Real Time, Non-Invasive Assessment of Leaflet Deformation in Heart Valve Tissue Engineering

Abstract

Abstract-In heart valve tissue engineering, most bioreactors try to mimic physiological flow and operate with a preset transvalvular pressure applied to the tissue. The induced deformations are unknown and can vary during culturing as a consequence of changing mechanical properties of the engineered construct. Real-time measurement and control of local tissue strains are desired to systematically study the effects of mechanical loading on tissue development and, consequently, to design an optimal conditioning protocol. In this study, a method is presented to assess local tissue strains in heart valve leaflets during culturing. We hypothesize that local tissue strains can be determined from volumetric deformation. Volumetric deformation is defined as the amount of fluid displaced by the deformed heart valve leaflets in a stented configuration, and is measured, noninvasively, using a flow sensor. A numerical model is employed to relate volumetric deformation to local tissue strains in various regions of the leaflets (e.g. belly and commissures). The flow-based deformation measurement method was validated and its functionality was demonstrated in a tissue engineering experiment. Tri-leaflet, stented heart valves were cultured in vitro and during mechanical conditioning, realistic values for volumetric and local deformation were obtained.

How to Make a Heart Valve: From Embryonic Development to Bioengineering of Living Valve Substitutes

“…The porous starter matrix is shaped like a heart valve and supports the formation of neotissue . In the bioreactor, the construct is subjected to biochemical and mechanical stimuli to enhance the production of ECM proteins in an effort to create a valve that has sufficient strength and durability to meet in vivo hemodynamic requirements (Mol et al 2005a;Kortsmit et al 2009). Particular attention has been focused on replicating the anisotropic architecture of the native leaflet Neidert and Tranquillo 2006;Balguid et al 2007;Rubbens et al 2009;Cox et al 2010;Sander et al 2011).…”

Nondestructive and Noninvasive Assessment of Mechanical Properties in Heart Valve Tissue Engineering

“…1). 27 The whole system was filled with 150 mL of culture medium. The silicone tube inside the polycarbonate cylinder, which functions as a pneumatic pump, was compressed and decompressed by pulsatile air pressure from the proportional valve.…”

“…Relative leakage values varied between 0% (valve 2-3) and 32% (valve 2-2). As seen in our previous study, 27 volumetric deformation measurements are not accurate Relationship between applied pressure difference (kPa) and induced volumetric deformation (mL) of the heart valve leaflets, numerically obtained for four different degrees of anisotropy. Isotropic material behavior is represented by ''isotropic,'' whereas ''anisotropic 1,'' ''anisotropic 2,'' and ''anisotropic 3'' indicate the degrees of anisotropy estimated in a previous study in tissue-engineered heart valves after 2, 3, and 4 weeks of culturing, 35 respectively.…”

“…An inverse experimental-numerical approach has been proposed by which leaflet deformation is assessed real-time and noninvasively 27 during culture in a bioreactor system. This technique allows a systematic study of the effects of mechanical straining on tissue development.…”

Quasi-Steady Flow Dynamics Study of Human Aortic Valve with Numerical Techniques

“…It should be noted that movement of heart valve leaflet is timedependent, and simulating this kind of displacement is not an easy work. In order to deal with this issue, numerous studies have been conducted by applying quasi-steady approach [8][9][10]. An important question is raised: Are the quasi-steady leaflet mechanical properties truly representative of their physiological behavior?…”