236 Dean et al.: Translation of vascular tissue engineering to pediatric CHD f u Tu r E Dir ECTio n S As TEVGs reach clinical fruition, fur- ther investigation will be necessary to ensure the long-term success and efficacy of this technology. The pilot clinical trial conducted in Japan is promising in finding growth po- tential, but also challenging in that it points to areas in need of improvement, namely prevention of long-term graft stenosis. The future of TEVG development will lie in both clinical and laboratory investigation. An FDA-approved clinical trial is currently under way at the Yale School of Medicine to establish a benchmark for evaluating the safety of tissue-engineered vascular grafts for use in the surgical management of pa- tients born with single ventricle anomalies. This clinical trial and additional investiga- tions on the mechanisms of neotissue for- mation and stenosis will be instrumental in improving outcomes in patients with CHD [53,54]. At the same time, the recent devel- opment of a mouse model and subsequent laboratory work has pointed toward the me- diators of neotissue formation and mecha- nisms of controlling graft stenosis. Second generation TEVGs will benefit from the un- folding understanding of how these cy- tokines dictate neotissue formation. Ultimately, cytokine-eluting TEVGs may re- place current technology and eliminate the need for seeding altogether. Equally impor- tant, current investigations into the develop- ment and structuring of extracellular matrix will improve upon scaffold design and open the door for novel methods of preventing stenosis. r Ef Er En CES 1. Veith FJ, Gupta SK, Ascer E, White-Flores S, Samson RH, Scher LA, et al. Six-year prospective multicenter randomized compar- ison of autologous saphenous vein and ex- panded polytetrafluoroethylene grafts in infrainguinal arterial reconstructions. J Vasc Surg. 1986;3(1):104-14. 2. Sapsford RN, Oakley GD, Talbot S. Early and late patency of expanded polytetrafluoroethyl- ene vascular grafts in aorta-coronary bypass. J Thorac Cardiovasc Surg. 1981;81(6):860-4. 3. Klinkert P, Post PN, Breslau PJ, Van bockel JH. Saphenous vein versus PTFE for above- knee femoropopliteal bypass. A review of the literature. Eur J Vasc Endovasc Surg. 2004;27(4):357-62. 4. Langer R, Vacanti JP. Tissue engineering. Science. 1993;260(5110):920-6. 5. Shinoka T, Shum-tim D, Ma PX, Tanel RE, Isogai N, Langer R, et al. Creation of viable pulmonary artery autografts through tissue engineering. J Thorac Cardiovasc Surg. 1998;115(3):536-45. 6. Matsumura G, Hibino N, Ikada Y, Kurosawa H, Shin’oka T. Successful application of tis- sue engineered vascular autografts: clinical ex- perience. Biomaterials. 2003;24(13):2303-8. 7. Matsumura G, Ishihara Y, Miyagawa-tomita S, Ikada Y, Matsuda S, Kurosawa H, et al. Evaluation of tissue-engineered vascular au- tografts. Tissue Eng. 2006;12(11):3075-83. 8. Watanabe M, Shin’oka T, Tohyama S, Hib- ino N, Konuma T, Matsumura G, et al. Tis- sue-engineered vascular autograft: inferior vena cava replacement in a dog model. Tissue Eng. 2001;7(4):429-39. 9. American Heart Association. 2008 Annual Report. 10. Van der linde D, Konings EE, Slager MA, Wit- senburg M, Helbing WA, Takkenberg JJ, et al. Birth prevalence of congenital heart disease worldwide: a systematic review and meta- analysis. J Am Coll Cardiol. 2011;58(21):2241- 7. 11. Samánek M. Children with congenital heart disease: probability of natural survival. Pedi- atr Cardiol. 1992;13(3):152-8. 12. Giannico S, Hammad F, Amodeo A, Michielon G, Drago F, Turchetta A, et al. Clinical outcome of 193 extracardiac Fontan patients: the first 15 years. J Am Coll Cardiol. 2006;47(10):2065-73. 13. Petrossian E, Reddy VM, Collins KK, Cul- bertson CB, MacDonald MJ, Lamberti JJ, et al. The extracardiac conduit Fontan operation using minimal approach extracorporeal cir- culation: early and midterm outcomes. J Tho- rac Cardiovasc Surg. 2006;132(5):1054-63. 14. Hoffman JI, Kaplan S. The incidence of con- genital heart disease. J Am Coll Cardiol. 2002;39(12):1890-900. 15. Conte MS. The ideal small arterial substitute: a search for the Holy Grail? FASEB J. 1998;12(1):43-5. 16. Kakisis JD, Liapis CD, Breuer C, Sumpio BE. Artificial blood vessel: the Holy Grail of peripheral vascular surgery. J Vasc Surg. 2005;41(2):349-54. 17. Dearani JA, Danielson GK, Puga FJ, Schaff HV, Warnes CW, Driscoll DJ, et al. Late fol- low-up of 1095 patients undergoing operation for complex congenital heart disease utiliz- ing pulmonary ventricle to pulmonary artery conduits. Ann Thorac Surg. 2003;75(2):399- 410. 18. Alexi-meskishvili V, Ovroutski S, Ewert P, Dähnert I, Berger F, Lange PE, et al. Optimal conduit size for extracardiac Fontan operation. Eur J Cardiothorac Surg. 2000;18(6):690-5.