钛表面构建生物活性分子与类骨磷灰石复合功能涂层

发布时间：2018-06-24 20:25

本文选题：钛植入体 + 纤连蛋白　；参考：《华中科技大学》2013年博士论文

【摘要】：钛及其合金是目前临床上广泛使用的一类植入物材料,具有良好的机械性能和生物相容性。然而,长期临床实践和相关研究表明,现有钛植入体材料尚面临许多问题,主要包括：骨再生能力差或再生缓慢,与周围骨组织整合不佳,平均使用寿命不能满足患者的需求。由于钛植入体在体内是通过其表面与周围人体组织相接触的,因此通过表面改性对获得综合性能优良的植入体具有现实意义。通过对材料进行表面改性,能够获得综合性能优良的钛植入体,这对于克服钛植入体的上述不足具有重要的现实意义。近年来,在医用钛植入体表面构建类骨磷灰石涂层,并进一步装载药物、生长因子等生物活性分子,已经成为医用钛领域的研究热点。这些表面改性技术赋予医用钛植入体特定的功能,例如骨传导性和骨诱导性,从而改善钛植入体的骨整合性能和使用寿命。本论文选用具有促细胞粘附的纤连蛋白(Fibronectin, FN)和促细胞向成骨分化的成骨生长肽(Osteogenic growth peptide, OGP),在钛表面构建了一系列的生物活性分子与类骨磷灰石复合功能涂层。我们首先研究了钛表面类骨磷灰石涂层的制备,并对仿生矿化液中类骨磷灰石涂层的生成机理进行了探讨；其次,在钛表面构建了纤连蛋白-类骨磷灰石和成骨生长肽-类骨磷灰石两种复合涂层,并对复合涂层的物相组成、微观形貌、精细结构等进行了检测和分析,研究了生物活性分子对类骨磷灰石生长的影响及作用机理；最后,我们通过不同的生物活性分子固定方法(共沉积法和／或表面吸附法)以及不同的固定顺序,将纤连蛋白和成骨生长肽共固定到具有类骨磷灰石涂层的钛表面,并对改性表面进行了相关的物化表征和体外生物学评价。本文的研究结果包括以下三个方面： (1)通过离子束辅助沉积和仿生矿化沉积相结合的方法,可以在钛表面构建出均匀且均一的类骨磷灰石涂层。实验结果表明,在类骨磷灰石涂层沉积的过程中,随着浸泡时间的延长,类骨磷灰石的XRD特征衍射峰增强,且逐渐窄化,DPBS溶液中钙离子浓度随着磷灰石薄膜的分解逐渐升高,到达峰值后,随着类骨磷灰石的沉积,溶液中钙离子的浓度逐渐降低。随着涂覆在钛表面的磷灰石薄膜结晶度的增加,仿生矿化液中钛表面类骨磷灰石成核的速率逐渐减慢,但随后晶核生长的速度有所增加。 (2)通过生物仿生矿化沉积法,可在磷灰石薄膜活化的钛表面沉积上纤连蛋白-类骨磷灰石或成骨生长肽-类骨磷灰石两种复合涂层。FESEM、confocal结果显示,在构建的复合涂层中,生物活性分子均匀地分布在类骨磷灰石涂层内。慢扫XRD数据的Rietveld精修结果表明,单纯的类骨磷灰石涂层无机化学组成为apatite和OCP,随着生物活性分子的共沉积,类骨磷灰石中OCP所占的百分比逐渐降低,apatite晶胞的c轴长度增加,a轴的长度发生改变。同时,生物活性分子的加入,会降低类骨磷灰石晶体的生长速率,并影响类骨磷灰石晶体的微观形貌。初步的物化表征和精细结构分析表明,生物活性分子的共沉积主要是由生物活性分子、材料表面及溶液中的离子三者之间的静电吸附介导的,在沉积过程中,生物活性分子参与了类骨磷灰石晶胞构建的过程。 (3)通过共沉积法、表面吸附法或两者相结合的方法能够将纤连蛋白和成骨生长肽共固定到具有类骨磷灰石涂层的钛表面。FESEM及XRD的的结果显示,表面吸附的生物活性分子对预沉积的类骨磷灰石的结构和物相没有影响,而共沉积的生物活性分子使沉积的类骨磷灰石的片层结构晶体增大,并且使沉积的类骨磷灰石的主相由apatite转变为OCP。体外释放结果证明,固定的生物活性分子在体外可以进行持续可控的释放。通过体外细胞实验研究表明,共固定的纤连蛋白／成骨生长肽能够显著的提高骨髓间充质干细胞的贴附和铺展能力,并能够有效的促进骨髓间充质干细胞的增殖和向成骨分化。研究证明,通过表面共吸附的方法能够在钛植入体表面同时固定多种生物活性分子,对生物医用植入体发挥长期疗效具有积极作用,在牙科和整形外科等领域具有良好的临床实用价值。
[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.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2013
【分类号】：R318.08

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