EXPERIMENTAL Anti-TGF- 2 Antibody Therapy Inhibits Postoperative Resynostosis in Craniosynostotic Rabbits

Pittsburgh, Pa.; Chapel Hill, N.C.; Columbus, Ohio; Los Angeles, Calif.; Ankara, Turkey; and Dallas, Texas Background: Postoperative resynostosis is a common clinical finding. It has been suggested that an overexpression of transforming growth factor (TGF)2 may be related to craniosynostosis and may contribute to postoperative resynostosis. Interference with TGF2 function with the use of neutralizing antibodies may inhibit resynostosis. The present study was designed to test this hypothesis. Methods: New Zealand White rabbits with bilateral coronal suture synostosis were used as suturectomy controls (group 1, n 9) or given suturectomy with nonspecific, control immunoglobulin G antibody (group 2, n 9) or suturectomy with anti-TGF2 antibody (group 3, n 11). At 10 days of age, a 3 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slowly resorbing collagen gel mixed with either immunoglobulin G (100 g per suture) or anti-TGF2 (100 g per suture). Three-dimensional computed tomography scan reconstructions of the defects were obtained at 10, 25, 42, and 84 days of age, and the sutures were harvested for histomorphometric analysis. Results: Computed tomography scan data revealed that the suturectomy sites treated with anti-TGF2 showed significantly (p 0.05) greater areas through 84 days of age compared with controls. Histomorphometry also showed that suturectomy sites treated with anti-TGF2 had patent suturectomy sites and more fibrous tissue in the defects compared with sites in control rabbits and had significantly (p 0.001) less new bone area (by approximately 215 percent) in the suturectomy site. Conclusions: These data support the initial hypothesis that interference with TGF2 function inhibited postoperative resynostosis in this rabbit model. They also suggest that this biologically based therapy may be a potential surgical adjunct to retard postoperative resynostosis in infants with craniosynostosis. (Plast. Reconstr. Surg. 119: 1200, 2007.)