股骨头坏死修复研究中可控释淫羊藿苷-β-磷酸三钙复合支架的制备

发布时间：2018-04-20 08:04

本文选题：β-磷酸三钙 + 淫羊藿苷　；参考：《南京中医药大学》2017年硕士论文

【摘要】：目的:评价淫羊藿苷-β-磷酸三钙多孔复合支架的成型工艺,了解其力学及生物学性能,以验证淫羊藿苷-β-磷酸三钙复合支架材料作为股骨头坏死植入材料的可行性。方法:利用Solidworks建模软件设计三维多孔支架模型,应用挤出式3D打印机制作多孔β-磷酸三钙支架胚体,经干燥、烧结过程得到多孔β-磷酸三钙支架成品。应用扫描电子显微镜观察其微观结构,用阿基米德法测定孔隙率、吸水率,电子万能材料试验机测试其抗压强度,并用X线衍射仪进行物相分析;通过超声乳化溶剂透析法制备含10-5M淫羊藿苷的聚乳酸-羟基乙酸共聚物/淫羊藿苷(PLGA/ICA)缓释微球,将淫羊藿苷/N,N-二甲基甲酰胺(ICA/DMF)和N,N-二甲基甲酰胺/聚乳酸-羟基乙酸共聚物(DMF/PLGA)在冰浴中超声条件下混合,然后将1%的聚乙烯醇溶液加入混合溶液中形成(O/W)复乳,将其置入透析袋中过夜以除去DMF,经过离心、清洗、冷冻干燥可得ICA/PLGA缓释微球;采用震荡+离心灌注的方法将缓释微球复合入多孔支架中,加入10%明胶后再次离心,经冷冻干燥后即得到淫羊藿苷-β-磷酸三钙复合支架;测定载药微球的微观结构、载药率、包封率,并进行体外药物缓释实验。结果:用3D打印机制得的β-磷酸三钙多孔支架外观尺寸约为11mm× 11mm×6mm,孔隙间距为600μm,支架宏观孔隙结构规则,孔隙连通性良好。经检测,多孔支架的孔隙率为(66.93±2.84)%。SEM观察支架表面有较多微观孔隙结构,微孔分布均匀,孔隙连通性较好。烧结前后β-TCP支架粉末的X线衍射分析结果显示烧结前后无相转变。对烧结后的β-TCP进行抗压性能测试,支架最大压缩强度为(2.98±0.78)MPa,且加入纳米ZnO,支架强度达到了(8.95±0.29)MPa,力学性能达到了松质骨的抗压强度。制得的ICA/PLGA缓释微球,大体外观结构为淡黄色的粉末状物质,扫描电镜下观察可见微球呈球形,粒径约在1～4μm之间,在支架表面分布均匀,且多分布于支架微孔间隙。结论:制得的β-TCP支架为互联多孔的结构体,微观孔隙结构分布均匀,孔隙连通性好。力学性能能够达到松质骨的强度,可提供较好的力学支撑性能。支架可促进细胞满足细胞黏附、增殖及血管生成能力,以提高骨长入。ICA/PLGA缓释微球30天药物累积释放量达到60%,具有药物缓释的能力。制备的淫羊藿苷-β-磷酸三钙复合支架可用于修复兔股骨头坏死的研究。
[Abstract]:Aim: to evaluate the molding process of icariin-尾-tricalcium phosphate composite scaffold, to investigate its mechanical and biological properties, and to verify the feasibility of icariin-尾-tricalcium phosphate composite scaffold as implant material for osteonecrosis of the femoral head. Methods: the three-dimensional porous scaffold model was designed with Solidworks software, and the porous 尾 -tricalcium phosphate scaffold embryo was made by extrusion 3D printer. The finished product of porous 尾 -tricalcium phosphate scaffold was obtained by drying and sintering. The microstructure was observed by scanning electron microscope (SEM), the porosity and water absorption were measured by Archimedes method, the compressive strength was measured by electronic universal material testing machine, and the phase was analyzed by X-ray diffractometer. The sustained release microspheres containing 10-5 M icariin were prepared by phacoemulsification solvent dialysis method. Icariin / NN- dimethylformamide (ICA / DMF) and NN- dimethylformamide / poly (lactic acid-glycolic acid) copolymer (DMF / PLGA) were mixed in ice bath under ultrasonic conditions, then 1% polyvinyl alcohol solution was added to the mixed solution to form an O / W) composite emulsion. ICA/PLGA sustained release microspheres can be obtained by centrifugation, washing and freeze-drying. The sustained release microspheres are mixed into porous scaffolds by concussion centrifugation, 10% gelatin is added and centrifuged again. Icariin-尾-tricalcium phosphate composite scaffold was obtained after freeze-drying, and the microstructure, drug loading rate and encapsulation efficiency of the microspheres were determined, and drug release experiments in vitro were carried out. Results: the size of the porous 尾 -tricalcium phosphate scaffold was about 11mm 脳 11mm 脳 6 mm, the pore spacing was 600 渭 m. The macroporous structure of the scaffold was regular, and the pore connectivity was good. The porosity of the porous scaffold was 66.93 卤2.84)%.SEM. The pore structure on the surface of the scaffold was observed. The micropore distribution was uniform and the pore connectivity was good. X-ray diffraction analysis of 尾 -TCP scaffold powder before and after sintering showed that there was no phase transition before and after sintering. The compressive properties of the sintered 尾 -TCP were tested. The maximum compressive strength of the scaffold was 2.98 卤0.78 mpa, and the tensile strength of the scaffold reached 8.95 卤0.29 mpa, and the mechanical properties reached the compressive strength of cancellous bone. The prepared ICA/PLGA sustained-release microspheres, with a broad appearance of yellowish powder substance, were observed to be spherical by scanning electron microscopy, with a particle size of about 1 渭 m, uniform distribution on the surface of the scaffold, and most of them distributed in the pore space of the scaffold. Conclusion: the 尾 -TCP scaffold is an interconnected porous structure with uniform distribution of micropore structure and good pore connectivity. Mechanical properties can reach the strength of cancellous bone and can provide better mechanical support properties. The scaffold could promote cell adhesion, proliferation and angiogenesis to increase the cumulative drug release of ICA / PLGA sustained-release microspheres for 30 days, which had the ability of drug sustained release. Icariin-尾-tricalcium phosphate composite scaffold can be used to repair femoral head necrosis in rabbits.
【学位授予单位】：南京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R318.08

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