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着机械心脏瓣膜（MHV）之间的选择 和生物瓣膜。对于年轻的患者，MHV是首选，因为它们的极端耐用性，但 他们的余生都依赖于抗凝治疗。有强烈的需要， MHV设计停滞不前，40年来没有实质性变化。最终目标 是引进新一代的MHV，实现完全独立于抗凝剂。Pl的 长期目标是创造和维持一个以学生为中心的设计研究环境， 改进瓣膜血流动力学性能的新型MHV设计范例的原型设计和测试， 减少血栓形成。大量的工作已经阐明了异常流的重要性 在铰链和MHV闭合附近触发血小板活化并因此凝血的特征。到 进一步推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，用于解释凝块沉积物对血管附近血流的影响。 MHV并允许再现两种血流动力学性能测试的可比真实流动条件 （需要光学透明的血液模拟物）和血栓形成性测试（需要真实的血液）。实现 PI将联合收割机与一个用于激光流量测量的流体动力学测试仪和一个前所未有的 MHV血栓形成测试仪基于无泵闭环中MHV的血液循环。 这项研究的基本假设是，与用于体外和数值研究的原始MHV不同， 研究表明，体内发生的MHV上的凝块沉积显著影响血流特征， 血小板的机械负荷和血栓生长速率。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变化。这项研究的具体目标是： 目标1.量化血栓存款程度、切应力与血小板损伤指标之间的关系。 目标二。与双叶MHV相比，研究三叶MHV的血流动力学和血栓形成。 目标3.量化阀门尺寸对MHV中阀门关闭附近的流速和剪应力的影响。 本项目将（1）建立一个全面的MHV血流动力学/血栓形成的准确平台 测试将推动主动脉瓣疾病治疗的创新;（2）证明血栓的作用 沉积物在血栓生长中发挥作用;（3）证明三叶MHV用于成人和儿童的可行性 人口数量。这些结果为未来无抗凝剂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。为 参与的研究生和本科生，包括来自代表性不足的少数民族的学生， 项目是一个独特的研究和教育机会，将丰富他们的专业和提高他们的 吸引潜在的招聘者。

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.