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可注射性硼酸鹽生物玻璃骨水泥的制備及對(duì)骨缺損修復(fù)的研究

發(fā)布時(shí)間:2018-09-08 08:34
【摘要】:目的:為臨床骨水泥應(yīng)用中存在的問題提供一種新的解決方案。本研究設(shè)計(jì)制備以硼酸鹽生物玻璃顆粒為固相的骨水泥(BBG cement),測(cè)定不同固液相(硼酸鹽生物玻璃顆粒/殼聚糖)比例的理化性質(zhì),選擇出一種適用于臨床應(yīng)用的BBG骨水泥。在體外,將骨水泥樣品浸泡在模擬體液(SBF)中,研究離子釋放和羥基磷灰石(HA)轉(zhuǎn)化情況;接種骨髓間充質(zhì)干細(xì)胞(BMSCs),檢測(cè)細(xì)胞的粘附、增殖和成骨分化;同時(shí)在兔股骨髁缺損模型中植入骨水泥,了解其在體內(nèi)的促成骨能力。此外,我們制備硼酸鹽生物玻璃粉體中摻入功能元素鍶(Sr),并測(cè)試Sr-BBG的理化性能,研究骨水泥表面的BMSCs生物學(xué)行為及體內(nèi)的生物相容性和骨生成作用。方法:將BBG粉體和殼聚糖溶液以不同的固液相比例制備出骨水泥,對(duì)可注射性、凝固時(shí)間、粘結(jié)性和抗壓強(qiáng)度進(jìn)行全面評(píng)價(jià)。用掃描電子顯微鏡(SEM)和X線衍射法(XRD)觀察其表面形貌和HA轉(zhuǎn)化。通過ICP-AES法測(cè)定骨水泥中的離子釋放。在體外,將BMSCs接種于骨水泥,通過SEM、CCK-8、ALP活性和qRT-PCR等方法研究骨水泥的細(xì)胞相容性以及骨水泥對(duì)細(xì)胞的粘附、增殖和分化的影響。體內(nèi)將骨水泥植入新西蘭大白兔股骨髁缺損區(qū),通過Micro-CT和組織學(xué)檢測(cè)方法對(duì)其成骨效果進(jìn)行評(píng)價(jià)。結(jié)果:制備的BBG骨水泥有著良好的可注射性、初凝時(shí)間、粘結(jié)性和抗壓強(qiáng)度。在SBF中,骨水泥釋放離子并發(fā)生HA轉(zhuǎn)化。體外實(shí)驗(yàn)中,BBG骨水泥對(duì)細(xì)胞沒有明顯毒性作用,BMSCs在BBG骨水泥表面上能夠良好粘附、增殖,并促進(jìn)其成骨分化。在缺損區(qū)植入骨水泥,結(jié)果發(fā)現(xiàn)BBG骨水泥較CS骨水泥有更多的骨組織新生。此外,鍶摻雜的BBG骨水泥同樣有著良好的可注射性、初凝時(shí)間和抗壓強(qiáng)度,相比較于不含鍶的BBG骨水泥,其能夠更好地促進(jìn)BMSCs的粘附、增殖和成骨分化,并顯著促進(jìn)缺損區(qū)域骨再生和提高宿主骨和植入物接觸(BIC)指數(shù)。結(jié)論:BBG骨水泥是一種具有臨床應(yīng)用潛力的骨修復(fù)材料,證實(shí)其具有可調(diào)控的可注射性和初凝時(shí)間,較強(qiáng)的抗壓強(qiáng)度及抗?jié)⑸⑿。在SBF中,骨水泥釋放具有成骨效應(yīng)的各種離子并發(fā)生HA轉(zhuǎn)化,促進(jìn)BMSCs的粘附、增殖和成骨分化。BBG骨水泥摻鍶后除了具有良好生物相容性和生物降解性外,也具有臨床使用中需要的可注射性、初凝時(shí)間和抗壓強(qiáng)度,并且更好地刺激BMSCs的增殖和分化,能誘導(dǎo)骨再生和骨整合。Sr-BBG骨水泥,為骨缺損(尤其是大面積骨缺損)的治療提供了一個(gè)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.
【學(xué)位授予單位】:上海交通大學(xué)
【學(xué)位級(jí)別】:博士
【學(xué)位授予年份】:2015
【分類號(hào)】:R318.08;R68

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

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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