The concept and practice of seeding cells onto degradable polymer scaffolds, such as poly(lactic acid) (PLA) or poly (glycolic acid) (PGA), in vitro followed by eventual in vivo implantation has become an important methodology in tissue engineering. These scaffolds provide structural support for the cells until they develop their own extracellular matrix, but scaffold mechanical properties have yet to be specifically designed to provide an environment that will match that of the native tissue. The specific interest of this project is the engineering of cardiovascular tissues. In the investigators' experiences with existing PLA or PGA tubular and valvular leaflet scaffolds, it has been difficult to sew them into the native tissue, bend them to fit a desired or required conformation within the animal, or replace all three pulmonary valve leaflets without leading to unacceptable valvular stenosis. The investigators' goals are to develop the next generation of tissue engineering polymer scaffolds with mechanical properties (e.g. elasticity) that closely model those of the native tissue (pulmonary valve leaflets, arteries) and to investigate the influence of such an environment on cell proliferation, tissue formation, and function of engineered tissues in vivo. Their hypothesis is that significant advances in tissue engineering may be realized if the biomaterials to be used as scaffolds can be specifically designed to resemble the mechanical properties of the native tissue in question. Accordingly, the Specific Aims are: 1) Synthesis and characterization of elastic, degradable polymers with appropriate mechanical properties for use as cardiovascular tissue engineering scaffolds; 2) Test the degradation profiles of the new polymers and monitor the changes in mechanical properties over time; 3) Test the polymer-cell compatibilities and interactions (attachment and spreading) on polymer films using appropriate cell types (e.g. endothelial cells, smooth muscle cells, fibroblasts). Cells will be provided by Dr. Mayer at Children's Hospital; 4) Select best candidates based on Aims 1-3, then design and prepare scaffolds in the shapes of tubes for blood vessels and leaflets or whole valves for heart valves; 5) Carry out in vitro cell seeding studies to determine the influence of polymer properties and bioreactor conditions on cell differentiation, proliferation, and tissue formation in conjunction with Drs. Vacanti, Bischoff, and Roth at Children's Hospital; 6) Implantation of cell-scaffold devices at the appropriate time frame based on the findings of Aim 5 in small animal models (to be carried out by Drs. Mayer and Vacanti at Children's Hospital).
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