Tissue-engineered Vascular Grafts Demonstrate Evidence of Growth and Development When Implanted in a Juvenile Animal Model

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Abstract
Introduction: 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 nonwoven mesh tubes (3-cm length, 1.3-cm id; Concordia Fibers) coated with a 10% copolymer solution of 50:50 l-lactide and ε-caprolactone were statically seeded with 1 × 106 cells/cm2 autologous bone marrow derived mononuclear cells. Eight TEVGs (7 seeded, 1 unseeded control) were implanted as inferior vena cava (IVC) interposition grafts in juvenile lambs. Subjects underwent bimonthly magnetic resonance angiography (Siemens 1.5 T) with vascular image analysis ( www.BioimageSuite.org ). One of 7-seeded grafts was explanted after 1 month and all others were explanted 6 months after implantation. Neotissue was characterized using qualitative histologic and immunohistochemical staining 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 magnetic resonance angiography at 1 month and 6 months. The volume of seeded TEVGs at explant averaged 126.9% ± 9.9% of their volume at 1 month. Magnetic resonance imaging demonstrated no evidence of aneurysmal dilation. TEVG resembled the native IVC histologically and had comparable collagen (157.9 ± 26.4 μg/mg), elastin (186.9 ± 16.7 μg/mg), and glycosaminoglycan (9.7 ± 0.8 μg/mg) contents. Immunohistochemical staining and Western blot analysis showed that Ephrin-B4, a determinant of normal venous development, was acquired in the seeded grafts 6 months after implantation. Conclusions: TEVGs demonstrate evidence of growth and venous development when implanted in the IVC of a juvenile lamb model.