三维打印介孔生物活性玻璃/PLGA同心圆柱复合支架用于抗骨结核药物的节律性缓释

项目名称： 三维打印介孔生物活性玻璃/PLGA同心圆柱复合支架用于抗骨结核药物的节律性缓释

项目编号： No.51302170

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 一般工业技术

项目作者： 朱敏

作者单位： 上海理工大学

项目金额： 25万元

中文摘要： 骨结核病手术后仍需至少半年的系统药物化疗。针对全身系统用药效率低下、耐药性易发及病人负担过重的问题，本项目创新性地设计了一种可节律性缓释多种抗结核药物的复合支架，同时用于骨结核术后残留骨质缺损的修复及原位长效化疗，具有重要的临床实用意义。 采用三维打印技术制备介孔生物玻璃（MBG）基复合载药支架。利用MBG的优良生物活性提高复合支架促进新骨再生的能力。通过介孔孔径控制和表面修饰，调节MBG对一线抗结核药物异烟肼(INH)/利福平(RFP)的装载量和释放速度，实现两种药物的联合高量装载和缓慢释放。选择具有合适降解速度的可降解生物高分子PLGA，与MBG复合通过三维打印构建二者层层交替的同心圆柱体结构，进一步延缓释放的同时保持药物以弦波形式规律释放，维持病灶处较长时间的有效杀菌浓度。该复合支架有望满足联合、高量及规律的临床抗结核化疗要求，是抗骨结核药物缓释支架研究领域的新发展，具有创新性。

中文关键词： 三维打印；介孔生物活性玻璃；抗骨结核支架；药物输运；骨修复

英文摘要： Here in this proposal, a novel composite scaffold for treating osteoarticular tuberculosis(TB) after surgical intervention is designed, which could load more than one sufficient anti-TB drugs simultaneously and release them in a controlled wave manner.The scaffold would repair the residul cavity resulted from surgery and realize in-situ advanced chemotherapy. A mesoporous bioactive glasses(MBG)/PLGA composite drug delivery scaffold via 3D-plotting is prepared. High doses of two drugs isoniazed (INH) and rifampicin (RFP) could be loaded in this composite, and then release extremely in a slow and rhythmic pattern. Firstly, MBG materials with proper pore diameters and surface properties are sythesized using different surfactant and post-grafting reactions. The loading amount of INH and RFP and their release rates are adjusted through selecting MBG with right mesoporous properties. Secondly, biodegradable polymer PLGA with proper degradation rate and the drug-loaded mesoporous powders together as alternative layers are 3D-plotted, leading to a concentric cylindrical architecture. INH and RFP are released from the 3D porous cylindrical scaffold in a wave mode, so that the drug concentration in the osseous foci are maintained above MIC (minimum inhibitory concentration). In vitro and in vivo drug release experiments

英文关键词： 3D printing；mesoporous bioactive glasses；anti-osteoarticular TB scaffold；drug delivery；bone repair