Crosslinking porcine aortic valve by radical polymerization for the preparation of BHVs with improved cytocompatibility, mild immune response, and reduced calcification

2021 ◽  
pp. 088532822098406
Author(s):  
Liangpeng Xu ◽  
Fan Yang ◽  
Yao Ge ◽  
Gaoyang Guo ◽  
Yunbing Wang

Over one million artificial heart valve transplantations are performed each year due to valvular stenosis or regurgitation. Among them, bioprosthetic heart valves (BHVs) are increasingly being used because of the absence of the need for lifelong anticoagulation. Almost all of the commercial BHVs are treated with Glutaraldehyde (GLUT). As GLUT-treated BHVs are prone to calcification and structural degradation, their durability is greatly reduced with a service life of only 12–15 years. The physiological structure and mechanical properties of the porcine aortic valve (PAV) are closer to that of a human heart valve, so in this study, PAV is used as the model to explore the comprehensive properties of the prepared BHVs by radical polymerization crosslinking method. We found that PAV treated by radical polymerization crosslinking method showed similar ECM stability and biaxial mechanical properties with GLUT-treated PAV. However, radical polymerization crosslinked PAV exhibited better cytocompatibility and endothelialization potential in vitro cell experiment as better anticalcification potential and reduced immune response than GLUT-treated PAV through subcutaneous animal experiments in rats. To conclude, a novel crosslinking method of non-glutaraldehyde fixation of xenogeneic tissues for the preparation of BHVs is expected.

2019 ◽  
Vol 9 (22) ◽  
pp. 4773 ◽  
Author(s):  
Evgeny Ovcharenko ◽  
Maria Rezvova ◽  
Pavel Nikishau ◽  
Sergei Kostjuk ◽  
Tatiana Glushkova ◽  
...  

Superior polymers represent a promising alternative to mechanical and biological materials commonly used for manufacturing artificial heart valves. The study is aimed at assessing poly(styrene-block-isobutylene-block-styrene) (SIBS) properties and comparing them with polytetrafluoroethylene (Gore-texTM, a reference sample). Surface topography of both materials was evaluated with scanning electron microscopy and atomic force microscopy. The mechanical properties were measured under uniaxial tension. The water contact angle was estimated to evaluate hydrophilicity/hydrophobicity of the study samples. Materials’ hemocompatibility was evaluated using cell lines (Ea.hy 926), donor blood, and in vivo. SIBS possess a regular surface relief. It is hydrophobic and has lower strength as compared to Gore-texTM (3.51 MPa vs. 13.2/23.8 MPa). SIBS and Gore-texTM have similar hemocompatibility (hemolysis, adhesion, and platelet aggregation). The subcutaneous rat implantation reports that SIBS has a lower tendency towards calcification (0.39 mg/g) compared with Gore-texTM (1.29 mg/g). SIBS is a highly hemocompatible material with a promising potential for manufacturing heart valve leaflets, but its mechanical properties require further improvements. The possible options include the reinforcement with nanofillers and introductions of new chains in its structure.


Author(s):  
Chad E. Eckert ◽  
Brandon T. Mikulis ◽  
Dane Gerneke ◽  
Danielle Gottlieb ◽  
Bruce Smaill ◽  
...  

Engineered heart valve tissue (EHVT) has received much attention as a potential pediatric valve replacement therapy, offering prospective long-term functional improvements over current options. A significant gap in the literature exists, however, regarding estimating tissue mechanical properties from tissue-scaffold composites. Detailed three-dimensional structural information prior to implantation (in vitro) and after implantation in (in vivo) is needed for improved modeling of tissue properties. As such, a novel high-resolution imaging technique will be employed to obtain three-dimensional microstructural information. Analysis techniques will be used to fully quantify constituents of interest including scaffold, collagen, and cellular information and to develop appropriate two-dimensional sectioning sampling protocols. It is the intent of this work to guide modeling efforts to better elucidate EHVT tissue-specific mechanical properties.


2021 ◽  
Vol 73 (7) ◽  
pp. 478-484
Author(s):  
Watcharit Anantakal ◽  
◽  
Somboon Thamtakerngkit ◽  
Vijarn Vachirawongsakorn ◽  
◽  
...  

Objective: To compare the heart valve circumference before and after 10% formalin fixation. Materials and Methods: The study analyzed 63 Thai human cadaveric hearts. Each heart valve circumference was separately measured in the fresh state by specifically designed equipment. After that, the hearts were fixed in 10% formalin for 3 days. Then each heart valve circumference was measured by the same equipment and by the thread and ruler technique. The results were analyzed using SPSS package to find the association between the heart valve circumference before and after formalin fixation. Results: This study showed that the average circumferences of the heart valve measured in the fresh state were 13.329 cm in the tricuspid valve, 10.617 cm in the mitral valve, 8.416 cm in the pulmonic valve, and 7.122 cm in the aortic valve. The average circumferences of the heart valve measured after 10% formalin fixation were 11.019 cm in the tricuspid valve, 8.714 cm in the mitral valve, 6.751 cm in the pulmonic valve, and 6.089 cm in the aortic valve. The average ratios of the heart valve circumference measured fresh and after 10% formalin fixation were 0.8267 in the tricuspid valve, 0.8235 in the mitral valve, 0.8050 in the pulmonic valve, and 0.8573 in the aortic valve. There were significant differences in the heart valve circumference between the fresh state and after formalin fixation (p < 0.001). Conclusion: This study revealed important information on the dimensional changes of all the formalin-fixed heart valves. We found that the heart valve shrank after formalin fixation, with the formalin-fixed hearts an estimated 0.8 times smaller than the fresh cadaveric hearts.


2021 ◽  
Vol 25 (3) ◽  
pp. 106
Author(s):  
R. N. Komarov ◽  
A. O. Simonyan ◽  
I. A. Borisov ◽  
V. V. Dalinin ◽  
A. M. Ismailbaev ◽  
...  

<p>Various types of autologous materials are used in heart valve surgery, particularly the aortic valve, and this article describes their historical development. The evolution of the use of various autogenous tissues, such as the aortic wall, fascia lata of the thigh, pericardium and others is described and discussed in detail. This paper presents the results of experimental and clinical publications devoted to the surgical techniques and the outcomes of heart valve reconstruction using such materials. The negative aspects of the use of a wide range of autografts are discussed, including the short service life and low strength, which led to declining interest in this group of reconstructive interventions. The method for treating the autopericardium with glutaraldehyde, proposed in 1986 by C.S. Love, J.W. Love and colleagues, raised the use of autologous materials in the reconstruction of heart valves to a new level, allowing surgeons to strengthen the autopericardial flaps and increase resistance to hemodynamic stress. Many surgeons, their interest in such treatment methods increased by this discovery, then reported their observations and further developed ways of using the treated autopericardium in aortic valve surgery. Particularly, the method of neocuspidisation of the aortic valve, introduced into wide practice by M.G. Duran and S. Ozaki, has become the quintessential reconstructive valve surgery involving the use of autologous materials.</p><p>Received 14 March 2021. Revised 26 April 2021. Accepted 27 April 2021.</p><p><strong>Funding:</strong> The study did not have sponsorship.</p><p><strong>Conflict of interest:</strong> The authors declare no conflicts of interests.</p><p><strong>Contribution of the authors</strong><br />Conception and study design: A.O. Simonyan, A.M. Ismailbaev<br />Drafting the article: A.O. Simonyan, A.M. Ismailbaev, N.O. Kurasov, M.I. Tcheglov<br />Critical revision of the article: R.N. Komarov, V.V. Dalinin, I.A. Borisov<br />Final approval of the version to be published: R.N. Komarov, A.O. Simonyan, I.A. Borisov, V.V. Dalinin, A.M. Ismailbaev, N.O. Kurasov, M.I. Tcheglov</p>


1992 ◽  
Vol 15 (11) ◽  
pp. 681-685 ◽  
Author(s):  
M.O. Wendt ◽  
M. Pohl ◽  
S. Pratsch ◽  
D. Lerche

Hemolytic and subhemolytic blood damage by mechanical heart valve prostheses have been observed in both clinical and in vitro investigations. A direct comparison between these studies is not possible. Nevertheless the transfer of some in vitro results to the behaviour of the valve in situ may be performed considering the similarity principle. This requires the use of dimensionless similarity numbers such as the plasma's hemoglobin concentration (PHb) or others, instead of dimensioned parameters. To evaluate the in vitro hemolysis of valve prosthesis a test chamber filled with human banked blood was used. An artificial ventricle ensuring an oscillatory flow through the valve was also used. The rise of PHb was evaluated in terms of a similarity number, called the lysis number. This number describes the probability of destroying a single red blood cell participating once in the hemolytic process under consideration. The lysis number, a Björk-Shiley valve (TAD 29), was found to be in the order of 2 × 10−4. From this, the survival time of erythrocytes in patients with an artificial heart valve was estimated. It was found to be in the order of 20 d of T50 Cr in agreement with clinical results


Author(s):  
Adel F. Badria ◽  
Petros G. Koutsoukos ◽  
Dimosthenis Mavrilas

AbstractCardiovascular diseases are the first cause of death worldwide. Among different heart malfunctions, heart valve failure due to calcification is still a challenging problem. While drug-dependent treatment for the early stage calcification could slow down its progression, heart valve replacement is inevitable in the late stages. Currently, heart valve replacements involve mainly two types of substitutes: mechanical and biological heart valves. Despite their significant advantages in restoring the cardiac function, both types of valves suffered from serious drawbacks in the long term. On the one hand, the mechanical one showed non-physiological hemodynamics and the need for the chronic anticoagulation therapy. On the other hand, the biological one showed stenosis and/or regurgitation due to calcification. Nowadays, new promising heart valve substitutes have emerged, known as decellularized tissue-engineered heart valves (dTEHV). Decellularized tissues of different types have been widely tested in bioprosthetic and tissue-engineered valves because of their superior biomechanics, biocompatibility, and biomimetic material composition. Such advantages allow successful cell attachment, growth and function leading finally to a living regenerative valvular tissue in vivo. Yet, there are no comprehensive studies that are covering the performance of dTEHV scaffolds in terms of their efficiency for the calcification problem. In this review article, we sought to answer the question of whether decellularized heart valves calcify or not. Also, which factors make them calcify and which ones lower and/or prevent their calcification. In addition, the review discussed the possible mechanisms for dTEHV calcification in comparison to the calcification in the native and bioprosthetic heart valves. For this purpose, we did a retrospective study for all the published work of decellularized heart valves. Only animal and clinical studies were included in this review. Those animal and clinical studies were further subcategorized into 4 categories for each depending on the effect of decellularization on calcification. Due to the complex nature of calcification in heart valves, other in vitro and in silico studies were not included. Finally, we compared the different results and summed up all the solid findings of whether decellularized heart valves calcify or not. Based on our review, the selection of the proper heart valve tissue sources (no immunological provoking residues), decellularization technique (no damaged exposed residues of the decellularized tissues, no remnants of dead cells, no remnants of decellularizing agents) and implantation techniques (avoiding suturing during the surgical implantation) could provide a perfect anticalcification potential even without in vitro cell seeding or additional scaffold treatment.


2018 ◽  
Vol 4 (1) ◽  
pp. 259-262 ◽  
Author(s):  
Finja Borowski ◽  
Michael Sämann ◽  
Sylvia Pfensig ◽  
Carolin Wüstenhagen ◽  
Robert Ott ◽  
...  

AbstractAn established therapy for aortic valve stenosis and insufficiency is the transcatheter aortic valve replacement. By means of numerical simulation the valve dynamics can be investigated to improve the valve prostheses performance. This study examines the influence of the hemodynamic properties on the valve dynamics utilizing fluidstructure interaction (FSI) compared with results of finiteelement analysis (FEA). FEA and FSI were conducted using a previously published aortic valve model combined with a new developed model of the aortic root. Boundary conditions for a physiological pressurization were based on measurements of ventricular and aortic pressure from in vitro hydrodynamic studies of a commercially available heart valve prosthesis using a pulse duplicator system. A linear elastic behavior was assumed for leaflet material properties and blood was specified as a homogeneous, Newtonian incompressible fluid. The type of fluid domain discretization can be described with an arbitrary Lagrangian-Eulerian formulation. Comparison of significant points of time and the leaflet opening area were used to investigate the valve opening behavior of both analyses. Numerical results show that total valve opening modelled by FEA is faster compared to FSI by a factor of 5. In conclusion the inertia of the fluid, which surrounds the valve leaflets, has an important influence on leaflet deformation. Therefore, fluid dynamics should not be neglected in numerical analysis of heart valve prostheses.


Author(s):  
Sarah C. Vigmostad ◽  
Brian D. Jeffrey ◽  
Sreedevi Krishnan ◽  
H. S. Udaykumar ◽  
K. B. Chandran

Bioprosthetic heart valves are valve replacements constructed from animal tissue. They are deformable and offer similar mechanical properties to their native counterpart. While tearing of these valves is frequently observed, it is still not fully understood, but may be the result of high induced bending and shear stresses in the valve leaflets[1].


Author(s):  
M. Salinas ◽  
D. Schmidt ◽  
R. Lange ◽  
M. Libera ◽  
S. Ramaswamy

There is extensive documented evidence that mechanical conditioning plays a significant role in the development of tissue grown in-vitro for heart valve scaffolds [1–3]. Modern custom made bioreactors have been used to study the mechanobiology of engineered heart valve tissues [1]. Specifically fluid-induced shears stress patterns may play a critical role in up-regulating extracellular matrix secretion by progenitor cell sources such as bone marrow derived stem cells (BMSCs) [2] and increasing the possibility of cell differentiation towards a heart valve phenotype. We hypothesize that specific biomimetic fluid induced shear stress environments, particularly oscillatory shear stress (OSS), have significant effects on BMSCs phenotype and formation rates. As a first step here, we attempt to quantify and delineate the entire 3-D flow field by developing a CFD model to predict the fluid induced shear stress environments on engineered heart valves tissue under quasi-static steady flow and dynamic steady flow conditions.


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