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

Abstract

D rug-eluting stents (DES) have dramatically reduced the long-term rate of reintervention and improved clinical outcomes among patients undergoing percutaneous coronary interventions.1 However, DES use still carries a small but critically important cumulative risk of late stent thrombosis. 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. 5,6 Although a slight decline in the overall stent thrombosis rate has been observed with the use of latest generation of DES platforms, these potentially lethal events still occur. Despite their efficacy in preventing restenosis, the antiproliferative effect of drugs used in commercially available DES appear to delay stent endothelialization. Technological approaches have been used to enhance stent endothelialization by modifying the stent surface with antibodies to selectively bind circulating endothelial progenitor cells. 7 An alternate strategy to encourage reendothelialization is to modify the stent surface to increase the natural rate of endothelial cell migration from adjacent arterial areas of intact healthy endothelium. Previous studies in our laboratory have shown that parallel microgrooves applied to the surface of different metals 8,9 increase the rate of human aortic endothelial cell migration by >2-fold compared with smooth coupons. More importantly, when this pattern was applied to the luminal surface of stents in an early pilot study, the endothelialization rate on these grooved stents was double compared with Background-Stent luminal surface characteristics influence surface endothelialization. We hypothesize that luminal stent microgrooves created in the direction of coronary flow accelerate endothelial cell migration, resulting in lower levels of neointimal formation. Methods and Results-Surface coverage efficiency was evaluated in vitro by allowing human aortic endothelial cells (HAEC) to migrate onto microgrooved (G) or smooth (NG) surfaces. HAEC functionality was assessed by proliferation rate, apoptosis rate, nitric oxide production, and inflammatory markers TNF-α and VCAM-1 expression. Early endothelialization and restenosis studies were performed using the porcine coronary injury model. Stainless steel stents of identical design with (GS) and without (NGS) luminal microgrooves were used. The commercially available Multi-Link Vision (MLVS) stent of identical design was used as a control. The degree of GS and NGS surface endothelialization was compared at 3 days. Biocompatibility and tissue response outcomes were evaluated at 28 days. The in vitro study demonstrated that at 7 days the presence of surface microgrooves increased HAEC migration distance >2-fold. Cell proliferation rate and nit...

Microgrooved Polymer Substrates Promote Collective Cell Migration To Accelerate Fracture Healing in an in Vitro Model

“…51 Parallel microgrooves increases endothelial cell migration rates. 52,53 Corneal epithelium cells were directed to migrate along the parallel grooves 54 (groove and ridge width of 1, 2, 5, and 10 μ m, groove depth of 1 and 5 μ m). These effects are different from the effect of nanoparticles on cellular migration, which strengthened intracellular tension and retard cellular migration.…”

Biological effect of microengineered grooved stents on strut healing: a randomised OCT-based comparative study in humans

“…Later on, microgroove development based on laser technology allowed to establish the ideal boundary conditions for endothelial cell (EC) migration speed and groove configuration, therefore aiding optimisation of engineering parameters 9. Recent technology developments using photolithographic techniques have achieved a markedly improved resolution in the development of the microgroove patterns 3. Accuracy of the manufacturing process has improved over time and allowed the development of groove features in the micron range.…”

“…Several studies have described delayed healing and neoatherosclerosis as the most important biological mechanisms responsible for this condition 2. In the experimental setting, accelerated strut endothelialisation results in the more rapid development of a lower and more organised neointimal response even in the absence of antiproliferative drugs 3. Then, technologies capable of accelerating strut endothelialisation have the potential to improve the safety profile of DES.…”

“…Specifically, the manufacturing of dedicated microengineered stent grooves (MSG) aligned towards the direction of the coronary flow is now technologically feasible 6 7. Experimental studies have shown that MSG accelerate strut endothelialisation and reduce neointimal proliferation compared with stents exposing flat metal surfaces 3 8. In this study, we aimed to test the safety and healing profile of MSG in humans by comparing the patterns of stent healing of identical bare metal stent (BMS) exposing two different luminal surfaces (MSG vs flat) using optical coherence tomography (OCT) analysis 3 weeks following stent implantation.…”

Nanomedicine in diagnostics and therapy of cardiovascular diseases: beyond atherosclerotic plaque imaging

“…The authors reported that already at 3 days post-implantation, the coronary artery stent endothelialization was significantly increased in the microgrooved stents (81.3%) compared with the smooth surface stents (67.5%). Moreover, at 28 days, the neointimal thickness was significantly lower in the microgrooved stent group compared with the smooth surface controls [103] . These results indicate that an enhanced rate of early endothelialization and significant inhibition of the neointimal hyperplasia can be achieved by the application of an appropriate surface structure to the bare metal stents.…”