Flexible Anti-thrombotic LVADs

项目摘要 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，这是有限的数量可用的捐赠者。然而，严重的并发症， 包括出血和血栓形成，显著恶化了患者的长期结果。这一拟议 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， 通过新型的Slippery Hydrophilic（SLIC）涂层减少泵血栓形成。本项目的目标是 开发一种具有柔性聚合物转子和新型抗血栓涂层的新型LVAD， 减少血液损伤并显著降低泵血栓形成的风险。 开发柔性抗血栓LVAD需要仔细优化柔性转子和SLIC 镀层.在目标1中，柔性聚合物转子的表征和优化以减少血液损伤， 我们将设计，制造和测试具有广泛灵活性的转子。柔性、水透明聚氨酯将 用于转子，这赠款光学访问转子通道。耐久性的特点是 aim通过定制的加速流体动力学试验台。血流动力学性能和血液 将使用2D和3D粒子在体外表征具有SLIC涂层的柔性LVAD的损伤潜力 图像测速 对血细胞造成的血液损伤将通过评估血液中的 从3D时间分辨颗粒跟踪获得的剪切历史。在目标2中，优化SLIC涂层， 抗血栓反应，我们建议在聚合物表面上制备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 （前进和后退角度测量）。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），以最大限度地提高抗血栓形成 反应将使用以下方法在体外对具有柔性转子和SLIC涂层的优化LVAD进行彻底评估： 在准稳态和动态条件下的血液回路。血液损伤和血栓形成水平 将与带有和不带有SLIC涂层的刚性对应物进行潜力比较，并沿着进行统计分析。 我们假设，通过优化的聚合物柔性刀片设计和SLIC涂层，LVAD可以实现 优异的血液相容性，显著降低血液损伤和血栓形成。这种新颖的设计 具有独特的SLIC涂层，有可能用于未来几代LVAD， 长期支持终末期心力衰竭患者作为心脏移植的非劣效替代方案。

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.