Core C: Computational and Experimental Biomechanical Assessment (CEBA)

核心 C：计算和实验生物力学评估 (CEBA)

• 批准号: 10378123
• 负责人: Jay D. Humphrey
• 金额: $ 22.22万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378123
• 关键词: Aneurysm; Aorta; Area; Behavior; Biological; Biological Assay; Biomechanics; Blood Platelets; Blood Vessels; Carotid Arteries; Catheters; Cells; Cessation of life; Collection; Computer Models; Computer Simulation; Computers; DNA Sequence Alteration; Data; Data Analyses; Data Collection; Descriptor; Devices; Disease; Dissection; Endothelial Cells; Endothelium; Environment; Extracellular Matrix; Fibroblasts; Gene Expression; Genetic; Geometry; Goals; In Vitro; Individual; Invaded; Liquid substance; Measures; Mechanics; Methods; Modeling; Molecular; Mus; Natural History; Nonparametric Statistics; Phenotype; Play; Property; Reporting; Reproducibility; Role; Rupture; Smooth Muscle; Smooth Muscle Myocytes; Solid; Specimen; Stress; Testing; Thoracic Aortic Aneurysm; Thoracic aorta; Time; base; biomechanical test; cell type; data modeling; disability; hemodynamics; human disease; in vivo; insight; knowledge translation; macrophage; mechanical properties; mechanical stimulus; mechanotransduction; microCT; monocyte; mouse model; novel; pressure; programs; public health relevance; shear stress; stem cells; stress state; therapeutic target; ultrasound

COMPUTATIONAL AND EXPERIMENTAL BIOMECHANICAL ASSESSMENT (CEBA) CORE C - PROJECT SUMMARY This Scientific Core will provide consistent and comprehensive biomechanical evaluation, both in vivo and in vitro, of the different mouse models used in this Program Project. First, mouse-specific aortic geometries will be determined using microCT whereas associated inlet and outlet flows and inlet pressures will be measured in vivo using ultrasound and Millar pressure catheters, respectively. Second, cylindrical specimens will be excised from the ascending, descending, suprarenal, and infrarenal segments of the aorta and subjected to novel, consistent, in vitro biomechanical phenotyping. Specifically, we will assess endothelial-dependent and independent vasodilatory capacity, compromised levels of induced biaxial smooth muscle cell contractility, and passive biaxial mechanical properties, and we will compare results across regions and groups using appropriate parametric and non-parametric statistics. Third, the biaxial material properties will be used to compute regional material and structural stiffnesses, energy storage, and layer-specific wall stresses, which in conjunction with the microCT and other in vivo data will inform unique fluid-solid-interaction computational simulations that can assess effects of altered geometry and wall properties on the micro-mechanical environment to which each of the primary cell types is exposed (e.g., endothelial shear stresses and smooth muscle and fibroblast intramural stress). These results, in turn, will be provided to each of the four Projects within the overall Program Project to enable correlations of mechanical stimuli with results from the myriad biological assays used in each project. In this way, collectively we will be able to evaluate, for the first time, critical roles of cellular mechanosensing and mechanoregulation of the extracellular matrix that endows the thoracic aorta with its compliance and strength and when compromised results in the loss of structural integrity that manifests as a potentially lethal thoracic aortic aneurysm.

预防性和实验性生物力学评估（CEBA） 核心C -项目总结 该科学核心将提供一致和全面的生物力学评价，无论是在体内， 体外，不同的小鼠模型在这个程序项目中使用。首先，小鼠特定的主动脉几何形状将 而相关的入口和出口流量以及入口压力将被测量 分别使用超声和Millar压力导管进行体内试验。其次，圆柱形试样将 从主动脉的升、降、肾上和肾下段切除， 新颖、一致的体外生物力学表型。具体而言，我们将评估内皮依赖性和 独立的血管舒张能力，诱导的双轴平滑肌细胞收缩性受损，以及 被动双轴力学性能，我们将比较不同地区和群体的结果， 适当的参数和非参数统计。第三，双轴材料的特性将用于 计算区域材料和结构刚度、能量储存和特定于层的壁应力， 结合microCT和其他体内数据将为独特的流体-固体相互作用计算提供信息， 可以评估改变的几何形状和壁特性对微机械性能的影响的模拟 每种主要细胞类型所暴露的环境（例如，内皮剪切应力和平滑 肌肉和成纤维细胞壁内应力）。这些结果将依次提供给四个项目中的每一个项目 在整个程序项目中，使机械刺激与无数结果相互关联 每个项目中使用的生物测定。通过这种方式，我们将能够第一次集体评估， 细胞机械感应和细胞外基质的机械调节的关键作用， 胸主动脉的顺应性和强度，当受损时会导致结构完整性的丧失 可能致命的胸主动脉瘤