Dean et al.: Translation of vascular tissue engineering to pediatric CHD 231 delayed until the patient grows to the point where an adult-sized conduit can be used. Performing the surgery prior to this point risks the need for reoperation when the child outgrows the original conduit, a precarious proposition associated with increased risk of complications and early post-operative mor- tality rates of up to 5 percent [17]. Implant- ing an oversized graft at an earlier age avoids the complications of delayed treatment and mitigates the possibility of the patient out- growing the conduit, but this approach car- ries an increased risk of complications [18]. Notably, a small subset of patients born with CHD is amenable to primary repair without the use of synthetic grafts. These patients are not susceptible to the inherent risks of syn- thetic conduits, and their outcomes are markedly improved [19]. Similarly, the use of autografts — vascular conduits created from an individual’s own tissue — results in long-term patency rates that exceed 80 per- cent [20]. This superior level of effectiveness compared to synthetic grafts is mitigated by limited availability, prompting the search for a man-made graft that retains growth poten- tial [17,19,20-22]. Pil o T Cl in iCAl Tr iAl Promising results in animal models led to the initiation of a clinical pilot study in Japan in 2001. The study was designed to evaluate the safety and efficacy of TEVGs for use in congenital heart surgery, specifi- cally the EC TCPC operation in patients born with single ventricle cardiac anomalies [23- 25]. TEVGs were created by seeding a biodegradable scaffold with autologous bone marrow mononuclear cells (BM-MNCs) fol- lowed by implantation in a cohort of 25 pa- tients with congenital cardiac anomalies. The initial follow-up period was set at 7 years and included imaging studies such as contrast an- giography and computed tomography (CT) scanning in order to monitor the progression of the implanted conduits. Each patient re- ceived between 3 and 6 months of an- tiplatelet and anticoagulation therapy immediately following the procedure [6,25]. Early results from the study were encourag- ing. The implanted conduits were universally functional with no evidence of failure due to thrombosis, stenosis, or obstruction of the TEVGs. Additionally, angiography and CT imaging revealed no evidence of aneurysm formation or calcification. All grafts were patent, and serial scans confirmed that the di- ameter of the neovessel increased with time. None of the patients required graft replace- ment, and there was no mortality relating to the implanted conduits. Antiplatelet and an- ticoagulant medications were successfully discontinued by all patients within 6 months of the procedure, a marked contrast to the lifetime requirement for anticoagulation when synthetic grafts are used. Additionally, 40 percent of patients did not require any daily medication regimen. Late analysis of the cohort again illustrated the absence of graft-related mortality. However, 16 percent of patients were revealed to have TEVG stenosis at long-term follow-up. This finding was frequently asymptomatic, and all pa- tients were successfully treated with angio- plasty or angioplasty and stenting [25]. Data from the initial clinical trial sug- gest that TEVGs are indeed safe and effec- tive for use in congenital heart surgery, but the mechanisms of neovessel formation and the processes leading to graft failure are in- completely understood. Both phenomena must be investigated thoroughly if an im- proved tissue-engineered vascular graft is to become a reality. Additionally, the results of the trial indicate that stenosis is the primary means of graft-related failure. It is therefore critical to gain a better understanding of the mechanisms underlying TEVG stenosis in order to identify the potential targets and strategies that could prevent this complica- tion. Ultimately, this would allow for the ra- tional design of a second generation TEVG with improved safety and efficacy. TEVg Co n STr u CTio n Scaffold Materials Ideal scaffold material should possess three characteristics, namely: (1) biodegrad- ability, (2) non-immunogenicity, and (3)