Bioresorbable Scaffold: The Emerging Reality and Future Directions

Bioresorbable Scaffold: The Emerging Reality and Future Directions

Yohei Sotomi, Yoshinobu Onuma, Carlos Collet, Erhan Tenekecioglu, Renu Virmani, Neal S. Kleiman, Patrick W. Serruys

Strut thickness and platelet activation. The thick protruding strut disrupts the laminar flow and induces flow disturbances, and thereby endothelial shear stress (ESS) microgradients (upper panel). The shear microgradients can induce the formation of stabilized discoid platelet aggregates, the size of which is directly regulated by the magnitude and spatial distribution of the gradient.72,73 Shear microgradient–dependent platelet aggregation requires 3 principal features: shear acceleration phase, peak shear phase, and shear deceleration phase. During shear acceleration, platelets in the central regions of blood flow exposed to laminar flow (constant physiological shear) are suddenly accelerated through the shear microgradient. During the peak shear phase, a proportion of the discoid platelets that are accelerated into the peak shear zone adhere to exposed thrombogenic surfaces through platelet membrane glycoprotein (GP) Ib/IX/V. Exposure of these platelets to elevated hemodynamic drag leads to the extrusion of thin filamentous membrane tethers. Membrane tether formation initiates discoid platelet adhesion with the thrombogenic surface and also facilitates the recruitment of discoid platelets into the downstream deceleration zone. During the shear deceleration phase, platelets transitioning into the flow deceleration zone experience decreasing hemodynamic drag forces. Reduced shear within this zone progressively favors the formation of integrin αIIbβ3 adhesion contacts. Integrin αIIbβ3 engagement is associated with low-frequency calcium spikes that trigger tether restructuring, leading to the stabilization of discoid platelet aggregates. Ongoing discoid platelet recruitment drives the propagation of the thrombus in the downstream deceleration zone, which may in turn amplify the shear microgradient and promote further platelet aggregation. Thus, the shear microgradients caused by the thick struts induce platelet aggregation, formation of microthrombi with potential embolization, and micromyocardial necrosis (so-called a nidus of thrombus). The magnitude of flow disturbance depends on the degree of protrusion of the strut into the lumen. Therefore, thin struts could be a potential solution for the less flow disturbance and thus less thrombogenic status (lower panel). There is another cascade of von Willebrand factor (VWF)/GPIb activation, namely agglutination-elicited GPIb signaling.73 In contrast to shear stress–induced GPIb-elicited signaling, agglutination-elicited GPIb signaling that activates integrin αIIbβ3 requires thromboxane A2 (TXA2). Agglutination-elicited TXA2 production is independent of Ca2+ influx and mobilization of internal Ca2+ stores. [Powerpoint File]

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