矿化胶原涂层的可控电化学制备及其性能研究

发布时间：2018-03-28 12:47

本文选题：生物材料　切入点：骨修复材料　出处：《浙江大学》2012年硕士论文

【摘要】：促进或加速骨组织修复效能是当今骨修复材料研究重点。在骨修复材料中,钛及钛合金由于有良好的力学性能、生物相容性以及抗腐蚀能力,而被广泛用于骨科及牙科手术中。但其生物活性以及与细胞响应性较差,因此,提高钛金属植入体生物响应性和生物活性因子/药物承载性是当前研究热点。骨细胞外基质主要由胶原蛋白等构成,而羟基磷灰石(HA)是骨组织的主要无机成分。因此,在钛表面构建出胶原/HA复合(矿化)涂层,肯定能促进骨细胞吸附、生长及增殖,以及增加生物活性因子/药物承载能力,从而有效提高植入体的骨整合能力和手术质量。为此本文采用电化学沉积技术,通过电沉积参数、电解液组成等调控,开展了钛植入体可控制备矿化胶原涂层的研究。在电化学沉积制备矿化胶原涂层过程中,对钛基板采用碱热处理,表面可形成多孔氧化层,可以有效提高沉积层的宏观均匀性,这是由于多孔氧化层有利于电子的传输,同时为涂层中磷酸钙和胶原分子的沉积提供了更大的比表面积,有利于涂层形成和结合强度的提高。沉积温度会影响涂层的形貌及矿化磷酸钙晶相的构成,在37℃以上沉积时能获得HA晶相,形成HA/胶原涂层。沉积电压会影响涂层的形貌,在较高电压下沉积形成多孔结构,在低电压下涂层不能有效沉积。其原因为沉积电压会改变阴极附近OH-浓度及分布,从而影响胶原的矿化和沉积行为。H2O2可作为电化学反应增强剂,其加入会改变阴极电化学反应类型,加速阴极处OH-的产生,在较短沉积时间和较低沉积电压时可实现涂层的沉积,提高了涂层制备的可控性。当H202浓度为18 mM,电解液pH 4.5,沉积温度37℃,在1.3～1.9 V时可制备致密矿化胶原涂层,在2～2.7 V时可制备多孔矿化胶原涂层。本实验中,多孔涂层和致密涂层的胶原纤维均为矿化形态,多孔涂层胶原矿化程度高,胶原纤维分布比较分散,致密涂层胶原矿化程度低,HA结晶程度弱,胶原堆积致密。涂层断面、剥离后各层形貌显示多孔涂层和致密涂层均呈空间准三维结构,涂层厚度为20～30μm,靠近基底为HA层,中间层为HA与矿化胶原混合层,外层为矿化胶原层。力学性能测试表明矿化胶原涂层与基板有一定的结合力。体外研究表明涂层在模拟体液中能稳定存在并发生进一步矿化,表现出良好的生物活性。细胞实验表明矿化胶原涂层能增加骨细胞的附着并促进其增殖。涂层可用作承载生物活性因子/药物的平台,实现抗菌药物的装载,释放具有一定的缓释能力,载万古霉素后的涂层显示了一定的杀菌效果。通过对沉积过程的分段模拟,建立了电化学沉积机理的模型,即矿化胶原沉积可分为三个步骤：首先,磷酸钙在钛基板的迅速沉积,并伴随胶原在等电点的自组装；然后,磷酸钙在胶原纤维上形核生长,形成胶原矿化；最终,矿化胶原在电场力的推动下向钛基板移动,并与磷酸钙层结合组装在钛基板上。胶原自组装和矿化行为对矿化胶原涂层的沉积行为起着决定作用,因此,通过调控阴极pH梯度、胶原等电点是实现矿化胶原涂层可控制备的关键。
[Abstract]:Promoting and accelerating bone repair efficiency is the focus of the study. Bone repair materials in bone repair materials, titanium and titanium alloy with good mechanical properties, corrosion resistance and biocompatibility, and is widely used in Department of orthopedics and dental surgery. But its biological activity and the response is poor, and therefore improve the cell. Titanium implant biological response and biological factor / drug loading is the focus of current research.
The bone extracellular matrix composed mainly of collagen, and hydroxyapatite (HA) is the main inorganic composition of bone tissue. Therefore, the titanium surface modification with collagen /HA composite coating (mineralization), can promote bone cell adhesion, growth and proliferation, and increase the biological factor / drug carrying capacity, so as to effectively improve the bone integration ability and operation quality of the implant. This paper uses electrochemical deposition technique, by electrodeposition parameters, electrolyte composition and regulation, to carry out research on titanium implant preparation of mineralized collagen coatings.
In the electrochemical deposition preparation of mineralized collagen coating process on titanium substrate by alkali heat treatment, the surface can form a porous oxide layer, can effectively improve the macroscopic uniformity of deposition layer, which is due to the porous oxide layer is conducive to electronic transmission, at the same time for the deposition of calcium phosphate coating and collagen molecules provides greater the specific surface area, is conducive to the formation and improve the bonding strength of the coating. The deposition temperature can affect the morphology and mineralization of calcium phosphate crystal coating phase composition, can obtain the HA phase deposition in 37 degrees above, the formation of HA/ collagen coating. The deposition voltage will affect the morphology of the coatings, deposited to form a porous structure under relatively high voltage, an effective coating can not be deposited at a low voltage. The reason for the change of deposition voltage near the cathode of OH- concentration and distribution, thus affecting the.H2O2 mineralization and deposition of collagen can be used as an electrochemical reaction enhancer, which added Will change the electrochemical reaction type, accelerate the cathode OH-, deposited in a short deposition time and low deposition voltage can be realized when the coating, improve the controllability of coating preparation. When the concentration of H202 was 18 mM, 4.5 pH electrolyte, deposition temperature of 37 DEG C, in 1.3 ~ 1.9 V can be prepared preparation of mineralized collagen coating in 2 ~ 2.7 V can be prepared porous mineralized collagen coating.
In this experiment, porous coating and dense coating of collagen fibers were mineralized collagen morphology, porous coating of a high degree of mineralization, the collagen fibers distributed, dense coating mineralized collagen low degree of crystallinity of HA weak collagen accumulation density. After peeling off the coating section, each layer morphology shows that the porous coating and dense coating showed space quasi three dimensional structure, the thickness of the coating is 20~30 m, close to the substrate for the HA layer, the middle layer is HA and mineralized collagen mixed layer, the outer layer of mineralized collagen layer. The mechanical properties test showed that the mineralized collagen coating and substrate binding force.
In vitro studies showed that the coating can exist stably and further mineralization in SBF, showed good biological activity. The cellular experiments of mineralized collagen coating can increase the adhesion of osteoblasts and promote its proliferation. Coating can be used as a biological factor / drug loading platform, realize the antibacterial drug loading, release with sustained ability after coating, vancomycin showed some sterilization effect.
Through the simulation of segmented deposition process, established the mechanism of electrochemical deposition model, namely the mineralized collagen deposition can be divided into three steps: first, the rapid deposition of calcium phosphate on titanium substrate, and with the isoelectric point of collagen self-assembly; then, nucleation and growth of calcium phosphate in the form of collagen fibers, the formation of mineralized collagen finally, in the promotion of mineralized collagen; electric field force to the titanium substrate moving, and assembled on the titanium substrate and calcium phosphate layer. The deposition behavior of the self-assembly of collagen and mineralization behavior of mineralized collagen coating plays a decisive role, therefore, through the regulation of the cathode pH gradient isoelectric point of collagen, mineralized collagen is coating preparation of the key.

【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R318.08

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