Grant: Operating Grant

Heart valve diseases are increasingly common but currently can only be treated by replacing the diseased valve with a synthetic valve. Synthetic valves are poorly suited for children and younger patients who increasingly are afflicted with the disease. This has motivated efforts to make living replacement heart valves that can grow, adapt, and repair themselves. Generally, engineered valves are produced by placing cells in biomaterials that are designed to guide the cells to produce valve tissue. This process is aided by bioreactors, devices that exercise and nourish the tissue. Selection of biomaterials and bioreactor conditions has been largely based on "best guesses", which may explain why no one has been able to engineer a functional aortic valve (the most commonly replaced valve) yet. We believe that improved heart valve tissue engineering requires systematic testing of combinations of biomaterial and bioreactor conditions. In the current proposal, we will apply novel microtechnologies we have developed and advanced statistical methods to widely screen cell sources, biomaterial designs, and bioreactors. From these screens, we will select biomaterial and bioreactor conditions that promote the growth of mechanically-robust heart valve tissue. We will then implant the most promising engineered tissues in rats to test whether they calcify, as this is the way synthetic valves fail. We expect this systematic and innovative approach to identify design criteria for next generation tissue engineered heart valves with improved function and resistance to calcification.