多孔钛铌合金的表征、生物相容性及在缺损性植骨中的研究
发布时间：2018-09-07 11:27
【摘要】：研究目的 骨缺损是指由先天或者后天性疾病引起的骨质缺失,常见的包括颅骨缺损,下颌骨缺损以及胫骨缺损等,而其中胫骨的骨缺损最为常见。骨缺损由于缺少骨质,因而骨再生困难造成创面难以愈合,并且伴有感染,所以在骨外科手术中骨缺损修复较为困难和复杂。目前骨缺损修复中临床常用的取骨植骨的方法依然存在一系列的问题,因而研究和开发理想的替代骨移植的人工合成材料(植入材料)已成为医学和生物材料科学的重要课题。目前人工合金材料虽然作为植入材料广泛使用,但其生物相容性以及力学相容性等问题是导致失败的主要原因之一。所以获得拥有良好的生物相容性与力学相容性的合金材料是修复骨缺损的关键所在。根据研究发现,钛铌合金是一种优良的植入材料。其中钛元素有良好的物理特性和效佳的生物相容性,而铌元素则可以提高钛合金的可加工性,而且能提高钛合金的强度,同时降低弹性模量,使其更接近于人类骨骼的密度。同时植入材料表面的多孔隙设计有利于骨细胞的附着,骨组织的长入。同时科学研究发现,一些相关的细胞因子参与了骨细胞分化,如骨形态发生蛋白(Bone Morphogenetic Protein, BMP),其能够诱导干细胞定向分化为骨细胞,在骨再生中有着非常重要的位置。因此将钛铌合金与BMP制成复合材料,能够提高植入材料对骨缺损修复的效率。 方法 经粉末冶金技术制作得到多孔隙率的钛铌合金,并随后对其生物力学强度、孔径及孔隙率等进行评价。第二部分以脐带间充质干细胞为基础,进行体外生物相容性检测,包括细胞毒性试验(MTT),细胞粘附以及增殖试验(丫啶橙染色及扫描电镜),皮下包埋检测炎症反应。第三部分以兔胫骨缺损模型为基础进行骨整合检测,将复合材料的合金试件植入,8周后进行X线摄片、扫描电镜、能谱分析及力学压缩实验,分析材料植入后骨缺损修复情况。 结果 (1).70%孔隙率多孔钛铌合金弹性模量约为2.23GPa,抗压强度约为94.8MPa和松质骨接近,拥有比较好的力学性能。同时其孔径约为200-500gm,孔隙间三维连通,材料表面粗糙；(2).MTT实验结果发现低弹性模量的钛铌合金材料对间充质干细胞的增殖没有明显抑制,不引起细胞的凋亡与坏死。而浸提液对于细胞毒性级别为0-1级。(3).细胞粘附和增殖试验显示多孔隙率的钛铌合金不影响细胞生长,并对间充质干细胞能够在孔隙生长,有良好的支架作用。(4).植入材料试件皮下包埋后在生物体内没有明显的降解与吸收情况出现,周围组织也没有明显的溃烂或恶变及炎症反应现象,说明材料的生物稳定性以及本身的低毒性。(5).新西兰大白兔胫骨骨缺损模型发现,植入材料不引起组织溃烂,肌肉萎缩以及炎症脓肿现象出现,伤口愈合良好。同时X摄片显示,复合植入材料显示出材料和骨组织结合紧密,较多骨质生长以松质骨为主,相对于其它对更好。(6).电镜实验和能谱分析发现材料表面和孔隙内亦有较多钙沉积,70%孔隙率多孔钛铌合金组与骨结合紧密,其间无明显分界线,骨组织能够向孔隙内生长。孔隙内类骨质形成,并能够向孔隙深部生长。(7).力学压缩实验说明复合材料组有更好的抗压效果,拥有较好的力学性质。 结论 (1).低弹性模量(70%孔隙率)的多孔钛铌合金类似松质骨的抗压强度和弹性模量；(2).70%孔隙率钛铌合金具有良好的生物相容性,低细胞毒性；(3).复合BMP的多孔钛铌合金材料拥有佳力学相容性,促进骨缺损的修复。
[Abstract]:research objective
Bone defect is a kind of bone defect caused by congenital or acquired diseases, including skull defect, mandibular defect and tibial defect. Tibial defect is the most common. Bone defect is difficult to heal because of lack of bone, and bone regeneration is difficult to heal, and accompanied by infection. It is difficult and complicated to repair the bone defect. At present, there are still a series of problems in the methods of bone grafting which are commonly used in clinic. Therefore, the research and development of ideal synthetic materials (implant materials) for replacing bone graft has become an important subject in medicine and biomaterials science. Titanium-niobium alloy is an excellent implant material. Among them, titanium has good biocompatibility and mechanical compatibility. Niobium can improve the machinability of titanium alloys, increase the strength of titanium alloys, reduce the modulus of elasticity, and make them closer to the density of human bones. It has been found that some related cytokines participate in bone cell differentiation, such as bone morphogenetic protein (BMP), which can induce stem cells to differentiate into osteocytes and play an important role in bone regeneration. The efficiency of recovery.
Method
Titanium-niobium alloy with porosity was prepared by powder metallurgy and its biomechanical strength, pore size and porosity were evaluated. In the second part, based on umbilical cord mesenchymal stem cells, biocompatibility in vitro was tested, including cytotoxicity test (MTT), cell adhesion test and proliferation test (acridine orange staining and scanning). In the third part, based on the rabbit tibial defect model, the composite alloy specimens were implanted. After 8 weeks, X-ray films, scanning electron microscopy, energy spectrum analysis and mechanical compression tests were performed to analyze the repair of bone defects.
Result
(1) The elastic modulus of porous Ti-Nb alloy with 70% porosity is about 2.23 GPa, and its compressive strength is about 94.8 MPa, which is close to cancellous bone and has good mechanical properties. Cell adhesion and proliferation tests showed that the porous Ti-Nb alloy had no effect on cell growth and had good scaffolding effect on mesenchymal stem cells in the pores. (4) After subcutaneous embedding of implant materials, the implant materials had good scaffolding effect. There was no obvious degradation and absorption in vivo, and there was no obvious ulceration or malignancy or inflammation in the surrounding tissues, indicating the biological stability of the material and its low toxicity. (5) New Zealand white rabbit tibial defect model found that implanted materials did not cause tissue ulceration, muscle atrophy and inflammatory abscess. At the same time, X-ray photographs showed that the composite implants showed a close bond between the material and bone tissue. Most of the bone grew mainly in cancellous bone, which was better than other pairs. (6) Electron microscopy and energy dispersive spectroscopy showed that there were more calcium deposits on the surface and in the pores of the material, and 70% porous Ti-Nb alloy group had a tight bond with the bone. Dense, there is no obvious boundary between them, and bone tissue can grow into the pores. Bone-like substances are formed in the pores and can grow deep into the pores. (7) Mechanical compression experiments show that the composite group has better compressive effect and better mechanical properties.
conclusion
(1) Low modulus of elasticity (70% porosity) porous titanium-niobium alloy similar to cancellous bone compressive strength and modulus of elasticity; (2) 70% porosity titanium-niobium alloy has good biocompatibility, low cytotoxicity; (3) BMP composite porous titanium-niobium alloy material has good mechanical compatibility, promote the repair of bone defects.
【学位授予单位】：中南大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R318.08
本文编号：2228123
[Abstract]:research objective
Bone defect is a kind of bone defect caused by congenital or acquired diseases, including skull defect, mandibular defect and tibial defect. Tibial defect is the most common. Bone defect is difficult to heal because of lack of bone, and bone regeneration is difficult to heal, and accompanied by infection. It is difficult and complicated to repair the bone defect. At present, there are still a series of problems in the methods of bone grafting which are commonly used in clinic. Therefore, the research and development of ideal synthetic materials (implant materials) for replacing bone graft has become an important subject in medicine and biomaterials science. Titanium-niobium alloy is an excellent implant material. Among them, titanium has good biocompatibility and mechanical compatibility. Niobium can improve the machinability of titanium alloys, increase the strength of titanium alloys, reduce the modulus of elasticity, and make them closer to the density of human bones. It has been found that some related cytokines participate in bone cell differentiation, such as bone morphogenetic protein (BMP), which can induce stem cells to differentiate into osteocytes and play an important role in bone regeneration. The efficiency of recovery.
Method
Titanium-niobium alloy with porosity was prepared by powder metallurgy and its biomechanical strength, pore size and porosity were evaluated. In the second part, based on umbilical cord mesenchymal stem cells, biocompatibility in vitro was tested, including cytotoxicity test (MTT), cell adhesion test and proliferation test (acridine orange staining and scanning). In the third part, based on the rabbit tibial defect model, the composite alloy specimens were implanted. After 8 weeks, X-ray films, scanning electron microscopy, energy spectrum analysis and mechanical compression tests were performed to analyze the repair of bone defects.
Result
(1) The elastic modulus of porous Ti-Nb alloy with 70% porosity is about 2.23 GPa, and its compressive strength is about 94.8 MPa, which is close to cancellous bone and has good mechanical properties. Cell adhesion and proliferation tests showed that the porous Ti-Nb alloy had no effect on cell growth and had good scaffolding effect on mesenchymal stem cells in the pores. (4) After subcutaneous embedding of implant materials, the implant materials had good scaffolding effect. There was no obvious degradation and absorption in vivo, and there was no obvious ulceration or malignancy or inflammation in the surrounding tissues, indicating the biological stability of the material and its low toxicity. (5) New Zealand white rabbit tibial defect model found that implanted materials did not cause tissue ulceration, muscle atrophy and inflammatory abscess. At the same time, X-ray photographs showed that the composite implants showed a close bond between the material and bone tissue. Most of the bone grew mainly in cancellous bone, which was better than other pairs. (6) Electron microscopy and energy dispersive spectroscopy showed that there were more calcium deposits on the surface and in the pores of the material, and 70% porous Ti-Nb alloy group had a tight bond with the bone. Dense, there is no obvious boundary between them, and bone tissue can grow into the pores. Bone-like substances are formed in the pores and can grow deep into the pores. (7) Mechanical compression experiments show that the composite group has better compressive effect and better mechanical properties.
conclusion
(1) Low modulus of elasticity (70% porosity) porous titanium-niobium alloy similar to cancellous bone compressive strength and modulus of elasticity; (2) 70% porosity titanium-niobium alloy has good biocompatibility, low cytotoxicity; (3) BMP composite porous titanium-niobium alloy material has good mechanical compatibility, promote the repair of bone defects.
【学位授予单位】：中南大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R318.08
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