结合缓释微球的ZK60镁合金支架应用于骨再生的研究

发布时间：2018-07-13 14:45

【摘要】：骨修复过程是一个受多种生长因子影响的过程,这个过程中,多种因子的时空分布,对骨修复的成功率和速率起关键作用。利用组织工程的方法修复骨缺损是研究的热点,也取得了很多的进展,然而当前的骨支架材料只结合了单一的活性因子,或者多个因子的简单混合,未能模拟骨自然修复过程中多因子的时空分布,从而影响了治疗方法的效率。因此,两种或多种因子的延时控制释放体系的研究是很有意义的。静电喷雾技术是一种利用强静电场作用来克服液体表面张力,从而获得微球的一种技术。利用同轴静电喷雾法可以制备壳-核结构的高分子微球,这种高分子微球能依时间顺序先后释放两种化学药物,如前1-2周释放一种药物,之后开始释放第二种药物。通过变化壳-核结构中核的相对大小,能精确控制两种药物的释放节奏。因此,可以利用同轴静电喷雾技术制备壳-核分别包含FGF-2和BMP-2这两种生长因子的微球,从而实现因子的延时控制释放,达到促进骨再生的目的。壳-核结构高分子微球,虽然有一定机械性能,但不能满足骨缺损部位,特别是受力部位的支撑作用,从而影响骨再生。ZK60镁合金具有与自然骨接近的机械性能,而其降解产物镁离子又是人体必需元素。所以,可以利用镁合金作为壳-核微球的外部支撑材料,从而满足骨再生的要求。但镁合金过快的降解速度影响了其应用,所以必需对其进行表面改性,延缓其降解速率。Ca和P都是骨基质的主要组成成分,研究结果显示Ca-P涂层具有良好的生物相容性,并有很好的骨传导性和诱骨活性。所以可以在ZK60镁合金表面进行Ca-P涂层,这样既可以延缓降解速率,又可以促进骨再生。本实验通过制备搭载包含两种生长因子的可控释放微球的Ca-P改性ZK60镁合金支架,即可以发挥壳-核结构微球的蛋白质缓释方面的优势,又可以在骨缺损处的应用提供机械支撑,从而提高修复大面积骨缺损的效率。
[Abstract]:The process of bone repair is a process influenced by many growth factors. In this process, the spatial and temporal distribution of multiple factors plays a key role in the success rate and rate of bone repair. The application of tissue engineering in repairing bone defects is a hot topic and has made a lot of progress. However, the current bone scaffold materials only combine a single active factor or a simple mixture of multiple factors. The failure to simulate the temporal and spatial distribution of multiple factors in the process of natural bone repair affects the efficiency of the treatment. Therefore, the study of delay controlled release systems with two or more factors is of great significance. Electrostatic spray technology is a kind of technology which uses the strong electrostatic field to overcome the surface tension of liquid and obtain microspheres. Coaxial electrostatic spray method can be used to prepare shell-core polymer microspheres which can release two kinds of chemical drugs in order of time such as the release of one drug in the first 1-2 weeks and then the release of the second drug. By changing the relative size of the nuclei in the shell-nucleus structure, the release rhythm of the two drugs can be precisely controlled. Therefore, the coaxial electrostatic spray technique can be used to prepare the microspheres containing FGF-2 and BMP-2, respectively, so that the delayed release of the factors can be achieved and the bone regeneration can be promoted. Although the shell core structure polymer microspheres have some mechanical properties, they can not meet the support function of bone defect, especially the bearing parts, thus affecting the mechanical properties of bone regeneration. ZK60 magnesium alloy has the mechanical properties close to that of natural bone. Mg ~ (2 +), the degradation product of magnesium ion, is an essential element in human body. Therefore, magnesium alloy can be used as an external support material for shell-nuclear microspheres to meet the requirements of bone regeneration. However, the rapid degradation rate of magnesium alloy affects its application, so it is necessary to modify its surface and delay its degradation rate. Ca and P are the main components of bone matrix. The results show that Ca-P coating has good biocompatibility. It also has good bone conduction and osteoinductive activity. Therefore, Ca-P coating can be applied on ZK60 magnesium alloy surface, which can delay degradation rate and promote bone regeneration. In this experiment, Ca-P modified ZK60 magnesium alloy scaffolds with controllable release microspheres containing two growth factors were prepared, which can play the advantage of protein sustained release of shell core microspheres and provide mechanical support for bone defects. So as to improve the efficiency of repairing large-area bone defects.
【学位授予单位】：湖南大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R318.08;R68

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