Mooney Mark P, Losken H Wolfgang, Moursi Amr M, Bradley James, Azari Kodi, Acarturk T Oguz, Cooper Gregory M, Thompson Brian, Opperman Lynne A, Siegel Michael I
Pittsburgh, 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.
Plast Reconstr Surg. 2007 Apr 1;119(4):1200-1212. doi: 10.1097/01.prs.0000258403.49584.ec.
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.
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.
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.
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.
术后颅骨缝再融合是一种常见的临床现象。有研究表明，转化生长因子（TGF）-β2的过度表达可能与颅骨缝早闭有关，并可能导致术后颅骨缝再融合。使用中和抗体干扰TGF-β2的功能可能会抑制再融合。本研究旨在验证这一假设。
将双侧冠状缝早闭的新西兰白兔作为颅骨缝切除术对照组（第1组，n = 9），或给予颅骨缝切除术并注射非特异性对照免疫球蛋白G抗体（第2组，n = 9），或给予颅骨缝切除术并注射抗TGF-β2抗体（第3组，n = 11）。在10日龄时，进行3×15毫米的冠状缝切除术。第2组和第3组的手术部位立即填充0.1毫升缓慢吸收的胶原凝胶，其中分别混合有免疫球蛋白G（每条缝100微克）或抗TGF-β2（每条缝100微克）。在10、25、42和84日龄时获取缺损部位的三维计算机断层扫描重建图像，并采集颅骨缝进行组织形态计量学分析。
计算机断层扫描数据显示，与对照组相比，至84日龄时，接受抗TGF-β2治疗的颅骨缝切除术部位的面积显著更大（p < 0.05）。组织形态计量学分析还显示，与对照兔的手术部位相比，接受抗TGF-β2治疗的颅骨缝切除术部位的手术部位仍保持开放，缺损部位有更多纤维组织，且颅骨缝切除术部位的新骨面积显著减少（约减少215%，p < 0.001）。
这些数据支持最初的假设，即干扰TGF-β2功能可抑制该兔模型中的术后颅骨缝再融合。它们还表明，这种基于生物学的治疗方法可能是一种潜在的手术辅助手段，可延缓患有颅骨缝早闭的婴儿的术后颅骨缝再融合。
