Vascular tissue engineering - Biomaterials and Devices for the Circulatory System - page 322

Recreating an artery with its tunicae intima, media and adventitia, and
their respective cellular and ECM components, has proved challenging.
Despite amalgamating the cellular components into a structure that resem-
bled a blood vessel, the conduits have faltered when subjected to mechani-
cal forces. Shear forces and intraluminal pressures, which equated to the
forces identifi ed and measured within the CVS, regularly disrupted the
engineered conduits' integrity. Experiments on these conduits were thus
restricted to the in vitro environment, with very few animal studies being
authorised and initiated owing to the high failure rate of tissue engineered
grafts.
The development of ex vivo gene therapy approaches for growth factor
delivery in combination with tissue engineering has opened up new avenues
for treatment of various diseases (Jabbarzadeh et al. , 2008). In bone, in vivo
implantation of biodegradable scaffolds containing adenovirus-transfected
stem cells secreting osteoinductive factors demonstrated improved new-
bone formation in murine models (Peterson et al. , 2005; Schreiber et al. ,
2005). In the development of vascular grafts, viral gene therapy was used
to overproduce anticoagulant proteins which inhibited conduit thrombosis
and helped enhance their integration once implanted (Fields et al. , 2003;
Ohno et al. , 2002).

12.5 The inclusion of cells in vascular constructs

Research groups do not consistently include cells in their tissue engineered
constructs. VSMCs and ECs have their specifi c location and function
within the vessel wall of naturally occurring blood vessels. Should the cells
function abnormally, the integrity and functioning of the vessel are imme-
diately compromised, which has far-reaching consequences, not only for
the vessel itself but also for the CVS and hence the patient as a whole. The
poor long-term outcome of tissue engineered vascular grafts may be asso-
ciated with the lack of cells within these structures. It is unclear whether
manufactured conduits, in which the usual reciprocal interaction between
vascular cells and other vascular wall components is absent, would mimic
native vessels.

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12.5.1 Endothelial cells

ECs line the luminal surface of the intima of the vessel wall. These cells
insulate the wall from the contents of the lumen and prevent thrombosis,
one of the main causes of early and medium-term graft failure, even in vein
grafts (Seifalian et al. , 2002). Depending on the technique used to engineer
a vascular graft, ECs are employed at various stages in its manufacture. A
recurrent theme, however, is the paucity of mature EC reserves and the