Polymer-based bioresorbable scaffolds (BRS) seek to eliminate long-term complications of metal stents. However, current BRS designs bear substantially higher incidence of clinical failures, especially thrombosis, compared with metal stents. Research strategies inherited from metal stents fail to consider polymer microstructures and dynamics--issues critical to BRS. Using Raman spectroscopy, we demonstrate microstructural heterogeneities within polymeric scaffolds arising from integrated strain during fabrication and implantation. Stress generated from crimping and inflation causes loss of structural integrity even before chemical degradation, and the induced differences in crystallinity and polymer alignment across scaffolds lead to faster degradation in scaffold cores than on the surface, which further enlarge localized deformation. We postulate that these structural irregularities and asymmetric material degradation present a response to strain and thereby clinical performance different from metal stents. Unlike metal stents which stay patent and intact until catastrophic fracture, BRS exhibit loss of structural integrity almost immediately upon crimping and expansion. Irregularities in microstructure amplify these effects and can have profound clinical implications. Therefore, polymer microstructure should be considered in earliest design stages of resorbable devices, and fabrication processes must be well-designed with microscopic perspective.
Drug eluting stents are associated with late stent thrombosis (LST), delayed healing and prolonged exposure of stent struts to blood flow. Using macroscale disturbed and undisturbed fluid flow waveforms, we numerically and experimentally determined the effects of microscale model strut geometries upon the generation of prothrombotic conditions that are mediated by flow perturbations. Rectangular cross-sectional stent strut geometries of varying heights and corresponding streamlined versions were studied in the presence of disturbed and undisturbed bulk fluid flow. Numerical simulations and particle flow visualization experiments demonstrated that the interaction of bulk fluid flow and stent struts regulated the generation, size and dynamics of the peristrut flow recirculation zones. In the absence of endothelial cells, deposition of thrombin-generated fibrin occurred primarily in the recirculation zones. When endothelium was present, peristrut expression of anticoagulant thrombomodulin (TM) was dependent on strut height and geometry. Thinner and streamlined strut geometries reduced peristrut flow recirculation zones decreasing prothrombotic fibrin deposition and increasing endothelial anticoagulant TM expression. The studies define physical and functional consequences of macro-and microscale variables that relate to thrombogenicity associated with the most current stent designs, and particularly to LST.
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