230 Dean et al.: Translation of vascular tissue engineering to pediatric CHD in Tr o Du CTio n Native vessels remain the gold standard in revascularization procedures; however, such autologous grafts are not always ob- tainable secondary to limited availability or concurrent disease. While synthetic grafts such as expanded polytetrafluoroethylene (Gortex®, W.L. Gore & Associates, Newark, DE) and polyethylene terephthalate (Dacron®, Dupont, Wilmington, DE) have been used in the past, they have an increased risk of thrombosis and intimal hyperplasia [1-3]. Moreover, the lack of growth potential associated with synthetic grafts is particu- larly limiting in the pediatric population, where multiple operations and graft oversiz- ing become necessary to ensure adequate blood flow. Tissue-engineered vascular grafts (TEVGs) represent a potentially limit- less supply of autologous grafts with the added benefit of growth potential. In its most basic form, vascular tissue engineering in- volves seeding autologous cells onto a biodegradable tubular scaffold which serves as a site of cell attachment and neotissue for- mation. Once the graft is implanted, neotis- sue begins to form while the biodegradable scaffold slowly dissolves. The end result is a neovascular conduit composed entirely of the autologous tissue [4]. Multiple large an- imal studies have demonstrated the feasibil- ity of tissue engineering in the construction of vascular grafts [5-8]. Tissue engineering has been described as “an interdisciplinary field that applies the principles of engineering and life sciences to- ward the development of biological substi- tutes that restore, maintain, or improve tissue function or a whole organ” [4]. As the field moves from the laboratory to the clinic, all aspects of TEVG construction (scaffold ma- terials, cells for seeding grafts, and seeding techniques) will need to be re-evaluated to ensure adequate safety and efficacy. Just as importantly, clinical experience should dic- tate laboratory investigation of the process of neotissue formation in a concerted effort to move beyond first generation TEVG and onto second generation TEVG with im- proved hemodynamic functionality and in vivo performance. Cl in iCAl Sig n if iCAn CE Even with the implementation of innova- tive medical and surgical treatment modali- ties, congenital heart disease (CHD) remains the most common form of death in the new- born period [9]. Estimates of the current birthrate indicate that approximately 1.35 mil- lion infants worldwide are born with CHD each year, representing a major global health burden [10]. The development of a man-made vascular conduit for use in pediatric patients with cardiac anomalies holds particular prom- ise for the advancement of the field. Single ventricle anomalies are comprised of a large and diverse group of structural ir- regularities that result in a life-threatening form of CHD characterized by chronic hy- poxia and cyanosis. This classification in- cludes diseases such as hypoplastic left heart syndrome, double inlet left ventricle, and pul- monary atresia. The unifying feature of each condition is the mixing of the oxygenated sys- temic circulation with the deoxygenated pul- monary circulation, leading to volume overload and heart failure with a mortality of up to 70 percent during the first year of life if left untreated [11]. Surgical reconstruction is the preferred approach in the management of single ventricle physiology. One of the more commonly performed procedures is a series of staged operations termed the modified Fontan operation with extracardiac total cavopulmonary connection (EC TCPC), which allows the single ventricle to pump oxygenated blood through the systemic circu- lation. The EC TCPC procedure is designed to directly connect the inferior vena cava (IVC) to the pulmonary artery and is the most commonly performed congenital heart opera- tion in which a large caliber vascular graft is implanted in a high-flow, low-pressure circu- lation. While the operation has resulted in sub- stantial improvements in long-term survival, it is ultimately considered a palliative procedure with significant morbidity and mortality [12,13], and it is widely accepted that the ideal conduit remains to be developed [14-16]. The most significant disadvantage of synthetic conduits is their lack of growth po- tential. Consequently, surgical repair may be