Vascular implants for peripheral arterial bypass and aortic aneurysm repair - Biomaterials and Devices for the Circulatory System - page 224

serve to stenose the outfl ow. This diminishes blood fl ow below the throm-
botic threshold velocity of the graft resulting in thrombosis.
The location of IH at the heel, toe and recipient artery fl oor has been
linked to areas of fl ow separation and division and regions of low WSS
found in standard ETS anastomoses (How et al. , 2000). This potential causal
link between IH and local haemodynamics has stimulated further work into
the effect of anastomotic geometry on fl ow, and cuffed anastomoses have
been shown to modify fl ow patterns with the formation of a vortex, improv-
ing WSS at the critical points in the anastomosis (Da Silva et al. , 1997; How
et al. , 2000; Fisher et al. , 2001). Clinical studies have confi rmed the modula-
tion of IH away from the recipient artery in cuffed anastomoses with a
benefi t in terms of outcome in below knee bypasses when compared with
standard ETS grafts (Stonebridge et al. , 1995; Tyrrell and Wolfe, 1997).
While minimising technical error at the anastomosis has long been known
to infl uence outcome, these studies pioneered the future of anastomotic
engineering, whereby geometry was explored in an attempt to optimise fl ow
and the haemodynamics, with the intention of inhibiting the accretion of
IH.

8.5 Tissue engineering of vascular grafts

In the quest to develop better small diameter vascular grafts, attention has
focused, over the past decade, on tissue engineering approaches. Ideally, the
engineered graft should be non-thrombogenic. It should also possess
mechanical properties to match those of the native vessel; the wall should
have the ability to be vascularised and exhibit vasoactivity without inducing
infl ammatory response and neointima proliferation and perhaps it should
also grow in concert with the changing needs of the body over time. In order
to achieve the fi rst requirement, the engineered graft should contain a
confl uent, adherent endothelial layer. To achieve the latter objectives, it
should have a well-organised extracellular matrix, which confers the bulk
of the mechanical properties, while resident cells perform metabolic and
biochemical functions that are similar to native vessels.
An early approach to render the surface non-thrombogenic was to seed
EC on non-biodegradable synthetic grafts (e.g. Herring 1991; Williams
et al. , 1994; Zilla and Greisler, 1999). However, problems related to cell
retention, synthetic materials and non-matching mechanical properties,
recognised as important in the pathogenesis of graft failures, remained
unresolved. The second approach moves towards using more natural mate-
rials to engineer the wall closer to that of native vessels. Weinberg and Bell
(1986) were the fi rst to create a multilayered vascular structure by seeding
EC, SMC and fi broblasts (FC) in collagen gel, but the graft was limited by
poor mechanical integrity despite being reinforced with Dacron mesh. This

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