结构有序纳米HA涂层的电化学构筑及钛/细胞界面原位EIS研究
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摘要
医用金属钛及其合金的表面活性改性及材料的生物学响应是生物材料研究领域的焦点之一。针对当前国内外在钛表面的羟基磷灰石(HA)涂覆、HA涂层组分和结构控制、HA涂层形成机理及主要影响因素以及生物材料与细胞的相互作用机理等关键技术和科学问题，本论文工作旨在从仿生学角度进一步发展温和的电化学沉积技术在医用钛金属表面构筑具有优良生物性能和力学性能的有序结构HA涂层，探明高生物活性涂层的形成机理及规律性；发展电化学交流阻抗谱(EIS)技术用于原位检测材料／细胞相互作用及其存在的电化学本质联系，以探明生物材料与细胞相互作用过程的界面结构。
本论文主要研究内容有：a)侧重采用低浓度体系的电化学沉积技术制备均匀纳米HA涂层，探索涂层结构设计和组分设计的可能性，以制备结构仿生复合人工骨涂层；b)考察相关实验参数对涂层性能的影响，深入探讨低浓度体系HA涂层的电化学沉积过程的规律性；c)深入探讨钙磷盐电化学沉积机理，并建立低浓度体系HA涂层的电化学沉积模型；d)建立材料／细胞界面EIS原位测量技术，探索钛／细胞界面相互作用过程的电化学本质。主要研究结果如下：
1．发展了低浓度体系电化学沉积方法，获得高结晶度、单一组分HA涂层，在此条件下制备的纯HA涂层具有花簇状、直立状和微孔状三种典型的微观形貌。首次实现了钛表面纳微米结构有序的纯HA涂层的构筑，细胞实验表明，这种特殊结构的HA涂层具有比其它结构的HA涂层更加优异的生物性能。
2．发展电化学共沉积方法构筑了具有独特微孔状结构的HA／胶原复合仿生骨涂层，红外谱图证明，涂层中有一定量胶原组分存在，SEM形貌和XRD谱图表明，该复合涂层中HA晶粒更加细化，结构特征比纯HA涂层更接近于自然骨。
3．系统考察了电化学沉积技术中各种影响因素的作用机制，从理论和实验上证实，对于低浓度体系，在相当宽的实验参数范围内，均能获得高结晶度HA涂层，而涂层中HA晶粒的尺寸分布、排列等形貌特征以及涂层的生长速度等与电化学沉积的实验参数关系密切。
4．研究表明，HA涂层沉积过程中的热力学和动力学条件直接决定其组成与结构，成核过程主要由热力学(ΔG)控制，生长过程主要由动力学环境控制。热力学分析证明，低浓度体系中的低钙磷物种浓度和较高沉积温度有利于单一组分HA的形成。动力学计算得到一定条件下涂层生长的表观活化能近似为174．9 kJ·mol~(-1)，涂层生长过程由动力学控制。探明HA电化学沉积过程的规律性，并初步提出了低浓度体系HA涂层的沉积模型。
5．设计了原位电解池，并引入Ag／AgCl参比电极，测试生物材料／细胞界面相互作用的电化学交流阻抗谱，解决了EIS测试过程中高频信号失真的问题。
6．钛／细胞界面EIS测量初步结果表明，细胞在电极材料表面附着可改变界面双电层组成和电极的表面状态。材料表面阻抗信号通常处于中低频段，而细胞膜层自身的电化学阻抗信号处于高频段，解析其相互关系可以得到材料／细胞相互作用机理方面的信息。
The surface modification for bioproperties and biological response of titaniumare among the most focal studies in biomaterials field.The emphases of this thesisresearch are put on some scientific and technical key problems,such as the novelcoating techniques of hydroxyapatite (HA),the control of composition and structureof HA coating,the mechanism and main influence factors of HA coating formationand the interaction of biomaterials and cells in biological environment.The aims ofthis work are to develop novel HA electrochemical deposition methods,from theaspect of bionics,to construct ordered nano structrured HA coating and its hybridcoating with both excellent biological and good mechanical properties on titaniumsubstrate,to further study the mechanism of HA formation on the Ti surface and todevelop electrochemical impedance spectroscopy (EIS) to in situ elucidate theinterfacial structure and the interactions of biomaterials and cells.
The main work includes:a) construction of nano HA coating byelectrochemical deposition technique in low concentration system,b) design andcontrol of structure and composition of HA coating for fabrication of bionic artificialbone coating,c) systematical investigation of the effects of main depositionparameters on coating properties,d) further understanding of the mechanism ofelectrochemical deposition of calcium phosphates on Ti in low concentration system,and e) establishment of an in situ electrochemical cell for studying the interaction oftitanium/MG63 cell by EIS measurement.The following conclusions can be drawn:
1.A pure HA coating with high crystallinity has been prepared byelectrochemical deposition method in low concentration system.The HAcoating exhibits three kinds of typical topographies,i.e.flower type,standing-up type and porous type topographies.The nano-micro structuredordered pure HA coating has been firstly constructed on titanium substrate.Preliminary in vitro test indicates that the HA coating with such specialnano-micro two level structure is of more excellent bioactivity comparedwith other kinds of HA coatings.
2.The HA/Collagen hybrid coating with nano-micro ordered structure has beenfabricated as well by using electrochemical co-deposition method.The FTIR spectra demonstrates the existence of collagen in the composite coating,andthe SEM and XRD results shows that the crystal size of HA in the compositecoating is significantly decreased with the addition of collagen component,and the structure of the composite coating is more mimetic to the naturalbone when compared with the pure HA coating.
3.The effect of the main preparing parameters on the HA electrochemicaldeposition in low concentration system has been systematically investigated.It is indicated that in a very wide range of preparing parameter,highlycrystallized and pure HA coating can be obtained,while the distribution ofthe crystal size,the arrangement of the crystal grains and the depositionvelocity of the HA coating are intimately related to the depositionparameters.
4.The chemical composition and structure of the electrochemically depositedcalcium phosphate coating are determined by both thermodynamic andkinetic conditions.The nucleation process is mainly influenced by thethermodynamic factors,such asΔG,and the growth behavior is mainlycontrolled by the dynamic environments.The thermodynamic analysisdemonstrates that both the lower concentration of calcium and phosphorusspecies and the higher temperature in the system facilitate the pure HAformation,comparing with the traditional high concentration system.According to kinetic calculation,the apparent activity energy of the HAformation in a specific low concentration system is estimated to be 174.9kJ·mol~(1).An electrochemical deposition model of HA coating in lowconcentration system has been proposed to further clarify the behaviors ofthe HA coating formation.
5.An in situ electrochemical cell has been designed for the ac impedancemeasurements at biomaterial/cell interface.A home-made Ag/AgCl electrodeis introduced to the in situ cell as a reference electrode to eliminate thedistortion phenomena during the ac impedance measurement in highfrequency range.
6.It is demonstrated,from the EIS analysis of titanium/cell interface,that theadhesion of cells onto the biomaterial surface may alter the surface states andstructure of double layer at the interface.The ac impedance information in the higher frequency range is mainly from the cell adsortion process ontitanium surface,which is helpful to understand the interaction betweenbiomaterials and living cells.
本论文主要研究内容有：a)侧重采用低浓度体系的电化学沉积技术制备均匀纳米HA涂层，探索涂层结构设计和组分设计的可能性，以制备结构仿生复合人工骨涂层；b)考察相关实验参数对涂层性能的影响，深入探讨低浓度体系HA涂层的电化学沉积过程的规律性；c)深入探讨钙磷盐电化学沉积机理，并建立低浓度体系HA涂层的电化学沉积模型；d)建立材料／细胞界面EIS原位测量技术，探索钛／细胞界面相互作用过程的电化学本质。主要研究结果如下：
1．发展了低浓度体系电化学沉积方法，获得高结晶度、单一组分HA涂层，在此条件下制备的纯HA涂层具有花簇状、直立状和微孔状三种典型的微观形貌。首次实现了钛表面纳微米结构有序的纯HA涂层的构筑，细胞实验表明，这种特殊结构的HA涂层具有比其它结构的HA涂层更加优异的生物性能。
2．发展电化学共沉积方法构筑了具有独特微孔状结构的HA／胶原复合仿生骨涂层，红外谱图证明，涂层中有一定量胶原组分存在，SEM形貌和XRD谱图表明，该复合涂层中HA晶粒更加细化，结构特征比纯HA涂层更接近于自然骨。
3．系统考察了电化学沉积技术中各种影响因素的作用机制，从理论和实验上证实，对于低浓度体系，在相当宽的实验参数范围内，均能获得高结晶度HA涂层，而涂层中HA晶粒的尺寸分布、排列等形貌特征以及涂层的生长速度等与电化学沉积的实验参数关系密切。
4．研究表明，HA涂层沉积过程中的热力学和动力学条件直接决定其组成与结构，成核过程主要由热力学(ΔG)控制，生长过程主要由动力学环境控制。热力学分析证明，低浓度体系中的低钙磷物种浓度和较高沉积温度有利于单一组分HA的形成。动力学计算得到一定条件下涂层生长的表观活化能近似为174．9 kJ·mol~(-1)，涂层生长过程由动力学控制。探明HA电化学沉积过程的规律性，并初步提出了低浓度体系HA涂层的沉积模型。
5．设计了原位电解池，并引入Ag／AgCl参比电极，测试生物材料／细胞界面相互作用的电化学交流阻抗谱，解决了EIS测试过程中高频信号失真的问题。
6．钛／细胞界面EIS测量初步结果表明，细胞在电极材料表面附着可改变界面双电层组成和电极的表面状态。材料表面阻抗信号通常处于中低频段，而细胞膜层自身的电化学阻抗信号处于高频段，解析其相互关系可以得到材料／细胞相互作用机理方面的信息。
The surface modification for bioproperties and biological response of titaniumare among the most focal studies in biomaterials field.The emphases of this thesisresearch are put on some scientific and technical key problems,such as the novelcoating techniques of hydroxyapatite (HA),the control of composition and structureof HA coating,the mechanism and main influence factors of HA coating formationand the interaction of biomaterials and cells in biological environment.The aims ofthis work are to develop novel HA electrochemical deposition methods,from theaspect of bionics,to construct ordered nano structrured HA coating and its hybridcoating with both excellent biological and good mechanical properties on titaniumsubstrate,to further study the mechanism of HA formation on the Ti surface and todevelop electrochemical impedance spectroscopy (EIS) to in situ elucidate theinterfacial structure and the interactions of biomaterials and cells.
The main work includes:a) construction of nano HA coating byelectrochemical deposition technique in low concentration system,b) design andcontrol of structure and composition of HA coating for fabrication of bionic artificialbone coating,c) systematical investigation of the effects of main depositionparameters on coating properties,d) further understanding of the mechanism ofelectrochemical deposition of calcium phosphates on Ti in low concentration system,and e) establishment of an in situ electrochemical cell for studying the interaction oftitanium/MG63 cell by EIS measurement.The following conclusions can be drawn:
1.A pure HA coating with high crystallinity has been prepared byelectrochemical deposition method in low concentration system.The HAcoating exhibits three kinds of typical topographies,i.e.flower type,standing-up type and porous type topographies.The nano-micro structuredordered pure HA coating has been firstly constructed on titanium substrate.Preliminary in vitro test indicates that the HA coating with such specialnano-micro two level structure is of more excellent bioactivity comparedwith other kinds of HA coatings.
2.The HA/Collagen hybrid coating with nano-micro ordered structure has beenfabricated as well by using electrochemical co-deposition method.The FTIR spectra demonstrates the existence of collagen in the composite coating,andthe SEM and XRD results shows that the crystal size of HA in the compositecoating is significantly decreased with the addition of collagen component,and the structure of the composite coating is more mimetic to the naturalbone when compared with the pure HA coating.
3.The effect of the main preparing parameters on the HA electrochemicaldeposition in low concentration system has been systematically investigated.It is indicated that in a very wide range of preparing parameter,highlycrystallized and pure HA coating can be obtained,while the distribution ofthe crystal size,the arrangement of the crystal grains and the depositionvelocity of the HA coating are intimately related to the depositionparameters.
4.The chemical composition and structure of the electrochemically depositedcalcium phosphate coating are determined by both thermodynamic andkinetic conditions.The nucleation process is mainly influenced by thethermodynamic factors,such asΔG,and the growth behavior is mainlycontrolled by the dynamic environments.The thermodynamic analysisdemonstrates that both the lower concentration of calcium and phosphorusspecies and the higher temperature in the system facilitate the pure HAformation,comparing with the traditional high concentration system.According to kinetic calculation,the apparent activity energy of the HAformation in a specific low concentration system is estimated to be 174.9kJ·mol~(1).An electrochemical deposition model of HA coating in lowconcentration system has been proposed to further clarify the behaviors ofthe HA coating formation.
5.An in situ electrochemical cell has been designed for the ac impedancemeasurements at biomaterial/cell interface.A home-made Ag/AgCl electrodeis introduced to the in situ cell as a reference electrode to eliminate thedistortion phenomena during the ac impedance measurement in highfrequency range.
6.It is demonstrated,from the EIS analysis of titanium/cell interface,that theadhesion of cells onto the biomaterial surface may alter the surface states andstructure of double layer at the interface.The ac impedance information in the higher frequency range is mainly from the cell adsortion process ontitanium surface,which is helpful to understand the interaction betweenbiomaterials and living cells.
引文
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