Past Event: Oden Institute Seminar

Biomechanics of Native and Engineered Heart Valve Tissues

Michael S. Sacks, Ph.D., W.K. Whiteford Professor, Department of Bioengineering, University of Pittsburgh

Abstract

On the most basic functional level, heart valves are essentially simple-check valves that serve to prevent retrograde blood flow. This seemingly simple function belies the structural complexity, elegant solid-fluid mechanical interaction, and durability necessary for normal valve function. For example, valves are capable of withstanding 30-40 million cycles per year, resulting in a total of ~3 billion cycles in single lifetime. Passive in nature, heart valves react to the inertial forces exerted by blood flow. Pressure differences operate on the valve leaflets to initiate rapid opening and closure of the valve. Functionally, the leaflet is required to exhibit diverse mechanical properties under varied states and modes of deformation. Robust constitutive models provide the fundamental framework for computational modeling of heart valve function. The complex multi-modal nature of valvular leaflet deformation warrants a treatment focused on the prediction of response to generalized mechanical stimuli. A complex interaction of constituents influences the structural response of the tissue. Structural proteins (collagen and elastin) and other extracellular matrix (ECM) components react to mechanical stimuli in varied modes to produce a highly nonlinear anisotropic tissue level response unique to the tissue type and tailored to specific physiological conditions. In general, the robust nature of a model can be characterized by the ability to capture the underlying physiologic function. Our laboratory has pioneered morphological based constitutive models that considers a broad range of strain and deformation modes, including the impact of low strain and bending response. The staggering level of valve performance can be cut short by aortic valve disease, the most common form being stenosis resulting from calcification. Currently, the treatment of valve disease is usually complete valve replacement. First performed successfully in 1960, surgical replacement of diseased human heart valves by valve prostheses is now commonplace and enhances survival and quality of life for many patients. However, they continue to have significant clinical problems and there is a profound need for new approaches to valve therapies based on sound scientific and engineering principals. Tissue engineering represents a spectrum of cross-disciplinary technologies aimed toward the repair, replacement, or enhancement of native valve function. The scaffolds amenability to tissue development, however, belies their intricate microstructure and the concomitant complexity of mechanical interactions occurring between scaffold, cellular, and extracellular matrix constituents in an engineered tissue construct. Mathematical models that simulate the composite mechanical behavior of the scaffold and the developing tissue could potentially facilitate the design of engineered tissues and mechanical conditioning regimens. Such models could thus play a pivotal role in the design and development of an engineered heart valve.