Nanomedicine for the reduction of the thrombogenicity of stent coatings

Abstract

The treatment of patients with drug-eluting stents (DES) continues to evolve with the current emergence of DES technology that offers a combination of pharmacological and mechanical approaches to prevent arterial restenosis. However, despite the promising short-term and mid-term outcomes of DES, there are valid concerns about adverse clinical effects of late stent thrombosis. In this study, we present an example of how nanomedicine can offer solutions for improving stent coating manufacturing, by producing nanomaterials with tailored and controllable properties. The study is based on the exploitation of human platelets response towards carbon-based nanocoatings via atomic force microscope (AFM). AFM can facilitate the comprehensive analysis of platelets behavior onto stent nanocoatings and enable the study of thrombogenicity. Platelet-rich plasma from healthy donors was used for the real-time study of biointerfacial interactions. The carbon nanomaterials were developed by rf magnetron sputtering technique under controllable deposition conditions to provide favorable surface nanotopography. It was shown that by altering the surface topography of nanocoatings, the activation of platelets can be affected, while the carbon nanocoatings having higher surface roughness were found to be less thrombogenic in terms of platelets adhesion. This is an actual solution for improving the stent coating fabrication.

Keywords: atomic force microscopy platelets nanotechnology; carbon coating; stents nanomedicine.

Figure 1

Three-dimensional AFM topography image of platelets (in circles) on a-C:H nanocoating after 15 minutes of incubation, at an early stage of activation.

Figure 2

Three-dimensional AFM topography image of activated platelets on a-C:H nanocoating after 2 hours of incubation, interconnected with pseudopodia.

Figure 3

A) Two-dimensional AFM topography image of activated platelets with pseudopodia on a-C:H nanocoating after 1 hour of incubation; B) Arbitary section (white line) in 3A, of one activated platelet (PLT) at three points (white circles) with measurements of its components.

Figure 4

Three-dimensional AFM topography image of: A) Platelets on type B carbon nanocoating (after 1 hour incubation (scan size 10 μm × 10 μm). The circle indicates an activated platelet having the egg-like type structure; B) Platelets on type B carbon nanocoating after 2 hours incubation time (10 μm × 10 μm). The circles denote the egg-like type activated platelets.

Figure 5

Three-dimensional AFM topography image of: A) Platelets on type A carbon nanocoating with 5% H₂ in plasma during deposition, after 1 hour of incubation (scan size 10 μm × 10 μm), B) Platelets on the same coatings as in Figure 5A, after 2 hours incubation time (scan size 21 μm × 21 μm). The arrows indicate the platelets aggregation and the formation of a cluster-like island.

Figure 6

Three-dimensional AFM topography image of: A) Platelets on type A carbon nanocoatings with 20% H₂ in plasma during deposition after 1 hour incubation (scan size 21 μm × 21 μm). They form aggregations as presented with the arrows, with a mean maximum height of approximately 659 nm, B) Platelets on type A carbon nanocoatings with 20% H₂ in plasma during deposition, after 2 hours of incubation (scan size 21 μm × 21 μm). The platelet clusters as denoted by the circles, have a height of more than 1000 nm.

Figure 7

Comparative diagram of peak-to-peak parameter and root mean square roughness of platelet clusters versus incubation time for the studied types A and B carbon nanocoatings.

Figure 8

SEM images of: A) a human platelet onto carbon substrate, B) inactivated platelets on type B carbon nanocoating with 5% H₂ in plasma during deposition, after one hour of incubation and C) activated platelets on to type A carbon nanocoating with 5% H₂ in plasma during deposition, after 1 hour of incubation.