本文選題：骨修復(fù) + 文石　； 參考：《清華大學(xué)》2014年博士論文

【摘要】：珍珠層憑借優(yōu)異的生物相容性和自身攜帶蛋白質(zhì)的特點(diǎn)，近年來成為骨組織工程的一個(gè)研究熱點(diǎn)。為了制備理想的骨組織工程支架，本論文探討了文石和球文石珍珠水可溶基質(zhì)的成骨特性，制備并表征了PLLA/文石和PLLA/球文石珍珠支架，通過動(dòng)物實(shí)驗(yàn)證實(shí)了PLLA/文石和PLLA/球文石支架具有良好的促進(jìn)骨再生的能力。 將珍珠水可溶有機(jī)基質(zhì)按分子量分為有機(jī)基質(zhì)1kDa和有機(jī)基質(zhì)3.5kDa，對(duì)比了文石和球文石不同分子量的有機(jī)基質(zhì)對(duì)小鼠MC3T3-E1細(xì)胞和人骨髓間充質(zhì)干細(xì)胞的作用。水可溶有機(jī)基質(zhì)對(duì)兩種細(xì)胞的增殖無促進(jìn)作用，但能夠促進(jìn)兩種細(xì)胞向成骨方向分化。細(xì)胞增殖和分化與有機(jī)基質(zhì)的分子量無明顯關(guān)系。水可溶有機(jī)基質(zhì)能夠促進(jìn)小鼠MC3T3-E1細(xì)胞的礦化，縮短礦化時(shí)間。總的有機(jī)基質(zhì)以及分子量1kDa的有機(jī)基質(zhì)能夠縮短人骨髓間充質(zhì)干細(xì)胞的礦化時(shí)間。以上結(jié)果均適用于文石和球文石有機(jī)基質(zhì)。 采用冷凍干燥法制備了PLLA、PLLA/文石珍珠粉和PLLA/球文石珍珠粉支架。復(fù)合支架和PLLA支架具有良好的多孔結(jié)構(gòu)，添加珍珠粉可以提高支架的壓縮強(qiáng)度和壓縮模量，而孔隙率略微下降。PLLA/文石珍珠粉、PLLA/貝殼珍珠層粉和PLLA/球文石珍珠粉復(fù)合膜的親水性順序?yàn)镻LLA/文石PLLA/貝殼珍珠層PLLA/球文石，與復(fù)合膜吸附蛋白的實(shí)驗(yàn)結(jié)果吻合。細(xì)胞相容性實(shí)驗(yàn)表明，PLLA/文石和PLLA/貝殼珍珠層支架均能促進(jìn)小鼠骨髓間充質(zhì)干細(xì)胞的增殖和分化，而PLLA/球文石支架卻有一定的抑制作用。 體外降解實(shí)驗(yàn)表明，，PLLA/文石和PLLA/球文石支架降解行為類似，在PBS中降解呈略堿性，因此減緩了支架的降解速度。其原因在于堿性環(huán)境可以中和PLLA降解產(chǎn)生的酸性，影響孔隙率的變化，減緩PLLA分子量的降低等。在降解過程中，隨著珍珠粉的不斷溶解，復(fù)合支架的體密度不斷下降，力學(xué)性能不斷下降，但其力學(xué)性能一直高于PLLA支架。 通過骨缺損修復(fù)的動(dòng)物實(shí)驗(yàn)證實(shí)，PLLA/文石支架在8周時(shí)有加速成骨的作用，12周時(shí)新生骨已經(jīng)與正常骨無異。PLLA/球文石支架在12周時(shí)也有很好的修復(fù)效果。說明PLLA/文石和PLLA/球文石支架均有良好的成骨作用。以上結(jié)果為珍珠作為骨修復(fù)材料的臨床應(yīng)用提供了理論和實(shí)驗(yàn)基礎(chǔ)。
[Abstract]:The pearl layer has become a research hotspot in bone tissue engineering in recent years because of its excellent biocompatibility and the characteristics of its own proteins. In order to prepare ideal scaffolds for bone tissue engineering, the osteogenic properties of dolomite and ductile pearl hydrosoluble matrix were investigated in this paper, and PLLA/ ductile pearl scaffolds were prepared and characterized. Animal experiments have proved that PLLA/ and PLLA/ ball stone scaffolds have a good ability to promote bone regeneration. Pearl soluble organic matrix was divided into organic matrix (1kDa) and organic matrix (3.5kDa) according to molecular weight. The effects of different molecular weight organic matrix on mouse MC3T3-E1 cells and human bone marrow mesenchymal stem cells were compared. The water-soluble organic matrix did not promote the proliferation of the two kinds of cells, but could promote the differentiation of the two kinds of cells towards osteogenesis. Cell proliferation and differentiation were not related to the molecular weight of organic matrix. Water soluble organic matrix can promote the mineralization of mouse MC3T3-E1 cells and shorten the mineralization time. The total organic matrix and the organic matrix with molecular weight 1kDa can shorten the mineralization time of human bone marrow mesenchymal stem cells. The above results are applicable to the organic matrix of aragonite and globulitic stone. PLLA-PLLA / dolomite pearl powder and PLLA/ ball pearlite powder scaffold were prepared by freeze-drying method. The composite scaffold and PLLA bracket have good porous structure, adding pearl powder can improve the compression strength and modulus of the scaffold. However, the hydrophilic order of PLLA / dollite / pearl powder and PLLA/ ball pearl powder composite membrane is PLLA/ aragonite PLLA/ shell pearl layer PLLA/ nodular dolomite, which is consistent with the experimental results of the composite membrane adsorption protein. The cytocompatibility test showed that both PLLA / aragonite and PLLA/ shell pearl layer scaffolds could promote the proliferation and differentiation of mouse bone marrow mesenchymal stem cells, while PLLA/ spheroid stone scaffolds could inhibit the proliferation and differentiation of mouse bone marrow mesenchymal stem cells. In vitro degradation experiments showed that the degradation behavior of PLLA / aragonite and PLLA/ ductile stone scaffolds was similar and slightly alkaline in PBS, so the degradation rate of stents was slowed down. The reason is that alkaline environment can neutralize the acidity produced by PLLA degradation, affect the change of porosity and slow down the decrease of PLLA molecular weight. In the process of degradation, with the continuous dissolution of pearl powder, the bulk density and mechanical properties of composite scaffolds decreased, but the mechanical properties of composite scaffolds were always higher than those of PLLA scaffolds. The animal experiment of bone defect repair confirmed that PLLA / aragonite scaffold could accelerate osteogenesis at 8 weeks. At 12 weeks, the new bone had the same effect as normal bone. PLLA / bulbstone scaffold also had good effect at 12 weeks. The results showed that both PLLA/ and PLLA/ spheroidal stone scaffolds had good osteogenic effect. These results provide a theoretical and experimental basis for the clinical application of pearl as bone repair material.
【學(xué)位授予單位】：清華大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R318.08

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相關(guān)期刊論文 前3條

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本文編號(hào)：1918315