Flexible Anti-thrombotic LVADs

项目总结 左心辅助装置(LVAD)是终末期心力衰竭患者的一种很有前途的治疗选择， 除了心脏移植，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。这项建议 共同努力旨在通过使用灵活的转子和显著减少血液损伤来解决这些问题 通过新型光滑亲水(SLIC)涂层减少泵血栓形成。这个项目的目标是 开发具有柔性聚合物转子和新型抗血栓涂层的新型LVAD，该涂层可以显著地 减少血液损伤，大大降低泵血栓形成的风险。 柔性抗血栓LVAD的开发需要对柔性转子和SLIC进行仔细的优化 涂层。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。灵活、清水的聚氨基甲酸酯将 用于转子，允许光学进入转子通道。耐用性将体现在这一点上 通过定制的加速水动力试验台瞄准。血流动力学表现和血液 具有SLIC涂层的柔性LVAD的损伤潜力将使用2D和3D粒子在体外进行表征 图像测速仪。 对血细胞造成的血液损害将通过评估 由三维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 为了对抗血栓反应，我们建议在聚合物表面制备SLIC涂层，并对其进行表征 原子力显微镜(AFM)、接触角测角法测量物理和化学不均匀性 (进退角测量)。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 回应。优化的带有柔性转子和SLIC涂层的LVAD将在体外进行彻底的评估 在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 潜力将与有和没有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刀片设计和SLIC涂层，LVAD可以实现 良好的血液相容性，显著减少血液损伤和血栓形成。这一新颖的设计结合了 具有独特的SLIC涂层具有在未来几代LVAD中使用的潜力，可以提供 对终末期心力衰竭患者的长期支持，作为心脏移植的非劣质替代方案。

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.