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Ralf Sodian
Sabine H. Daebritz
David P. Martin
John E. Mayer, Jr
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Ann Thorac Surg 2000;70:140-144
© 2000 The Society of Thoracic Surgeons


Original articles: Cardiovascular

Tissue engineering of heart valves: in vitro experiences

Ralf Sodian, MDa, Simon P. Hoerstrup, MDa, Jason S. Sperling, MDa, Sabine H. Daebritz, MDa, David P. Martin, PhDa, Frederick J. Schoen, MD, PhDa, Joseph P. Vacanti, MDa, John E. Mayer, Jr, MDa,b

a Department of Cardiac Research, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
b Department of Cardiac Surgery, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

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

Background. Tissue engineering is a new approach, whereby techniques are being developed to transplant autologous cells onto biodegradable scaffolds to ultimately form new functional tissue in vitro and in vivo. Our laboratory has focused on the tissue engineering of heart valves, and we have fabricated a trileaflet heart valve scaffold from a biodegradable polymer, a polyhydroxyalkanoate. In this experiment we evaluated the suitability of this scaffold material as well as in vitro conditioning to create viable tissue for tissue engineering of a trileaflet heart valve.

Methods. We constructed a biodegradable and biocompatible trileaflet heart valve scaffold from a porous polyhydroxyalkanoate (Meatabolix Inc, Cambridge, MA). The scaffold consisted of a cylindrical stent (1 x 15 x 20 mm inner diameter) and leaflets (0.3 mm thick), which were attached to the stent by thermal processing techniques. The porous heart valve scaffold (pore size 100 to 240 µm) was seeded with vascular cells grown and expanded from an ovine carotid artery and placed into a pulsatile flow bioreactor for 1, 4, and 8 days. Analysis of the engineered tissue included biochemical examination, enviromental scanning electron microscopy, and histology.

Results. It was possible to create a trileaflet heart valve scaffold from polyhydroxyalkanoate, which opened and closed synchronously in a pulsatile flow bioreactor. The cells grew into the pores and formed a confluent layer after incubation and pulsatile flow exposure. The cells were mostly viable and formed connective tissue between the inside and the outside of the porous heart valve scaffold. Additionally, we demonstrated cell proliferation (DNA assay) and the capacity to generate collagen as measured by hydroxyproline assay and movat-stained glycosaminoglycans under in vitro pulsatile flow conditions.

Conclusions. Polyhydroxyalkanoates can be used to fabricate a porous, biodegradable heart valve scaffold. The cells appear to be viable and extracellular matrix formation was induced after pulsatile flow exposure.




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