Vascular tissue engineering - Biomaterials and Devices for the Circulatory System - page 304

terminal phenotype. The VSMC phenotypic spectrum incorporates a range
of structural and functional characteristics. The spectrum characteristically
has synthetic, poorly differentiated cells on one extreme and contractile,
well-differentiated cells on the other extreme (Owens, 1995). In reality,
VSMCs adopt a combination of these phenotypic characteristics in accor-
dance with environmental signals, such as stretch, functional requirements,
such as repair after vessel injury and the maintenance of blood pressure
(Birukov et al. , 1995; Owens, 1995). VSMCs with a predominantly synthetic
phenotype proliferate, migrate and synthesise extracellular matrix (ECM)
components which induce thickening of the vessel wall and hence restenosis
which compromises circulation (Ip et al. , 1990; Newby and Zaltsman, 2000).
VSMCs possessing a primarily contractile phenotype predominate in
healthy adult arteries where these cells modify vascular tone in response to
physiological requirements, thereby contributing to cardiovascular homeo-
stasis (Owens, 1995).
The abrupt and excessive mechanical stretching to which the vein graft
is subjected when arterial circulation is restored immediately damages its
tunicae intima and media. This damage is perpetuated by sustained exces-
sive mechanical stretching. As mentioned above, the excessive mechanical
stretching concurrently stimulates VSMCs within the tunica media to alter
their phenotype from contractile to synthetic. The resultant VSMC migra-
tion, proliferation and ECM synthesis provoke thickening of the vessel wall
and intimal hyperplasia. The consequence is narrowing of the vessel lumen,
a major cause of medium to long-term graft failure (Mitra et al. , 2006; Zhou
et al. , 2003).
Long-term high intraluminal pressure causes hypertrophy of the venous
graft's wall, which induces remodelling and alters the histology (Zubilewicz
et al. , 2001). Using a rabbit carotid model, Wong et al. reported cell prolif-
eration and ECM manufacture within four weeks of a vein graft being
implanted (Wong et al. , 2008). A second phase of changes within the venous
wall, characterised by apoptosis and a reduction in ECM synthesis, particu-
larly collagen, results in a 40% increase in lumen area (Wong et al. , 2008).
Intimal thickening continues despite the relative reduction in cell prolifera-
tion and ECM production during the second phase. The latter occurs
because cell proliferation and ECM production are still increased com-
pared with control levels (Wong et al. , 2008).
In most cases, autologous arterial and venous grafts are capable of imme-
diately coping with abrupt changes in intraluminal pressure and do not
rupture or dilate. These conduits may, however, undergo structural changes
in the medium to long term as mentioned above, i.e. intimal hyperplasia at
the sites of anastomosis, or aneurysmal dilatation. Although autologous
arterial and venous grafts are preferred during bypass procedures, a major
stumbling block to their use is that they are available in only 30% of cases

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