【作者】 杨艳芳；

【导师】 袁晓燕；

【作者基本信息】 天津大学 ， 材料学， 2010， 博士

【摘要】 作为骨组织工程三要素之一的多孔支架,被用作骨细胞分化的模板,与生物活性物质结合,起着支撑、调控和引导细胞与骨组织生长的重要作用。构建具有生物活性的可生物降解多孔支架,对于骨组织的成功修复具有重要意义。采用热致相分离/粒子洗去法制备聚(丙交酯-co-乙交酯)(PLGA)和PLGA/β-磷酸三钙(β-TCP)多孔支架。支架的孔隙率由致孔剂含量控制。形貌受聚合物溶液浓度和冷冻温度的影响较大。力学性能随致孔剂含量的增加、冷冻温度的降低和溶液浓度的降低而下降。分别在动态(循环压应力)和静态(水浴摇床)条件下考察PLGA和PLGA/β-TCP支架的降解行为。结果表明,循环压应力能明显加速两种支架水解降解,并以此提出了PLGA多孔支架体外受力降解的三阶段模型。细胞实验显示,支架的降解会影响成骨细胞在其上的增殖。以聚乙二醇单甲醚(mPEG)与L-聚丙交酯的共聚物(PELA)为载体,用复乳法分别制备包载牛血清白蛋白(BSA)和维生素C (Vc)的微球,并借助于溶结后处理法将微球载入PLGA支架孔壁上。考察分别载有BSA和Vc的微球-支架在动/静态条件下的药物释放行为。结果表明,与微球的释放行为相比,微球-支架体系中BSA和Vc的释放速度较慢。循环压应力明显加速药物从微球-支架中的释放。与BSA相比,Vc从PELA微球和微球-支架中均具有较高的释放速度。分别使用喷雾干燥法和复乳法制备包载地塞米松(Dex)和BSA的PLGA微球。考察合成PLGA的引发剂、LA/GA摩尔比和相对分子质量对Dex和BSA的控释能力。优化组合具有不同释放速度的包载Dex和BSA的PLGA微球,同时载入到PLGA/β-TCP多孔支架内部。结果显示,合成PLGA的引发剂、LA/GA摩尔比、相对分子质量等均影响Dex和BSA从PLGA微球中的释放速度。mPEG引入PLGA微球载体中可以提高药物包封率、减缓药物释放速度。GA含量的增加可以加速药物的释放。相对分子质量越大,药物从微球中释放越慢。双组分药物释放结果表明,通过优化设计,可以实现对Dex和BSA在不同时间段从PLGA/β-TCP多孔支架中不同释放速度和不同释放量的控制。更多还原

【Abstract】 As one of three factors in bone tissue engineering, a porous scaffold is often used as a template to guide the differentiation of cells. Furthermore, a scaffold containing bioactive factors plays a special important role in successful repair and regeneration of the bone.In this study, porous poly(lactide-co-glycolide) (PLGA) and PLGA/β-tricalcium phosphate (β-TCP) scaffolds were prepared by thermally induced phase separation and porogen leaching. The porosity of the scaffolds was mainly controlled by the content of porogen, and the morphology was primarily influenced by the freezing temperature and the polymer solution concentration. The compressive properties decreased with increasing the porogen content, decreasing the freezing temperature and diluting the polymer solution concentration. The degradation behaviors of PLGA and PLGA/β-TCP scaffolds were investigated under dynamic condition (cyclic loading) and static condition (water shaking bath), and it was found that cyclic loading could indeed accelerate the degradation rate of the scaffold. The degradation behavior of PLGA scaffolds under dynamic condition showed a three stage degradation model. The viability of osteoblasts cultured on both PLGA and PLGA/β-TCP scaffolds showed a drop tendency with the degradation time of the scaffolds.Bovine serum albumin (BSA) and vitamin C (Vc), as model drugs, were loaded into poly(ethylene glycol)-b-poly(L-lactide) (PELA) microspheres through the method of double emulsion/solvent evaporation. BSA and Vc-loaded PELA microspheres were incorporated into the PLGA scaffolds by using post-seeding method. The release behavior of BSA and Vc from the microspheres incorporated PLGA scaffold under dynamic and static condition was studied. The results showed that comparing with the drug release from PELA microspheres, the drug release from the microspheres incorporated PLGA scaffold showed a lower release rate and a prolonged release time. And the cyclic loading could speed up the release of the drugs from the scaffold. Meanwhile, Vc with low molecular mass showed higher release rate than BSA from both PELA microspheres and PLGA scaffold.Dexamethasone (Dex) and BSA contained PLGA microspheres were prepared by spray drying and double emulsion/solvent evaporation respectively. The effect of initiator, molar ratio of lactic acid (LA) and glycolic acid (GA) and relative molecular mass on the drug release rate was investigated. The release behaviors of Dex and BSA from these microspheres were studied. Selected Dex-loaded and BSA-loaded PLGA microspheres with varied release rate were incorporated into PLGA/β-TCP scaffolds. The in vitro release study indicated that the introduction of m-poly(ethylene glycol) in PLGA could improve the drug encapsulation efficiency in microspheres and reduce the drug release rate from the microspheres. Microspheres prepared from PLGA with lower GA content and higher relative molecular mass showed a prolonged drug release profile. The controllable release rate and release amount of Dex and BSA from PLGA/β-TCP scaffolds could be achieved by selecting the drug-loaded microspheres within the matrix having different degradation rate.更多还原