Establishment of new treatment for cleft lip and palate patients-basic research for the application of in vitro hybrid artificial bone-

目前，自体髂骨松质骨移植已成为修复牙槽突裂最常用的方法。近年来，我们将术前正侧位X线片分析的裂/鼻腔比和SBG术后3个月CT分析的残留皮质骨比确定为影响自体髂骨松质骨移植临床效果的参数。然而，自体髂骨松质骨移植治疗唇腭裂患者的一些临床结果与我们先前的研究不一致。因此，研究新的供体材料，如人工骨，有可能成为一种修复牙槽裂的新方法，具有重要意义。将兔骨髓基质细胞三维培养于经四种细胞因子(FGF2、BMP-2、4、7)处理的胶原海绵中。经成纤维细胞生长因子-2处理的胶原海绵较骨形态发生蛋白-2、骨形态发生蛋白-2、骨形态发生蛋白-2、骨形成蛋白-4、骨形态发生蛋白-7的胶原海绵有更多的基质矿化。此外，为了证实成纤维细胞生长因子-2在体内的作用，将兔骨髓基质细胞注入经成纤维细胞生长因子-2处理或不经成纤维细胞生长因子-2处理的胶原海绵中，并将这些复合体移植到人工制造的兔颅骨圆形缺损(直径7.0 mm)中。对移植部位的纵向评估显示，经FGF2处理的胶原海绵有明显的骨化。因此，这些结果表明，利用FGF2的新的治疗方法可能在唇腭裂患者的治疗中是有用的。

Currently, autograft of iliac crest cancellous bone has become the most commonly utilized method for restoration of the alveolar cleft. In recent years, we have identified the cleft / nasal cavity ratio analyzed by presurgical frontal cephalograms and the residual cortical bone ratio, which was analyzed by CT taken at 3 months after SBG, as parameters affecting the clinical outcome of the autograft of iliac crest cancellous bone. However, several clinical outcomes of autograft of iliac crest cancellous bone for cleft lip and palate patients, were not corresponded to our previously studies. Therefore, it is of imperative importance to investigate the new donor materials, such as the artificial bone which might be a new method for restoration of the alveolar cleft. The stromal cells of rabbit bone marrow were three-dimensionally cultured in collagen sponge treated with four cytokines (FGF2, BMP-2, 4, 7) in vitro. The collagen sponge treated with FGF-2 showed increased matrix mineralization as compared with BMP-2, 4, 7. Furthermore, in order to confirm the effect of FGF-2 in vivo, stromal cells of rabbit bone marrow were injected into collagen sponge treated with or without FGF-2 and these complexes were grafted in round defects (diameter; 7.0 mm) artificially created in rabbit calvarial bone. Longitudinal evaluation of grafted site showed significant ossification of collagen sponge treated with FGF2. Therefore, these results suggested that new treatment method utilized FGF2 might be useful in the treatment of cleft lip and palate patients.