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J Thorac Cardiovasc Surg 2000;119:732-740
© 2000 The American Association for Thoracic Surgery


SURGERY FOR CONGENITAL HEART DISEASE

TISSUE-ENGINEERED VALVED CONDUITS IN THE PULMONARY CIRCULATION

Ulrich A. Stock, MDa, Mitsugi Nagashima, MDa, Philipe N. Khalil, MDa, Georg D. Nollert, MDa, Tanja Herdena, Jason S. Sperling, MDa, Adrian Moran, MDc, Jamie Lien, BAf, David P. Martin, PhDe, Frederick J. Schoen, MD, PhDd, Joseph P. Vacanti, MDb, John E. Mayer, Jr , MDa

From the Department of Cardiovascular Surgery,a Department of Surgery,b Department of Cardiology,c Children’s Hospital, Boston, Mass; the Department of Pathology,d Brigham and Women’s Hospital, Boston, Mass; Metabolix Inc,e Cambridge, Mass; and the Department of Chemical Engineering,f Massachusetts Institute of Technology, Cambridge, Mass.

Supported by grants from the Department of Cardiac Surgery, Children’s Hospital, Boston, Mass; Deutsche Forschungsgemeinschaft (Sto 359/1-1); and the National Institutes of Health (HL-97-005).

Address for reprints: John E. Mayer, Jr, MD, Department of Cardiovascular Surgery, Children’s Hospital Harvard Medical School, 300 Longwood Ave, Boston, MA 02115 (E-mail: mayer{at}a1.tch-harvard.edu ).

Objective: Bioprosthetic and mechanical valves and valved conduits are unable to grow, repair, or remodel. In an attempt to overcome these shortcomings, we have evaluated the feasibility of creating 3-leaflet, valved, pulmonary conduits from autologous ovine vascular cells and biodegradable polymers with tissue-engineering techniques.
Methods: Endothelial cells and vascular medial cells were harvested from ovine carotid arteries. Composite scaffolds of polyglycolic acid and polyhydroxyoctanoates were formed into a conduit, and 3 leaflets (polyhydroxyoctanoates) were sewn into the conduit. These constructs were seeded with autologous medial cells on 4 consecutive days and coated once with autologous endothelial cells. Thirty-one days (±3 days) after cell harvesting, 8 seeded and 1 unseeded control constructs were implanted to replace the pulmonary valve and main pulmonary artery on cardiopulmonary bypass. No postoperative anticoagulation was given. Valve function was assessed by means of echocardiography. The constructs were explanted after 1, 2, 4, 6, 8, 12, 16, and 24 weeks and evaluated macroscopically, histologically, and biochemically.
Results: Postoperative echocardiography of the seeded constructs demonstrated no thrombus formation with mild, nonprogressive, valvular regurgitation up to 24 weeks after implantation. Histologic examination showed organized and viable tissue without thrombus. Biochemical assays revealed increasing cellular and extracellular matrix contents. The unseeded construct developed thrombus formation on all 3 leaflets after 4 weeks.
Conclusion: This experimental study showed that valved conduits constructed from autologous cells and biodegradable matrix can function in the pulmonary circulation. The progressive cellular and extracellular matrix formation indicates that the remodeling of the tissue-engineered structure continues for at least 6 months.




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