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可注射性硼酸盐生物玻璃骨水泥的制备及对骨缺损修复的研究

发布时间:2018-09-08 08:34
【摘要】:目的:为临床骨水泥应用中存在的问题提供一种新的解决方案。本研究设计制备以硼酸盐生物玻璃颗粒为固相的骨水泥(BBG cement),测定不同固液相(硼酸盐生物玻璃颗粒/壳聚糖)比例的理化性质,选择出一种适用于临床应用的BBG骨水泥。在体外,将骨水泥样品浸泡在模拟体液(SBF)中,研究离子释放和羟基磷灰石(HA)转化情况;接种骨髓间充质干细胞(BMSCs),检测细胞的粘附、增殖和成骨分化;同时在兔股骨髁缺损模型中植入骨水泥,了解其在体内的促成骨能力。此外,我们制备硼酸盐生物玻璃粉体中掺入功能元素锶(Sr),并测试Sr-BBG的理化性能,研究骨水泥表面的BMSCs生物学行为及体内的生物相容性和骨生成作用。方法:将BBG粉体和壳聚糖溶液以不同的固液相比例制备出骨水泥,对可注射性、凝固时间、粘结性和抗压强度进行全面评价。用扫描电子显微镜(SEM)和X线衍射法(XRD)观察其表面形貌和HA转化。通过ICP-AES法测定骨水泥中的离子释放。在体外,将BMSCs接种于骨水泥,通过SEM、CCK-8、ALP活性和qRT-PCR等方法研究骨水泥的细胞相容性以及骨水泥对细胞的粘附、增殖和分化的影响。体内将骨水泥植入新西兰大白兔股骨髁缺损区,通过Micro-CT和组织学检测方法对其成骨效果进行评价。结果:制备的BBG骨水泥有着良好的可注射性、初凝时间、粘结性和抗压强度。在SBF中,骨水泥释放离子并发生HA转化。体外实验中,BBG骨水泥对细胞没有明显毒性作用,BMSCs在BBG骨水泥表面上能够良好粘附、增殖,并促进其成骨分化。在缺损区植入骨水泥,结果发现BBG骨水泥较CS骨水泥有更多的骨组织新生。此外,锶掺杂的BBG骨水泥同样有着良好的可注射性、初凝时间和抗压强度,相比较于不含锶的BBG骨水泥,其能够更好地促进BMSCs的粘附、增殖和成骨分化,并显著促进缺损区域骨再生和提高宿主骨和植入物接触(BIC)指数。结论:BBG骨水泥是一种具有临床应用潜力的骨修复材料,证实其具有可调控的可注射性和初凝时间,较强的抗压强度及抗溃散性。在SBF中,骨水泥释放具有成骨效应的各种离子并发生HA转化,促进BMSCs的粘附、增殖和成骨分化。BBG骨水泥掺锶后除了具有良好生物相容性和生物降解性外,也具有临床使用中需要的可注射性、初凝时间和抗压强度,并且更好地刺激BMSCs的增殖和分化,能诱导骨再生和骨整合。Sr-BBG骨水泥,为骨缺损(尤其是大面积骨缺损)的治疗提供了一个新的方法。
[Abstract]:Objective: to provide a new solution for clinical application of bone cement. In this study, bone cement (BBG cement),) with borate bioglass particles as solid phase was prepared to determine the physical and chemical properties of different solid-liquid phase (borate bioglass particles / chitosan) ratios, and a BBG bone cement suitable for clinical application was selected. In vitro, bone cement samples were immersed in simulated body fluid (SBF) to study ion release and hydroxyapatite (HA) transformation. Bone marrow mesenchymal stem cells (BMSCs) were inoculated with (BMSCs), to detect cell adhesion, proliferation and osteogenic differentiation. At the same time, bone cement was implanted into rabbit femoral condylar defect model to understand its ability to promote bone in vivo. In addition, we prepared borate bioglass powder doped with strontium (Sr), and tested the physical and chemical properties of Sr-BBG, and studied the biological behavior of BMSCs on the surface of bone cement and its biocompatibility and bone formation in vivo. Methods: bone cement was prepared from BBG powder and chitosan solution with different solid / liquid ratio. The injectability, solidification time, adhesion and compressive strength were evaluated. The surface morphology and HA transformation were observed by scanning electron microscope (SEM) (SEM) and X-ray diffraction (XRD). Ion release in bone cement was determined by ICP-AES method. In vitro, BMSCs was inoculated into bone cement. The cellular compatibility of bone cement and the effect of bone cement on cell adhesion, proliferation and differentiation were studied by means of SEM,CCK-8,ALP activity and qRT-PCR. Bone cement was implanted into the femoral condylar defect of New Zealand white rabbits. The osteogenic effect was evaluated by Micro-CT and histology. Results: the BBG cement has good injectability, initial setting time, adhesion and compressive strength. In SBF, bone cement releases ions and transforms HA. There was no obvious toxic effect of BBG bone cement on cells in vitro. BMSCs could adhere well to the surface of BBG bone cement, proliferate and promote its osteogenic differentiation. Bone cement was implanted in the defect area. The results showed that BBG bone cement had more bone tissue regeneration than CS bone cement. In addition, strontium doped BBG bone cement also has good injectability, initial setting time and compressive strength. Compared with BBG bone cement without strontium, it can promote the adhesion, proliferation and osteogenic differentiation of BMSCs. Bone regeneration and (BIC) index of host bone and implants were increased significantly. Conclusion the bone cement WBBG is a kind of bone repair material with clinical application potential. It is proved that the bone cement has adjustable injectability, initial setting time, strong compressive strength and anti-collapsibility. In SBF, bone cement releases various ions with osteogenic effect and transforms HA, which promotes the adhesion of BMSCs, proliferation and osteogenic differentiation. Besides, it has good biocompatibility and biodegradability. It also has the injectability, initial setting time and compressive strength needed in clinical use, and can stimulate the proliferation and differentiation of BMSCs, and can induce bone regeneration and bone integration. Sr-BBG bone cement. It provides a new method for the treatment of bone defects, especially large bone defects.
【学位授予单位】:上海交通大学
【学位级别】:博士
【学位授予年份】:2015
【分类号】:R318.08;R68

【参考文献】

相关期刊论文 前1条

1 Anjan P Kaushik;Anusuya Das;Quanjun Cui;;Osteonecrosis of the femoral head: An update in year 2012[J];World Journal of Orthopedics;2012年05期



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