A significant number of congenital cardiac malformations include either stenosis or atresia of the pulmonary valve with most able to be corrected early in life. The homograft, prosthetic, or bioprosthetic options available to serve as a pulmonary valve lack growth potential and are susceptible to infection, thrombosis, or calcification. They also commit the children to multiple operations. Tissue engineering using living cells seeded on scaffolds in vitro offers the potential to create a living valve structure, which could overcome the shortcomings of currant devices. Significant progress has been made toward realization of this goal with tissue-engineered valves having been implanted and functioning in animals for up to 6 months. In order to continue progressing toward a clinically applicable TE pulmonary valve, fundamental questions regarding the types of cells to be used to seed the polymer scaffold, the optimal in vitro physical signaling conditions, and the optimal biomechanical characteristics of the polymer scaffold remain to be answered. The studies proposed will address if cells obtained relatively non-invasively from blood and/or bone marrow will be suitable for TE valves, the influence of biomechanical properties of the scaffold in the development of TE valves in vitro, and the effects of shear stress and hydrostatic pressure signals on the in vitro development of TE valves. The final studies will address the relationship between the characteristics of the TE valve at the time of implantation and the long-term function of these valves. ? ? ?
