Biomedical Engineering Reference
In-Depth Information
enhance the hemocompatibility of the protein matrix. This approach also
reduces the amount of polymer used, facilitating degradation and increas-
ing the elasticity of the construct [51]. Functional testing of these composite
valves have been performed under physiological systemic load conditions
using a pulse duplicator system [247, 271]. Decellularized porcine heart valves
coated with P3HB-4HB have been tested without any cellular preseeding in
the aortic and pulmonary position in sheep. While the two valves in aor-
tic position performed well, with complete endothelialization and limited
inflammatory cell invasion after 12 weeks, one of the two valves in the pul-
monary position failed, probably due to bacterial endocarditis [272].
Vascular Grafts
PGA/P4HB dip-coated composites have been formed into tubular scaffolds
using a heat application welding technique to test their potential for tissue
engineering of blood vessels. The tubes were seeded with ovine vascular my-
ofibroblasts for 4 days under static culture conditions, followed by seeding
of endothelial cells and incubation for 28 days in a pulse duplicator system.
The result was significantly more cells and collagen production as well as
higher mechanical strength compared to the static controls [45]. Dynamic ro-
tational seeding and culturing in a hybridization oven has also been shown
to be an effective method to culture ovine vascular myofibroblasts onto these
PGA/P4HB scaffolds [253].
P4HB porous tubes have been fabricated by a solution-casting/salt-
leaching method in a cylindrical mold containing a cylindrical core. These
tubular scaffolds (inner diameter 15 mm, wall thickness 2 mm) were seeded
with ovine vascular smooth muscle cells, derived by enzymatic dispersion
in order to limit the amount of differentiated myofibroblast-like cells. They
were incubated for 4 days under static conditions and 14 days under dy-
namic conditions, followed by another static culture with endothelial cells for
2 days. The result was the creation of tissue-engineered aortic blood vessels.
The dynamically cultured tubes showed confluent layered tissue formation
with significantly increased ECM synthesis, DNA, and protein content com-
pared to static controls, as well as mechanical properties approaching those
of native aorta [46]. Protein expression profiles of the tissue-engineered P4HB
tubes revealed distinct differences from native aorta or carotid arteries at
this early stage of remodeling [251]. The tissue-engineered constructs were
tested under high-pressure conditions in sheep by replacing a 4-cm segment
of the descending aorta. The tubes were wrapped into decellularized ovine
small intestinal submucosa prior to implantation in order to stimulate angio-
genesis and increase mechanical stability. No intimal thickening, dilatation
or stenosis were observed 12 weeks after implantation; however, small areas
of thrombi were formed despite endoluminal endothelial cell-layering. Di-
latation causing increased thrombus formation was observed 24 weeks after
implantation (Fig. 17). Compared to native aorta, regenerated tissue con-
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