中国组织工程研究

中国组织工程研究 ›› 2019, Vol. 23 ›› Issue (2): 232-238.doi: 10.3969/j.issn.2095-4344.0689

• 药物控释材料 drug delivery materials • 上一篇    下一篇

Ca-P涂层镁合金支架负载缓释微球修复股骨缺损

卢燕勤1，易 芳1，鞠 巍2，李文杰1，雷 蕾1   

  • 收稿日期:2018-07-28 出版日期:2019-01-18 发布日期:2019-01-18
  • 通讯作者: 雷蕾，助理研究员，中南大学湘雅口腔医学院正畸科，湖南省长沙市 410008
  • 作者简介:卢燕勤，女，1970年生，江西省清江市人，汉族，2005年北京大学口腔医学院毕业，博士，副教授，主要从事生物力学研究。

Reparation of femoral defects with a Ca-P coated magnesium alloy scaffold carrying sustained release microspheres

Lu Yanqin1, Yi Fang1, Ju Wei2, Li Wenjie1, Lei Lei1   

  1. 1Department of Orthodontics, Xiangya School of Stomatology (Xiangya Stomatological Hospital), Central South University, Changsha 410008, Hunan Province, China; 2School of Biology, Hunan University, Changsha 410082, Hunan Province, China
  • Received:2018-07-28 Online:2019-01-18 Published:2019-01-18
  • Contact: Lei Lei, Assistant professor, Department of Orthodontics, Xiangya School of Stomatology (Xiangya Stomatological Hospital), Central South University, Changsha 410008, Hunan Province, China
  • About author:Lu Yanqin, MD, Associate professor, Department of Orthodontics, Xiangya School of Stomatology (Xiangya Stomatological Hospital), Central South University, Changsha 410008, Hunan Province, China

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文题释义：
核壳结构微球：指先将一种高分子生物降解材料与药物复合作为微球的内核，外面再用另一种高分子生物降解材料将其包裹成为外壳，所制得具有核壳结构的双层微球。
静电喷雾技术：是一种利用外加电场克服按一定流速流出聚合物溶液或熔体表面的力，使溶液或熔体喷射而出，制备微米及纳米粒子或者纤维状物质的方法。
 
 
背景：以往研究多单独探讨镁合金或含生长因子核壳微球的骨再生促进作用，但有关镁合金支架联合含成纤维细胞生长因子2(fibroblast growth factor-2，FGF-2)和骨形态发生蛋白2(bone morphogenetic protein-2，BMP-2)核壳微球的骨修复效果未见相关报道。
目的：观察Ca-P涂层ZK60镁合金支架负载缓释微球修复大鼠股骨缺损的效果。
方法：采用同轴静电喷雾技术制备负载FGF-2和BMP-2的聚乳酸-羟基乙酸共聚物和聚左旋乳酸壳-核控释微球，将其填入ZK60镁合金中空管状支架中，在镁合金表面进行Ca-P涂层。将Ca-P涂层ZK60镁合金支架与无涂层ZK60镁合金支架分别浸泡于Hanks液中30 d，检测抗腐蚀性能。取18只SD大鼠，建立股骨缺损模型，随机分6组干预，空白组不植入任何材料；ZK组植入Ca-P涂层ZK60镁合金；FGF组植入负载FGF-2微球的Ca-P涂层ZK60镁合金，BMP组植入负载BMP-2微球的Ca-P涂层ZK60镁合金，DUAL组植入负载FGF-2微球与BMP-2微球的Ca-P涂层ZK60镁合金(核内、壳内均含有FGF-2和BMP-2，生长因子同时释放)，SEQ组植入负载FGF-2/BMP-2微球的Ca-P涂层ZK60镁合金(FGF-2在壳内，BMP-2在核内，生长因子序贯释放)，术后8周进行骨缺损区Micro-CT和骨组织病理切片观察。

结果与结论：①浸泡在Hanks溶液中30 d后，无涂层ZK60镁合金表面出现了明显大腐蚀坑，Ca-P涂层ZK60镁合金表面仅可见腐蚀裂痕；②Micro-CT显示，空白组外表覆盖了一层软组织，缺损区内部几乎为空的；ZK组缺损区域内有组织生成，但未填满缺损区域；FGF组较ZK组新生组织较多，但缺损区域也未完全填充；BMP组和DUAL组缺损区内部填满了新生组织，DUAL组的组织密度较大；SEQ组缺损区填满了组织且组织密度最大；③骨组织病理切片显示，空白组骨缺损明显，ZK组缺损部位有所修复，FGF组、BMP组、DUAL组修复较ZK组好，SEQ组修复效果最佳；④结果表明，负载FGF-2/BMP-2缓释微球的Ca-P涂层镁合金支架可促进骨再生。

ORCID: 0000-0002-7958-6504(卢燕勤)

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: Ca-P涂层, ZK60镁合金, 核壳微球, 骨缺损, 骨再生, 生物材料

Abstract:

BACKGROUND: Previous studies often discuss that magnesium alloy or core-shell microspheres containing growth factors can promote bone regeneration, but there are no relevant reports on the bone regeneration effect of magnesium alloy scaffolds combined with core-shell microspheres containing fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2).

OBJECTIVE: To investigate the effect of Ca-P coated ZK60 magnesium alloy scaffolds combined with core-shell microspheres in the rats with femoral defects.
METHODS: The poly(lactic-co-glycolic acid) and poly-L-lactic acid core-shell sustained release microspheres loaded with FGF-2 and BMP-2 were prepared by means of coaxial electrostatic spraying, and they were filled into the hollow tubular scaffolds of ZK60 magnesium alloy. Ca-P coating was applied to the surface of the magnesium alloy. The Ca-P coated ZK60 magnesium alloy scaffolds and uncoated ZK60 magnesium alloy scaffolds were immersed in Hanks solution for 30 days, and then the corrosion resistance of the alloys was tested. Eighteen Sprague-Dawley rats were randomly divided into six groups, and the model of femoral defects was established in each rat. The defects were implanted with nothing (Blank group), Ca-P coating ZK60 magnesium (ZK group), Ca-P coating ZK60+FGF microspheres (FGF group), Ca-P coating ZK60+BMP microspheres (BMP group), Ca-P coating ZK60+FGF+BMP microspheres (DUAL group, release of the growth factor at the same time), or Ca-P coating ZK60+FGF/BMP microspheres (SEQ group, sequential release). The rats were sacrificed at 8 weeks postoperatively. The defects were evaluated by gross observation, Micro-CT and bone tissue pathological observation.
RESULTS AND CONCLUSION: (1) After 30 days of immersion in Hanks solution, there was a significant corrosion pit on the surface of uncoated ZK60 magnesium alloy, while only corrosion cracks were visible on the surface of Ca-P coated ZK60 magnesium alloy. (2) The Micro-CT results showed that the bone defect of the BLANK group was obvious, and was only covered with a layer of soft tissue. The defect site of ZK group was repaired, but not completely. The repair of FGF group was better than that of the ZK group, but the repair was still incomplete. The defects of BMP and DUAL groups were filled with new tissues, and the tissue density was higher in the DUAL group than the BMP group. The repair effect of SEQ group was the best with the highest density of the new tissues. (3) The histopathological sections of bone tissues showed that the bone defect was obvious in the BLANK group, and the defect was somewhat repaired in the ZK group. The defect repair of FGF group, BMP group and DUAL group was better than that of ZK group, and the repair effect of SEQ group was the best. To conclude, Ca-P coated magnesium alloy scaffolds carrying sustained release FGF-2/BMP-2 microspheres can promote bone regeneration. 

Key words: Bone Morphogenetic Proteins, Fibroblast Growth Factors, Bone Regeneration, Microspheres, Tissue Engineering

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