Postoperative Anti-Tgf-β2 Antibody Therapy Improves Intracranial Volume and Craniofacial Growth in Craniosynostotic Rabbits

Abstract

Postoperative resynostosis and secondary craniofacial growth abnormalities are common sequelae after craniofacial surgery. It has been suggested that an overexpression of transforming growth factor-beta2 (Tgf-beta2) may be related to craniosynostosis and contribute to postoperative resynostosis. Interference with Tgf-beta2 function using neutralizing antibodies may inhibit resynostosis and improve postoperative craniofacial growth; the present study was designed to test this hypothesis. Twenty-nine New Zealand white rabbits with bilateral coronal suture synostosis were used: 1) suturectomy controls (n=9); 2) suturectomy with nonspecific, control IgG antibody (n=9); and 3) suturectomy with anti-Tgf-beta2 antibody (n=11). At 10 days of age, a 3 mm x 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slow resorbing collagen gel mixed with either IgG (100 microg/suture) or anti-Tgf-beta2 (100 microg/suture). Three-dimensional computed tomography scan reconstructions of the skulls and cephalographs were obtained at 10, 25, 42, and 84 days of age. Computed tomography scan data revealed patent suturectomy sites and significantly (P<0.05) greater intracranial volumes by 84 days of age in rabbits treated with anti-Tgf-beta2 compared with controls. Cephalometric analysis revealed significant (P<0.05) differences in craniofacial, cranial vault, and cranial base growth by 84 days of age in rabbits treated with anti-Tgf-beta2 compared with controls. These data support the initial hypothesis that interference with Tgf-beta2 function inhibited postoperative resynostosis and improved cranial vault growth in this rabbit model. Thus, this biologically based therapy may be a potential surgical adjunct in the treatment of infants with craniosynostosis.