Neomycin binding preserves extracellular matrix in bioprosthetic heart valves during in vitro cyclic fatigue and storage

This review describes the first studies on successful conversion of porcine soft-tissue bioprostheses into viable permanently functional tissue in humans. This process includes gradual degradation of the porcine tissue, with concomitant neo-vascularization and reconstruction of the implanted bioprosthesis with human cells and extracellular matrix. Such a reconstruction process is referred to in this review as “humanization”. Humanization was achieved with porcine bone-patellar-tendon-bone (BTB), replacing torn anterior-cruciate-ligament (ACL) in patients. In addition to its possible use in orthopedic surgery, it is suggested that this humanization method should be studied as a possible mechanism for converting implanted porcine bioprosthetic heart-valves (BHV) into viable tissue valves in young patients. Presently, these patients are only implanted with mechanical heart-valves, which require constant anticoagulation therapy. The processing of porcine bioprostheses, which enables humanization, includes elimination of α-gal epitopes and partial (incomplete) crosslinking with glutaraldehyde. Studies on implantation of porcine BTB bioprostheses indicated that enzymatic elimination of α-gal epitopes prevents subsequent accelerated destruction of implanted tissues by the natural anti-Gal antibody, whereas the partial crosslinking by glutaraldehyde molecules results in their function as “speed bumps” that slow the infiltration of macrophages. Anti-non gal antibodies produced against porcine antigens in implanted bioprostheses recruit macrophages, which infiltrate at a pace that enables slow degradation of the porcine tissue, neo-vascularization, and infiltration of fibroblasts. These fibroblasts align with the porcine collagen-fibers scaffold, secrete their collagen-fibers and other extracellular-matrix (ECM) components, and gradually replace porcine tissues degraded by macrophages with autologous functional viable tissue. Porcine BTB implanted in patients completes humanization into autologous ACL within ~2 years. The similarities in cells and ECM comprising heart-valves and tendons, raises the possibility that porcine BHV undergoing a similar processing, may also undergo humanization, resulting in formation of an autologous, viable, permanently functional, non-calcifying heart-valves.

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In-vitro Calcification Assessment of Bioprosthetic Heart Valves: Development and Validation of a Near-physiological Test Fluid

Structural Heart ◽

10.1080/24748706.2020.1717192 ◽

2020 ◽

Vol 4 (sup1) ◽

pp. 53-53

Author(s):

Nicole Kiesendahl ◽

Christoph Schmitz ◽

Ulrich Steinseifer

Keyword(s):

Heart Valves ◽

Test Fluid ◽

Bioprosthetic Heart Valves ◽

Development And Validation

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Cross-Linking Methacrylated Porcine Pericardium by Radical Polymerization Confers Enhanced Extracellular Matrix Stability, Reduced Calcification, and Mitigated Immune Response to Bioprosthetic Heart Valves

ACS Biomaterials Science & Engineering ◽

10.1021/acsbiomaterials.9b00091 ◽

2019 ◽

Vol 5 (4) ◽

pp. 1822-1832 ◽

Cited By ~ 5

Author(s):

Linhe Jin ◽

Gaoyang Guo ◽

Wanyu Jin ◽

Yang Lei ◽

Yunbing Wang

Keyword(s):

Immune Response ◽

Extracellular Matrix ◽

Radical Polymerization ◽

Heart Valves ◽

Cross Linking ◽

Bioprosthetic Heart Valves ◽

Matrix Stability ◽

Porcine Pericardium

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Simulation of the Role of Oscillatory Shear Stress on Mesenchymal Stem Cell Proliferation and Extracellular Matrix Production in Engineered Heart Valve Tissue Formation

Volume 1A: Abdominal Aortic Aneurysms; Active and Reactive Soft Matter; Atherosclerosis; BioFluid Mechanics; Education; Biotransport Phenomena; Bone, Joint and Spine Mechanics; Brain Injury; Cardiac Mechanics; Cardiovascular Devices, Fluids and Imaging; Cartilage and Disc Mechanics; Cell and Tissue Engineering; Cerebral Aneurysms; Computational Biofluid Dynamics; Device Design, Human Dynamics, and Rehabilitation; Drug Delivery and Disease Treatment; Engineered Cellular Environments ◽

10.1115/sbc2013-14180 ◽

2013 ◽

Author(s):

João S. Soares ◽

Trung B. Le ◽

Fotis Sotiropoulos ◽

Michael S. Sacks

Keyword(s):

Extracellular Matrix ◽

Heart Valves ◽

Structural Evolution ◽

Biodegradable Scaffolds ◽

Cell Sources ◽

Hemodynamic Performance ◽

Tissue Engineered Heart Valves ◽

Oscillatory Shear Stress

Living tissue engineered heart valves (TEHV) may circumvent ongoing problems in pediatric valve replacements, offering optimum hemodynamic performance and the potential for growth, remodeling, and self-repair [1]. TEHV have been constructed by seeding vascular-derived autologous cells onto biodegradable scaffolds and exhibited enhanced extracellular matrix (ECM) development when cultured under pulsatile flow conditions in-vitro [2]. After functioning successfully for up to 8 months in the pulmonary circulation of growing lambs, TEHV underwent extensive in vivo remodeling and structural evolution and have demonstrated the feasibility of engineering living heart valves in vitro [3]. The employment of novel cell sources, which are clinically obtainable in principle such as bone marrow-derived mesenchymal stem cells (MSCs), is key to achieve viable clinical application [4].

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Extracellular matrix degrading enzymes are active in porcine stentless aortic bioprosthetic heart valves

Journal of Biomedical Materials Research ◽

10.1002/jbm.a.10066 ◽

2003 ◽

Vol 66A (4) ◽

pp. 755-763 ◽

Cited By ~ 19

Author(s):

Dan T. Simionescu ◽

Joshua J. Lovekamp ◽

Narendra R. Vyavahare

Keyword(s):

Extracellular Matrix ◽

Heart Valves ◽

Bioprosthetic Heart Valves ◽

Degrading Enzymes ◽

Matrix Degrading Enzymes

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In vitro endothelialization of bioprosthetic heart valves provides a cell monolayer with proliferative capacities and resistance to pulsatile flow

Journal of Thoracic and Cardiovascular Surgery ◽

10.1067/mtc.2001.110251 ◽

2001 ◽

Vol 121 (1) ◽

pp. 108-115 ◽

Cited By ~ 14

Author(s):

Katarina Jansson ◽

Lars Bengtsson ◽

Jesper Swedenborg ◽

Anders Haegerstrand

Keyword(s):

Pulsatile Flow ◽

Heart Valves ◽

Cell Monolayer ◽

Bioprosthetic Heart Valves ◽

A Cell

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Ultrastructural pathology of bioprosthetic heart valves with infectious endocarditis

Fundamental and Clinical Medicine ◽

10.23946/2500-0764-2021-6-3-25-34 ◽

2021 ◽

Vol 6 (3) ◽

pp. 25-34

Author(s):

R. A. Mukhamadiyarov ◽

I. V. Milto ◽

A. G. Kutikhin

Keyword(s):

Extracellular Matrix ◽

Heart Valves ◽

Osmium Tetroxide ◽

Giant Cells ◽

Uranyl Acetate ◽

Diglycidyl Ether ◽

Multinucleated Giant Cells ◽

Bioprosthetic Heart Valves ◽

Sputter Coating ◽

Backscattered Scanning Electron Microscopy

Aim. To study the ultrastructure of mitral bioprosthetic heart valves (BHVs) which failed due to infective endocarditis.Materials and Methods. Here we examined 7 ethylene glycol diglycidyl ether-treated xenopericardial BHVs excised during repeated BHV replacement because of prosthetic endocarditis. After being fixed in formalin and postfixed in osmium tetroxide, BHVs were dehydrated and stained in uranyl acetate with the subsequent embedding into epoxy resin, grinding, polishing, and lead citrate counterstaining. Upon the sputter coating with carbon, we visualised the BHV microanatomy by means of backscattered scanning electron microscopy at 15 kV voltage.Results. The extracellular matrix underwent degradation and disintegration resulting in loosening, fragmentation, and reduction in the electron density of collagen and elastin fibers. We observed a number of recipient cells (macrophages, multinucleated giant cells, neutrophils, endothelial cells and smooth muscle cells) within the BHVs. The highest number of cells was localized on the valve surfaces. The localization of the recipient cells on the ventricular and atrial surfaces was different. The central part of the valves was abundantly populated by macrophages.Conclusion. Prosthetic endocarditis is accompanied by the migration of recipient cells into the BHV structure, which is the consequence of surface and extracellular matrix disintegration.

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In Vitro Calcification of Bioprosthetic Heart Valves: Test Fluid Validation on Prosthetic Material Samples

Annals of Biomedical Engineering ◽

10.1007/s10439-020-02618-6 ◽

2020 ◽

Author(s):

N. Kiesendahl ◽

C. Schmitz ◽

M. Menne ◽

T. Schmitz-Rode ◽

U. Steinseifer

Keyword(s):

Heart Valves ◽

Dynamic Contact ◽

Test Fluid ◽

Prosthetic Material ◽

Fluid Composition ◽

Time Saving ◽

Bioprosthetic Heart Valves ◽

X Ray

Abstract Calcification is a major failure mode of bioprosthetic heart valves. So far, cost and time saving in vitro analyses of calcification potentials are unreliable, mostly due to superficial or spontaneous precipitation of the applied fluids. In this study, we developed a near-physiological non-spontaneously precipitating fluid for an accelerated in vitro calcification assessment, and validated it by analyzing the calcification potential of two prosthetic materials within two reference-tests. The first test focused on the comparison of four calcification fluids under dynamic contact with n=12 commercial bovine pericardium patches. The second one focused on the validation of the most appropriate fluid by analyzing the calcification potential of pericardium vs. polyurethane. The patches were mounted in separate test compartments and treated simultaneously with the respective fluids at an accelerated test frequency. Calcification propensity and progression were detected macroscopically and microscopically. Structural analyses of all deposits indicated hydroxyapatite by X-ray powder diffraction, which is also most commonly observed in vivo. Histological examination by von Kossa staining showed matrix internal and superficial calcifications, depending on the fluid composition. The present study reveals promising results towards the development of a meaningful, cost and time saving in vitro analysis of the calcification potential of bioprosthetic heart valves.

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