In Vitro Calcification of Bioprosthetic Heart Valves: Test Fluid Validation on Prosthetic Material Samples
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Annals of Biomedical Engineering ( 2020) https://doi.org/10.1007/s10439-020-02618-6
Original Article
In Vitro Calcification of Bioprosthetic Heart Valves: Test Fluid Validation on Prosthetic Material Samples N. KIESENDAHL,1,3 C. SCHMITZ,1,3 M. MENNE,1 T. SCHMITZ-RODE,2 and U. STEINSEIFER 1 1
Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Helmholtz Institute Aachen, RWTH Aachen University, Pauwelsstraße 20, 52074 Aachen, Germany; 2Institute of Applied Medical Engineering, Helmholtz Institute Aachen, RWTH Aachen University, Aachen, Germany; and 3ac.biomed GmbH, Aachen, Germany (Received 25 May 2020; accepted 10 September 2020) Associate Editor Smadar Cohen oversaw the review of this article.
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 nonspontaneously 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.
ABBREVIATIONS ACP CaT DCPD EvG HAP HE I IP IZKF Ksp OCP PE PT PU PVC SCaP T XRD
Amorphous calcium phosphate Total calcium Dicalciumphosphate-dihydrate Elastic Van Gieson stain Hydroxyapatite Hematoxylin and eosin stain Ionic strength Thermodynamic ionic product Interdisciplinary Center for Clinical Research Thermodynamic solubility constant Octacalcium phosphate Polyethylene Total phosphate Polyurethane Polyvinyl chloride Degree of supersaturation Temperature X-ray powder diffraction
Keywords—Fluid validation, Spontaneous precipitation, Intrinsic calcification, Structural identification.
INTRODUCTION
Address correspondence to U. Steinseifer, Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Helmholtz Institute Aachen, RWTH Aachen University, Pauwelsstraße 20, 52074 Aachen, Germany. Electronic mail: [email protected]
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