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Anti-TGF-beta2 antibody therapy inhibits postoperative resynostosis in craniosynostotic rabbits
Mark P Mooney1, H Wolfgang Losken, Amr M Moursi
1Pittsburgh, Pa.; Chapel Hill, N.C.; Columbus, Ohio; Los Angeles, Calif.; Ankara, Turkey; and Dallas, Texas From the Departments of Oral Medicine and Pathology, Anthropology, Plastic and Reconstructive Surgery, Orthodontics, and Orthopedic Surgery, the Cleft Palate-Craniofacial Center, and the School of Dental Medicine, University of Pittsburgh; the Department of Plastic Surgery, School of Medicine, University of North Carolina; Department of Pediatric Dentistry, College of Dentistry, Ohio State University; Division of Plastic and Reconstructive Surgery, University of California, Los Angeles; Division of Plastic Surgery, University of Pittsburgh Medical Center; Department of Plastic and Reconstructive Surgery, Gülhane Military Medical Academy; and Department of Biomedical Sciences, Baylor College of Dentistry, Texas A & M University System Health Science Center.
Background:
Postoperative resynostosis is a common clinical finding. It has been suggested that an overexpression of transforming growth factor (TGF)-beta2 may be related to craniosynostosis and may contribute to postoperative resynostosis. Interference with TGF-beta2 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-beta2 antibody (group 3, n = 11). At 10 days of age, a 3 x 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 mug per suture) or anti-TGF-beta2 (100 mug 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-beta2 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-beta2 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-beta2 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.
Insights
Interfering with transforming growth factor (TGF)-beta2 function using antibodies significantly inhibited resynostosis in a rabbit model. This suggests a potential new therapy to prevent suture fusion after surgery for craniosynostosis.
Area of Science:
- Craniofacial surgery
- Developmental biology
- Tissue engineering
Background:
- Postoperative resynostosis is a common complication after craniosynostosis surgery.
- Overexpression of transforming growth factor (TGF)-beta2 is implicated in craniosynostosis and resynostosis.
- Neutralizing TGF-beta2 may prevent resynostosis.
Purpose of the Study:
- To test the hypothesis that TGF-beta2 neutralization inhibits postoperative resynostosis.
- To evaluate the efficacy of anti-TGF-beta2 antibodies in preventing suture fusion.
Main Methods:
- New Zealand White rabbits underwent coronal suturectomy.
- Suturectomy sites were treated with control IgG or anti-TGF-beta2 antibodies.
- Three-dimensional CT scans and histomorphometry were used to assess suture patency and bone formation.
Main Results:
- Anti-TGF-beta2 treatment significantly increased suturectomy site area up to 84 days post-surgery.
- Histomorphometry revealed patent suturectomy sites with more fibrous tissue in the anti-TGF-beta2 group.
- New bone formation was significantly reduced by approximately 215% in the anti-TGF-beta2 treated sites.
Conclusions:
- Interference with TGF-beta2 function effectively inhibited postoperative resynostosis in this rabbit model.
- Anti-TGF-beta2 therapy shows promise as an adjunct to reduce resynostosis after craniosynostosis surgery in infants.
