IMR OpenIR
骨组织工程用镁支架材料的研究
其他题名Study on Magnesium-based Bone Tissue Engineering Scaffold Material
耿芳
学位类型博士
导师杨柯
2008-12-03
学位授予单位中国科学院金属研究所
学位授予地点金属研究所
学位专业材料加工工程
关键词多孔镁 骨组织工程支架 生物降解 表面处理 生物活性
摘要目前常用的骨组织工程支架材料中,陶瓷和高分子等均有力学方面不适配的缺点。随着对骨组织工程支架材料研究的不断深入,开发具有良好力学性能、又可在体内安全降解的新型骨组织工程支架材料具有重要意义。多孔镁基材料由于具有良好的生物学特性、力学相容性以及可降解性,有望作为一种新型骨组织工程支架材料。本论文对多孔镁及AZ31镁合金作为骨组织工程支架材料的可行性进行了全面的研究。 根据骨组织结构的特点,利用金属材料优良的可加工性能,本文采用激光加工技术成功地制备出孔隙均匀排布,孔径尺寸在200–500μm之间,孔隙率在40-52%之间,具有通孔蜂窝网状结构的多孔镁支架。与其它制备开孔多孔镁的方法相比,激光加工法制备出的多孔镁支架强度较高,当AZ31镁合金支架孔隙率在42%时,其压缩强度可达到28.88MPa。利用计算机模拟技术对支架的力学压缩性能分析结果表明,孔壁尺寸是影响多孔镁强度的重要因素。 为了控制镁及镁合金的降解速度并提高其表面生物活性,采用两步低温化学处理的方法成功地在镁及AZ31镁合金表面制备出具有良好生物活性的钙磷可降解陶瓷涂层。首先通过预磷化处理制备出的磷化膜层提高了镁及镁合金的耐蚀性,并为后续的钙磷形核提供了条件。进一步采用正交实验确定钙化处理条件,结果表明,可在形状复杂和多孔的镁及镁合金基体表面获得不同厚度(10-20μm,40-50μm,70-90μm)的钙磷生物活性涂层,以满足不同植入部位的需要,所获得的钙磷涂层进一步提高了镁及镁合金的抗腐蚀性能,并且表面能够诱导类骨磷灰石的形成,表现出了良好的生物活性。 对表面处理前后的镁和AZ31镁合金在三种不同模拟体液(Hank’s、SBF、DMEM)中的降解性能研究结果表明,表面处理前后镁及AZ31镁合金在三种不同模拟体液中的降解行为明显不同,因此不能用某种独立的体外模拟实验来描述其体外降解行为。表面制备的钙磷涂层可使镁及AZ31镁合金在浸泡初期的降解速率降低1-3倍,同时抑制pH值的升高。并且随着镁和涂层的不断降解,新的类骨磷灰石不断形成,表现出良好的生物活性。 通过对表面处理前后的镁及AZ31镁合金的浸提液生物相容性实验,初步确定表面处理后的镁及AZ31镁合金无细胞毒性作用。类成骨细胞与表面处理后的镁基材料复合培养后,细胞在材料表面生长良好,分泌大量细胞外基质,碱性磷酸酶具有正常的分泌活性,表明钙磷涂覆的镁基材料为细胞的生长提供了适合的环境条件,具有作为骨组织工程支架材料的潜力。 多孔镁及AZ31镁合金支架与具有良好生物相容性的PLA高分子、β-TCP陶瓷支架的对比研究结果表明,MG63成骨细胞在镁基支架上与在PLA、β-TCP支架上具有相近的细胞存活率及ALP分泌活性,说明镁基支架材料同样具有良好的生物相容性,适合作为骨组织工程支架材料。
其他摘要Currently, materials used for the bone tissue engineering scaffolds are porous bioactive ceramics, polymer foams and their composites. A major limitation of these materials is their uncompetitive mechanical property. Therefore, development of the scaffolds with appropriate mechanical properties and good biodegradation is an important issue in the tissue engineering research field. Compared with other commonly used biomaterials, magnesium (Mg) is attractive as a bone tissue engineering scaffold material due to its good biocompatibility, suitable biomechanical compatibility as well as biodegradation. In the present work, the focus is concentrated on the feasibility of porous Mg-based bone tissue engineering scaffold material, including pure Mg and AZ31 alloy. Considering the configuration of bone and excellent machining properties of metals, a type of novel porous Mg-based scaffold was successfully manufactured by laser perforation technique in this study, which has uniform pore distribution and interconnecting pores of three-dimensional honeycomb-like structure. The pore size is from 200μm to 500μm and the porosity is between 42% and 52%. The porous Mg-based scaffold fabricated by laser perforation technique possesses much more attractive strength than those produced by other methods. When the porosity of AZ31 alloy was 42%, the corresponding compressive strength could attain 28.88MPa. The mechanical properties of porous Mg-based scaffold were analyzed by computer simulation technique and it was found that the mechanical properties of this type of porous Mg-based scaffold significantly depended on the dimension of pore strut. To control the biodegradation rate of Mg and AZ31 alloy and improve the surface bioactivity, a biodegradable Ca-P coating was successfully precipitated on the surface of porous Mg-based scaffold by a low-temperature soft chemical approach with two steps. Firstly, the phosphate coating produced by pre-treatment improved the corrosion resistance of Mg-based materials, which could trigger the subsequent precipitation of calcium phosphate. Then, the bioactive Ca-P coatings of different thickness, such as 10-20μm,40-50μm,70-90μm, can be adapted to the different parts of human body, and can be produced on the surface of porous Mg-based scaffold with complex shapes from the result of orthogonal arrays. The Ca-P coating prepared on the Mg-based scaffold can further improve its corrosion resistance and bioactivity, which can further induce the formation of apatite. The Mg-based materials before and after surface treatment were soaked in Hank’s、SBF、DMEM solutions, respectively, in order to evaluate the biodegradation behaviors. The results showed that the biodegradations were obviously different. Therefore the biodegradable property of Mg-based materials in vitro can not be analyzed by only a certain experiment. The Ca-P coating could slow down the corrosion rate of Mg-based materials for 1-3 times in the initial stage of soaking in those solutions and effectively slacken the rise of pH of the extracted solutions. The continuous formation of bonelike apatite showed good bioactivity with the degradations of Mg substrate and Ca-P coating in simulated body solution. The biocompatibility of extracted solution of Ca-P coated Mg and AZ31 alloy was studied, respectively. The results indicated nontoxicity of Mg and AZ31 with Ca-P coating. The osteoblast-like MG63 cells seeded on Mg-based scaffolds could grow well and a plenty of extracellular matrix proteins were synthesized and had good ALP activity. Compared to the β-TCP ceramic and PLA polymer scaffolds, the surface treated Mg and AZ31 alloy showed the same excellent biocompatibility. The above results proved that porous Mg-based materials with bioactive Ca-P coatings are expected to be used as bone tissue engineering scaffolds.
页数126
语种中文
文献类型学位论文
条目标识符http://ir.imr.ac.cn/handle/321006/17127
专题中国科学院金属研究所
推荐引用方式
GB/T 7714
耿芳. 骨组织工程用镁支架材料的研究[D]. 金属研究所. 中国科学院金属研究所,2008.
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