Flexible Anti-thrombotic LVADs

灵活的抗血栓 LVAD

• 批准号: 10706608
• 负责人: Lakshmi Prasad Dasi
• 金额: $ 18.82万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 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/10706608
• 关键词: 3-Dimensional; Acceleration; Address; Adsorption; Affinity; Analysis of Variance; Architecture; Atomic Force Microscopy; Blood; Blood Cells; Blood Proteins; Chemicals; Complex; Coupled; Custom; Development; Electrostatics; Evaluation; Feasibility Studies; Future Generations; Generations; Goals; Grant; Hardness; Heart; Heart Transplantation; Heart failure; Hemolysis; Hemorrhage; Hydration status; Image; In Vitro; Joints; Lateral; Measurement; Measures; Methods; Molecular; Normalcy; North Carolina; Optics; Patient-Focused Outcomes; Patients; Performance; Polymers; Polyurethanes; Property; Proteins; Public Health; Pump; Quality of life; Reaction; Recording of previous events; Research; Resolution; Risk; Risk Reduction; 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; thrombotic

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.

项目摘要 左心室辅助装置（LVAD）是最终心力衰竭患者的有前途的治疗选择， 除心脏移植外，还受到可用捐助者数量的限制。但是，严重的并发症， 包括出血和血栓形成，显着恶化了患者的长期结局。这提出了 联合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，并急剧 通过新型湿滑的亲水性（SLIC）涂层来减少泵血栓形成。这个项目的目的是 开发具有柔性聚合物转子和新型抗血栓形成涂层的新型LVAD 减少血液损害，并大大降低泵血栓形成的风险。 柔性抗栓性LVAD的发展需要仔细优化柔性转子和切片 涂料。在AIM 1中，柔性聚合转子的表征和优化以减少血液损伤， 我们将使用各种灵活性设计，制造和测试转子。柔性，清除的聚氨酯将 可用于转子，该转子可以允许光学访问转子通道。耐久性将在此特征 通过定制的加速流体动力测试钻机瞄准。血液动力学性能和血液 使用2D和3D粒子将柔性LVAD带有切片涂层的损伤潜力在体外表征 图像速度法。 通过评估，将对血细胞造成的血液损害将进行实验量化 从3D时间分辨的粒子跟踪获得的剪切历史。在AIM 2中，优化切片涂料以最大 抗血栓形成反应，我们建议在聚合物表面上制造切片涂层，并表征 通过原子力显微镜（AFM）的物理和化学不均匀性，接触角性角度计量法 （前进和退缩角度测量）。 X射线光电子光谱（XPS），近边缘X射线 吸收精细结构（Nexafs），静电显微镜（EFM），以最大化抗脉动 回复。具有柔性转子和切片涂层的优化LVAD将在体外进行彻底评估 在准稳态和动态条件下的血环。血液损害和血栓形成水平 电势将与带有和没有切片涂层的刚性对应物以及统计分析进行比较。 我们假设通过优化的聚合物柔性刀片设计和切片涂层，LVAD可以实现 出色的血流相容性，大大减少了血液损伤和血栓形成。这个小说设计结合了 凭借独特的切片涂层，有可能在子孙后代使用可以提供的LVAD 长期支持终阶段心力衰竭患者是心脏移植的非内部替代方案。