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WIREs Nanomed Nanobiotechnol
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Microfabrication and nanotechnology in stent design

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Abstract Intravascular stents were first introduced in the 1980s as an adjunct to primary angioplasty for management of early complications, including arterial dissection, or treatment of an inadequate technical outcome due to early elastic recoil of the atherosclerotic lesion. Despite the beneficial effects of stenting, persistent high rates of restenosis motivated the design of drug‐eluting stents for delivery of agents to limit the proliferative and other inflammatory responses within the vascular wall that contribute to the development of a restenotic lesion. These strategies have yielded a significant reduction in the incidence of restenosis, but challenges remain, including incomplete repair of the endothelium at the site of vascular wall injury that may be associated with a late risk of thrombosis. A failure of vessel wall healing has been attributed primarily to the use of polymeric stent coatings, but the effects of the eluted drug and other material properties or design features of the stent cannot be excluded. Improvements in stent microfabrication, as well as the introduction of alternative materials may help to address those limitations that inhibit stent performance. This review describes the application of novel microfabrication processes and the evolution of new nanotechnologies that hold significant promise in eliminating existing shortcomings of current stent platforms. WIREs Nanomed Nanobiotechnol 2011 3 256–268 DOI: 10.1002/wnan.123 This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants

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Scanning electron microscope images at different magnifications of the expanded Translumina YUKON® DES Coronary Stent System with PEARL surface coated with leflunomide. The microporous stent surface allows for the incorporation of drugs with slower release kinetics without the need for a polymer coating. The roughness of the stent surface is 1.96 ± 0.21 µm. (Reprinted with permission from Ref 89. Copyright 2008 Elsevier Ireland Ltd.)

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Surface modification strategies capable of enhancing endothelialization include: (a) surface roughening to increase topography, (b) discreet patterning, (c) chemical modification of the surface, and (d) covalent attachment of biopharmaceuticals.

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The Cordis NEVO™ stent with reservoirs machined into the stent struts. (Courtesy of Cordis Corporation.)

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Micro‐ and nanofabrication methods have altered the methods used to deliver drugs from stent platforms. (a) A cross‐section of a single bare metal stent strut expanded in the vessel pressed against the endothelium with the smooth muscle cells beyond the endothelium. (b) Drug containing polymer coated strut representing the first generation of drug eluting stents. Newer strategies include the incorporation of (c) microtopographic features that provide increased surface area for drug loading, (d) lumen‐oriented reservoirs, and (e) drug reservoirs that extend throughout the strut structure.

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The difference between femtosecond laser pulses and nanosecond laser pulses on thin steel films. The SEM image on the left shows a hole drilled in a 100 µm thick steel foil with 200 fs, 120 µJ, F = 0.5 J/cm2 laser pulses at 780 nm. The SEM image on the right shows the molten material left behind when holes were drilled in a 100 µm thick steel foil with 3.3 ns, 1 mJ, F = 4.2 J/cm2 laser pulses at 780 nm. (Reprinted with permission from Ref 33. Copyright 1996 Springer‐Verlag.)

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Example of two laser machined bioabsorbable stents. The top stent is courtesy of Laser Zentrum Hannover (Copyright Laser Zentrum Hannover e.V. (LZH)) and the bottom stent is courtesy of Resonetics (Copyright Resonetics).

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A number of laser specific variables, including intensity, wavelength, and pulse length, as well as material ablation formats are selected with respect to specific material properties for optimal stent fabrication.

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Illustrates the magnetic targeting of bovine aortic endothelial cells (BAECs) under flow conditions to stainless‐steel stents in vitro and in vivo. Magnetically responsive BAECS are shown captured on SS stents based on (a) red fluorescence of the MNPs and (b) Calcein staining of live cells. To determine in vivo capture BAECs were loaded with fluorescent MNPs and injected into the ventricular cavity. (c) Rats were exposed to a magnetic field of 1000 G for 5 min then sacrificed and the stents were explanted and imaged. (d) Control rats were not exposed to magnetic field. (Reprinted with permission from Ref 115. Copyright 2008 The National Academy of Sciences of the USA.)

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