Vascular tissue engineering - Biomaterials and Devices for the Circulatory System - page 311

into its lactic acid monomer which is incorporated into the tricarboxylic
acid cycle and is excreted by the lung as carbon dioxide. PGA is degraded
through hydrolysis and non-specifi c esterases and caroboxy-peptidases into
its glycolic acid monomer which enters the tricarboxylic acid cycle or is
excreted in the urine (Liu and Czernuszka, 2007). PLA and PGA degrada-
tion therefore induces acidic by-products which may disrupt homeostasis
and increase infl ammation in poorly perfused tissue (Anderson, 2001; Liu
and Czernuszka, 2007).
To avoid in vivo failure of engineered grafts which incorporate bioresorb-
able scaffolds, the conduits must produce ECM of suffi cient strength before
the scaffold degrades and loses its integrity. The excessive manufacture of
ECM is also undesirable. The mechanical strength of the scaffolds can be
manipulated by combining two or more biopolymers with different resorp-
tion rates or through the inclusion of a non-resorbable component (Xue
and Greisler, 2003). PLA and PGA have been combined into a copolymer
called poly(DL-lactic acid-co-glycolic acid) (PLGA) (Liu and Czernuszka,
2007). PGA does not possess cell anchoring sites and SMCs attached to this
material's residual fragments demonstrate a poorly differentiated pheno-
type with few contractile proteins (Yue et al. , 1988). Cell adhesion to PGA
was enhanced by treating the scaffold with sodium hydroxide or incorporat-
ing the Arg-Gly Asp (RGD) sequence to the polymer surface (Drumheller
and Hubbell, 1994; Patel et al. , 1998).
In a novel approach employing biocompatible and bioresorbable scaf-
folds, in situ scaffold cellularisation was attempted in a porcine aorta model.
A three layer porous patch comprising an inner PGA/collagen sponge-
compound layer, an outer poly-L-lactic acid (PLLA) layer with a polycap-
rolactone layer sandwiched in between was manufactured. Combining the
polymers ensured that the PGA/collagen sponge-compound, which demon-
strated better cell attachment but degraded within three weeks, was rein-
forced by the outer PLLA layer which endured for 12 months. After one
month in vivo , the conduit was lined by EC-like cells with underlying SMCs
which proliferated with time. Structural enhancement paralleled improved
functionality including appropriate responses to inotropes. The grafts main-
tained their integrity and patency and were well integrated after 12 months
in vivo apart from the persistence of the PLLA layer (Torikai et al. , 2008).
A similar approach employed a construct combining collagen sponge and
a two layer woven scaffold of inner PGA and outer PLLA. After implanta-
tion in a canine carotid model for up to 12 months the conduits had main-
tained their integrity and patency and had not induced an infl ammatory
foreign body response. After complete regeneration, conduits had similar
pliability and collagen content to native vessels, possessed a subtle elastic
lamina and were lined with ECs with an outer SMC layer (Yokota et al. ,
2008).

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