Biocompatibility of cardiovascular devices - Biomaterials and Devices for the Circulatory System - page 69

ECM deposition to greater extents than non-resorbable materials like
PET (Greisler, 1982; Greisler et al. , 1985, 1986, 1992b). However,
increased prosthetic compliance coincident with endogenous cell repopu-
lation potentially compromised the biomechanical biocompatibility of
these materials. The advent of newer formulations of bioresorbable mate-
rials such as poly(L-lactide-co- -caprolactone), poly(glycerol sebacate),

poly-(L-lactic acid), and others, copolymerization with bioresorbable
materials, and the mechanical preconditioning of biomaterials, have made
the use of these materials as either device coatings or scaffolds for com-
pletely bioresorbable devices a likely wave of the future in cardiovascular
device technology (Gao et al. , 2008; Uchida et al. , 2008). A fully biore-
sorbable stent comprising a poly-L-lactic acid backbone and a coating of
poly-D-L-lactic acid containing the antiproliferative agent everolimus has
recently been implanted in the fi rst-in-human trials with promising toler-
ance and clinical results up to 24 months (Ormiston et al. , 2007, 2008;
Serruys et al. , 2009). Bioresorbable polymer coatings on coronary stents
have also been used in humans for the delivery of sirolimus (Grube and
Buellesfeld, 2006; Han et al. , 2009), rapamycin (Wessely et al. , 2007;
Bhargava et al. , 2008), and paclitaxel (Kohler et al. , 2007; Buszman et al. ,
2008) among other pharmacologic agents, and have demonstrated bene-
fi ts such as inhibited SMC proliferation, upregulation of SMC apoptotic
and anti-proliferative pathways modulated by MAP kinase, receptor tyro-
sine kinases and PKA (Nguyen et al. , 2004), have demonstrated safety
and low rates of thrombosis and restenosis, and have demonstrated
improved neointimal formation compared with some bare metal stents
(Frohlich et al. , 2003).
Other ongoing applications of bioresorbable materials include the cre-
ation of cardiac patches of either gelatin, PGA, or copolymers made of
ε

ε

-caprolactone and L-lactic acid reinforced with a poly-L-lactide knitted or
woven fabric, which supported endogenous cellular infi ltration and ECM
production during bioresorption in comparison to ePTFE patches (Ozawa
et al. , 2002; Fujimoto et al. , 2007) Poly(

￿ ￿ ￿ ￿ ￿

-caprolactone) has been used for
the tissue engineering of heart valves (Del Gaudio et al. , 2008). Bioresorb-
able fi lms have even been studies in canine models as epicardial patches
which contain electrodes to replace the needle stabbed epicardial pacing
wires used after cardiac surgery (Narita et al. , 2006).
It is likely that the use of bioresorbable polymers will become increas-
ingly common for use not only in coronary stents, but also for all cardio-
vascular devices. While ample data appear to demonstrate the safety and
non-inferiority of these devices to standard drug eluting stents, longer-term
data need to be obtained to confi rm improved restenosic rates secondary
to intimal hyperplasia, improved cytotoxicity profi les, and reductions in
thrombotic and infl ammatory mediated complications compared with other

ε