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

磁悬浮 LVAD 具有可扩张支架入口和抗血栓涂层，可改善血液相容性

基本信息

批准号：
10736998
负责人：
Lakshmi Prasad Dasi
金额：
$ 75.25万
依托单位：
TEXAS HEART INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10736998
关键词：
3-Dimensional Adopted Adsorption Affinity Animal Model Architecture Blood Blood Proteins Cannulas Cessation of life Chemicals Complication Destinations Development Device Designs Devices Electrocardiogram Evaluation Feasibility Studies Heart Heart Rate Heart Transplantation Heart Valves Heart failure Hemolysis Hemorrhage Hydration status Image Implant In Vitro Infection Interdisciplinary Study Investigation Left Longevity Machine Learning Magnetism Molecular Outcome Patients Performance Persons Positioning Attribute Property Proteins Public Health Pump Quality of life Reaction Research Project Grants Resolution Risk Series Signal Transduction Speed Stents Stroke Surface System Technology Testing Therapeutic Thrombosis Validation Velocimetries Ventricular blood damage blood pump care burden design experimental study hemocompatibility hemodynamics hydrophilicity implantation improved in vivo infection risk innovation left ventricular assist device novel particle prototype response sensor success surface coating thrombotic transmission process

项目摘要

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.

项目概要/摘要美国有近 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。心力衰竭造成重大的公共医疗负担，并显着降低流动性和生活质量。左心室辅助装置（LVAD）是终末期患者有前途的治疗选择除心脏移植外的心力衰竭患者，心脏移植受到可用捐赠者数量的限制。然而，严重并发症，包括出血和血栓形成，显着恶化患者的长期结果植入 LVAD。这项创新的跨学科工作旨在最大限度地提高 LVAD 血液相容性来自两个不同的方面：血液相容性光滑亲水 (SLIC) 涂层和创新支架式入口设计。我们假设通过使用 SLIC 涂层和创新设计优化，装置将实现优异的血液相容性，并显着降低血液损伤和血栓形成的风险。这该项目的目标是开发一种具有优异血液相容性的新型磁悬浮 (maglev) LVAD 显着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原型将在大型动物体内进行评估和验证模型。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，非劣质结果的阈值。提出要完成四个目标这个项目。在目标 1（优化 SLIC 涂层以实现最大抗血栓反应）中，我们将制造并表征 SLIC 涂层的物理和化学不均匀性。涂层将覆盖整个装置，包括驱动系统和入口插管。涂层的性能和耐久性将得到彻底的改善已测试。在目标 2（优化 LVAD 设计并开发新型支架入口以降低血栓形成风险）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坏并消除入口处血栓形成的风险。该装置的血流动力学性能为通过使用 2D 和 3D 粒子图像测速法进行体外评估。目标 3（设计和评估磁悬浮驱动器）具有用于速度控制的心率感应系统），我们将开发磁悬浮驱动系统以减少溶血并结合调速调节，减少局部出血的发生停滞。最后，SLIC LVAD 将在目标 4（评估体外和体内血液相容性）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性能和设备能量传输效率。这种新颖的设备可能会被开发为一种低血栓形成感染风险的治疗方法，是心脏移植的更好替代方案，可提供长期治疗对终末期心力衰竭患者的长期支持。