中国组织工程研究

中国组织工程研究 ›› 2021, Vol. 25 ›› Issue (28): 4441-4446.doi: 10.12307/2021.055

• 组织工程骨材料Tissue-engineered bone • 上一篇    下一篇

3D打印不同孔径钛合金支架修复兔股骨缺损：600 μm孔径更有利于骨整合

王  庆1，翁益平2，刘宏伟2，张  文3，施  勤3，张润泽1，蒋俊锋4，王彩梅5   

  1. 1大连医科大学研究生院，辽宁省大连市  116044；2南京医科大学附属常州第二人民医院骨科，江苏省常州市  213003；3苏州大学骨科研究所，江苏省苏州市  215006；4河海大学物联网工程学院，江苏省常州市  213022；5北京爱康宜诚股份有限公司，北京市  102200
  • 收稿日期:2020-07-01 修回日期:2020-07-04 接受日期:2020-08-15 出版日期:2021-10-08 发布日期:2021-05-15
  • 通讯作者: 刘宏伟，主任医师，南京医科大学附属常州第二人民医院骨科，江苏省常州市 213003 E-mail:lhw_2689@qq.com
  • 作者简介:王庆，男，1994年生，四川省广安市人，汉族，大连医科大学在读硕士，医师，主要从事3D打印、骨缺损修复、骨组织工程研究。
  • 基金资助:
    国家自然科学面上基金资助项目(61772172)，项目参与者：蒋俊锋、刘宏伟；常州市卫计委重大项目资助(ZD201617)，项目负责人：刘宏伟

Three-dimensional printed porous titanium alloy scaffolds with different apertures in repair of femoral defects in rabbits: 600 μm aperture is more conducive to osseointegration

Wang Qing1, Weng Yiping2, Liu Hongwei2, Zhang Wen3, Shi Qin3, Zhang Runze1, Jiang Junfeng4, Wang Caimei5   

  1. 1Graduate School, Dalian Medical University, Dalian 116044, Liaoning Province, China; 2Department of Orthopedics, Changzhou Second People’s Hospital Affiliated to Nanjing Medical University, Changzhou 213003, Jiangsu Province, China; 3Institute of Orthopedics, Soochow University, Suzhou 215006, Jiangsu Province, China; 4School of Internet of Things Engineering, Hehai University, Changzhou 213022, Jiangsu Province, China; 5Beijing Aikang Yicheng Co., Ltd., Beijing 102200, China
  • Received:2020-07-01 Revised:2020-07-04 Accepted:2020-08-15 Online:2021-10-08 Published:2021-05-15
  • Contact: Liu Hongwei, Chief physician, Department of Orthopedics, Changzhou Second People’s Hospital Affiliated to Nanjing Medical University, Changzhou 213003, Jiangsu Province, China E-mail:lhw_2689@qq.com
  • About author:Wang Qing, Master candidate, Physician, Graduate School, Dalian Medical University, Dalian 116044, Liaoning Province, China
  • Supported by:
    the National Natural Science Foundation of China, No. 61772172 (to JJF and LHW); the Major Project Funding Project of Changzhou Municipal Health Planning Commission, No. ZD201617 (to LHW)

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摘要：

文题释义：
3D打印多孔钛合金支架：指以数字模型文件为基础，利用激光或电子束熔融钛合金粉末，通过“分层制造、逐层叠加”的方式快速制造出具有某种多孔结构的钛合金材料。该方法能精确控制其内部结构和外部形状，具有快速、精准、智能、个性化制造的特点。
骨整合：指在光学显微镜下植入体与周围骨组织之间无纤维结缔组织的直接接触，又称骨性结合、骨融合，这种骨性结构由于将植入体与组织连接成为一个整体，可有效分散应力，增强植入体的稳固性。

背景：多孔钛合金的微孔结构不但能为成骨细胞的增殖与迁移提供充分的空间，而且能增强间充质干细胞的成血管作用，影响成骨基因的表达和成骨细胞分化，是骨整合的重要因素。
目的：分析不同孔径3D打印多孔钛合金支架修复兔股骨外髁骨缺损的骨整合能力。
方法：将20只新西兰兔40条后腿随机分为A、B、C、D组，制备股骨外髁5 mm×5 mm骨缺损模型，A、B、C组分别植入200，600，1 000 μm孔径多孔钛合金支架，D组不植入材料。术后4，8周拍摄X射线片，观察植入物有无移位、脱出及植入物周围是否存在骨溶解、骨坏死等现象；术后8周时，Micro-CT检测股骨标本骨小梁厚度、骨小梁数量、骨小梁相对体积、骨表面积密度、骨小梁分离度，组织学观察骨整合情况。实验方案经苏州大学动物实验伦理委员会批准。
结果与结论：①X射线片显示，内植物位置良好，无明显移位和脱落，材料周围骨形成良好，未见骨溶解、骨坏死等现象；②Micro-CT检测显示，3组植入物的孔隙内及植入物周围均不同程度地有骨组织存在，B组微孔的骨小梁数量及骨表面积密度高于A、C组(P < 0.05)，A组微孔的骨小梁厚度大于B、C组(P < 0.05)；③甲苯胺蓝染色显示，B组几乎所有表层微孔内均有新生骨组织长入，部分新生骨延伸进入支架的深层孔隙中，与多孔结构结合紧密，形成机械交锁；A、C组仅有少量表层微孔存在新生骨组织长入，深层孔隙无明显的新生骨质形成，新生骨与植入物结合较差；④结果表明相对于200，1 000 μm孔径，600 μm孔径3D打印多孔钛合金支架更有利于新骨形成。
https://orcid.org/0000-0003-2064-5415 (王庆)

中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

关键词: 骨, 材料, 孔径, 多孔, 钛合金, 新骨形成, 3D打印, 电子束熔融技术, 骨缺损

Abstract:

BACKGROUND: The microporous structure of a porous titanium alloy can not only provide sufficient space for the proliferation and migration of osteoblasts, but also promote the angiogenesis of mesenchymal stem cells, affect the expression of osteogenic genes and the differentiation of osteoblasts, which is an important factor for bone integration.

OBJECTIVE: To analyze the osseointegration ability of three-dimensional printed porous titanium alloy scaffolds with different apertures in repairing rabbit femoral condyle defect.
METHODS: Totally 40 hind legs of 20 New Zealand rabbits were randomly divided into group A, group B, group C, and group D. A 5 mm×5 mm bone defect model was established. Groups A, B, and C were implanted with porous titanium alloy scaffolds with a diameter of 200, 600, and 1 000 μm, while group D was not implanted. X-ray films were taken at 4 and 8 weeks after operation to observe whether there was displacement, prolapse and osteolysis, and osteonecrosis around the implants. At 8 weeks after operation, the trabecular thickness, trabecular number, trabecular volume, bone surface area density, and trabecular separation were detected by micro CT. The osseointegration was observed by histology. The experimental protocol was approved by the Animal Experiment Ethics Committee of Soochow University. 
RESULTS AND CONCLUSION: (1) X-ray films showed that the implants were in good position, without obvious displacement or falling off, and the bone around the materials was good, without osteolysis, osteonecrosis or other bad phenomena. (2) Micro-CT examination showed that bone tissue existed in the pores and around the implants in three groups. The number of trabeculae and bone surface area density in group B were significantly higher than those in the groups A and C (P < 0.05). The trabecular thickness of micropores in the group A was significantly higher than that in the groups B and C (P < 0.05). (3) Toluidine blue staining showed that the new bone tissue grew into almost all the surface micropores in group B, and some of the new bone extended into the deep pores of the experimental scaffold, closely combined with the porous structure, forming mechanical interlocking. Groups A and C had only a small amount of new bone tissues in surface micropores, and there was not new bone tissues in deep pores. The combination of new bone and implant was poor. (4) The results showed that the three-dimensional printed porous titanium alloy scaffold with 600 μm aperture was more conducive to new bone formation compared with 200 μm and 1 000 μm aperture.

Key words: bone, material, aperture, porosity, titanium alloy, new bone formation, 3D printing, electron beam melting, bone defect

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