Topic: A. Basic Science
Tissue Engineered Vascular Grafts Demonstrate Evidence of Growth and Development When Implanted in a Juvenile Animal Model
Matthew P Brennan, Alan Dardik, Narutoshi Habino, Jason D Roh, Gregory N Nelson, Xenophon Papademitris, Toshiharu Shinoka, Christopher K Breuer
Yale University School of Medicine, New Haven, CT
The development of a living, autologous vascular graft with the ability to grow holds great promise for advancing the field of pediatric cardiothoracic surgery.
OBJECTIVE: To evaluate the growth potential of a tissue engineered vascular graft (TEVG) in a juvenile animal model.
METHODS: Polyglycolic acid non-woven mesh tubes (3cm length, 1.3 cm id; Concordia Fibers) coated with a 10% copolymer solution of 50:50 L-lactide and epsilon-caprolactone were statically seeded with 2 x10^6 cells/cm2 autologous bone marrow derived mononuclear cells (BM-MNCs). Eight TEVGs (7 seeded, 1 unseeded control) were implanted as inferior vena cava (IVC) interposition grafts in juvenile lambs. Subjects underwent monthly magnetic resonance angiography; (Siemens 1.5T) with vascular image analysis (www.BioimageSuite.org). One of seven seeded grafts was explanted after one month, all others were explanted six months after implantation. Neotissue was characterized using qualitative histological stains and quantitative biochemical analysis.
RESULTS: All grafts explanted at 6 months were patent and increased in volume as measured by difference in pixel summation in MRA at 1 month and 6 months. The volume of seeded TEVGs at explant averaged 126.9% (SD=24.32). MRI demonstrated no evidence of aneurismal dilation. TEVG resembled the native IVC histologically and had comparable collagen (157.9 +/- 26.4 mcg/mg), elastin (186.9+/-16.7mcg/mg), and glycosaminoglycan (9.7+/-0.8mcg/mg) contents. Immunohistochemical staining and western blot analysis for Ephrin B4, a marker of venous development was expressed in the seeded grafts six months after implantation.
CONCLUSIONS: Tissue engineered vascular grafts demonstrate evidence of growth and development when implanted in a juvenile lamb model.