中国组织工程研究

中国组织工程研究 ›› 2018, Vol. 22 ›› Issue (6): 865-870.doi: 10.3969/j.issn.2095-4344.0060

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

可控释淫羊藿苷-β-磷酸三钙复合支架的制备

薛  鹏1，杜  斌1，王礼宁2，曹良权1，孙光权1，刘  锌1，于恒恒1
  

  1. 1南京中医药大学附属江苏省中医院骨伤科，江苏省南京市  210029；2南京中医药大学骨伤研究所、骨伤修复与重建新技术实验室，江苏省南京市  210023
  • 收稿日期:2017-11-27 出版日期:2018-02-28 发布日期:2018-02-28
  • 通讯作者: 杜斌，教授，主任，博士生导师，南京中医药大学附属江苏省中医院骨伤科，江苏省南京市 210029
  • 作者简介:薛鹏，男，1992年生，江苏省张家港市人，硕士，主要从事创伤与骨关节病研究。
  • 基金资助:
    江苏省卫计委中医药管理局项目(YB2015025)

Preparation of a controlled-release icariin/beta-tricalcium phosphate composite scaffold

Xue Peng1, Du Bin1, Wang Li-ning2, Cao Liang-quan1, Sun Guang-quan1, Liu Xin1, Yu Heng-heng1
  

  1. 1Department of Orthopaedics, Jiangsu Provincial Hospital of TCM, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China; 2Institute of Traumatology, New Technology on Trauma Repairment and Reconstruction Laboratory, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
  • Received:2017-11-27 Online:2018-02-28 Published:2018-02-28
  • Contact: Du Bin, Professor, Doctoral supervisor, Department of Orthopaedics, Jiangsu Provincial Hospital of TCM, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
  • About author:Xue Peng, Master, Department of Orthopaedics, Jiangsu Provincial Hospital of TCM, Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
  • Supported by:

    the Project of the Administration Department of Traditional Chinese Medicine, Jiangsu Provincial Family Planning Commission, No. YB2015025

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摘要：

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文题释义：
3D打印：是快速成型技术的一种，它是一种以数字模型文件为基础，运用粉末状金属或塑料等可粘合材料，通过逐层打印方式来构造物体的技术。3D打印通常是采用数字技术材料打印机来实现的，常在模具制造、工业设计等领域被用于制造模型，后逐渐用于一些产品的直接制造，已有使用这种技术打印而成的零部件。
骨组织工程支架：指能与骨组织活体细胞结合并能植入生物体的不同组织，并根据具体替代组织具备的功能的材料；常采用磷酸钙水泥、羟基磷灰石、磷酸三钙、生物活性陶瓷(如生物活性玻璃陶瓷)、细胞外基质陶瓷类材料等制备支架，可自行降解，植入体内可起到支撑、替代爬行等作用，多用于骨缺损的重建及股骨头坏死的修复。
 
背景：淫羊藿苷可促进骨形成、抑制骨吸收，然而其难溶于水，且在体内生物利用度极低，因此其生物活性的发挥需要一种合适的载体。
目的：制备淫羊藿苷-β-磷酸三钙复合支架，并表征其生物学特性。
方法：应用3D打印技术制得含纳米氧化锌的多孔β-磷酸三钙支架，检测加入纳米氧化锌前后多孔β-磷酸三钙支架的抗压强度，以及含纳米氧化锌多孔β-磷酸三钙支架的吸水率与孔隙率；采用超声乳化溶剂透析法制备含有淫羊藿苷的聚乳酸-羟基乙酸共聚物缓释微球，检测其包封率、载药率。将含纳米氧化锌多孔β-磷酸三钙支架与聚乳酸-羟基乙酸共聚物缓释微球混悬液混合，制备淫羊藿苷-β-磷酸三钙复合支架，采用扫描电镜观察复合支架的微观结构，同时检测其吸水率与孔隙率；将复合支架浸入PBS中，在相应的时间点检测上清液中淫羊藿苷浓度，绘制淫羊藿苷累积释放曲线。
结果与结论：①多孔β-磷酸三钙支架微观孔隙结构较为规整，分布均匀，连通性较好，孔隙间距约为600 μm；加入纳米氧化锌颗粒后，支架表面结构更为致密，结晶度更高；②聚乳酸-羟基乙酸共聚物缓释微球呈球形，直径1-4 μm，微球大小均匀；③多孔β-磷酸三钙支架的最大抗压强度为(2.98±0.78)MPa，加入纳米氧化锌后，支架最大抗压强度达(8.95±0.29)MPa；④含纳米氧化锌多孔β-磷酸三钙支架的吸水率为(25.09±0.96)%，孔隙率为(66.93±2.84)%；淫羊藿苷-β-磷酸三钙复合支架的吸水率为(28.46±1.85)%，孔隙率为(32.65±3.32)%；⑤聚乳酸-羟基乙酸共聚物缓释微球的平均包封率为(78.87±2.31)%，载药量为(6.04±1.0)%；⑥淫羊藿苷-β-磷酸三钙复合支架经历突释阶段后，到16 d时，淫羊藿苷释放量可达总量的52%，32 d中可以缓慢释放淫羊藿苷，总淫羊藿苷释放量达到60%；⑦结果表明，淫羊藿苷-β-磷酸三钙复合支架具备良好的力学性能及缓释性能。

关键词: β-磷酸三钙, 淫羊藿苷, 骨组织工程支架, 药物缓释, 载药微球, 生物材料, 药物控释材料

Abstract:

BACKGROUND: Icariin can promote bone formation and inhibit bone resorption, but it is difficult to dissolve in water, and its bioavailability is very low in vivo. Therefore, a suitable carrier is essential to fully utilize the biological activity of icariin.
OBJECTIVE: To prepare an icariin/β-tricalcium phosphate (β-TCP) composite scaffold and to characterize its biological characteristics.
METHODS: Three-dimensional printing technology was utilized to prepare porous β-TCP scaffolds carrying nano zinc oxide, and the compressive strength of porous β-TCP scaffolds was detected before and after addition of nano zinc oxide. Water absorption and porosity of the porous β-TCP scaffolds were also measured. Ultrasonic emulsification solvent dialysis was performed to prepare icariin/   poly(lactic-co-glycolic acid) (PLGA) microspheres, followed by the detection of water absorption and porosity. The porous β-TCP scaffolds and icariin/PLGA microsphere suspension were mixed to prepare icariin/β-TCP composite scaffolds. Microstructure observation of the composite scaffolds was done by scanning electron microscope, and meanwhile, water absorption and porosity were detected. The composite scaffold was then immersed into PBS, and icariin concentration in the supernatant was measured at corresponding time points, based on which Icariin cumulative release curve was drawn.
RESULTS AND CONCLUSION: (1) The porous microstructure of the porous β-TCP scaffold was regular, well distributed, and the connectivity was good. The pore spacing was about 600 μm. After addition of nano zinc oxide particles, the surface structure of the scaffold was more compact and the crystallinity was higher. (2) PLGA microspheres were spherical with a diameter of 1-4 μm, and the microspheres were uniform in size. (3) The maximum compressive strength of the porous beta tricalcium phosphate scaffold was (2.98±0.78) MPa, and increased to (8.95±0.29) MPa after addition of nano zinc oxide. (4) The water absorption rate and porosity were (25.09±0.96)% and (66.93±2.84)% for the porous β-TCP scaffold, (28.46±1.85)% and (32.65±3.32)% for the icariin/β-TCP composite scaffold, respectively. (5) The average encapsulation efficiency of the PLGA microspheres was (78.87±2.31)%, and the drug loading was (6.04±1)%. (6) The release amount of icariin could reach 52% of the total amount at 16 days and 60% of the total amount at 32 days. These findings indicate that the icariin/β-TCP composite scaffold has good mechanical properties and sustained-release performance.

Key words: Calcium Phosphates, Drugs, Chinese Herbal, Delayed-Action Preparations, Tissue Engineering

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