Maglev LVAD with expandable stented inlet and anti-thrombotic coating to improve hemocompatibility

项目摘要/摘要 在美国，近500万人患有心力衰竭，其中约40万人与心力衰竭有关 每年都会发生死亡事件。心力衰竭造成了巨大的公共医疗负担，并显著减少了 机动性和生活质量。左心辅助装置(LVAD)是一种很有前途的终末期治疗选择 除了心脏移植，还有心力衰竭患者，这受到可用捐赠者数量的限制。然而， 严重的并发症，包括出血和血栓形成，会显著恶化患者的长期预后 植入了左心室反搏装置。这一拟议的跨学科创新努力旨在最大限度地提高LVAD 来自两个不同方面的血液相容性：血液相容性滑动亲水性(SLIC)涂层和创新 有支架的入口设计。我们假设，通过使用SLIC涂层和创新的设计优化， 该设备将实现良好的血液相容性，并显著降低血液损伤和血栓形成风险。这个 本项目的目标是开发一种新型的具有良好血液相容性的磁悬浮(Maglev)LVAD 以显著减少血栓形成和并发症的发生。经过一系列的体外验证测试和 血液相容性评估，LVAD原型将在大动物体内进行评估和验证 模特们。这些突破性的创新将给LVAD技术带来巨大的飞跃，最终跨越 与心脏移植相比，非劣质结局的门槛。提出了要实现的四个目标 这个项目。在目标1(优化SLIC涂层以获得最大的抗血栓反应)中，我们将制造和 表征SLIC涂层的物理和化学不均匀性。涂层将覆盖整个 装置，包括驱动系统和进气套管。涂层的性能和耐久性将是彻底的 测试过。在目标2(优化LVAD设计和开发新型支架入口以降低血栓风险)中，我们将 使用基于机器学习的优化框架和创新的支架入口设计来减少血液 损害并消除入口处血栓形成的风险。该设备的血流动力学性能将是 用二维和三维粒子图像测速仪进行体外评价。目标3(设计和评估磁悬浮驱动器 )，我们将开发磁悬浮驱动系统，以减少 溶血，并结合速度控制调节，以减少局部血液的发生 停滞不前。最后，SLIC LVAD将在AIM 4(体外和体内血液相容性评估)中进行验证 泵原型)通过体外血液循环实验和大型动物模型进行血液相容性研究 性能和设备能量传输效率。这一新型设备可能会被开发为 一种低血栓感染风险的治疗方法，是心脏移植的更好选择，提供长期- 对终末期心力衰竭患者的长期支持。

PROJECT SUMMARY/ABSTRACT Nearly 5 million people in the USA suffer from heart failure, with approximately 400,000 heart failure-related deaths occurring yearly. Heart failure causes a significant public healthcare burden and significantly reduces mobility and quality of life. Left ventricular assist device (LVAD) is a promising therapeutic option for end-stage heart failure patients besides cardiac transplant, which is limited by the number of available donors. However, severe complications, including bleeding and thrombosis, significantly worsen the long-term outcome in patients with implanted LVADs. This proposed innovative interdisciplinary effort aims to maximize the LVAD hemocompatibility from two different fronts: hemocompatible slippery hydrophilic (SLIC) coatings and innovative stented inlet design. We hypothesize that by using the SLIC coating and innovative design optimization, the device will achieve excellent hemocompatibility and dramatically reduce blood damage and thrombosis risk. The objective of this project is to develop a novel magnetic levitated (maglev) LVAD with excellent hemocompatibility to reduce thrombosis and complication incidents significantly. After a series of in vitro validation testing and hemocompatibility evaluation, the LVAD prototype will be evaluated and validated in vivo with large animal models. These breakthrough innovations will bring LVAD technology a giant leap forward, eventually crossing the threshold of non-inferior outcomes compared to cardiac transplants. Four aims are proposed to complete this project. In Aim 1 (Optimize SLIC Coatings for Maximum Antithrombotic Response), we will fabricate and characterize the physical and chemical inhomogeneities of SLIC coatings. The coating will cover the entire device, including drive system and inlet cannula. The properties and durability of the coatings will be thoroughly tested. In Aim 2 (Optimize LVAD Design and Develop Novel Stented Inlet to Reduce Thrombosis Risk), we will use a machine learning-based optimization framework and an innovative stented inlet design to reduce blood damage and eliminate the risk of thrombosis at the inlet. The device's hemodynamic performance will be evaluated in vitro by using 2D and 3D particle image velocimetry. In Aim 3 (Design and Evaluate Maglev Drive System with Heart Rate Sensing for Speed Control), we will develop the Maglev drive system to reduce the hemolysis and incorporate it with speed control modulation to reduce the occurrence of regional blood stagnation. Finally, the SLIC LVAD will be validated in Aim 4 (Evaluate In Vitro and In Vivo Hemocompatibility of the Pump Prototype) by both in vitro blood loop experiments and large-animal models for hemocompatibility performance and device energy transmission efficiency. This novel device will potentially be developed as a low-thrombosis-infection-risk therapeutic, a better alternative to cardiac transplant, providing long- term support to end-stage heart failure patients.