Linking Multiscale Dynamics of Shear-induced Blood Damage to CFD modeling

描述（由申请人提供）：心血管医疗器械的治疗提高了许多其他无望的疾病患者的生存率。不幸的是，在许多情况下，这些装置会引起危险的病理并发症，特别是血栓形成和血栓栓塞，这与作用于流经这些装置的血液的非生理条件直接相关。计算流体动力学（CFD）辅助模拟和分析是生物工程师使用的最重要的设计和分析工具之一。通过CFD分析，可以计算和评估流体通过这些装置引起的机械应力。血流路径中的非生理性机械剪切应力和停滞流动区域可以精确识别。本文的目的是建立剪切血损伤动力学与CFD建模之间的联系。我们建议研究血流诱导的血液损伤的基本方面：溶血、血小板活化、细胞裂解和相关副产物（LDH、聚集体、碎片、凝血级联）。我们将进行一系列协调的多尺度生物和工程实验，并通过基于cfd的建模将血液损伤的结果测量与其机制起源联系起来。拟议项目的具体目标是：(1)确定从植入心室辅助装置（VADs）的人类患者和动物中获得的cfd衍生流体动力学变量（剪切应力、暴露时间、血流模式）与血液损伤数据（血小板活化、血栓形成和溶血）之间的相关性。(2)建立多尺度体外实验平台，研究特定流体动力学特性对血细胞损伤的影响。利用这些平台，生成血流损伤的综合数据库。(3)基于血损伤集体数据库，开发并实现了经过验证的生物医学器械血流损伤CFD模型。这些研究的长期目标是开发准确、稳健和生理上真实的数值模型，能够预测心血管装置的功能特征和生物/血液相容性。这些模型可以帮助开发新的设计，以改善设备的功能特性和生物/血液相容性。血液接触生物医学设备已经并将继续在卫生保健和临床实践中发挥重要作用。这些设备的持续改进依赖于医学、科学和工程的多学科知识，以及我们对更好技术的不懈追求。本提案的目的是建立设计和开发工具、CFD建模和血流诱导的血液损伤动力学之间的联系，特别是溶血、血小板活化、细胞裂解和相关副产物。

DESCRIPTION (provided by applicant): The treatment with cardiovascular medical devices enhances survival for many patients with otherwise hopeless medical conditions. Unfortunately, in many cases these devices cause dangerous pathological complications, in particular thrombosis and thromboembolism, which are directly related to non-physiological conditions acting on the blood flowing through these devices. One of the most important design and analysis tools used by bioengineers is computational fluid dynamics (CFD) aided simulation and analysis. With CFD analysis, the fluid induced mechanical stresses through these devices can be computed and assessed. The regions of non-physiologic mechanical shear stresses and stagnant flow in blood flow paths can be precisely identified. The objective of this proposal is to build the link between the dynamics of the shear-induced blood damage and CFD modeling. We propose to examine foundational aspects of flow-induced blood damage hemolysis, platelet activation, cell lysis, and associated byproducts (LDH, aggregates, fragments, coagulation cascade). We will conduct a series of coordinated multi-scale biologic and engineering experiments and link the outcome measures of the blood damage to their mechanistic origins through CFD-based modeling. The specific aims of the proposed project are to: (1) Identify the correlation between CFD-derived fluid-dynamic variables (shear stress, exposure time, flow pattern) and blood damage data (platelet activation, thrombosis, and hemolysis) obtained from human patients and animals implanted with ventricular assist devices (VADs). (2) Develop multi-scale in-vitro experimental platforms to investigate the influence of specific fluid dynamic characteristics on blood cell damage. Using these platforms, generate comprehensive databases of flow-induced blood damage. (3) Based on the collective databases of blood damage, develop and implement a validated CFD model of flow-induced blood damage in a biomedical device. The long-term goal of these studies is to develop accurate, robust, and physiologically realistic numerical models capable of predicting the functional characteristics and bio/hemo-compatibility of cardiovascular devices. The models can aid in the development of new designs in order to improve the functional characteristics and bio/hemo-compatibility of the devices. PUBLIC HEALTH RELEVANCE Blood contacting biomedical devices have played and will continue to play a major role in health care and clinical practice. Continued improvement of these devices relies on multidisciplinary knowledge of medicine, science, and engineering, as well as our persistence in pursuing better technologies. The objective of this proposal is to establish a link between the design and development tool, CFD modeling, and the dynamics of flow-induced blood damage, specifically, hemolysis, platelet activation, cell lysis, and associated byproducts.