中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (12): 2106-2110.doi: 10.3969/j.issn.1673-8225.2010.12.005

• 组织工程骨及软骨材料 tissue-engineered bone and cartilage materials • 上一篇    下一篇

透明质酸钠复合重组人骨形态发生蛋白2注射剂对下颌骨量的扩增作用

赖仁发1,刘湘宁1,赵清桐1,汪  炬2,弓  健3,李  红1   

  1. 暨南大学附属第一医院,1口腔医疗中心,3核医学科,广东省广州市  510630;2暨南大学生命科学技术学院生物医学工程研究所,广东省广州市 510632
  • 出版日期:2010-03-19 发布日期:2010-03-19
  • 作者简介:赖仁发☆,男,1963年生,广东省梅州市人,汉族,1999年德国柏林洪堡大学毕业,博士,主任医师,主要从事口腔颌面外科临床及科研教学工作。 Tlrf@jnu.edu.cn; Prof.Dr.Lai@163.com
  • 基金资助:

    广东省科学技术厅资助项目(2006 B35801004)。

Effects of recombinant human bone morphogenetic protein-2 combined with sodium hyaluronate on mandible augmentation

Lai Ren-fa1, Liu Xiang-ning1, Zhao Qing-tong1, Wang Ju2, Gong Jian3, Li Hong1   

  1. 1 Stomatology Center, 3Department of Nuclear Medicine, First Affiliated Hospital of Jinan University, Guangzhou  510630, Guangdong Province, China; 2 Institute of Biomedical Engineering, College of Life Science and Technology, Jinan University, Guangzhou  510632, Guangdong Province, China
  • Online:2010-03-19 Published:2010-03-19
  • About author:Lai Ren-fa☆, Doctor, Chief physician, Stomatology Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, Guangdong Province, China Tlrf@jnu.edu.cn; Prof.Dr.Lai@163.com
  • Supported by:

    Guangdong Science and Technology Development Foundation, No. 2006B35801004*

摘要:

背景:对牙槽骨骨量需要扩增的患者而言,固态的支架材料并不太适用。寻找具有流动性和黏附能力、不占体积的材料是目前研究热点。
目的:观察透明质酸钠(sodium hyaluronate,SH)复合重组人骨形态发生蛋白2(recombinant human bone morphogenetic protein,rhBMP-2)注射剂对兔下颌骨量的扩增作用。
方法:60只兔按随机区组设计分为4组:rhBMP-2-SH组、rhBMP-2组、SH组分别于双侧下颌骨膜下置入rhBMP-2-SH复合物0.2 mL、rhBMP-2 0.5 mg、SH 0.2 mL。空白对照组双侧均切开后不作处理即关闭伤口。术后第2,4,8周分批处死动物。处死前作99Tcm-MDP骨显像;处死后切取标本作苏木精-伊红染色观察、胶原I免疫组化、碱性磷酸酶活性、骨钙素含量检测。
结果与结论: ①rhBMP-2-SH组99Tcm-MDP骨显像下颌骨感兴趣区计数比值于2,8周时高于其他各组(P < 0.05),4周时明显高于其他各组(P < 0.01)。②组织学观察rhBMP-2-SH组于术后2周即有新生骨小梁生成,至8周钙化成板层骨块,并且4周时可见透明软骨细胞出现,胶原Ⅰ免疫组化只在2周骨基质中呈强阳性表达。③rhBMP-2-SH组碱性磷酸酶活性指数明显高于其他各组(P < 0.01);并随着时间延长而逐渐增高(P < 0.01)。④rhBMP-2-SH组骨钙素含量于4周及8周时明显高于其他各组(P < 0.01),并随着时间延长而逐渐增高(P < 0.01)。提示rhBMP-2-SH注射剂能于兔下颌骨表面稳定地形成新骨从而达到骨量扩增效应。成骨方式为混合型成骨方式,以膜内成骨为主。

关键词: 骨形态发生蛋白, 透明质酸钠, 注射型, 载体, 骨量扩增

Abstract:

BACKGROUND: The solid stent material is unsuitable for patient needs for mandible augmentation. Therefore, it is a research focus to explore a new material which characterized by fluidity, attachment and small volume.  
OBJECTIVE: To evaluate the bone augmentation efficacy of recombinant human bone morphogenetic protein (rhBMP-2) and sodium hyaluronate (SH) composite injection on mandibula of rabbits.
METHODS: According to random block design, 60 rabbits were randomly divided into 4 groups: rhBMP-2-SH, rhBMP-2, SH and blank control groups. 0.2 mL rhBMP-2-SH composites, 0.5 mg rhBMP-2, or 0.2 mL SH were placed beneath both sides of mandible periosteum in the rhBMP-2-SH group, rhBMP-2 and SH groups, respectively. Nothing was placed in control group. rabbits were sacrificed at weeks 2, 4, and 8 after operation. 99Tcm-MDP bone scan was performed before sacrificed. While other exams, including haematoxylin-eosin staining, collagen I immunochemical staining, alkaline phosphatase (ALP) activity, bone gla protein (BGP) content, were performed after sacrificed.
RESULTS AND CONCLUSION:  ① Ratio of region of interest count of the rhBMP-2-SH group was greater than that in other groups at weeks 2 and 8 (P < 0.05), especially significantly higher at week 4 (P < 0.01). ② Histological observation showed that newly formed bone trabeculae were found at 2 weeks, which calcifying into lamellar bone at 8 weeks. Cartilaginous cells were only found at 4 weeks, and strong expression of collagen I was only found in the osteoblast stroma. ③ ALP activity index was significantly higher than that in other groups (P < 0.01), and increased with time prolonged (P < 0.01). ④ BGP content was significantly higher than that in other groups at weeks 4 and 8 (P < 0.01), and increased with time prolonged (P < 0.01). Bone formation and augmentation efficacy of rhBMP-2-SH composite injection on the bone surface of rabbit mandibula were verified. That osteoinductive manner is a kind of mixed ossification, mainly with intramembranous ossification.

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