Synergistic effect of shear and ADP on platelet growth on ZTA and Ti6Al4V surfaces

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 300{\mu}m2, 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.