A comprehensive testing platform for mechanical heart valves to propel innovation towards anticoagulant-independence

项目摘要 需要主动脉瓣置换术的患者面临机械心脏瓣膜(MHV)的选择 和生物瓣膜。对于年轻患者来说，MHV更可取，因为它们极其耐用，但 他们的余生都依赖于抗凝治疗。有一种强烈的需求来激发 对停滞不前的MHV设计的创新，这40年来没有实质性的变化。终极目标 是迎来新一代完全不依赖抗凝剂的MHV。全日空的 长期目标是为设计创造和维持一个以学生为中心的研究环境， 改善瓣膜血流动力学性能的新型MHV设计范例的原型和测试 降低血栓形成能力。大量的工作已经阐明了异常流动的重要性 触发血小板激活，从而在铰链附近凝血和关闭MHV的特征。至 进一步促进对流动诱导的血液凝固的理解，并确定无抗凝剂的MHV设计， PI将开发一个MHV测试平台，用于研究血栓沉积对附近血液流动的影响 MHV，并允许为两种血流动力学性能测试重现可比的真实流动条件 (需要光学透明的血液模拟物)和血栓形成试验(需要真血)。要实现 PI将结合用于激光流量测量的流体动力测试仪和前所未有的 MHV血栓性测试仪，基于MHV在无泵闭环中的血液循环。 这项研究的基本假设是，与用于体外和数值计算的原始MHV不同 研究表明，体内MHV上的凝块沉积显著影响血液流动特征， 血小板机械负荷和血栓生长率。未来的MHV设计策略应考虑 MHV植入后发生的基本血流动力学改变。这项研究的具体目的是： 目的1.量化血栓沉积程度、切应力与血小板损伤指数之间的关系。 目的2.比较三叶和双叶中高压的血流动力学和血栓形成能力。 目的3.定量研究阀门尺寸对MHV中阀门关闭附近的流速和剪应力的影响。 该项目将(1)建立一个全面的MHV血流动力学/血栓形成的准确平台 将推动治疗主动脉瓣疾病的创新的测试；(2)证明血栓的作用 沉淀物在血栓形成中发挥作用；(3)展示成人和儿童三叶式MHV的生存能力 人口。这些结果为未来无抗凝血剂的MHV的研究奠定了基础 改变年轻患者和发展中国家患者的治疗选择和预后。对于 参与的研究生和本科生，包括来自代表性不足的少数族裔的学生，这 项目是一个独特的研究和教育机会，将丰富他们的专业知识并增加他们的 吸引潜在的招聘人员。

Project Summary Patients needing aortic valve replacement are faced with a choice between mechanical heart valves (MHVs) and bioprosthetic valves. For younger patients, MHVs are preferable because of their extreme durability, but they become dependent on anticoagulant therapy for the rest of their life. There is a strong need to spark innovation over the stagnant MHV design, which has not substantially changed in 40 years. The ultimate goal is to usher in a new generation of MHVs that achieve complete independence from anticoagulants. The Pl's long-term objective is to create and sustain a student-centered research environment for the design, prototyping and testing of novel MHV design paradigms that improve valve hemodynamic performance and reduce thrombogenicity. A substantial amount of work has already elucidated the importance of abnormal flow features in triggering platelet activation, and thus blood clotting, near the hinges and the closing of MHVs. To further advance the understanding of flow-induced blood clotting and identify anticoagulant-free MHV designs, the PI will develop a MHV testing platform that accounts for the effect of clot deposits on blood flow near the MHV and allows to reproduce comparable realistic flow conditions for both hemodynamic performance tests (which require an optically-clear blood analog) and thrombogenicity tests (which require real blood). To achieve that, the PI will combine a hydrodynamic tester for laser-based flow measurements and an unprecedented MHV thrombogenicity tester based on blood circulation through MHVs in a pumpless closed loop. The underlying hypothesis of this research is that, unlike with the pristine MHVs used for in-vitro and numerical studies, the deposition of clot on the MHV that occurs in-vivo significantly affects blood flow features, mechanical loading of platelets, and thrombus growth rate. Future MHV design strategies should consider the fundamental hemodynamic changes occurring after MHV implantation. The specific aims of this study are: Aim 1. Quantify the relationship between clot deposit extent, shear stress and platelet damage indices. Aim 2. Investigate hemodynamics and thrombogenicity of trileaflet MHVs, compared to bileaflet MHVs. Aim 3. Quantify the effect of valve size on flow velocities and shear stress near valve closure in MHVs. This project will (1) establish an accurate platform for comprehensive MHV hemodynamics/thrombogenicity testing that will propel innovation in the treatment of aortic valve disease; (2) demonstrate the role thrombus deposits play in thrombus growth; (3) demonstrate the viability of trileaflet MHVs for adult and pediatric populations. These outcomes lay the ground work for future research on anticoagulant-free MHVs that will transform treatment options and prognosis for younger patients and patients from developing countries. For the graduate and undergraduate students involved, including students from underrepresented minorities, this project is a unique research and educational opportunity that will enrich them professionally and increase their appeal to potential recruiters.