Multi-scale biomechanical modeling of heart valve tissue

The pioneering work of Y.C. Fung in 1979 was the genesis for a broad spectrum of constitutive models specifically tailored for soft tissues. Over the last three decades researchers have demonstrated the value of predictive models in applications involving cardiac tissue, skin and blood vessels. In recent years predictive computational modeling has been demonstrated as a valuable tool in the study of heart valve function. Motivated by concerns such as identification of pathological initiators, development of prosthetic devices and guidance for engineered tissue scaffolds, researchers have tailored a class of constitutive models to features unique to the valves of the heart. This dissertation aims to extend the scope of these models.;The constitutive models and modeling techniques developed in this work will serve as predictive tools to be leveraged by future studies. In particular, robust computational implementation of a class of models is a central aim. Concepts which extend the scale-dependent physiologic fidelity of current modeling approaches will be presented and implemented into a finite element framework. To complement the constitutive model development, a methodology to transform, in vivo patient specific medical image data into high fidelity three-dimensional models is presented.;The clinical relevance of this work is directed at applications of congenital heart disease and tissue engineering. A study of the biomechanical response of a polymer-based tissue engineered scaffold is presented using the modeling techniques developed herein. Guidelines relevant to the design of these constructs are a natural conclusion of the analysis performed. A methodology to explore risk factors associated with the bicuspid aortic valve is outlined. This work will establish a set of biomechanically-based metrics associated with disease predisposition risk factors.