剪切和ADP对血小板在ZTA和Ti6Al4V表面生长的协同作用
Synergistic effect of shear and ADP on platelet growth on ZTA and Ti6Al4V surfaces
摘要：
连续流心室辅助装置（VAD）已成为晚期心力衰竭患者越来越常见的挽救生命的治疗方法，但由于非生理性血流动力学和合成生物材料的结合，会增加血栓形成的风险。有限的工作已经完成，以解决血小板粘附和聚集的人工表面下流与阈下浓度的弱激动剂。我们在400和1000 s-1的剪切速率下将含有血红蛋白耗尽的红细胞和荧光标记的血小板的血液模拟物灌注在钛合金（Ti6Al4V）和氧化锆增韧氧化铝（ZTA）表面上。在样本上游，以0、5和10 nM的浓度均匀引入亚阈值浓度的ADP。记录血小板沉积的时间推移视频，并量化覆盖的表面百分比。比较了每种ADP浓度和材料表面组合在400 s-1和1000 s-1时的表面覆盖率。我们观察到ADP的阈值浓度，加快血小板沉积，这是依赖于剪切和材料表面化学。此外，当血栓面积超过300 μ m2时，我们观察到栓塞，这取决于剪切力、ADP浓度和材料表面的组合。这项工作是第一次同时检查导致血栓事件的三个关键因素。我们的研究结果有助于考虑替代材料的选择，构成VAD和需要解决的材料反应，在评估抗血小板药物试验。
英文摘要：
Continuous-flow ventricular assist devices (VADs) have been an increasingly common, life-saving therapy for advanced heart-failure patients, but elevate the risk of thrombosis due to a combination of non-physiological hemodynamics and synthetic biomaterials. Limited work has been done to address platelet adhesion and aggregation on artificial surfaces under flow with sub-threshold concentrations of weak agonists. We perfused a blood analog containing hemoglobin-depleted red blood cells and fluorescently labeled platelets across a titanium alloy (Ti6Al4V) and zirconia-toughened alumina (ZTA) surface at shear rates of 400 and 1000 s-1. Upstream of the specimen, sub-threshold concentrations of ADP were uniformly introduced at concentrations of 0, 5, and 10 nM. Time-lapse videos of depositing platelets were recorded, and the percentage of the surface covered was quantified. Surface coverage percentages at 400 s-1and 1000 s-1were compared for each concentration of ADP and material surface combination. We observed a threshold concentration of ADP that expedites platelet deposition that is dependent on both shear and material surface chemistry. Additionally, we observed embolization when thrombus areas exceeded 300μm2, which was dependent on the combination of shear, ADP concentration, and material surface. This work is the first to simultaneously examine the three key contributing factors leading to thrombotic events. Our findings assist in considering alternative material choices constituting VADs and the need to address material reactivity in assessing antiplatelet agent tests.
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