Flexible Anti-thrombotic LVADs

灵活的抗血栓 LVAD

基本信息

批准号：
10575664
负责人：
Lakshmi Prasad Dasi
金额：
$ 23.94万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-19 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10575664
关键词：
3-Dimensional Address Adsorption Affinity Analysis of Variance Architecture Atomic Force Microscopy Blood Blood Cells Blood Proteins Chemicals Complex Coupled Custom Development Diffuse Electrostatics Evaluation Feasibility Studies Future Generations Generations Goals Grant Hardness Heart Heart Transplantation Heart failure Hemolysis Hemorrhage Hydration status Image In Vitro Institutes Joints Lateral Lead Measurement Measures Methods Molecular Normalcy North Carolina Optics Patient-Focused Outcomes Patients Performance Polymers Polyurethanes Problem Solving Property Proteins Public Health Pump Quality of life Reaction Recording of previous events Research Resolution Risk Roentgen Rays Spectrum Analysis Statistical Data Interpretation Structure Surface Technology Testing Therapeutic Thrombosis Time Universities Velocimetries Water Wing Work absorption blood damage care burden design effective therapy flexibility hemocompatibility hemodynamics hydrophilicity implantable device innovation left ventricular assist device novel particle patient mobility response success

项目摘要

PROJECT SUMMARY 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 of the patients. This proposed joint effort aims to solve these problems by reducing blood damage using flexible rotors and dramatically reducing pump thrombosis through novel Slippery Hydrophilic (SLIC) coatings. The objective of this project is to develop a novel LVAD with flexible polymeric rotors and novel anti-thrombotic coatings that can dramatically reduce blood damage and dramatically reduce the risk of pump thrombosis. Development of the flexible anti-thrombotic LVAD requires careful optimization of the flexible rotors and SLIC coatings. In Aim 1, Characterization and Optimization of Flexible Polymeric Rotors to Reduce Blood Damage, we will design, fabricate and test rotors with a wide range of flexibilities. Flexible, water-clear polyurethanes will be used for the rotor, which grants optical access to the rotor passage. Durability will be characterized in this aim through a custom-built accelerated hydrodynamic testing rig. The hemodynamic performance and blood damage potential of the flexible LVAD with SLIC coatings will be characterized in-vitro using 2D and 3D particle image velocimetry. Blood damage caused to the blood cells will be quantified experimentally by evaluating the shear history obtained from 3D time-resolved particle tracking. In Aim 2, Optimize SLIC coatings for Maximum Anti-thrombotic Response, we propose to fabricate SLIC coatings on polymeric surfaces and characterize the physical and chemical inhomogeneities through Atomic Force Microscopy (AFM),contact angle goniometry (advancing and receding angle measurements). X-ray photoelectron spectroscopy (XPS), near-edge x-ray absorption fine structure (NEXAFS), electrostatic force microscopy (EFM), to maximize the anti-thrombotic response. The optimized LVAD with flexible rotors and SLIC coatings will be thoroughly evaluated in-vitro using a blood loop under both quasi-steady and dynamic conditions. Levels of the blood damage and thrombosis potential will be compared with a rigid counterpart with and without SLIC coatings, along with statistical analysis. We hypothesize that through optimized polymeric flexible blade designs and SLIC coatings, LVADs can achieve excellent hemocompatibility, dramatically reducing blood damage and thrombosis. This novel design coupled with the unique SLIC coating has the potential to be used in future generations of LVADs that can provide long-term support to end-stage heart failure patients as a non-inferior alternative to cardiac transplants.

项目概要左心室辅助装置（LVAD）是终末期心力衰竭患者的一种有前途的治疗选择，除了心脏移植之外，心脏移植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，显着恶化患者的长期结果。这个提议共同努力旨在通过使用柔性转子减少血液损伤来解决这些问题，并显着通过新型光滑亲水 (SLIC) 涂层减少泵血栓形成。该项目的目标是开发一种新型 LVAD，具有柔性聚合物转子和新型抗血栓涂层，可显着减少血液损伤并显着降低泵血栓形成的风险。柔性抗血栓 LVAD 的开发需要仔细优化柔性转子和 SLIC 涂料。在目标 1 中，表征和优化柔性聚合物转子以减少血液损伤，我们将设计、制造和测试具有广泛灵活性的转子。柔韧、透明的聚氨酯将用于转子，其允许光学进入转子通道。耐用性将在此体现通过定制的加速水动力测试装置来实现目标。血流动力学性能和血液具有 SLIC 涂层的柔性 LVAD 的潜在损伤将使用 2D 和 3D 粒子进行体外表征图像测速。对血细胞造成的血液损伤将通过评估从 3D 时间分辨粒子跟踪获得的剪切历史。在目标 2 中，优化 SLIC 涂层以实现最大抗血栓反应，我们建议在聚合物表面制造 SLIC 涂层并表征通过原子力显微镜 (AFM)、接触角测角法测量物理和化学不均匀性（前进角和后退角测量）。 X 射线光电子能谱 (XPS)、近边 X 射线吸收精细结构（NEXAFS）、静电力显微镜（EFM），最大限度地抗血栓回复。具有柔性转子和 SLIC 涂层的优化 LVAD 将使用以下方法进行彻底的体外评估：准稳态和动态条件下的血液循环。血液损伤和血栓形成的程度潜力将与具有和不具有 SLIC 涂层的刚性对应物进行比较，并进行统计分析。我们假设，通过优化的聚合物柔性叶片设计和 SLIC 涂层，LVAD 可以实现优异的血液相容性，显着减少血液损伤和血栓形成。这种新颖的设计结合了具有独特的 SLIC 涂层有潜力用于未来几代 LVAD，可提供作为心脏移植的非劣等替代方案，为终末期心力衰竭患者提供长期支持。