Cardiovascular stents - Biomaterials and Devices for the Circulatory System - page 199

that was comparable to the Cypher and out-performed the Endeavour
stents. However, longer-term clinical advantage has yet to be proven.
Other nanotechnology-based approaches have already been applied with
some disappointing outcomes. In the last decade studies have been under-
taken on stainless steel stents coated with a thin layer (500 nm) of alumin-
ium via vapour deposition, followed by the electrochemical conversion of
the metallic layer into nanoporous alumin/aluminium oxides that acted as
carriers for the immunosuppressive drug tacrolimus (Wieneke et al. , 2003).
Despite the apparent success of this in vitro study in terms of inhibition of
intima proliferation, Kollum and coworkers demonstrated in a porcine
restenosis model that particle debris shed from the surface of drug eluting
aluminium oxide stainless steel stents eliminated the antiproliferative
effects of tacrolimus and increased neointimal growth and luminal stenosis
compared to bare stents (Kollum et al. , 2005). Moreover, drug elution from
the nanoporous matrix has been shown to be heavily dependent on pore
depth and pore diameter, suggesting that more tightly controlled engineer-
ing of the nanoporous surface is required to produce a predictable uptake
and elution, as well as a rapid release of drug located on the surface of the
coating rather than from within the pores (Kang et al. , 2007). There are,
therefore, signifi cant challenges in applying nanotechnology to stent-based,
as well as any other biomaterial-based application. Nonetheless, studies are
ongoing and more recently Nakano and coworkers have again exploited
nanotechnology to formulate a nanoparticle eluting stent system using
cation electrodeposition coating technology which may provide an innova-
tive approach to the production of less invasive nanodevices targeting car-
diovascular disease (Nakano et al. , 2009). A recent patent application
(Lloyd et al. , 2008) suggested the functionalisation of stent surfaces with
semi-demdrimers able to regulate cell adhesion and proliferation via the
exposure of bioligands and the delivery of bioactive molecules.
Clearly, any advances in material design and drug delivery need to be
driven by a greater understanding of the infl ammatory processes, cell
responses and tissue remodelling in response to implanted stents and the
procedures to place them over the stenotic lesions: for example, the fi ne
control of the macrophage phenotype by either novel surfaces or drugs could
lead to a controlled tissue repair process allowing stent integration in the
vessel wall and avoiding the excessive thickening of the neointimal tissue.

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7.9 Sources of further information and advice

• Steven Allender, Viv Peto, Peter Scarborough, Asha Kaur and Mike
Rayner (2008) Coronary heart disease statistics, British Heart Founda-
tion Health and Promotion Research Group, Department of Public
Health, University of Oxford.