we performed an investigation of BMVs and BTVs which have been pairwise-excised from 4 patients during the BHV replacement because of BMV failure. The amount of valvular calcification was measured by multislice computed tomography and quantified using Pydicom script. Immune cell infiltration and lipid deposition in sectioned leaflets were evaluated by hematoxylin and eosin and Oil Red O staining, respectively; the semi-quantitative analysis of whole slide images was conducted by QuPath and Fiji software. In addition, we conducted an ultrastructural examination of BHVs by backscattered scanning electron microscopy after epoxy resin embedding (EM-BSEM technique).Results and discussionAll BMVs had a significant extent of lipid deposition, hemorrhages, and tears, which eventually led to its mechanical incompetence. Strikingly, BMVs had less amount of immune cell infiltration as compared with BTVs. These results indicate that mechanical fatigue prevails over immune cell infiltration in driving the development of SVD.

Background: Infective endocarditis (IE) is an infectious disease caused by the hematogenous dissemination of bacteria into heart valves. Improving the identification of pathogens that cause IE is important to increase the effectiveness of its therapy and reduce the mortality caused by this pathology. Methods: Ten native heart valves obtained from IE patients undergoing heart valve replacements were analyzed. Bacterial invasion in the heart valves was studied by Gram staining of histological sections. Histopathological changes accompanied with bacterial invasion were studied by immunohistochemical analysis of pan-leukocyte marker CD45, platelet marker CD41, and neutrophil myeloperoxidase. The taxonomic diversity of the bacteria was analyzed using 16S rRNA metabarcoding. Results: Gram staining of the histological sections revealed bacterial cells localized on the atrial surface at the leaflet’s free edge or on the ventricular surface at the leaflet’s base within fibrin deposits in only three of the studied heart valves. Bacterial colonies were co-localized with microthrombi (CD41+ cells) containing single leucocytes (CD45+ cells), represented by segmented neutrophils. As a result of 16S rRNA metabarcoding, we detected the following bacterial genera: Pseudomonas (70% of the studied heart valves), Roseateles (60%), Acinetobacter (40%), Sphingomonas (40%), Enterococcus (30%), Reyranella (20%), Sphingobium (20%), Streptococcus (20%), Agrobacterium (20%), Ralstonia (10%), and Bacillus (10%). Conclusions: A number of opportunistic microorganisms that could not be detected by routine laboratory tests and were not eliminated during antibiotic therapy were identified in the IE-affected heart valves. The obtained results show the importance of 16S rRNA metabarcoding of heart valves removed due to IE not only as an independent diagnostic method but also as a highly accurate approach that complements routine tests for pathogen identification.

Highlights Prosthetic endocarditis (PE) was the main cause of dysfunctions of biological prosthetic heart valves of the UniLine model that occurred during the first 4 years of operation. The main factor in the development of PD insolvency in the later time period was structural valvular degeneration (SKD). The key macroscopic signs of SCD included calcification and ruptures of the valve apparatus. At the microscopic level, PD with SCD was characterized by moderate cellular infiltration with a predominance of macrophages. In turn, for valves with PE, thickening of the valves and the formation of vegetation were noted, the development of which was accompanied by aggressive invasion of neutrophils. The results of cluster analysis of data on 46 key clinical and pathomorphological features supported the division of the studied PD sample into 2 stable clusters corresponding to the patterns of CD and PE. Abstract Aim. This study aimed to comprehensively evaluate the pathomorphological changes in “Uniline” bioprosthetic heart valves (BHVs) explanted due to dysfunction. Methods. A total of 44 “Uniline” BHVs, retrieved from an equal number of recipients during valve re-replacement procedures were examined. To determine cellular composition and assess biomaterial microstructure, valve leaflets were sectioned and stained using hematoxylin and eosin, Russell-Movat pentachrome, Oil Red O, and Alizarin Red S. Bacterial colonies were identified using Gram staining. Immunohistochemistry was performed with the NovoLink Polymer DS detection system and antibodies against the pan-leukocyte marker (CD45), T-lymphocytes (CD3), B-lymphocytes (CD19), macrophages (CD68), neutrophils (MPO), and platelets (CD62p). Stained sections were scanned on an MT5300L microscope, and the resulting histological slides were analyzed using QuPath and Fiji software. Cluster analysis was performed to identify pathomorphological patterns of BHV dysfunction. Results. Clinical and pathomorphological data confirmed PE and SVD as the underlying causes of dysfunction within the cohort. Patients in the PE and SVD groups showed no significant clinical or demographic differences. The mean duration of BHV function was 30 months for PE and 74 months for SVD. Valves explanted due to SVD exhibited leaflet calcification and tears. Most BHVs with PE were characterized by the presence of vegetations on the leaflets. SVD-affected valves displayed moderate macrophage infiltration, whereas PE cases showed aggressive neutrophil invasion. Cluster analysis algorithms identified two stable patterns of dysfunction: the first was characterized by features typical of SVD, including chronic inflammation and calcification, while the second corresponded to persistent acute inflammation associated with PE. Conclusion. PE and SVD are key pathomorphological patterns of dysfunction in “Uniline” BHVs, treated with ethyleneglycol diglycidyl ether. The identified patterns are the same as the main causes of degeneration in BHVs treated with glutaraldehyde. This underscores fundamental limitations in using chemically cross-linked xenopericardium for BHV manufacturing and, consequently, highlights the necessity for developing new materials and methods aimed at improving the durability of artificial heart valves.

The unique properties of hydrogels have enabled their widespread use in various biomedical applications, including heart valve and blood vessel replacements. However, their current applications are limited by poor mechanical properties, including low strength, susceptibility to plastic deformation, and inadequate wear resistance, which are critical for load-bearing tissue replacements. Nanocomposite cryogels composed of polyvinyl alcohol and carbon nanotubes prepared using a DMSO/H2O solvent mixture, present a promising solution to address these limitations. Addition of nanoparticles up to 0.5% of the polymer mass showed a remarkable 59% increase in mechanical strength compared to single component cryogels. The reinforcement effect was also pronounced in strain hardening at large deformations. CNTs addition also enhanced the adhesion of Ea.hy 926 cells. However, the overall cell coverage on the cryogel surface was lower compared to control culture plastic, suggesting selective adhesion behavior. Comprehensive hemocompatibility testing showed minimal adsorption of protein molecules such as albumin and fibrinogen and no platelet adhesion when exposed to platelet rich plasma. Post contact platelet aggregation was same as untreated plasma. The studied materials also elicited minimal inflammatory response and no calcification unlike polytetrafluoroethylene which is clinically used, further proving biocompatibility. These findings suggest that PVA-based nanocomposite cryogels synthesized with dispersed CNTs hold significant promise for applications in cardiovascular surgery, particularly in the development of mechanically robust and biocompatible vascular grafts and heart valve prostheses.

Highlights Average cycle stress for the developed concepts was 413.6–528.0 MPa. Hydrodynamic tests were successful – effective orifice area was 3.41 ± 0.08 and 3.52 ± 0.07 cm 2 . Two frame concepts were unsuitable, and the third requires geometric optimization. Aim. To develop and analyze concepts of support frames for transcatheter aortic valves based on numerical modeling methods in order to evaluate their mechanical characteristics, strength properties and hydrodynamic efficiency. Methods. The study used three-dimensional models of the support frames created using SolidWorks software (Dassault Systemes, France). The mechanical characteristics were assessed in the Abaqus/CAE environment (Dassault Systèmes, France) using the finite element method. The study included an analysis of the stress-strain state, fatigue strength, and radial forces arising during crimping and implantation of the prosthesis. The hydrodynamic characteristics were assessed using the Pulse Duplicator II stand (Vivitro Labs, Canada), which simulates the operating conditions of the prosthesis in the left ventricle of the heart. Results. Numerical modeling analysis showed that two of the three concepts studied demonstrated exceedance of the material strength limit, which makes them unsuitable for further use. One of the concepts demonstrated lower stress levels, but some areas of the design require further refinement. Radial stability tests revealed a predictable pattern of material deformation, which confirms the stability of the design under physiological conditions. Hydrodynamic tests showed compliance of the valve operation with established standards, the absence of critical turbulence zones and acceptable regurgitation levels. Conclusion. The obtained results indicate the need for further optimization of the geometry of the supporting frame of the developed device to reduce local stresses, as well as improvement of the surface finishing technology to improve the roughness index. The manufactured prototypes of the prosthesis have satisfactory hydrodynamic characteristics.

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. 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.

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.

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.

Background . Detailed study of the histopathological events and mechanisms accompanying the infectious process in native heart valves and their biological prostheses is very important due to the variability of clinical manifestation of infective endocarditis (IE). Aim : To study cellular infiltration of aortic heart valves (AVs) and bioprosthetic heart valves (BPs) affected by infection, as well as to search for common patterns or differences of native and BPs characterized by degenerative changes in the leaflet apparatus. Material and Methods . We studied the leaflets of AVs affected IE (n = 10) or calcific aortic stenosis (CAS) (n = 11), as well as the leaflets of BPs affected by IE (n = 5) or structural valve degeneration (SVD) (n = 10) and removed from the mitral position during re-prosthetics surgery. Histological sections were prepared using a cryostat microtome. Cell typing was performed by staining with antibodies to the CD45, CD68 CD3, CD19, myeloperoxidase (MPO) and CD31 markers using immunohistochemical analysis. Bacteria were visualized by Gram staining of histological sections. The expression of MPO in the studied samples was determined by Western blotting. Results . Colonies of gram-positive cocci and gram-negative rod-shaped bacteria were registered into native AKs affected by IE. BPs affected by SVD are characterized by the presence of mixed colonies of gram-positive cocci and gram-negative rod-shaped bacteria. Immunophenotyping demonstrated leukocyte infiltration (CD45+) in all studied heart valves. AVs and BPs with infectious lesions and BPs affected by SVD were characterized by inflammatory infiltrates included macrophages (CD68+), neutrophils (MPO+) and single T-lymphocytes (CD3+). In calcified AVs, we found no neutrophils; the clusters of immune cells were represented by macrophages and single T-lymphocytes. In both groups of AVs, single cells positive for the vascular endothelial marker CD31 were noted in the fibrous layer. The highest expression of MPO was observed in AVs affected by IE in comparison to other studied valves. Conclusion . AVs affected by infection compared to native heart valves affected by CAS are characterized by aggressive infiltration by neutrophils. Neutrophils and bacterial agents were also detected in BPs regardless of the diagnosed IE. These results indicate the involvement of bacterial invasion in the development of SVD of the biological element of BPs and indicate the necessarily for a detailed study of this phenomenon.

HighlightsMicro-computed tomography allows specialists to qualitatively and quantitatively assess the structure of calcified areas of explanted bioprosthetic heart valves.This method enables the evaluation of changes in the structure of the bioprosthesis that have occurred during its prolonged operation. Aim of the study. To evaluate the potential of high-resolution tomography for the study of mitral valve bioprostheses of different designs explanted due to dysfunction and various calcification patterns (microcalcification and macrocalcification).Methods. Single samples of the «UniLine» and «PeriCor» bioprostheses were the objects of study, they were explanted due to dysfunction developed after 76 and 87 months of operation in recipients. The peculiarities of calcification localization in the structure of bioprostheses were studied using high-resolution tomography followed by reconstruction of volumetric images and quantitative analysis of radiodense areas. Moreover, we used light microscopy with Alizarin Red S staining to detect calcifications.Results. The study results showed that the nature of the distribution and volume of calcinates significantly differ between the studied samples: for the «UniLine» bioprosthesis, the affected areas were located in the leaflet material and constituted 21.1% of the total biological tissue volume; for the «PeriCor» bioprosthesis, calcifications were diffusely distributed in small structural formations, accounting for a total of 5.1% of the biological material, primary localized on the «auxiliary» structures of the prosthesis – the covering made of porcine or calf xenopericardium. In addition, high-resolution tomography allowed us to determine the degree of deformation of the «UniLine» bioprosthesis frame, with the posts deviating inward by 1.1–1.4 mm.Conclusion. The possibility of using computed microtomography for qualitative and quantitative assessment of calcified xeno-pericardial and xeno-aortal bioprostheses has been demonstrated. However, this method is limited in its ability to detect macrocalcification within the leaflet thickness.

Highlights:Epoxy-treated xenopericardium modified with polyvinyl alcohol has increased resistance to calcification and proteolytic degradation in vitro.Cyclic loads negatively affect fatigue life of studied material, moreover, this process is accompanied by deterioration of its anti-calcium and anti-enzyme properties. Additional studies aimed at improving the wear resistance of the hydrogel in the biological material are required. Aim. To study the resistance of epoxy-treated bovine pericardium modified with polyvinyl alcohol to calcification and proteolytic degradation in collagenase after exposure to cyclic loading.Material and methods. The epoxy-treated patches made with xenopericardium were treated with polyvinyl alcohol according to the original method, after that they were subjected to cyclic loading (70 million cycles) using the HiCycle wear tester system. Visualization of the surface and internal structure of the biomaterial was performed by scanning electron microscopy. The resistance to calcification was assessed by incubating the samples in a solution saturated with calcium ions and phosphate ions for 3 and 6 weeks, followed by quantitative measurement of the calcium by spectrophotometry. The susceptibility of the samples to proteolytic degradation was determined by weight loss after incubation in a solution of clostridial collagenase for 24 hours. The control group consisted of patches of unmodified epoxy-treated bovine pericardium.Results. After cyclic loading, patches of xenopericardium modified with polyvinyl alcohol showed signs of fatigue (cracks on the surface and large cavities in the internal structure). Although cyclic loading significantly worsened the resistance of the modified tissue to calcification and proteolytic degradation (by 3 and 5 times, respectively, relative to the values obtained for patches stored under static conditions), patches from this group showed better results compared to unmodified patches. Thus, they contained 1.5 to 2 times less calcium after 3 and 6 weeks of incubation in a calcium-saturated solution. Mass loss after incubation in collagenase was 1.5 times lower for patches of modified biomaterial undergoing cyclic loading compared to unmodified patches.Conclusion. The proposed modification method of the epoxy-treated xenopericardium with polyvinyl alcohol increases the resistance of biological tissue to calcification and proteolytic degradation. Although cyclic loading negatively affects the protective properties of the polymer coating over time, this type of modification can potentially slow down the degeneration of biomaterial used in manufacturing of bioprosthetic heart valves.

Percutaneous coronary intervention, a common treatment for atherosclerotic coronary artery lesions, occasionally results in perforations associated with increased mortality rates. Stents coated with a bioresorbable polymer membrane may offer an effective solution for sealing coronary artery perforations. Additionally, such coatings could be effective in mitigating neointimal hyperplasia within the vascular lumen and correcting symptomatic aneurysms. This study examines polymer membranes fabricated by electrospinning of polycaprolactone, polydioxanone, polylactide-co-caprolactone, and polylactide-co-glycolide. In uniaxial tensile tests, all the materials appear to surpass theoretically derived elongation thresholds necessary for stent deployment, albeit polydioxanone membranes are found to disintegrate during the experimental balloon expansion. As revealed by in vitro hemocompatibility testing, polylactide-co-caprolactone membranes exhibit higher thrombogenicity compared to other evaluated polymers, while polylactide-co-glycolide samples fail within the first day post-implantation into the abdominal aorta in rats. The PCL membrane exhibited significant water leakage in the permeability test. Comprehensive evaluation of mechanical testing, bio- and hemocompatibility, as well as biodegradation dynamics shows the advantage of membranes based on and the mixture of polylactide-co-caprolactone and polydioxanone over other polymer groups. These findings lay a foundational framework for conducting preclinical studies on stent configurations in large laboratory animals, emphasizing that further investigations under conditions closely mimicking clinical use are imperative for making definitive conclusions.

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.

HighlightsImmune processes and mechanisms underlying bioprosthetic heart valve degeneration and rejection of allografts and xenografts are similar.Manufacturers and surgeons can implement effective approaches to prevent immune rejection in the process of production and implantation of prosthetic heart valves in order to delay the process of structural valve degeneration. AbstractBioprosthetic heart valves (BHV) are characterized by low thrombogenicity, thus circumventing the need for long‐term anticoagulation. However, BHV lifespan is limited to 10–15 years because its tissue components are subject to degeneration. Recent research data indicate that immune responses forming the basis of humoral and cellular rejection of allografts and xenografts play a major role in the development of structural valve degeneration (SVD). This review summarizes up-to-date data on immune processes involved in SVD pathogenesis. Moreover, the latest achievements in the development of strategies to reduce the immunogenicity of BHV, such as data on immune compatibility of allogeneic material and the process of deriving low immunogenic biomaterial from genetically modified animals, decellularization of BHV, and the ways of slowing the process of degeneration are analyzed.

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.