Tissue-engineering Valve from Cell-Remodeled Biopolymer

描述（由申请人提供）：本BRP旨在开发组织工程心血管瓣膜，最初重点是主动脉瓣置换术。将使用“组织等效”方法制造生物人工组织，其中纤维状生物聚合物凝胶（I型胶原或纤维蛋白）通过截留的组织细胞收缩、对齐和重塑。将应用组织力学理论来确定最佳模具设计，使得模具表面周围的凝胶的细胞介导的压实产生目标几何形状和ECM纤维对齐。将使用脉动流中瓣膜功能的耦合固体流体力学模型来定义我们的“瓣膜等效物”（VE）在适当瓣膜功能的孵育之后所需的依赖于瓣膜的机械特性，并模拟VE功能。将实施各种实验策略，以操纵这些属性在孵育过程中。将开发瓣叶运动的高速超声成像，并沿着粒子成像测速术使用，以验证模型并可视化瓣膜功能。除了全面的生物学和生物力学特性的VE，新的成体干细胞将被评估为内皮细胞的来源，并可能，间质小叶细胞的VE制造。

DESCRIPTION (provided by applicant): 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.