Vascular tissue engineering - Biomaterials and Devices for the Circulatory System - page 313

extensively studied and are easily extracted, attention has focused on their
potential as pivotal components in tissue engineered constructs.
The benefi t of employing collagen, a fi brous protein, as a scaffold in
vascular tissue engineering applications was recognised very early
(Weinberg and Bell, 1986). Collagen is the principal reason arteries main-
tain their structural integrity, in the face of considerable cyclic stretch.
Within arteries, type I collagen is particularly ubiquitous, has been purifi ed
and employed as fi bres or a gel inducing low intensity immunogenicity and
infl ammation. This protein is non-toxic to cells and is bioresorbable. Disap-
pointingly, the mechanical strength of collagen scaffolds is easily disrupted,
making their in vivo reliability tenuous without prior modifi cation
(L'Heureux et al. , 1993; Weinberg and Bell, 1986). Collagen constructs can
be manipulated with relative ease, thereby reinforcing their architecture,
structural integrity and augmenting the capability of cells, in particular
SMCs, to integrate and contract (Brinkman et al. , 2003; Chanda et al. , 1998a;
Charulatha and Rajaram, 2003; Elbjeirami et al. , 2003; Ma et al. , 2004;
Orban et al. , 2004). Substances such as glutaraldehyde, employed to improve
collagen scaffold structure through cross-linking, may be toxic to seeded
cells (Luyn et al. , 1995).
An important ECM component of naturally occurring vessels is elastin,
which has both a structural and a regulatory role. Elastin confers elasticity
to muscular and elastic arteries and also closely regulates VSMC pheno-
type, which directly affects vascular function and contributes to the devel-
opment of pathology (Lillie and Gosline, 2002; Silver et al. , 2001). In fact,
the elastin-cellular interaction is reciprocal as SMCs and fi broblasts manu-
facture ECM elastin (Pasquali-Ronchetti and Baccarani-Contri, 1997). Via
a G-protein coupled pathway, elastin encourages actin stress fi bre organi-
sation, inhibits VSMC proliferation and regulates migration (Rodgers and
Weiss, 2005). VSMCs associated with an ECM devoid of elastin, prolifer-
ate, a major cause of intimal hyperplasia and hence medium-term vessel
stenosis (Li et al. , 1998). Despite the pivotal role elastin plays in blood
vessels, this protein is seldom included in the composition of tissue engi-
neered conduits (Patel et al. , 2006). This exclusion occurs despite elastin
constituting, approximately, 50% of the ECM dry weight (Karnik et al. ,
2003) and thereby dictating tissue mechanics at low strains before stiffer
collagen fi bres are engaged (Long and Tranquillo, 2003). Purifying intact
native elastin is complex due to its inherent stability encouraged by its
cross-linked fi bre network (Daamen et al. , 2001; Debelle and Tamburro,
1999). In order to incorporate elastin in TEBVs, tissue engineers have
employed elastin-producing SMCs which have been seeded onto, for
example, collagen scaffolds (Isenberg and Tranquillo, 2003). Other
approaches have attempted to extract soluble and insoluble elastic from
tissue (Daamen et al. , 2001). In order to gain the benefi t of both collagen

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