Tissue-engineering Valve from Cell-Remodeled Biopolymer

描述（由申请人提供）：该 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）通过捕获的组织细胞收缩、排列和重塑。将应用组织力学理论来确定最佳模具设计，以便细胞介导的模具表面周围凝胶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耦合固体流体力学模型将用于定义我们的“阀门等效物”（VE）在孵化后所需的与对齐相关的机械特性以实现正确的阀门功能，并模拟 VE 功能。将实施各种实验策略来在孵化期间操纵这些特性。瓣叶运动的高速超声成像将与粒子成像测速一起开发和使用，以验证模型并使瓣膜功能可视化。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.