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中华口腔医学研究杂志(电子版)

中华口腔医学研究杂志(电子版) ›› 2019, Vol. 13 ›› Issue (06) : 328 -335. doi: 10.3877/cma.j.issn.1674-1366.2019.06.002

所属专题： 文献；

基础研究

个体化假体复合组织工程技术修复兔下颌骨缺损
陈俊兰1, 吴纪楠1,†(), 彭伟2, 陈觉尧1, 郑巧仪1   
  1. 1. 中山市人民医院口腔分院　528403
    2. 中山大学附属第一医院，广州　510080
  • 收稿日期:2019-09-02 出版日期:2019-12-01
  • 通信作者: 吴纪楠

An experimental study of rabbit mandibular defect reconstruction with individualized prosthesis and tissue engineering

Junlan Chen1, Jinan Wu1,†(), Wei Peng2, Jueyao Chen1, Qiaoyi Zheng1   

  1. 1. Hospital of Stomatology, People′s Hospital, Zhongshan 528403, China
    2. The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China
  • Received:2019-09-02 Published:2019-12-01
  • Corresponding author: Jinan Wu
  • About author:
    Corresponding author: Wu Jinan, Email:
  • Supported by:
    National Natural Science Foundation of China(81371111); Science and Technology Plan of Guangdong Province(2008B030301291); Zhongshan Science and Technology Plan(2019B1098)
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引用本文：

陈俊兰, 吴纪楠, 彭伟, 陈觉尧, 郑巧仪. 个体化假体复合组织工程技术修复兔下颌骨缺损[J]. 中华口腔医学研究杂志(电子版), 2019, 13(06): 328-335.

Junlan Chen, Jinan Wu, Wei Peng, Jueyao Chen, Qiaoyi Zheng. An experimental study of rabbit mandibular defect reconstruction with individualized prosthesis and tissue engineering[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2019, 13(06): 328-335.

目的

研究快速成型（RP）技术辅助下制作的个体化假体复合珊瑚羟基磷灰石（CHA）、重组人骨形成蛋白2（rhBMP-2）修复兔下颌骨缺损的成骨效果。

方法

以27只新西兰大白兔为实验对象，随机数字表法平均分成3组（每组9只），全部建立下颌骨连续性缺损模型，并在兔下颌骨缺损区分别植入个体化假体+自体骨（A组）、个体化假体+CHA（B组）、个体化假体+CHA+rhBMP-2（C组）。分别于术后4、12、24周3个时间点处死动物取材，进行大体标本观察，以及骨钙素（OC）、Ⅰ型胶原（COL-1）的免疫组化观察，分别比较各组修复骨缺损的能力，并对实验数据进行重复测量设计资料的单因素方差分析。

结果

术后24周各组实验兔外形均对称，通过OC及COL-1的吸光度检测，骨缺损区均有大量新骨形成，A组（0.537 ± 0.010）、C组（0.530 ± 0.010）可见大量骨小梁及编织骨结构，缺损区的新骨OC、COL-1的免疫组化观察基本一致，差异无统计学意义（t = 0.007，P>0.05）；但A组强于B组（0.415 ± 0.009，t = 0.122，P<0.001）；C组也强于B组（t = 0.121，P<0.001），差异均有统计学意义。

结论

在兔下颌骨缺损修复中，通过RP技术和组织工程技术相结合，CHA复合rhBMP-2后成骨能力明显增强，成骨效能肯定，为后期的临床应用提供可靠的实验基础。

关键词: 下颌骨损伤, 下颌假体, 羟基磷灰石类, 重组人骨形成蛋白2, 反求工程, 快速成型
Objective

To evaluate the effect of individualized prosthesis combined with coralline hydroxyapatite (CHA) and recombinant human bone morphogenetic protein-2 (rhBMP-2) on the reconstruction of rabbit mandibular defect with the aid of rapid prototyping (RP) .

Methods

The radial defect models were made in 27 rabbits, which were evenly divided into 3 groups randomly. Individualized prostheses were obtained with RP. The 3 groups were treated with different materials: group A, individualized prostheses with autogenous bone; group B, individualized prostheses with CHA; group C, individualized prostheses with CHA and rhBMP-2. The measurement of bone mineral density (BMD) and the detection of osteocalcin (OC) and collagen Ⅰ (COL-1) with immunohistochemical staining were performed in 4, 12, and 24 weeks after the operation so as to compare the capacity of bone reconstruction among the three groups. Data were analyzed with One-Way ANOVA.

Results

Both group A (0.537 ± 0.010) and group C (0.530 ± 0.010) showed a large number of trabecular and woven bone, whereas the contents of OC and COL-1 in the defect area were similar (t = 0.007, P>0.05) , both of which were significantly higher than group B (0.415 ± 0.009) (tAB = 0.122, PAB<0.001; tAB = 0.121, PAB<0.001) .

Conclusions

Upon the individualized three-dimensional titanium with RP, CHA combined with rhBMP-2 was found to have an improved osteoinductive ability, leading to a satisfactory recovery in both the contour and function of rabbit mandibles, which provided a reliable basis for individualized functional reconstruction of mandibular defects.

Key words: Mandibular injuries, Mandibular prosthesis, Hydroxyapatites, Recombinant human bone morphogenetic protein-2, Reverse engineering, Rapid prototyping
图1 制备完成的重组人骨形成蛋白2（rhBMP-2）和珊瑚羟基磷灰石（CHA）的复合物
图6 个体化假体和珊瑚羟基磷灰石（CHA）/重组人骨形成蛋白2（rhBMP-2）修复兔下颌骨缺损区
图7 不同时间点各组骨移植材料植入实验兔下颌骨缺损后骨钙素的表达（免疫组化染色　× 200）　术后4周：图A、图B、图C示弱阳性（+）；术后12周：图D、图E、图F示阳性（++）；术后24周：图G、图H、图I示强阳性（+++）
图8 三组骨移植材料植入实验兔下颌骨缺损后不同时间点骨钙素的平均吸光度（A）值比较
表1 不同时间点各组骨移植材料植入实验兔下颌骨缺损后骨钙素的图像分析结果（A值， ± s）
组别 例数 4周 12周 24周
A组 9 0.384 ± 0.009 0.494 ± 0.005 0.537 ± 0.010
B组 9 0.300 ± 0.006 0.399 ± 0.010 0.415 ± 0.009
C组 9 0.350 ± 0.010 0.473 ± 0.005 0.530 ± 0.010
图9 不同时间点各组骨移植材料植入兔下颌骨缺损后Ⅰ型胶原的表达（免疫组化　× 200）　术后4周：图A、图B、图C示弱阳性（+）；术后12周：图D、图E、图F示阳性（++）；术后24周：图G、图H、图I示强阳性（+++）
图10 三组骨移植材料植入实验兔下颌骨缺损后不同时间点Ⅰ型胶原的平均吸光度（A）值比较
表2 不同时间点各组骨移植材料植入兔下颌骨缺损后Ⅰ型胶原的图像分析结果（A值， ± s）
组别 例数 4周 12周 24周
A组 9 0.308 ± 0.016 0.475 ± 0.007 0.507 ± 0.013
B组 9 0.215 ± 0.012 0.351 ± 0.010 0.419 ± 0.006
C组 9 0.257 ± 0.008 0.421 ± 0.008 0.505 ± 0.015
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