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(Circulation. 2008;118:S52-S57.)
© 2008 American Heart Association, Inc.

Myocardial Protection, Perioperative Management, and Vascular Biology

Bioengineered Three-Layered Robust and Elastic Artery Using Hemodynamically-Equivalent Pulsatile Bioreactor

Kiyotaka Iwasaki, PhD; Koji Kojima, MD, PhD; Shohta Kodama, MD, PhD; Ana C. Paz, BS; Melody Chambers, BS; Mitsuo Umezu, PhD; Charles A. Vacanti, MD

From the Laboratory for Tissue Engineering and Regenerative Medicine (K.I., K.K., S.K., A.C.P., M.C., C.A.V.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Waseda Institute for Advanced Study (K.I.), Tokyo, Japan; the Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Medical Care (K.I., M.U.), Waseda University, Tokyo Japan; and the Major in Integrative Bioscience and Biomedical Engineering (M.U.), Graduate School of Waseda University, Tokyo, Japan.

Correspondence to Koji Kojima, Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women’s Hospital, Harvard Medical School. 75 Francis Street, Thorn 1327, Boston, MA 02115. E-mail kojima{at}zeus.bwh.harvard.edu

Background— There is an essential demand for tissue engineered autologous small-diameter vascular graft, which can function in arterial high pressure and flow circulation. We investigated the potential to engineer a three-layered robust and elastic artery using a novel hemodynamically-equivalent pulsatile bioreactor.

Methods and Results— Endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts were harvested from bovine aorta. A polyglycolic acid (PGA) sheet and a polycaprolactone sheet seeded with SMCs, and a PGA sheet seeded with fibroblast, were wrapped in turn on a 6-mm diameter silicone tube and incubated in culture medium for 30 days. The supporting tube was removed, and the lumen was seeded with ECs and incubated for another 2 days. The pulsatile bioreactor culture, under regulated gradual increase in flow and pressure from 0.2 (0.5/0) L/min and 20 (40/15) mm Hg to 0.6 (1.4/0.2) L/min and 100 (120/80) mm Hg, was performed for an additional 2 weeks (n=10). The engineered vessels acquired distinctly similar appearance and elasticity as native arteries. Scanning electron microscopic examination and Von Willebrand factor staining demonstrated the presence of ECs spread over the lumen. Elastica Van Gieson and Masson Tricrome Stain revealed ample production of elastin and collagen in the engineered grafts. Alpha-SMA and calponin staining showed the presence of SMCs. Tensile tests demonstrated that engineered vessels acquired equivalent ultimate strength and similar elastic characteristics as native arteries (Ultimate Strength of Native: 882±133 kPa, Engineered: 827±155 kPa, each n=8).

Conclusions— A robust and elastic small-diameter artery was engineered from three types of vascular cells using the physiological pulsatile bioreactor.

Key Words: arteries • elasticity • vascular grafts