中国组织工程研究 ›› 2018, Vol. 22 ›› Issue (6): 914-920.doi: 10.3969/j.issn.2095-4344.0068

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

碱性成纤维细胞生长因子-聚乳酸羟基乙酸微球/羟基磷灰石/聚左旋乳酸有孔骨架材料的生物相容性

李志跃1,朱智波2,赵  群1,向思宇1,赵  鹏1,徐哲伟1 
  

  1. 1中南大学湘雅三医院骨科,湖南省长沙市  410013;2永州市中心医院,湖南省永州市  425006
  • 收稿日期:2017-09-07 出版日期:2018-02-28 发布日期:2018-02-28
  • 通讯作者: 朱智波,硕士,主治医师,永州市中心医院,湖南省永州市 425006
  • 作者简介:李志跃,男,1969年生,湖南省邵阳县人,汉族,2001年中山医科大学毕业,博士,副主任医师,主要从事骨组织工程、脊髓损伤修复研究。

Biocompatibility of basic fibroblast growth factor-poly(lactic-co-glycolic acid) microspheres/ hydroxyapatite/poly(l-lactic acid) porous materialsBiocompatibility of basic fibroblast growth factor-poly(lactic-co-glycolic acid) microspheres/ hydroxyapatite/poly(l-lactic acid) porous materials

Li Zhi-yue1, Zhu Zhi-bo2, Zhao Qun1, Xiang Si-yu1, Zhao Peng1, Xu Zhe-wei1
  

  1. 1Department of Orthopedics, Xiangya Third Hospital of Central South University, Changsha 410013, Hunan Province, China; 2the Central Hospital of Yongzhou, Yongzhou 425006, Hunan Province, China
  • Received:2017-09-07 Online:2018-02-28 Published:2018-02-28
  • Contact: Zhu Zhi-bo, Master, Attending physician, the Central Hospital of Yongzhou, Yongzhou 425006, Hunan Province, China
  • About author:Li Zhi-yue, M.D., Associate chief physician, Department of Orthopedics, Xiangya Third Hospital of Central South University, Changsha 410013, Hunan Province, China

摘要:

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文题释义:
聚乳酸羟基乙酸:是目前研究中应用最多的药物载体,因为其生物降解性好,可在人体内完全降解,且降解产物一般对人体细胞、组织、器官无明显毒副作用,更为重要的是因为其可塑性好、包裹性好,可形成圆球性立体结构,此结构增加其与细胞接触的表面积,增加了药物释放比例,目前已逐渐成为缓释药物的首选载体。
成纤维细胞生长因子:是一组肝素粘合多肽,主要的家族成员为酸性成纤维细胞生长因子、碱性成纤维细胞生长因子。碱性成纤维细胞生长因子能促进体外培养细胞集落的形成,促进细胞增殖。除此之外,还具有上调血管内皮生长因子表达、促进血管向骨折端长入、加速植骨块内的新骨代谢、改善成骨细胞活性的作用。
 
背景:迄今为止尚无一种材料能够完全满足临床使用的所有要求,但是复合材料拥有生物可降解性、生物相容性、骨传导性等方面的优点,成为了目前人工骨修复材料的研究热点。
目的:制备碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)-聚乳酸羟基乙酸(lactic-co-glycolic acid,PLGA)微球/羟基磷灰石(hydroxyapatite,HAP)/聚左旋乳酸(poly L-lactic acid,PLLA)复合有孔材料,观察其理化特性和生物相容性。
方法:用复乳法制备bFGF-PLGA微球,将微球与HAP、有孔PLLA混合,制成6种有孔材料:PLLA,HAP/PLLA,PLGA微球/PLLA,PLGA微球/HAP/PLLA,bFGF/HAP/PLLA,bFGF-PLGA微球/HAP/PLLA;通过粒径分析仪、透射电子显微镜、X射线衍射仪、傅里叶变换红外光谱仪、微机差热天平、扫描电子显微镜等进行相关表征;最后通过骨髓间充质干细胞的细胞毒性实验及骨髓间充质干细胞的增殖情况,分析有孔骨架材料的生物相容性。
结果与结论:①所制得的bFGF-PLGA微球的粒径约为250 nm,载药率为(26.03±0.17)%,包封率为(90.65±2.68)%,形貌为球形且分散性良好;②所制得的复合有孔材料空隙均匀,孔径大小相似,微球及颗粒在复合有孔材料中分布合理;③bFGF-PLGA微球/HAP/PLLA,bFGF/HAP/PLLA,HAP/PLLA材料的细胞毒性级别为1级(细胞相对存活率≥80%),说明没有明显毒性或者有轻微毒性;④上述6种材料均能促进骨髓间充质干细胞增殖,其中bFGF-PLGA微球/HAP/PLLA复合有孔材料对骨髓间充质干细胞增殖最有利,具有良好的生物相容性。

关键词: 聚乳酸羟基乙酸, 成纤维细胞生长因子, 聚左旋乳酸, 羟基磷灰石, 生物相容性, 骨髓间充质干细胞, 生物材料

Abstract:

BACKGROUND: To date, no single material can completely meet the clinical requirements. However, the composite materials characterized by good biodegradability, biocompatibility and osteoconductivity have become a highlight of the artificial bone materials.
OBJECTIVE: To synthesize the basic fibroblast growth factor (bFGF)-poly(lactic-co-glycolic acid) (PLGA) microspheres/hydroxyapatite (HA)/poly(l-lactic acid) (PLLA) porous bone scaffolds, and to observe the physicochemical properties and biocompatibility of the composite material.
METHODS: The bFGF-PLGA microspheres were prepared by double emulsion method, and then six kinds of materials were made including PLLA, PLLA/HA, PLLA/PLGA, PLLA/HA/PLGA, PLLA/HA/bFGF, and bFGF-PLGA microspheres/PLLA/HA. The characterization of the materials were observed by particle size analyzer, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectrometer, microcomputer differential thermal balance, and scanning electron microscope. Toxicity of these materials and proliferation of bone marrow mesechymal stem cells seeded onto these materials were analyzed and compared.
RESULTS AND CONCLUSION: The average particle size of bFGF-PLGA microspheres was about 250 nm, the average drug-loading capacity was (26.03±0.17)%, and the entrapment percentage was (90.65±2.68)%. The prepared bFGF-PLGA microspheres were spherical and had good dispersibility. In addition, all the six kinds of materials had a porous structure with similar pore diameter, in which the microspheres and particles exhibited a rational distribution. The toxic level of bFGF-PLGA microspheres/PLLA/HA, bFGF/HA/PLLA and HAP/PLLA was graded as 1 (with a relative survival rate ≥ 80%), indicating no obvious toxicity or slight toxicity. All these six kinds of composite materials can promote the proliferation of bone marrow mesenchymal stem cells, and the bFGF-PLGA microspheres/PLLA/HA shows the best effects on cell proliferation and has good biocompatibility. 

Key words: Fibroblast Growth Factors, Hydroxyapatites, Biocompatible Materials, Tissue Engineering

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