本文選題：鈦植入體 + 纖連蛋白�。� 參考：《華中科技大學(xué)》2013年博士論文

【摘要】：鈦及其合金是目前臨床上廣泛使用的一類植入物材料,具有良好的機(jī)械性能和生物相容性。然而,長期臨床實(shí)踐和相關(guān)研究表明,現(xiàn)有鈦植入體材料尚面臨許多問題,主要包括：骨再生能力差或再生緩慢,與周圍骨組織整合不佳,平均使用壽命不能滿足患者的需求。由于鈦植入體在體內(nèi)是通過其表面與周圍人體組織相接觸的,因此通過表面改性對(duì)獲得綜合性能優(yōu)良的植入體具有現(xiàn)實(shí)意義。通過對(duì)材料進(jìn)行表面改性,能夠獲得綜合性能優(yōu)良的鈦植入體,這對(duì)于克服鈦植入體的上述不足具有重要的現(xiàn)實(shí)意義。近年來,在醫(yī)用鈦植入體表面構(gòu)建類骨磷灰石涂層,并進(jìn)一步裝載藥物、生長因子等生物活性分子,已經(jīng)成為醫(yī)用鈦領(lǐng)域的研究熱點(diǎn)。這些表面改性技術(shù)賦予醫(yī)用鈦植入體特定的功能,例如骨傳導(dǎo)性和骨誘導(dǎo)性,從而改善鈦植入體的骨整合性能和使用壽命。 本論文選用具有促細(xì)胞粘附的纖連蛋白(Fibronectin, FN)和促細(xì)胞向成骨分化的成骨生長肽(Osteogenic growth peptide, OGP),在鈦表面構(gòu)建了一系列的生物活性分子與類骨磷灰石復(fù)合功能涂層。我們首先研究了鈦表面類骨磷灰石涂層的制備,并對(duì)仿生礦化液中類骨磷灰石涂層的生成機(jī)理進(jìn)行了探討；其次,在鈦表面構(gòu)建了纖連蛋白-類骨磷灰石和成骨生長肽-類骨磷灰石兩種復(fù)合涂層,并對(duì)復(fù)合涂層的物相組成、微觀形貌、精細(xì)結(jié)構(gòu)等進(jìn)行了檢測(cè)和分析,研究了生物活性分子對(duì)類骨磷灰石生長的影響及作用機(jī)理；最后,我們通過不同的生物活性分子固定方法(共沉積法和／或表面吸附法)以及不同的固定順序,將纖連蛋白和成骨生長肽共固定到具有類骨磷灰石涂層的鈦表面,并對(duì)改性表面進(jìn)行了相關(guān)的物化表征和體外生物學(xué)評(píng)價(jià)。本文的研究結(jié)果包括以下三個(gè)方面： (1)通過離子束輔助沉積和仿生礦化沉積相結(jié)合的方法,可以在鈦表面構(gòu)建出均勻且均一的類骨磷灰石涂層。實(shí)驗(yàn)結(jié)果表明,在類骨磷灰石涂層沉積的過程中,隨著浸泡時(shí)間的延長,類骨磷灰石的XRD特征衍射峰增強(qiáng),且逐漸窄化,DPBS溶液中鈣離子濃度隨著磷灰石薄膜的分解逐漸升高,到達(dá)峰值后,隨著類骨磷灰石的沉積,溶液中鈣離子的濃度逐漸降低。隨著涂覆在鈦表面的磷灰石薄膜結(jié)晶度的增加,仿生礦化液中鈦表面類骨磷灰石成核的速率逐漸減慢,但隨后晶核生長的速度有所增加。 (2)通過生物仿生礦化沉積法,可在磷灰石薄膜活化的鈦表面沉積上纖連蛋白-類骨磷灰石或成骨生長肽-類骨磷灰石兩種復(fù)合涂層。FESEM、confocal結(jié)果顯示,在構(gòu)建的復(fù)合涂層中,生物活性分子均勻地分布在類骨磷灰石涂層內(nèi)。慢掃XRD數(shù)據(jù)的Rietveld精修結(jié)果表明,單純的類骨磷灰石涂層無機(jī)化學(xué)組成為apatite和OCP,隨著生物活性分子的共沉積,類骨磷灰石中OCP所占的百分比逐漸降低,apatite晶胞的c軸長度增加,a軸的長度發(fā)生改變。同時(shí),生物活性分子的加入,會(huì)降低類骨磷灰石晶體的生長速率,并影響類骨磷灰石晶體的微觀形貌。初步的物化表征和精細(xì)結(jié)構(gòu)分析表明,生物活性分子的共沉積主要是由生物活性分子、材料表面及溶液中的離子三者之間的靜電吸附介導(dǎo)的,在沉積過程中,生物活性分子參與了類骨磷灰石晶胞構(gòu)建的過程。 (3)通過共沉積法、表面吸附法或兩者相結(jié)合的方法能夠?qū)⒗w連蛋白和成骨生長肽共固定到具有類骨磷灰石涂層的鈦表面。FESEM及XRD的的結(jié)果顯示,表面吸附的生物活性分子對(duì)預(yù)沉積的類骨磷灰石的結(jié)構(gòu)和物相沒有影響,而共沉積的生物活性分子使沉積的類骨磷灰石的片層結(jié)構(gòu)晶體增大,并且使沉積的類骨磷灰石的主相由apatite轉(zhuǎn)變?yōu)镺CP。體外釋放結(jié)果證明,固定的生物活性分子在體外可以進(jìn)行持續(xù)可控的釋放。通過體外細(xì)胞實(shí)驗(yàn)研究表明,共固定的纖連蛋白／成骨生長肽能夠顯著的提高骨髓間充質(zhì)干細(xì)胞的貼附和鋪展能力,并能夠有效的促進(jìn)骨髓間充質(zhì)干細(xì)胞的增殖和向成骨分化。研究證明,通過表面共吸附的方法能夠在鈦植入體表面同時(shí)固定多種生物活性分子,對(duì)生物醫(yī)用植入體發(fā)揮長期療效具有積極作用,在牙科和整形外科等領(lǐng)域具有良好的臨床實(shí)用價(jià)值。
[Abstract]:Titanium and its alloys are a kind of implant materials widely used clinically, with good mechanical properties and biocompatibility. However, long-term clinical practice and related studies show that the existing titanium implant materials are still faced with many problems, including poor bone regeneration or slow regeneration, poor integration with surrounding bone tissue, and average making Life can not meet the needs of the patient. Because the titanium implant is in contact with the surrounding tissue in the body, the surface modification is of practical significance to the implants with excellent comprehensive performance. By surface modification of the material, the titanium implants with excellent comprehensive properties can be obtained, which can be used to overcome the titanium implant. In recent years, the construction of bone like apatite coating on the surface of medical titanium implant and further loading of bioactive molecules such as drugs and growth factors have become a hot spot in the field of medical titanium. These surface modification techniques give medical titanium implants specific functions, such as bone conductivity. And bone induction, thereby improving the osseointegration and life span of titanium implants.
In this paper, Fibronectin (FN) with cell adhesion and osteogenic growth peptide (Osteogenic growth peptide, OGP) for osteogenic differentiation were used to construct a series of bioactive molecules and bone like apatite composite coatings on the titanium surface. First, we studied the preparation of the apatite coating on the titanium surface. The formation mechanism of bone like apatite coating in biomimetic mineralized fluid was discussed. Secondly, two kinds of composite coatings were constructed on the titanium surface, including fibronectin like bone apatite and osteogenic growth peptide - bone apatite, and the phase composition, micromorphology and fine structure of the composite coating were detected and analyzed, and the bioactive molecules were studied. The effect and mechanism on the growth of bone like apatite; finally, we co immobilize fibronectin and osteogenic growth peptide onto the titanium surface with bone like apatite coating by different bioactive molecular immobilization methods (co deposition and / or surface adsorption) and different fixation sequences, and have related materials to the modified surface. Characterization and in vitro biological evaluation. The results of this study include the following three aspects:
(1) a homogeneous and homogeneous bone like apatite coating can be constructed on the titanium surface by the combination of ion beam assisted deposition and biomimetic mineralization. The experimental results show that the XRD characteristic diffraction peak of bone like apatite is enhanced and gradually narrowed in the DPBS solution during the deposition of the bone like apatite coating. The concentration of calcium ion increases with the decomposition of apatite film gradually. After the peak of the apatite, the concentration of calcium ions in the solution decreases gradually with the deposition of bone like apatite. With the increase of the crystallinity of the apatite film coated on the titanium surface, the rate of the titanium like bone phosphorus ash Shi Chenghe in the biomimetic mineralized fluid gradually slows down, but then the nucleation is grown. The speed has increased.
(2) by biomimetic mineralized deposition, two composite coatings of fibronectin like bone apatite or osteogenic apatite can be deposited on the activated titanium surface of the apatite film. The results of confocal show that in the composite coating, the bioactive molecules are evenly distributed in the apatite coating of the bone like bone. Slow sweep of XRD data in the composite coating. The results of Rietveld refinement showed that the inorganic chemical composition of pure bone like apatite coating was apatite and OCP. With the co deposition of bioactive molecules, the percentage of OCP in bone like apatite gradually decreased, the c axis length of apatite cell increased and the length of a axis changed. At the same time, the addition of bioactive molecules would reduce the phosphorus like ash. The growth rate of stone crystals affects the micromorphology of the bone like apatite crystals. Preliminary physicochemical characterization and fine structure analysis show that the co deposition of bioactive molecules is mainly mediated by the electrostatic adsorption between the bioactive molecules, the surface of the material and the ions of the three ions in the solution. In the process of deposition, the bioactive molecules are involved. The process of construction of bone like apatite crystal cell.
(3) by co deposition, the surface adsorption or combination method can co immobilize fibronectin and osteogenic growth peptide to.FESEM and XRD on the titanium surface with bone like apatite coating. The results show that the bioactive molecules adsorbed on the surface have no effect on the structure and phase of the predeposited osseous phosphonite, and the co deposition of the bioactive molecules. The active molecules of the material increase the lamellar structure of the deposited bone like apatite, and change the main phase of the deposited bone apatite from apatite to the release of OCP. in vitro. The immobilized bioactive molecules can be released continuously and controlled in vitro. Bone growth peptide can significantly improve the adhesion and spreading ability of bone marrow mesenchymal stem cells, and can effectively promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. It is proved that a variety of bioactive molecules can be immobilized on the surface of titanium implant by surface CO adsorption. The curative effect has positive effect, and has good clinical practical value in dentistry and plastic surgery.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2013
【分類號(hào)】：R318.08

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本文編號(hào)：2062804