BIOLOGICAL RECONSTRUCTION OF PERIODONTAL TISSUE USING CYTOKINE AND FIBROUS COLLAGEN MEMBRANE

使用细胞因子和纤维胶原膜对牙周组织进行生物重建

• 批准号: 04557078
• 负责人: KUBOKI Yoshinori
• 金额: $ 6.78万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04557078/
• 关键词: Bone morphogenetic protein; BMP; Carriers; Fibrous collagen membrane; Periodontal tissues; 骨形成タンパク質; コラーゲン複合線維膜; 人工歯根膜; 不溶性骨基質; ハイドロキシアパタイト; 生物学的再建

Bone morphogenetic protein (BMP) is a growth and differntiation factor that stimulates immature mesemchymal cells to create a process similar to endochonral ossification when it is implanted with insoluble bone matrix (IBM) as a carrier. Roles of this carrier is still unkown and carriers other than IBM have not been investigated. We have deviced a fibrous collagen membrane (FCM), in order to combine it with BMP and to implant subcutanuously for ectopic bone formation. In this research project, first we succeeded in generating the ectopic formation of bone and cartilage independently in FCM/BMP implant. Thus, in order to clarify the mechanism behind the phenomenon of carrier-dependent pehonotype expression by BMP, we prepared and deviced at least six different types of carriers, combined them with the chromatographically-purified BMP, and compared the phenotype expression upon implantation. New BMP-carriers other than IBM and FCM included the porous particles of hydroxyapatite (PPHAP), solid particles of hydroxyapatite (SPHAP), honeycomb shaped hydroxyapatite and fibrous glass membrane (fine and coarse FGM). Most striking finding was that the coarse FGM/BMP induced only cartilage inside the membrane, while the PPHAP/BMP induced only bone within the pore of the PPHAP.It was found that SPHAP/BMP and the fine FGM/BMP did not induce bone nor cartilage at all. Honeycomb HAP, which is consistedof cylindrical blocks (1.4 x 0.7 mm) with seven tubular holes of 0.12 mmdiameter, induced very unique shape of bone, generating the columnar bone in the center of each tubular hole, not on the inner surface of tubular holes. It was interpreted that pores in the PPHAP provided the space for vasculature which was feasible for direct bone formation, while FGM rejected vasculature but permitted mesenchymal cells entering into the membrane, which provided a feasible circumstances for cartilage formation. Above results indicate that geometrical factors are important in the use of FCM and

骨形态发生蛋白（Bone morphogenetic protein， BMP）是一种生长和分化因子，以不溶性骨基质（insoluble Bone matrix， IBM）为载体植入后，刺激未成熟间充质细胞产生类似软骨内骨化的过程。该运营商的角色仍然是未知的，除了IBM之外的运营商也没有被调查。我们设计了一种纤维胶原膜（FCM），目的是将其与BMP结合，用于异位骨形成的皮下植入。在本研究项目中，我们首先成功地在FCM/BMP种植体中独立生成骨和软骨异位形成。因此，为了阐明BMP载体依赖pehonotype表达现象背后的机制，我们制备并装置了至少6种不同类型的载体，将它们与经色谱纯化的BMP结合，并比较了植入后的表型表达。除IBM和FCM外，新的bmp载体包括羟基磷灰石多孔颗粒（PPHAP）、羟基磷灰石固体颗粒（SPHAP）、蜂窝状羟基磷灰石和纤维玻璃膜（细粒和粗粒FGM）。最引人注目的发现是粗FGM/BMP只诱导膜内的软骨，而PPHAP/BMP只诱导PPHAP孔内的骨。SPHAP/BMP和精细FGM/BMP均未形成骨和软骨。蜂窝HAP由圆柱块（1.4 x 0.7 mm）和7个直径为0.12 mm的管状孔组成，形成了非常独特的骨形状，在每个管状孔的中心产生柱状骨，而不是在管状孔的内表面。这解释为PPHAP的孔隙为血管提供了空间，这对直接骨形成是可行的，而FGM拒绝血管，但允许间充质细胞进入膜，这为软骨形成提供了可行的环境。以上结果表明几何因素在FCM和FCM的使用中是重要的

项目成果

Kuboki, Y.: "Time-Dependent Changes of Collagen Cross-Links and their Precursors in the Culture of Osteogenic Cells." Calcif Tissue Int. 50. 473-480 (1992)

Kuboki, Y.：“成骨细胞培养中胶原交联及其前体的时间依赖性变化。”

Ono,I.: "A Study on Bone Induction in Hydroxyapatite Combined with Bone Morphogenetic Protein" Plastic and Reconstructive Surgery. 90. 870-879 (1992)

小野，I.：“羟基磷灰石与骨形态发生蛋白相结合的骨诱导研究”整形与重建外科。

Yoshinori Kuboki: "Apatite" Japanese Association of Apatite Science, 536 (1992)

Yoshinori Kuboki：“磷灰石”日本磷灰石科学协会，536（1992）

Fujisawa, R.: "Differences in composition of cell-attachment sialoproteins between dentin and bone." J.Dent.R.72. 1222-1226 (1993)

Fujisawa, R.：“牙本质和骨骼之间细胞附着唾液蛋白的组成差异。”

Morimichi Mizuno,Yoshinori Kuboki et al.: "An Osteonectin-Like Protein in the Matrix of Cultured Osteogenic Cell-Line MC3T3-E1,Which is Associated with Calcification" Calcif Tissue Int. 51. 156-161 (1992)

Morimichi Mizuno、Yoshinori Kuboki 等人：“培养的成骨细胞系 MC3T3-E1 基质中的骨连接素样蛋白，与钙化相关”Calcif Tissue Int。