Anti-TGF-β2 antibody therapy inhibits postoperative resynostosis in craniosynostotic rabbits

BACKGROUND: Postoperative resynostosis is a common clinical finding. It has been suggested that an overexpression of transforming growth factor (TGF)-β2 may be related to craniosynostosis and may contribute to postoperative resynostosis. Interference with TGF-β2 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-TGF-β2 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 μg per suture) or anti-TGF-β2 (100 μg 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-TGF-β2 showed significantly (p < 0.05) greater areas through 84 days of age compared with controls. Histomorphometry also showed that suturectomy sites treated with anti-TGF-β2 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 TGF-β2 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.