Tissue engineering of autologous aorta using a new biodegradable polymer.
BACKGROUND
Ovine pulmonary valve leaflets and pulmonary arteries have been tissue-engineered (TE) from autologous cells and biodegradable polyglycolic acid (PGA)-polyglactin copolymers. Use of this cell-polymer construct in the systemic circulation resulted in aneurysm formation. This study evaluates 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 seeded onto 7-mm diameter PHA-PGA tubular scaffolds. The autologous cell-polymer 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 were replaced with acellular polymer tubes. Vascular patency was evaluated with echography. All control animals were sacrificed when the grafts became occluded. 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 content, deoxyribonucleic acid (DNA) content, structural and ultrastructural examination, mechanical strength, and matrix metalloproteinase (MMP) activity.


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 sacrifice. There was one mild stenosis at the anastomotic site after 5 months postoperatively. The percent collagen and DNA contents approached the native 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%+/-16.9 [5 months], p < 0.05). Histology demonstrated elastic fibers in the medial layer and endothelial specific von Willebrand factor on the luminal surface. 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 resembling the native aorta can be created using TE approach. This may allow the development of "live" vascular grafts.
Shum-Tim
D
D
Department of Cardiovascular Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Stock
U
U
Hrkach
J
J
Shinoka
T
T
Lien
J
J
Moses
M A
MA
Stamp
A
A
Taylor
G
G
Moran
A M
AM
Landis
W
W
Langer
R
R
Vacanti
J P
JP
Mayer
J E
JE
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000502:physiology / Q000601:surgery*; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D001696:Biomechanical Phenomena; D001709:Biotechnology; D002339:Carotid Arteries / Q000166:cytology*; D017690:Cell Transplantation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006083:Graft Occlusion, Vascular; D020782:Matrix Metalloproteinases / Q000378:metabolism; D011098:Polyglactin 910; D011108:Polymers; D012756:Sheep; D014182:Transplantation, Autologous; D014654:Vascular Patency
D001672:Biocompatible Materials; D011108:Polymers; D011098:Polyglactin 910; D003094:Collagen; D004247:DNA; D020782:Matrix Metalloproteinases