An injectable tissue-engineered embolus prevents luminal recanalization after vascular sclerotherapy C. Jason Smithers a,e , Adam M. Vogel a,e , Harry P.W. Kozakewich b,e , Deborah A. Freedman c , Patricia E. Burrows d,e , Dario O. Fauza a , Steven J. Fishman a,e, * a Department of Surgery, Children’s Hospital Boston and Harvard Medical School, Boston, MA 02115, USA b Department of Pathology, Children’s Hospital Boston and Harvard Medical School, Boston, MA 02115, USA c Vascular Biology Program, Department of Surgical Research, Children’s Hospital Boston and Harvard Medical School, Boston, MA 02115, USA d Department of Radiology, Children’s Hospital Boston and Harvard Medical School, Boston, MA 02115, USA e Vascular Anomalies Center, Children’s Hospital Boston and Harvard Medical School, Boston, MA 02115, USA Abstract Background/Purpose: Sclerotherapy for vascular malformations is often limited by luminal recanalization. This study examined whether an injectable tissue-engineered construct could prevent this complication in a rabbit model of venous sclerotherapy. Methods: Ethanol sclerotherapy of a temporarily occluded jugular vein segment was performed in 46 rabbits, which were then divided into 3 groups. Group I (n = 16) had no further manipulations. In groups II (n = 15) and III (n = 15), 0.5 mL collagen hydrogel was injected intraluminally, respectively, devoid of and seeded with autologous fibroblasts. At 1, 4, and 20 to 24 weeks postoperatively, vein segments were examined for patency and resected for histological evaluation. Statistical analysis was by Fisher’s Exact test. Results: All vein segments were occluded at 1 and 4 weeks in all groups, despite histological evidence of progressive endothelial ingrowth. However, at 20 to 24 weeks, angiography demonstrated restoration of vessel patency in groups I (3/6) and II (3/5), but not in group III (0/6; P = .043), in which histology confirmed an obliterated lumen for all vessels. Conclusion: An injectable, fibroblast-based, engineered construct prevents midterm to long-term recanalization in a leporine model of vascular sclerotherapy. This novel therapeutic approach may prevent recurrence of vascular malformations after sclerotherapy, thus reducing the need for repeated procedures and morbid operative resections. D 2005 Elsevier Inc. All rights reserved. Treatment of congenital venous malformations (VMs) by intravascular sclerotherapy is fraught with recurrence. Sclerotherapy is designed to shrink lesions by causing direct endothelial damage and thrombosis. Therapeutic failure relates to recanalization as a consequence of thrombus organization, in a process that is analogous to 0022-3468/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2005.03.005 Presented at the 56th Annual Meeting of the Section on Surgery of the American Academy of Pediatrics, San Francisco, California, October 8-10, 2004. T Corresponding author. Department of Surgery, Children’s Hospital Boston, Boston, MA 02115, USA. Tel.: +1 617 355 3040; fax: +1 617 730 0477. E-mail address: steven.fishman@childrens.harvard.edu (S.J. Fishman). Index words: Congenital vascular malformation; Venous malformation; Sclerotherapy; Tissue engineering; Fibroblasts; Thrombus organization; Endothelial recanalization; Rabbit; External jugular vein Journal of Pediatric Surgery (2005) 40, 920 – 925 www.elsevier.com/locate/jpedsurg