Tissue-engineered arterial grafts: long-term results after implantation in a small animal model Tamar L. Mirensky a,b, ⁎ , Gregory N. Nelson a , Matthew P. Brennan a,b , Jason D. Roh a , Narutoshi Hibino a , Tai Yi a , Toshiharu Shinoka a,b , Christopher K. Breuer a,b a Yale University School of Medicine, New Haven, CT 06510, USA b Yale-New Haven Hospital, New Haven, CT 06510, USA Received 9 February 2009; accepted 17 February 2009 Key words: Tissue engineering; Vascular graft; Congenital heart defect; Cardiothoracic surgery; Vascular conduit Abstract Background: Use of prosthetic vascular grafts in pediatric vascular surgical applications is limited because of risk of infection, poor durability, potential for thromboembolic complications, and lack of growth potential. Construction of an autologous neovessel using tissue engineering technology offers the potential to create an improved vascular conduit for use in pediatric vascular applications. Methods: Tissue-engineered vascular grafts were assembled from biodegradable tubular scaffolds fabricated from poly-L-lactic acid mesh coated with ɛ-caprolactone and L-lactide copolymer. Thirteen scaffolds were seeded with human aortic endothelial and smooth muscle cells and implanted as infrarenal aortic interposition grafts in SCID/bg mice. Grafts were analyzed at time-points ranging from 4 days to 1 year after implantation. Results: All grafts remained patent without evidence of thromboembolic complications, graft stenosis, or graft rupture as documented by serial ultrasound and computed tomographic angiogram, and confirmed histologically. All grafts demonstrated extensive remodeling leading to the development of well- circumscribed neovessels with an endothelial inner lining, neomedia containing smooth muscle cells and elastin, and a collagen-rich extracellular matrix. Conclusions: The development of second-generation tissue-engineered vascular grafts shows marked improvement over previous grafts and confirms feasibility of using tissue engineering technology to create an improved arterial conduit for use in pediatric vascular surgical applications. © 2009 Elsevier Inc. All rights reserved. Currently used prosthetic vascular grafts lack growth potential and are associated with significant morbidity and mortality that limit their use in pediatric patients. In fact, lack of an adequate vascular conduit for use in pediatric surgery has stifled its development. The development of a tissue- engineered vascular graft (TEVG) created by seeding autologous cells onto a biodegradable tubular scaffold that is replaced by host tissue holds great promise for making the first man-made vascular graft with growth potential that could improve our ability to treat children with vascular disease secondary to congenital anomalies, malignancy, or trauma. The development of TEVGs for use as vascular conduits in high-flow, low-pressure circulatory systems in animal models has previously been described [1]. In a pilot clinical study, we demonstrated the feasibility, safety, and efficacy of this TEVG including confirmation of its growth potential. [2] Unfortunately, we have found that use of this same TEVG as ⁎ Corresponding author. Yale University School of Medicine, PO Box 208062, New Haven, CT 06510, USA. Tel.: +1 203 927 4247; fax: +1 203 785 3820. E-mail address: tamar.mirensky@yale.edu (T.L. Mirensky). www.elsevier.com/locate/jpedsurg 0022-3468/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2009.02.035 Journal of Pediatric Surgery (2009) 44, 1127–1133