Cardiovascular stents - Biomaterials and Devices for the Circulatory System - page 183

7.4.3 Natural coatings

Natural coatings offer the potential to minimise the infl ammatory response
to foreign materials. One biomolecule that has been exploited for its poten-
tial to reduce the problem of sub-acute thrombosis and thrombotic compli-
cations is heparin (Haude et al. , 2003). In 2003, Haude and coworkers
investigated the use of heparin coated stents for the treatment of in-stent
restenosis in small coronary arteries of symptomatic patients. They used
JOSTENT fl ex stents with a Corline heparin coating attached to a proteo-
glycan-like conjugate of covalently bound unfractionated heparin to the
stent at a surface concentration of heparin of 0.5-1 µg/cm. The heparin was
not released from the stent upon device expansion. The study concluded
that no difference was seen in terms of angiographic results and clinical
events between the heparin coated and bare metal stents (Haude et al. ,
2003). Moreover, Cruz et al. reported a case of sub-acute stent thrombosis
in a patient shortly after receiving a heparin coated stent, with heparin-
induced thrombocytopenia and diffuse thrombus after stent implantation.
This raised the question of the safety of heparin coated stents in patients
who develop heparin associated antibodies as they may have in increased
risk of sub-acute stent thrombosis (Cruz et al. , 2003).
A number of other biopolymers, including hyaluronic acid, chitosan and
fi brin, have all also been applied to the surface of metal stents either as
single coatings or polyelectrolyte multilayers in attempts to reduce throm-
bogenesis and encourage endothelialisation (Holmes et al. , 1994; Verheye
et al. , 2000; Thierry et al. , 2003; Huang & Yang, 2006). Although the applica-
tion of these biopolymers is appealing they are yet to progress beyond
promising animal and in vitro studies.
Efforts have also been made to improve stent performance by covering
them in harvested segments of autologous vein or arteries (Colombo et al. ,
1996; Stefanadis et al. , 1996, 1997; Keriakes et al. , 2002) and a 5 year follow-
up study carried out on stents covered by autologous venous grafts has
shown reduced rates of ISR and TVR (Toutouzas et al. , 2002).
A further approach that has been explored is the seeding of genetically
modifi ed endothelial cells onto stainless steel stents to provide a
natural coating able to secrete high levels of therapeutic protein (beta-
galactosidase or plasminogen activator) for the localised delivery of anti-
coagulant, thrombolytic or anti-proliferative molecules (Dichek et al. ,
1989). However, early results demonstrated limited cell retention after
stent expansion and pulsatile fl ow exposure (Scott et al. , 1995).
Circulating endothelial progenitor cells are known to play a key role in
re-endothelialisation and, if supported by a suitable surface may lead to a
functional endothelial layer. This layer may play a key role in the prevention
of neointimal proliferation and thrombus formation if it is formed at an

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