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Ann Thorac Surg 1999;68:2298-2304
© 1999 The Society of Thoracic Surgeons

Original Articles

Tissue engineering of autologous aorta using a new biodegradable polymer

Dominique Shum-Tim, MDa, Ulrich Stock, MDa, Jeff Hrkach, PhDb, Toshiharu Shinoka, MDa, Jamie Lien, BAb, Marsha A. Moses, PhDc, Andrea Stamp, BScb, George Taylor, MDd, Adrian M. Moran, MDe, William Landis, PhDf, Robert Langer, PhDb, Joseph P. Vacanti, MDc, John E. Mayer, Jr, MDa

a Department of Cardiovascular Surgery, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
b Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
c Department of Surgery, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
d Department of Radiology, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
e Department of Cardiology, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
f Department of Orthopedic Surgery, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

Address reprint requests to Dr Mayer, Department of Cardiovascular Surgery, Children’s Hospital, 300 Longwood Ave, Boston, MA 02115

Presented at the Poster Session of the Thirty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, Jan 25–29, 1999.

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.


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