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

将剪切引起的血液损伤的多尺度动力学与 CFD 建模联系起来

• 批准号: 7815733
• 负责人: Zhongjun Jon Wu
• 金额: $ 2.06万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7815733
• 关键词: Animals; Area; Assisted Circulation; Biomedical Engineering; Blood; Blood Cells; Blood flow; Cardiovascular Diseases; Cardiovascular system; Cells; Characteristics; Clinical; Clinical Data; Coagulation Process; Computer Assisted; Computer Simulation; Cytolysis; Data; Databases; Development; Device Designs; Devices; Elements; Engineering; Evaluation; Event; Goals; Healthcare; Heart Valves; Hemolysis; Human; Implant; In Vitro; Investments; Knowledge; Lactate Dehydrogenase; Link; Liquid substance; Mechanical Stress; Mechanics; Medical; Medical Device; Medicine; Modeling; Outcome Measure; Patients; Pattern; Physiological; Platelet Activation; Play; Prosthesis; Research; Role; Safety; Science; Series; Stents; Surface; Technology; Thromboembolism; Thrombosis; Time; Validation; Vascular Graft; base; biomaterial compatibility; blood oxygenator; cell injury; clinical practice; computerized tools; design; improved; in vivo; innovation; multidisciplinary; novel; prototype; public health relevance; research study; shear stress; simulation; theories; tool; tool development; ventricular assist device

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.

描述(由申请人提供)：心血管医疗设备的治疗提高了许多原本没有希望的医疗条件下患者的存活率。不幸的是，在许多情况下，这些设备会导致危险的病理并发症，特别是血栓形成和血栓栓塞症，这与作用于通过这些设备的血液的非生理性条件直接相关。计算流体力学(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，可以计算和评估流经这些装置的流体引起的机械应力。可以准确地识别血流路径中的非生理性机械切应力和停滞流区域。这项建议的目的是在剪切性血液损伤的动力学和CFD建模之间建立联系。我们建议检查流动诱导的血液损伤、溶血、血小板激活、细胞溶解以及相关的副产物(乳酸脱氢酶、聚集体、碎片、凝血级联)的基本方面。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指标与其机制来源联系起来。该项目的具体目标是：(1)确定CFD衍生的流体动力学变量(剪切应力、暴露时间、流动模式)和血液损伤数据(血小板激活、血栓形成和溶血)之间的相关性，这些数据来自植入了心室辅助装置(VAD)的人类患者和动物。(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。使用这些平台，生成流动诱导的血液损伤的全面数据库。(3)在收集的血液损伤数据库的基础上，开发并实现了生物医学设备中流动诱导的血液损伤的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，能够预测心血管设备的功能特征和生物/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/血液兼容性。与公共卫生相关血液接触生物医学设备已经并将继续在医疗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、科学和工程学的多学科知识，以及我们对更好技术的坚持不懈。这项建议的目的是在设计和开发工具、CFD建模和流动诱导的血液损伤的动力学之间建立联系，特别是溶血、血小板激活、细胞溶解和相关的副产品。