Background. Ovine pulmonary valve leaflets and pulmonary arteries have been
tissue-engineered (TE) from autologous cells and biodegradable polyglycoli
c acid (PGA)-polyglactin copolymers. Use of this cell-polymer construct in
the systemic circulation resulted in aneurysm formation. This study evaluat
es a TE vascular graft in the systemic circulation which is based on a new
copolymer of PGA and polyhydroxyalkanoate (PHA).
Methods. Ovine carotid arteries were harvested, expanded in vitro, and seed
ed onto 7-mm diameter PHA-PGA tubular scaffolds. The autologous cell-polyme
r vascular constructs were used to replace 3-4 cm abdominal aortic segments
in lambs (group TE, n = 7). In a control group (n = 4), aortic segments we
re replaced with acellular polymer tubes. Vascular patency was evaluated wi
th echography. All control animals were sacrificed when the grafts became o
ccluded. Animals in TE group were sacrificed at 10 days (n = 1), 3 (n = 3),
and 5 months (n = 3). Explanted TE conduits were evaluated for collagen co
ntent, deoxyribonucleic acid (DNA) content, structural and ultrastructural
examination, mechanical strength, and matrix metalloproteinase (MMP) activi
ty.
Results. The 4 control conduits became occluded at 1, 2, 55, and 101 days.
All TE grafts remained patent, and no aneurysms developed by the time of sa
crifice. There was one mild stenosis at the anastomotic site after 5 months
postoperatively. The percent collagen and DNA contents approached the nati
ve aorta over time (% collagen = 25.7% +/- 3.4 [3 months] vs 99.6% +/- 11.7
[5 months], p < 0.05; and % DNA = 30.8% +/- 6.0 [3 months] vs 150.5% +/- 1
6.9 [5 months], p < 0.05). Histology demonstrated elastic fibers in the med
ial layer and endothelial specific von Willebrand factor on the luminal sur
face. The mechanical strain-stress curve of the TE aorta approached that of
the native vessel. A 66 kDa MMP-2 was found in the TE and native aorta but
not in control group.
Conclusions. Autologous aortic grafts with biological characteristics resem
bling the native aorta can be created using TE approach. This may allow the
development of "live" vascular grafts. (C) 1999 by The Society of Thoracic
Surgeons.