INTERSTITIAL CELL SEEDING AND DYNAMIC CONDITIONING OF AORTIC HEART VALVE SCAFFOLDS

In 2011, U.S. Markets for Heart Valve Repair and Replacement Products estimated that roughly four million people in the United States are diagnosed with a heart valve disorder annually. And in the following year, the American Heart Association reported that approximately 35,000 deaths in the US were either directly or indirectly attributed to heart valve disease. Diseases of the heart valve are degenerative in nature and therefore progressively worsen unbeknownst to the patient until symptoms become clinically relevant. By this time, the valve is in such poor condition that complete replacement is often the only effective treatment. Current solutions are mechanical and bioprosthetic replacements, but each is associated with its own inadequacies. As a result, science is now looking to the promising field of tissue engineering for solutions to the limitations of current valve replacement options. A patient-tailored, translational approach to heart valve replacement that is safe and effective will expectantly be the result of efforts put into this rapidly growing area of research. Present experiments hypothesize that the success of tissue engineered heart valves lies in the complete recellularization of a scaffold with autologous cells prior to implantation. While external cell seeding of the valve to avoid thrombogenicity seems to be the most obvious need, additional focus on interstitial recellularization is necessary to obtain a truly biocompatible replacement capable of valve remodeling and regeneration. Our short term goal is to obtain a fully recellularized, viable valve scaffold. Thus far, infiltration of externally seeded cells into the acellular tissue scaffold has been shown to some extent, but has led to many questions concerning the effectiveness of those seeding methods. More specifically, there are concerns about the characterization of the cell phenotypes found in the interstices of the cusp and their effect on the success of the entire valve construct in vivo. The following document proposes a novel method of cell injection into acellular aortic heart valve cusp scaffolds followed by mechanical conditioning as a prerequisite to complete valve recellularization that will yield proper valvular interstitial cell phenotype within the construct. Present studies have optimized the cellular injection technique, determined appropriate conditioning methods, and shown cell retention and differentiation within the interstices of the cusp