Development of a Tubular Biological Tissue-Engineered Heart Valve with Growth Potential

Abstract

This thesis investigates tissue-engineered cardiovascular devices for pediatric patients and their function and growth potential in preclinical testing. Specifically, engineered tissue tubes were fabricated by entrapping dermal fibroblasts in a fibrin gel and allowing them to replace it with circumferentially-aligned extracellular matrix. Following in vitro culture, the engineered tubes possessed physiological strength and were decellularized to increase their shelf-life and reduce their immunogenicity. An allogeneic tubular heart valve was fabricated by inserting one engineered tube inside of another and attaching them together using degradable sutures. Extensive hemodynamic testing was performed in order to optimize and verify valve design. The growth potential and in vivo function of a single engineered tube (as a pulmonary artery replacement) and pulmonary heart valve were evaluated in a growing lamb model. We observed extensive host cell invasion and growth of the valve root/single tube, but to a lesser degree in the leaflets, which resulted in diminished valve function. A modified animal model is proposed and proof-of-concept studies were performed in order to address this shortcoming.