YALE JOURNAL OF BIOLOGY AND MEDICINE 85 (2012), pp.229-238. Copyright © 2012. FOCUS: BIOMEDICAL ENGINEERING Current Advances in the Translation of Vascular Tissue Engineering to the Treatment of Pediatric Congenital Heart Disease Ethan W. Dean, Brooks Udelsman, and Christopher K. Breuer* Interdepartmental Program in Vascular Biology and Therapeutics, Yale School of Medicine, New Haven, Connecticut Tissue-engineered vascular grafts (TEVGs†) hold great promise for the improvement of out- comes in pediatric patients with congenital cardiac anomalies. Currently used synthetic grafts have several limitations, including thrombogenicity, increased risk of infection, and lack of growth potential. The first pilot clinical trial of TEVGs demonstrated the feasibility of this new technology and revealed an excellent safety profile. However, long-term follow-up from this trial revealed the primary graft-related complication to be stenosis, affecting 16 percent of grafts within 7 years post-implantation. In order to determine the mechanism be- hind TEVG stenosis and ultimately to create improved second generation TEVGs, our group has returned to the bench to study vascular neotissue formation in a variety of large and small animal models. The purpose of this report is to review the recent advances in the un- derstanding of neotissue formation and vascular tissue engineering. *To whom all correspondence should be addressed: Christopher K. Breuer, Interdepart- mental Program in Vascular Biology and Therapeutics, Yale School of Medicine, 10 Amis- tad Street #301, New Haven, CT 06520; Tele: 203-785-270; Fax: 203-785-3820; Email: christopher.breuer@yale.edu. †Abbreviations: TEVGs, tissue-engineered vascular grafts; CHD, congenital heart dis- ease; EC TCPC, extracardiac total cavopulmonary connection; IVC, inferior vena cava; BM-MNCs, bone marrow mononuclear cells; CT, computed tomograpic; PGA, polyglycolic acid; PLA, polylactic acid; PCL, polycaprolactone; GAG, glycosaminoglycan; MRI, mag- netic resonance imaging; USPIO, superparamagnetic iron oxide; ECM, extracellular ma- trix; MMP, matrix metalloproteinase; IL-1B, interleukin-1 beta; MCP-1, monocyte chemoattractant protein-1. Keywords: tissue-engineered vascular grafts, congenital heart disease, translational re- search, tissue engineering, vascular remodeling, bone marrow-derived mononuclear cells, extracellular matrix Ethan Dean and Brooks Udelsman contributed equally to this work and are co-first au- thors. 229