Research
Overview
Cardiovascular disease (CVD) is the leading cause of death in the developed world. According to the American Heart Association, approximately 37% of all Americans (nearly 80 million people) suffer from CVD, which resulted in over 870,000 deaths in 2004 (AHA, 2007). The majority of CVD result in impaired heart function, leading to heart attack or congestive heart failure. Extremely important to the function of the heart are the valves, which ensure unidirectional blood circulation. For an average heart rate of 70 beats per minute, these valves open and close three billion times! The mechanical performance and durability of the valve leaflets are unmatched by any manmade material to date, especially when the hazards of blood clot formation and immune responses are factored in. The key to this incredible performance is the fact that the tissue is alive with resident cells that are capable of sensing and responding to the local environment, and constantly modifying the extracellular matrix (repairing damage, strengthening, etc.) to maintain function. The interactions between these cells, matrix proteins, and the local mechanical environment are highly complex and therefore poorly understood.
What is known is that deficiencies in one or more of these relationships restricts the valve’s ability to endure this constant loading, leading to potentially catastrophic tissue failure unless treated. The current therapy for valve disease is prosthetic valve replacement with a nonliving biological or mechanically based surrogate. When tailored to the needs of the patient, these valves can function for 20 years or more, but with significant lifestyle limitations. While generally acceptable for older patients, prosthetic valves are a poor choice for growing children or adults with active lifestyles and/or demanding work environments. Tissue engineering has the capability to alleviate these concerns by creating a replacement valve that incorporates the living cellular components necessary to thrive within this demanding environment. While proof of principal has been established, major hurdles remain before this technology can be clinically useful.
A key determinant for the pathogenesis of heart valve disease is the presence of congenital heart defects (CHD). CHD is a general term that includes any alteration in normal embryonic cardiac development. Approximately 1% of all Americans (3 million people) are living with CHD, a majority of which affect heart valves. Some may appear benign but can lead to premature valve failure because its deleterious effect builds up over years of dynamic mechanical loading. Others can be immediately life threatening if not surgically repaired at or soon after birth. Approximately 50% of all preterm fetal deaths are caused by CHD, the plurality of which are a valve based defect. Clinical studies show that 90% of all CHD is not caused by a single gene deficiency, suggesting that alterations in the microenvironment (i.e. mechanical forces) may therefore be responsible. Embryonic cardiogenesis and valvulogenesis are extremely complex, rapidly occurring 3D processes that have been difficult to study experimentally, and as a result very little has been learned about the mechanisms behind the morphological changes.
Our research focus thus is to identify principals regulating embryonic valvular development and use these to motivate regenerative engineering strategies for heart and valve disease. Our lab has developed expertise in three areas necessary to undertake this effort: mechanobiology, developmental biology, and tissue engineering. To this end our lab has three research thrusts that synergize together to accelerate the transition from basic science to clinical benefit:
 Thrust 1Mechanical Regulation of Embryonic Valvulogenesis |
 Thrust 2Developmental Redux of Adult Valve Disease |
 Thrust 3Embryonically Inspired Heart Valve Regenerative Engineering |
Also see Publications.