Biomedical Engineering Reference
In-Depth Information
PerspectivesofRelease-ControlledCoatings
In 2001, >500,000 angioplasties were performed in the United States, more than double the
number of coronary artery bypass graft surgeries (American Heart Association, 2003). In
Europe, the reported number of coronary stenting procedures was 395,000 in 2000 (Balmer
et al., 2005), stents being applied to 71% of coronary angioplasties. In patients who undergo
conventional balloon angioplasty without stenting, >40% of patients develop restenosis
within 6 months of the procedure (Fischman
et al., 1994). Clinical trials have shown that
stenting reduces the occurrence of restenosis by 30% compared with angioplasty alone
(Fischman et al., 1994; Serruys et al., 1994). In 2002-2003, DES were approved by regulatory
bodies in Europe and the USA after initial studies showed a dramatic reduction in rates
of restenosis compared with bare metal (Morice
et al., 2002; Moses et al., 2003; Stone et al.,
2004, 2005). Using DES, neointimal proliferation can be reduced further to less than 10%.
Controlled release coatings are the format used in DES, generally comprising a polymeric
matrix material and drug mixture. However, one challenge in polymeric matrix stents is
the onset of late stent thrombosis, in the causation of which the polymer matrix materials
are often implicated. Coronary stents are foreign bodies that can trigger platelet adhesion
and activation of the coagulation cascade. However, high-pressure implantation generally
causes some vessel injury, including exposure of the thrombogenic subintima, media, and
atherosclerotic plaque components to blood. Studies (Kukreja et al., 2008) have shown that
healing takes place over an extended period (Figure 6.36), including thrombosis (14 days),
inflammation (90 days), smooth muscle cell migration/proliferation (more than 3 months
from day 14), extracellular matrix production (3 until 15 months), and extracellular matrix
reabsorption (post 1-year event).
The reason that late stent thrombosis is claimed to be a matrix material-induced event is
that all the drugs from DES are released within 1 year, with only polymer matrix remain-
ing. Together with the bare metal, polymer matrix is likely to be the component respon-
sible for late stent thrombosis. More biocompatible materials have demonstrated better
clinical performance than conventional nonerodible polymer matrix stents (e.g., Cypher
and Taxus).
The first perspective of the released controlled coatings is to improve the biocompatibil-
ity of the polymer matrix or coating materials in order to target the post-1-year late stent
thrombosis. Although not fully accepted by the FDA, erodible polymers such as PLA and
PLGA are still used as matrix materials in new DES, such as the Axxess Plus stent (Devax),
a nitinol (nickel-titanium) self-expanding thin strut stent, coated with abluminal PLA and
Smooth muscle cell
migration/proliferation
Extracellular matrix
production
Extracellular matrix
reabsorption
rombosis
Inflammation
3
14
14
90
440
1000
Days post injury
FIGURE 6.36
Typical vessel healing response following bare-metal stent implantation. (Reproduced with permission from
Elsevier Ltd. Kukreja et al.,
Pharmacol. Res.
, 57, 171-180, 2008.)
