Suturectomy Site Healing Following Postoperative TGF-b3 Therapy in Craniosynostotic Rabbits

Objectives: Postoperative resynostosis is a common clinical correlate following surgical release of the synostosed suture. It has been suggested that an under-expression of Tgf-b3 can cause craniosynostosis and postoperative resynostosis. Addition of exogenous Tgf-b3 postoperatively may prevent subsequent resynostosis and thus facilitate craniofacial growth. The present study was designed to test this hypothesis in a craniosynostotic rabbit model.

Methods: Twenty-nine New Zealand white rabbits with coronal suture synostosis were divided into 3 groups: 1) Suturectomy controls (n=13); 2) Suturectomy treated with BSA (Bovine Serum Albumin, 1000ng/suture) (protein control group) (n=8). 3) Suturectomy treated with Tgf-b3 Protein (1000ng/suture) (n=8). At 10 days of age, a 3mm x 15mm coronal suturectomy was performed. The sites in Groups 2 and 3 were immediately filled with 0.1cc of a slow resorbing collagen gel mixed with either BSA or Tgf-b3. The suturectomy sites were harvested for histomorphometric analysis at 84 days of age. New bone area in the suturectomy site was quantified using Northern Eclipse Imaging Software and mean new bone areas were compared among groups using a 3x1, oneway ANOVA.

Results: At 84 days of age, extensive reossification of the coronal suturectomy site was seen in both control groups. In contrast, rabbits treated with Tgf-b3 protein therapy showed reossification mainly at the suturectomy margins with fibrous nonunions in the suturectomy site. Histomorphometry of the defects revealed that rabbits treated with Tgf-b3 had signifcantly less new bone area (by approximately 195%) compared to controls (F=6.55;p<0.001). No significant differences (p>0.05) were noted between control groups.

Conclusions: These data support the hypothesis that Tgf-b3 therapy inhibits postoperative resynostosis (possibly by altering osteoblast proliferation, extracellular matrix formation, osteoid formation, or apoptosis) in this model. These findings also suggest that this molecular-based therapy may have potential clinical in the surgical management of craniosynostosis.

NIDCR (DE13078)