This BRP aims to develop a tissue-engineered cardiovascular valve, with the initial focus being an aortic valve replacement. The """"""""tissue-equivalent"""""""" approach to fabricating bioartificial tissues, in which a fibrillar biopolymer gel (type I collagen or fibrin) is contracted, aligned, and remodeled by entrapped tissue cells, will be used. A tissue mechanical theory will be applied to determine the optimal mold design such that cell-mediated compaction of the gel around the mold surfaces yields the target geometry and ECM fiber alignment. A coupled solid fluid mechanical model of valve function in pulsatile flow will be used to define what alignment-dependent mechanical properties of our """"""""valve-equivalent"""""""" (VE)are desired following incubation for proper valve function, and to simulate what the VE function will be. Various experimental strategies will be implemented to manipulate these properties during incubation. High-speed ultrasonic imaging of leaflet motion will be developed and used along with particle imaging velicometry in order to validate the model as well as visualize valve function. In addition to comprehensive biological and biomechanical characterization of the VE, novel adult stem cells will be assessed as a source of endothelial cells and, potentially, interstitial leaflet cells for VE fabrication. ? ?
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