Tissue-engineering Valve from Cell-Remodeled Biopolymer

描述（由申请人提供）：本BRP旨在开发一种组织工程心血管瓣膜，最初的重点是主动脉瓣置换术。将使用“组织等效”方法来制造生物人工组织，其中纤维状生物聚合物凝胶（I型胶原蛋白或纤维蛋白）被包裹的组织细胞收缩、排列和重塑。组织力学理论将应用于确定最佳模具设计，使细胞介导的凝胶在模具表面的压实产生目标几何形状和ECM纤维对齐。脉动流中阀门功能的耦合固流力学模型将用于定义在适当的阀门功能孵卵后，我们的“阀门等效”（VE）的定位相关力学特性，并模拟VE功能。在孵化期间，将实施各种实验策略来操纵这些特性。高速超声成像的小叶运动将发展和使用与粒子成像速度测定，以验证模型和可视化的瓣膜功能。除了对VE进行全面的生物学和生物力学表征外，还将评估新型成体干细胞作为内皮细胞的来源，并可能作为VE制造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.