Patterns of activation and deposition of platelets exposed to the polymeric surface of the paclitaxel eluting stent

Abstract

The interaction of platelets with the polymeric surface of drug eluting stents has not been fully described in the literature. Our aim was to analyze the patterns of activation and deposition of platelets exposed to two different stent platforms; (a) the polymeric surface of the paclitaxel eluting stent (Taxus((R)) stent, PES,) and (b) the metallic surface of a stent with identical structural design (Express((R)) stent, BMS). Platelet activation was tested by deploying stents in an in vitro flow chamber model. Anticoagulated blood of 25 healthy volunteers was circulated (flow rate 10 ml/min for 60 min) into the flow chamber system. P-selectin expression, glycoprotein IIb/IIIa activation (PAC-1 binding) and platelet-monocyte complexes (PMC) formation were evaluated at 0, 10, 30 and 60 min. Surface platelet deposition was assessed by surface electron microscopy in stents implanted in the in vitro system for 60 min and in stents implanted in normal porcine coronary arteries for 24 h. Platelet activation evaluation showed a higher P-Selectin expression (92.9% of baseline in PES versus 68.3 % in BMS, P = 0.01) and higher PMC formation (125.7 % of baseline in PES versus 75.6% in BMS, P < 0.01) in the PES compared to the BMS control group. PAC-1 binding levels did not differ among groups. In the in vitro study, SEM analysis of the stent surface showed no statistical differences on platelet deposition between the groups. In addition, presence of proteinaceous material was more frequently seen on the BMS group (moderate to complete coverage = 80% in BMS versus 26% in PES, P < 0.01). In the in vivo study, complete platelet coverage was similar between groups (PES = 7% versus BMS = 8%, P = NS). However, there was an overall trend towards less platelet deposition on the BMS surface (mild and moderate coverage = 83%, 9% in BMS versus 49%, 44% in PES, P < 0.001 for both) but thrombus formation was not observed in either group. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface. The biological implications of these findings on the patterns of vascular healing need to be further studied in vivo. Condensed Abstract The interaction of human platelets with the surface of drug eluting stents has not been fully characterized. Patterns of platelet activation and adhesion were evaluated in vitro and in vivo after exposing platelets to the surface of the paclitaxel-eluting stent and identical bare metal stent. The degree of PMC formation and P-selectin expression was increased in PES compared to BMS. In the in vivo study, complete platelet coverage was similar between groups. There was an overall trend towards less platelet deposition on the BMS surface, however, thrombus formation was not observed on either surface. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface.

Impact of Parallel Micro-Engineered Stent Grooves on Endothelial Cell Migration, Proliferation, and Function

“…Human pathology studies suggest that delayed healing leads to incomplete strut coverage, which has been associated with late thrombotic events. 2 Moreover, early DES platforms elicited enhanced platelet adhesion 3 and endothelial dysfunction. 4 Most DES technologies now embody thinner metallic platforms containing minimal amounts of polymeric drug formulations while maintaining drug concentrations and release profiles.…”

Assessing the Durability of Durable Stent Polymers: Will They Pass the Test of Time?

“…Ex vivo studies based on flowchamber models suggest that the patterns of platelet activation and adhesion are altered by the type of polymeric coating. 10 It is conceivable that the acute mechanical defects observed following stent expansion may enhance platelet adhesion and contribute at least in part to acute thrombotic events. Another important biological effect is the impact of polymeric defects and vessel wall inflammation.…”

“…However reassuring this study may seem in general terms, it still leaves other questions about these polymers unanswered. Ex vivo studies based on flow‐chamber models suggest that the patterns of platelet activation and adhesion are altered by the type of polymeric coating 10 . It is conceivable that the acute mechanical defects observed following stent expansion may enhance platelet adhesion and contribute at least in part to acute thrombotic events.…”

Dynamic Observation of Artery Endothelial Cell Layers in Response to Bare Metal Stent and Paclitaxel‐Eluting Stent In Vitro

“…OCT has become the standard method used to evaluate artery healing and analyze stent‐strut coverage in detail . SEM analyses provide detailed three‐dimensional information of an endothelial surface at a high resolution . However, such methods cannot allow a dynamic observation on the response of epithelial cells to stents in real time; thus, informative data about endothelial cells adaption to PES underlying a vulnerable position to thrombosis might be lost.…”