Biocompatibility of cardiovascular devices - Biomaterials and Devices for the Circulatory System - page 57

and peripheral vascular system after device implantation or intravascular
intervention impacts the long-term biocompatibility of cardiovascular
devices (Mikucki and Greisler, 1999). This phenomenon is not simply a
function of insuffi cient EC proliferation, as the cessation of EC ingrowth
approximately 1-3 cm from the edges of vascular anastomoses is seen even
in the presence of elevated EC mitotic activity at these points on standard
ePTFE grafts (30 µm internodal distance) (Reidy et al. , 1983; Clowes et al. ,
1985, 1986) Interestingly, the utilization of more porous ePTFE (60 µm
internodal distance) has been associated with increased EC coverage of the
grafts in some animal models, likely as a result of transmural angiogenic
mechanisms (Clowes et al. , 1986; Greisler et al. , 1987, 1988; Clowes and
Kohler, 1991; Hirabayashi et al. , 1992).
Thus, the endothelialization of cardiovascular implants is a function of
spontaneous endothelial ingrowth, angiogenic mechanisms, and, likely, the
deposition and differentiation of endothelial progenitor cells onto the de-
endothelialized surface within the circulation. While the association of spe-
cifi c biomaterials with EC proliferation, turnover, and functionality, if any,
remains confusing with a variety of contradictory studies, suffi cient litera-
ture does suggest that EC-biomaterial interactions in the context of the in
vivo environment are more likely than not a contributor to the longevity
of cardiovascular devices (McGuigan and Sefton, 2007). Variations in
culture techniques, bioengineering methods, and cell sources may account
for some of the discrepancies in the literature. One study compared the
production of prostacylin, an inhibitor of platelet aggregation, by the endo-
thelium generated on polyglactin 910 (PG910), PET, and polydiaxonone
(PDS) grafts which had been interposed into rabbit aortas under ex vivo
fl ow conditions. After one month, the endothelium generated on PDS and
PG 910 demonstrated signifi cantly less prostacyclin production in response
to arachidonic acid compared with normal aorta, while prostacyclin produc-
tion by the endothelium of PET did not differ from normal aorta. By three
months, all groups demonstrated equal prostacylin production to normal
aorta (Greisler et al. , 1990b). How the apparent delay in normal endothelial
function affects the long-term biocompatibility of the implanted material is
a critical question as patency exceeded 90% in all groups up to six months.
However, increased incidence of atherosclerosis, thrombosis, and intima/
media ratios in prostacyclin receptor knockout mice suggest it is likely an
important factor in device longevity (Arehart et al. , 2007).
Biomaterials may induce the release of EC growth factors which can
modulate mesenchymal cell mitogenesis and the subsequent myointimal
hyperplastic response. For example, in vitro data have demonstrated PET-
induced release of the SMC mitogen basic fi broblast growth factor (bFGF)
by ECs (Cenni et al. , 1999). In addition, infl ammatory and other cells
in contact with specifi c biomaterials may also modulate EC growth on

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