Comparison of Craniofacial Phenotype in Craniosynostotic Rabbits Treated with Anti–Tgf-β2 at Suturectomy Site

Abstract

Overexpression of transforming growth factor-beta 2 has been associated with craniosynostosis and resynostosis following surgery. We examined the effects of localized transforming growth factor-beta 2 inhibition on craniofacial phenotype in rabbits with craniosynostosis. Twenty-five New Zealand white rabbits with bilateral coronal craniosynostosis were divided into three treatment groups: (1) suturectomy control (n=8); (2) suturectomy with nonspecific, control immunoglobulin G antibody (n=6); and (3) suturectomy with anti-transforming growth factor-beta 2 antibody (n=11). At 10 days of age, a coronal suturectomy was performed on all rabbits. The sites in groups 2 and 3 were immediately filled with a slow-resorbing collagen gel mixed with either immunoglobulin G or anti-transforming growth factor-beta 2 antibody. Computed tomography scans of each rabbit were acquired at ages 10, 25, and 84 days. Craniofacial landmarks were collected from three-dimensional computed tomography reconstructions, and growth and form were compared among the three groups. Rabbits treated with anti-transforming growth factor-beta 2 antibody differed in form at 84 days of age compared with suturectomy control rabbits, specifically in the snout and posterior neurocranium. Growth in some areas of the skull was greater in rabbits from the anti-transforming growth factor-beta 2 group than in suturectomy control rabbits, but not significantly greater than in IgG control rabbits. We find support for the hypothesis that transforming growth factor-beta 2 inhibition alters adult form, but these changes do not appear to be localized to the suturectomy region. Slight differences in form and growth between the two control groups suggest that the presence of the collagen vehicle itself may affect skull growth.