In Vitro Calcification of Bioprosthetic Heart Valves: Investigation of Test Fluids

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Annals of Biomedical Engineering ( 2019) https://doi.org/10.1007/s10439-019-02347-5

In Vitro Calcification of Bioprosthetic Heart Valves: Investigation of Test Fluids N. KIESENDAHL,1 C. SCHMITZ,1 A. VON BERG,4 M. MENNE,1 T. SCHMITZ-RODE,2 J. ARENS,1 and U. STEINSEIFER 1,2,3 1 Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Helmholtz Institute Aachen, RWTH Aachen University, Aachen, Germany; 2Institute of Applied Medical Engineering, Helmholtz Institute Aachen, RWTH Aachen University, Pauwelsstraße 20, 52074 Aachen, Germany; 3Monash Institute of Medical Engineering and Department of Mechanical and Aerospace Engineering, Monash University, Melbourne, Australia; and 4Institute of Crystallography, RWTH Aachen University, Aachen, Germany

(Received 6 May 2019; accepted 16 August 2019) Associate Editor Jane Grande-Allen oversaw the review of this article.

Abstract—Calcification is a major reason for the failure of bioprosthetic heart valves. Therefore, several attempts towards an accelerated in vitro model were undertaken in order to provide a cost- and time-saving method for the analysis of calcification processes. Due to the problem of superficial or spontaneous precipitation, which occurred in the fluids applied, we focused our study on the development of a near-physiological calcification fluid. The desired fluid should not precipitate spontaneously and should neither promote nor inhibit calcification. Eleven different fluid compositions were tested without contact to potentially calcifying materials. Crucial factors regarding the fluid properties were the ionic product, the ionic strength, and the degree of supersaturation concerning dicalciumphosphate-dihydrate, octacalciumphosphate, and hydroxyapatite. The fluids were kept in polyethylene bottles and exposed to a slight vibration within a durability tester at 37 C. The precipitation propensity was monitored optically and colorimetrically. A structural analysis of the deposits was carried out by x-ray powder diffraction and IR-spectroscopy, which showed the development of the crystal phases that are relevant in vivo. Only two of the fluids did not precipitate. Resulting from the computations of the effective fluid contents, the saturation degree concerning dicalciumphosphate-dihydrate seems to be the key factor for spontaneous precipitation. Keywords—Fluid study, Spontaneous precipitation, Ionic strength, Ionic products, Supersaturation.

Address correspondence to U. Steinseifer, Institute of Applied Medical Engineering, Helmholtz Institute Aachen, RWTH Aachen University, Pauwelsstraße 20, 52074 Aachen, Germany. Electronic mail: [email protected]

ABBREVIATIONS au CaT Ca-Gluc DCPD fz FTIR HAP I IP IR Ksp OCP PE PT PU SCaP SBF T XRD

Arbitrary unit Total calcium Calcium gluconate Dicalciumphosphate-dihydrate Activity coefficient of z-valent ionic species Fourier transform infrared spectroscopy Hydroxyapatite Ionic strength Thermodynamic ionic product Infrared Thermodynamic solubility constant Octacalcium phosphate Polyethylene T