Coupling 3D Fluid-Structure Interaction and System Biology to Model Calcification of the Aortic Valve

Heart valve calcification is a condition where calcium buildup in the valve causes tissue stiffening, narrowed valve opening, reduced flow output, and even failure of the valve. Calcification results from either fibroblastic or osteogenic differentiation of valvular interstitial cells (VICs) and involves a complex biochemical process that responds to the mechanical stresses and damages experienced by the valve tissue. Therefore, there is a strong interplay of the fluid-structure interaction (FSI) of the valve and the biochemical formation of calcification. In this work, we aim to develop a multiscale and Multiphysics framework that integrates 3D FSI of aortic valve with a system biology model of calcification chemical kinetics to track leaflet calcification over time. The FSI simulations will be solved using an in-house immersed boundary code and will capture the mechanical stresses and strains in the tissue and the shear stresses from the flow. The system biology model will utilize the stress and strain data and solve the chemical kinetics equations governing relevant processes such as Nitric Oxide (NO) synthesis, LDL cholesterol penetration, and TGF-beta signaling and their effects on calcium uptake into the leaflet tissue. Using a multiscale approach, the integrated model will simulate the FSI for only a limited number of cardiac cycles but will simulate the calcification growth over years. Such a framework could be potentially used as patient-specific models predicting the progression of heart valve calcification.