Biocompatibility of cardiovascular devices - Biomaterials and Devices for the Circulatory System - page 70

earlier generation bare metal and non-bioresorbable devices (Macaya and
Moreno, 2008). However, the progress made in the development and utiliza-
tion of this fi eld has opened potential avenues of real progress for the
treatment of cardiac patients.

3.4.4 Gene therapy
While progress in the fi eld of gene therapy in medicine and cardiovas-
cular disease has been slow in general, the strategic genetic modifi cation
of host cells which respond to cardiovascular devices or of cells seeded
in or on tissue engineered constructs provides theoretical opportunities
for improving the biocompatibility of cardiovascular devices (Brewster
et al. , 2006). Adenoviral delivery of

-interferon has been demonstrated
to decrease SMC proliferation in vitro and to reduce the intima/media
ratio in the porcine balloon injury artery model (Stephan et al. , 1997).
The inhibition of transcription factors E2F with transfected decoy oli-
godeoxynucleotides using therapeutic ultrasound was found to minimize
neointimal formation in a rat carotid artery injury model (Hashiya et
al. , 2004). Results employing this approach in human implants have
been evaluated, but early results appear less promising than would be
predicted from the preclinical animal studies (Hoel and Conte, 2007).
VEGF gene transfer into bovine pericardium and metallic stents can
accelerate endothelialization of xenogeneic heart valves and potentially
improve the biocompatibility of valves and coronary stents (Van Belle
et al. , 1997; Zhang et al. , 2002) The delivery of inducible nitric oxide
synthase by adenovirus from polymer coated stents has demonstrated
reduced restenosis rates and suggests a potential future combinatorial
gene and drug delivery strategy with the simultaneous use of polymers
and adenoviral gene vectors (Ye et al. , 1998; Green et al. , 2006; Fishbein
et al. , 2008).

β

￿ ￿ ￿ ￿ ￿

3.5 Conclusions

The immensely complicated interactions which occur at blood-biomaterial
interfaces are dynamic and interdependent processes leading to the ulti-
mate failure of a disturbingly large percentage of implanted cardiovascular
devices. However, dramatic advances in biomaterial science and cell and
molecular biology have opened the door for exciting avenues of investiga-
tion likely to provide real clinical benefi ts for our patient population. Con-
tinued investigation of bioresorbable material science and the furthering of
stem cell and gene therapy sciences should augment the advancements
which have already occurred.