中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (3): 452-456.doi: 10.3969/j.issn.1673-8225.2010.03.017

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

壳聚糖微球/纳米羟基磷灰石/聚乳酸-羟基乙酸复合支架制备及其蛋白缓释效果：与单纯纳米羟基磷灰石/聚乳酸-羟基乙酸支架、壳聚糖微球的比较

许尧祥，李亚莉，陈立强，于佳友，孙  健   

  1. 青岛大学医学院附属医院口腔颌面外科，山东省青岛市 266021
  • 出版日期:2010-01-15 发布日期:2010-01-15
  • 通讯作者: 孙 健，博士，教授，主任医师，硕士生导师，青岛大学医学院附属医院口腔颌面外科，山东省青岛市 266021 sunjianqy@126.com
  • 作者简介:许尧祥★，男，1983年生，山东省青岛市人，汉族，青岛大学医学院在读硕士，主要从事组织工程骨方面的研究。 gentlexubo@163.com

Preparation and releasing behavior of chitosan microspheres/nano-hydroxyapatite/PLGA scaffolds: Compared to nano-hydroxyapatite/PLGA scaffolds and chitosan microspheres

Xu Yao-xiang, Li Ya-li, Chen Li-qiang, Yu Jia-you, Sun Jian   

  1. Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Medical College of Qingdao University, Qingdao  266021, Shandong Province, China
  • Online:2010-01-15 Published:2010-01-15
  • Contact: Sun Jian, Doctor, Professor, Chief physician, Master’s supervisor, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Medical College of Qingdao University, Qingdao 266021, Shandong Province, China sunjianqy@126.com
  • About author:Xu Yao-xiang★, Studying for master’s degree, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Medical College of Qingdao University, Qingdao 266021, Shandong Province, China gentlexubo@163.com

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摘要：

背景：骨组织工程骨构建中如何使生长因子持续高效发挥作用是影响成骨速度和质量的关键，现多以各种材料的微球或支架作为缓释载体，但缓释作用有待提高。
目的：实验拟制备壳聚糖微球，然后复合到纳米羟基磷灰石/聚乳酸-羟基乙酸支架上，形成双重缓释作用，并测量对牛血清白蛋白的释放效果。
方法：以牛血清白蛋白为模型药物，采用乳化交联法制备壳聚糖微球。将微球与纳米羟基磷灰石、聚乳酸-羟基乙酸按一定比例混合，以冰粒子为致孔剂，采用冷冻干燥法制备壳聚糖微球/纳米羟基磷灰石/聚乳酸-羟基乙酸复合支架。利用扫描电镜、激光粒度分析仪、压泵仪和力学性能测试仪检测复合支架的形态性能，考察药物在缓释支架上的体外释放规律。
结果与结论：所制备的壳聚糖微球形态良好，呈规则圆球形，粒径集中分布在20~40 μm，微球药物包封率为86.5%，载药量为0.8%，随牛血清白蛋白初始用量的增加，载药量可升高至2.6%，但包封率下降至74.1%。壳聚糖微球能均匀分布在聚乳酸-羟基乙酸支架上，形成壳聚糖微球/纳米羟基磷灰石/聚乳酸-羟基乙酸复合支架，孔径为100~400 μm，孔隙率> 80%，压缩强度为1.1~2.3 MPa，10周降解率为26.5%。单纯纳米羟基磷灰石/聚乳酸-羟基乙酸支架其牛血清白蛋白在36 h累积释放量达85%以上，壳聚糖微球其牛血清白蛋白10 d累积释放量为33.6%，复合支架其牛血清白蛋白40 d累积释放量为81.5%。结果证实包埋壳聚糖微球的纳米羟基磷灰石/聚乳酸-羟基乙酸支架其压缩强度和降解速率合适，对蛋白类药物具有良好的缓释作用，有望作为组织工程的支架材料和生长因子的缓释载体。

关键词: 聚乳酸-羟基乙酸, 支架, 壳聚糖, 缓释载体, 骨修复材料, 组织工程, 生物材料

Abstract:

BACKGROUND: How to make growth factor plays a role persistently and efficiently is a key in constructing bone tissue engineered bone. Currently, varied microspheres or scaffolds were used as release carriers, however, the delayed release effects needs elevating.
OBJECTIVE: To prepare chitosan microspheres/nano-hydroxyapatite/poly (lactic-co-glycolic acid) (CMs/nHA/PLGA) scaffolds, and to measure its characteristics of delayed release of bovine serum albumin (BSA).
METHODS: CMs were prepared by an emulsifying cross linking method with BSA as a model protein. Using ice particulates as porogen, composite CMs/nHA/PLGA scaffolds were prepared by freeze-drying. The characteristic and morphology of the composite were observed by scanning electron microscope, later particle size analyzer, mercury porosimeter and universal testing machine, and the release behavior of BSA was investigated in vitro.
RESULTS AND CONCLUSION: The CMs were spherical shape with a regular surface, with diameters of 20-40 μm. The encapsulation efficiency of the CMs was 86.5%, and the loading capacity was 0.8%. With the increase of initial BSA dosage, the loading capacity increased to 2.6%, while the encapsulation efficiency decreased to 74.1%. The CMs can be uniformly distributed in PLGA scaffolds to form CMs/nHA/PLGA scaffolds, which had 100-400 μm pore diameter and over 80% porosity, with 1.1-2.3 μMPa compressive strength, and 26.5% cumulative degradation at 10 weeks. The cumulative release of BSA from nHA/PLGA scaffolds was above 85% at 36 hours, which from CMs was 33.6% at 10 days, and that from CMs/nHA/PLGA scaffolds was 81.5% at 40 days. The results demonstrated that CMs/nHA/PLGA scaffolds have an excellent releasing efficiency for protein drugs with suitable compressive strength and degradation, which would be used as delivery system and tissue engineering scaffolds.

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