Tissue-engineered vascular grafts demonstrate evidence of growth and development when implanted in a juvenile animal model

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 E-caprolactone were statically seeded with 1 x 10(6) cells/cm(2) 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 mu g/mg), elastin (186.9 +/- 16.7 mu g/mg), and glycosaminoglycan (9.7 +/- 0.8 mu g/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.