Tissue-engineering Valve from Cell-Remodeled Biopolymer

描述(申请人提供)：该BRP旨在开发一种组织工程化心血管瓣膜，最初的重点是主动脉瓣置换。将使用“组织等效”的方法来制造生物人工组织，在这种方法中，纤维状生物聚合物凝胶(I型胶原或纤维蛋白)收缩、排列并由包裹的组织细胞重塑。将应用组织力学理论来确定最优的模具设计，使细胞介导的凝胶在模具表面周围的压实产生目标几何形状和ECM纤维排列。脉动流中阀门功能的固体流体耦合力学模型将被用来定义在孵化适当的阀门功能后，我们的“阀门当量”(VE)需要哪些与排列有关的机械性能，并模拟VE功能将是什么。在孵化过程中，将实施各种实验策略来操纵这些特性。为了验证模型的有效性和瓣膜功能的可视化，将开发高速的叶运动超声成像技术，并与粒子成像测速技术一起使用。除了VE的全面生物学和生物力学特征外，新型成体干细胞将被评估为内皮细胞的来源，并有可能成为制造VE的间质小叶细胞的来源。

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.