Biomechanical Response of Platelets to Superhydrophobic Surface in Mechanical Heart Valves and Other Blood-Contacting Medical Devices

 描述(申请人提供)：作为工业化国家的主要死亡原因和发展中国家日益严重的问题，心血管疾病的治疗可以影响非常大的人口。心血管疾病常见的干预措施包括接触血液的医疗设备，这些设备有发生血栓(血栓)的风险。由于这些设备上的血栓形成可能导致重要器官的缺血和可能的死亡，因此它是至关重要的 以减轻风险。因此，患者通常接受抗血小板和抗凝血药物治疗。不幸的是，这些疗法会增加出血风险，并不能完全预防血栓形成的风险。因此，许多材料科学家一直在研究替代目前使用的非血栓形成材料，以最大限度地减少对药物治疗的需求。超疏水表面是一种在静态条件下在减缓血栓生长过程中表现出优异效果的表面处理方法。然而，在与心血管设备更相关的流动环境中，血液对超疏水材料的反应仍然不明确。这种环境由空间变化的剪切力组成，这已被证明对血小板聚集有非常大的影响。因此，这项拟议工作的最终目标是评估这种环境中的超疏水材料，以确定是否应该进一步研究这些材料以用于人工心脏瓣膜或支架等设备。对于这项研究，我们有两个目标：1)制备和表征剪切速率变化较大的微流控通道中的超疏水表面。一系列不同纹理和表面能量的表面处理将通过评估接触角、表面结构和表面流动来表征。这些处理将应用于涉及流动收缩的微流体通道，以评估材料在剪切环境中的耐用性，并确定沿超疏水表面是否存在气囊，这对于具有纹理和低表面能的表面是常见的。具体目的2)使用一种新的芯片实验室方法分析血流动力学剪切力的空间变化对血细胞动力学的影响以及化学激活剂的作用。我们将测试超疏水表面在剪切梯度中防止血小板聚集的能力。为了测试这一点，将开发一系列微流控设备，用于在与医疗设备相关的流动环境中高通量评估材料的血栓形成能力。这些工具将与成像技术相结合，以评估不同的剪切环境，以指导未来的心血管设备设计，并确定可溶性激动剂血小板激活在超疏水表面聚集过程中的作用。

 DESCRIPTION (provided by applicant): As the leading cause of death in industrialized nations and as an increasing problem in developing countries, the treatment for cardiovascular disease can impact a very large population. Interventions common to cardiovascular disease involve blood-contacting medical devices that are at-risk for thrombosis (blood clots). Since thrombosis on these devices can lead to ischemia in vital organs and possible death, it is critical to mitigate the risk. Therefore, patients are commonly placed on antiplatelet and anticoagulant drug regimens. Unfortunately, these therapies can create additional bleeding risks and do not completely prevent the risk for thrombosis. Therefore, many material scientists have been investigating alternative non-thrombogenic materials to those currently used in order to minimize the need for drug therapeutics. Superhydrophobic surfaces are one of the surface treatments that has exhibited excellent results in static conditions at mitigating processes involved in thrombus growth. However, the response of blood to superhydrophobic materials remains ill-defined in a flow environment more relevant to cardiovascular devices. This environment consists of spatially changing shear, which has been shown to have a very large impact on platelet aggregation. Therefore the ultimate goal of the proposed work is to assess superhydrophobic materials in this environment to determine if these materials should be investigated further for devices such as prosthetic heart valves or stents. For this investigation we have 2 aims: Specific Aim 1) Prepare and characterize superhydrophobic surfaces in microfluidic channels involving large changes in shear rate. A series of surface treatments of varying texture and surface energy will be characterized by evaluating contact angles, surface structure, and flow over the surfaces. These treatments will be applied to microfluidic channels involving flow constrictions to assess material durability in a shear environment and to determine if air pockets exist along the superhydrophobic surface, which is common to surfaces with texture and low surface energy. Specific Aim 2) Analyze the impact of spatially varying hemodynamic shear forces on blood cell dynamics and the role for chemical activators using a novel Lab-on-Chip approach. We will be testing the ability for superhydrophobic surfaces to prevent platelet aggregation in a shear gradient. To test this, a series of microfluidic devices wil be developed for high throughput evaluation of material thrombogencity in a flow environment pertinent to medical devices. These tools will be combined with imaging techniques to evaluate different shear environments to guide future cardiovascular device designs and to determine the role for soluble agonist platelet activation in the aggregation process for superhydrophobic surfaces.