【摘要】：研究目的 骨缺損是指由先天或者后天性疾病引起的骨質(zhì)缺失,常見的包括顱骨缺損,下頜骨缺損以及脛骨缺損等,而其中脛骨的骨缺損最為常見。骨缺損由于缺少骨質(zhì),因而骨再生困難造成創(chuàng)面難以愈合,并且伴有感染,所以在骨外科手術(shù)中骨缺損修復(fù)較為困難和復(fù)雜。目前骨缺損修復(fù)中臨床常用的取骨植骨的方法依然存在一系列的問題,因而研究和開發(fā)理想的替代骨移植的人工合成材料(植入材料)已成為醫(yī)學(xué)和生物材料科學(xué)的重要課題。目前人工合金材料雖然作為植入材料廣泛使用,但其生物相容性以及力學(xué)相容性等問題是導(dǎo)致失敗的主要原因之一。所以獲得擁有良好的生物相容性與力學(xué)相容性的合金材料是修復(fù)骨缺損的關(guān)鍵所在。根據(jù)研究發(fā)現(xiàn),鈦鈮合金是一種優(yōu)良的植入材料。其中鈦元素有良好的物理特性和效佳的生物相容性,而鈮元素則可以提高鈦合金的可加工性,而且能提高鈦合金的強(qiáng)度,同時(shí)降低彈性模量,使其更接近于人類骨骼的密度。同時(shí)植入材料表面的多孔隙設(shè)計(jì)有利于骨細(xì)胞的附著,骨組織的長入。同時(shí)科學(xué)研究發(fā)現(xiàn),一些相關(guān)的細(xì)胞因子參與了骨細(xì)胞分化,如骨形態(tài)發(fā)生蛋白(Bone Morphogenetic Protein, BMP),其能夠誘導(dǎo)干細(xì)胞定向分化為骨細(xì)胞,在骨再生中有著非常重要的位置。因此將鈦鈮合金與BMP制成復(fù)合材料,能夠提高植入材料對骨缺損修復(fù)的效率。 方法 經(jīng)粉末冶金技術(shù)制作得到多孔隙率的鈦鈮合金,并隨后對其生物力學(xué)強(qiáng)度、孔徑及孔隙率等進(jìn)行評價(jià)。第二部分以臍帶間充質(zhì)干細(xì)胞為基礎(chǔ),進(jìn)行體外生物相容性檢測,包括細(xì)胞毒性試驗(yàn)(MTT),細(xì)胞粘附以及增殖試驗(yàn)(丫啶橙染色及掃描電鏡),皮下包埋檢測炎癥反應(yīng)。第三部分以兔脛骨缺損模型為基礎(chǔ)進(jìn)行骨整合檢測,將復(fù)合材料的合金試件植入,8周后進(jìn)行X線攝片、掃描電鏡、能譜分析及力學(xué)壓縮實(shí)驗(yàn),分析材料植入后骨缺損修復(fù)情況。 結(jié)果 (1).70%孔隙率多孔鈦鈮合金彈性模量約為2.23GPa,抗壓強(qiáng)度約為94.8MPa和松質(zhì)骨接近,擁有比較好的力學(xué)性能。同時(shí)其孔徑約為200-500gm,孔隙間三維連通,材料表面粗糙；(2).MTT實(shí)驗(yàn)結(jié)果發(fā)現(xiàn)低彈性模量的鈦鈮合金材料對間充質(zhì)干細(xì)胞的增殖沒有明顯抑制,不引起細(xì)胞的凋亡與壞死。而浸提液對于細(xì)胞毒性級別為0-1級。(3).細(xì)胞粘附和增殖試驗(yàn)顯示多孔隙率的鈦鈮合金不影響細(xì)胞生長,并對間充質(zhì)干細(xì)胞能夠在孔隙生長,有良好的支架作用。(4).植入材料試件皮下包埋后在生物體內(nèi)沒有明顯的降解與吸收情況出現(xiàn),周圍組織也沒有明顯的潰爛或惡變及炎癥反應(yīng)現(xiàn)象,說明材料的生物穩(wěn)定性以及本身的低毒性。(5).新西蘭大白兔脛骨骨缺損模型發(fā)現(xiàn),植入材料不引起組織潰爛,肌肉萎縮以及炎癥膿腫現(xiàn)象出現(xiàn),傷口愈合良好。同時(shí)X攝片顯示,復(fù)合植入材料顯示出材料和骨組織結(jié)合緊密,較多骨質(zhì)生長以松質(zhì)骨為主,相對于其它對更好。(6).電鏡實(shí)驗(yàn)和能譜分析發(fā)現(xiàn)材料表面和孔隙內(nèi)亦有較多鈣沉積,70%孔隙率多孔鈦鈮合金組與骨結(jié)合緊密,其間無明顯分界線,骨組織能夠向孔隙內(nèi)生長。孔隙內(nèi)類骨質(zhì)形成,并能夠向孔隙深部生長。(7).力學(xué)壓縮實(shí)驗(yàn)說明復(fù)合材料組有更好的抗壓效果,擁有較好的力學(xué)性質(zhì)。 結(jié)論 (1).低彈性模量(70%孔隙率)的多孔鈦鈮合金類似松質(zhì)骨的抗壓強(qiáng)度和彈性模量；(2).70%孔隙率鈦鈮合金具有良好的生物相容性,低細(xì)胞毒性；(3).復(fù)合BMP的多孔鈦鈮合金材料擁有佳力學(xué)相容性,促進(jìn)骨缺損的修復(fù)。
[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.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2012
【分類號】：R318.08

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