可载药生物高分子/磷酸钙多孔复合涂层的制备、表征及生物学评价
|
摘要
生物医用纯钛植入体具有密度低、耐蚀性优越、无致敏性和生物相容性良好等特点,是一种重要的修复承重骨缺损的植入体材料。目前,纯钛植入材料有待解决的一个主要问题是如何提高植入体骨整合的速度和质量。针对此问题,本文的解决思路为：通过在其表面构建组成和结构可控的生物活性涂层,以提高细胞相容性,诱导骨细胞粘附和增长,进而提升骨整合速度；与此同时,通过在表面形成药物缓释,以达到抗菌抗感染等效能,进而为骨整合过程提供适宜骨组织生长的微环境。
为此,首先对钛基体表面进行碱热处理,形成一层Ti02薄层,以增强其在体内的生物相容性；通过电化学法在基体表面沉积孔径可调的多孔壳聚糖麟酸钙复合涂层(多孔CPC涂层)；再进一步通过电化学法将胶原与壳聚糖和钙磷酸盐共沉积,并控制胶原在表面形成矿化层,形成多孔胶原／壳聚糖/磷酸钙复合涂层(多孔CC涂层)；对涂层组成、结构特征及细胞相容性和药物释放行为等方面进行了深入的研究。
主要研究内容及结果：
(1)磷酸钙盐、壳聚糖(cS)电解液体系电化学沉积制备多孔CPC涂层。研究表明：通过调控沉积电压、CS和磷酸钙盐的浓度可以获得多孔涂层,涂层与钛基的剥离强度较之除无CS外在同等条件下制备的磷酸钙沉积涂层有了明显提升。通过磷酸钙体系热力学和成孔过程的分析,证明多孔CPC涂层的形成机理为氢气泡模板成孔机理,为制备不同孔径的CPC涂层提供理论基础。根据前面的结果,当pH值的变化范围为4.3-5.5时,对应的在1.5V-1.1V的范围内调节沉积电压,可调控氢气泡的产生速率,进而调控涂层孔径的平均大小(500nm-5μm)。孔结构为其外层孔洞直径大于内层孔洞直径,贯通性良好。
(2)磷酸钙盐、CS及胶原(Co1)电解液体系电化学沉积制备CC复合涂层。研究表明：当pH=4.9,U=1.3V,T=37.C,Ccs.3.4mg/mL,Ccol=0.16mg/mL, CCa=40mM,CP=13.3mM时,电化学沉积体系中CPC涂层表面满足Col自组装沉积的pH值,Col所成纤维束和膜可沉积于CPC涂层表面构建Col矿化层,与CS、磷酸钙构筑的多孔中间层和CS构筑的致密基层一起形成三明治结构。Col对于磷酸钙的矿化有诱导作用,所以在沉积过程中Col的矿化不可避免。矿化Col层的覆盖程度主要受电解液中的Col浓度影响,而矿化Col层的矿化状态受电解液中的pH值、沉积电压和钙磷浓度共同作用；通过调节以上参数可制备不同Col覆盖度及不同矿化状态的CC复合涂层,进而调控CC复合涂层生物学性能和载药释药特性。
(3)多孔涂层的生物活性及细胞学评价：模拟体液(SBF)浸泡实验表明多孔CPC复合涂层材料和CC复合涂层材料均具有较高的生物活性和矿化功能,其中以CC涂层材料的生物活性和矿化功能更突出；激光共聚焦测试和SEM观察结果均显示MG63细胞初期(4h)在CC涂层表面活性和铺展情况最好,CPC次之碱处理的钛基板效果再次之,较长时间的培养表明三种涂层均具有良好的细胞相容性；MTT结果显示MG63细胞的粘附数目为CC>CPC>Ti;以上结果均显示出Col促进细胞粘附的能力。细胞测试结果同时显示MC3T3-e1细胞在大孔和小孔涂层上的细胞增殖数量上高于中孔涂层,其原因是较大的孔径有利于细胞的伪足伸入其中,增强黏附和增殖；而小孔径涂层表面较平坦,有利于细胞的铺展。评价结果显示Col对矿化和细胞粘附能力有较大贡献,涂层孔径对细胞的粘附和增殖也有较大的影响,同时还显示Col层的矿化状态和磷酸钙的晶相对矿化和体外细胞行为有一定贡献。
(4)多孔复合涂层的药物承载和释放行为研究结果表明：CPC涂层的孔径越大,其药物释放速度越快；相近孔径的CC涂层较CPC涂层的药物缓释速度稍慢；多孔CPC涂层载药后采用CS膜包封可增强药物缓释作用。将不同孔径的CPC涂层加入载药壳聚糖微球,这种多孔CPC涂层既载药又载含药CS微球可达到术后早期释药强度较高,又能满足中后期药物缓释保持一定药物作用强度的要求；且不同孔径载入微球后微球的释药速度不同。评价显示多孔涂层孔径的增大会导致释药速度的增快,但有利于承载含药CS微球；矿化Col层的构建有利于增强缓释的效果,因为矿化层部分延缓了药物的释放速度。
本研究表明碱处理钛基多孔壳聚糖麟酸钙复合涂层材料和胶原／壳聚糖麟酸钙复合涂层材料有良好的生物响应性及一定承载和缓释抗生素的能力,其中多孔胶原／壳聚糖／磷酸钙复合涂层材料性能更优,可期望其在骨修复的过程中能够良好地促进骨整合,在承重骨替代材料方面具有广泛的应用前景。
Biomedical titanium implants can meet the application for bear-loading bone repair, because titanium has good properties such as low density, excellent corrosion resistance, no sensitization response and good biocompatibility. A key issue for implants is to accelerate osteointegration and improve its quality. In this thesis, an approach was adopted by controlling the surface composition and structure for facilitating the attachment and proliferation of cells, as well as to loading and sustained release of antibiotics against for providing a desired environment for bone growth.
Titanium substrate was firstly treated with alkali-heat treatment to form titanium dioxide on th surface. Then, porous chitosan/calcium phosphate (CPC) coating was deposited on the substrate by electrochemical method. Collagen/Chitosan/Calcium phosphate (CC) coating was prepared by electrochemical co-deposition. The composition and surface topography, biological behaviors and drug release behaviors of the coatings were studied. The main results are summarized as:
(1) For electrochemical deposition of porous CPC coating by calcium phosphate and chitosan in the electrolyte, the results showed:The coating with porous structure could be achieved by adjusting deposition potential, the concentration of chitosan and calcium phosphate in the electrolyte. The scratch strength between substrate and the CPC coating was obviously increased with the addition of chitosan. The mechanism of porous CPC coating formation was proposed as hydrogen gas bubble modeling based on the thermodynamics of calcium phosphate systems and the pore formation behavior. When the pH in electrolyte was ranged from4.3to5.5, the deposition potential was crucial for controlling the formation rate of hydrogen gas bubbles, and the average pore size from5um to500nm could be formed if the potential was fixed from1.5V to1.1V. And the outer interconnecting pore size was bigger than the inner ones.
(2) For electrochemical deposition of CC composite coating by calcium phosphate, chitosan and collagen in the electrolyte, the result showed that when the deposition parameters were set as pH=4.9, U=1.3V, T=37℃, CCs=3.4mg/mL, CCol=0.16mg/mL, CCa=40mM, Cp=13.3mM, the collagen could be self-organized to form collagen fibril and mineralized to form a layer, and the mineralized layer existed as the out layer of the coating. During the deposition, the mineralization of collagen was easy to mineralize because the collagen could induce the formation of calcium phosphate, and the mineralization degree could be controlled by the collagen concentration in the electrolyte; the microstructure of the mineralized collagen layer also depended on the pH, electrolyte and the deposition potential.
(3) For evaluation of bioactivity and cell behavior in vitro, soaking in stimulated body fluid (SBF) showed that the porous CPC coating and CC coating both had good bioactivity, and the CC coating was better; The laser scanning confocal microscope (LSCM) and SEM observations of the MG63cell cultured on the coatings indicated that the CC coatings were more favorable for cell spreading at the starting stage (4h) than CPC coatings; the MTT results showed the CC coating> the CPC coating> Ti for cell attachment; these could be attributed to that collagen played a significant role in enhancing mineralization and cell attachment. The MC3T3-el cell culture result indicated that the pore size of the coatings influenced the cell behaviors, and the microstructure of mineralized collagen layer in CC coating and the crystalline phases of calcium phosphate in CPC coating also had impacts on cell behavior.
(4) For the drug loading and release behavior evaluation for the coatings, the release of antibiotic was faster in the coating with larger pores. The drug release rate in CC coating was slower than that in CPC coating. The drug sustained release behavior could be enhanced with coverage of CS membranes. A better approach was suggested to incorporate drug loaded CS nano-particles into the porous coating, and the present porous coatings with larger pore size could provide a platform to accommodate the nano-particles.
Our work demonstrated that the chitosan/calcium phosphate coatings and collagen/chitosan/calcium phosphate coatings on alkali treated titanium substrates had good cytocompatibility and reasonably good drug loading-release behavior, these coatings could be used to enhanced ossteointegration and make significances in bear-loading bone substitution.
为此,首先对钛基体表面进行碱热处理,形成一层Ti02薄层,以增强其在体内的生物相容性；通过电化学法在基体表面沉积孔径可调的多孔壳聚糖麟酸钙复合涂层(多孔CPC涂层)；再进一步通过电化学法将胶原与壳聚糖和钙磷酸盐共沉积,并控制胶原在表面形成矿化层,形成多孔胶原／壳聚糖/磷酸钙复合涂层(多孔CC涂层)；对涂层组成、结构特征及细胞相容性和药物释放行为等方面进行了深入的研究。
主要研究内容及结果：
(1)磷酸钙盐、壳聚糖(cS)电解液体系电化学沉积制备多孔CPC涂层。研究表明：通过调控沉积电压、CS和磷酸钙盐的浓度可以获得多孔涂层,涂层与钛基的剥离强度较之除无CS外在同等条件下制备的磷酸钙沉积涂层有了明显提升。通过磷酸钙体系热力学和成孔过程的分析,证明多孔CPC涂层的形成机理为氢气泡模板成孔机理,为制备不同孔径的CPC涂层提供理论基础。根据前面的结果,当pH值的变化范围为4.3-5.5时,对应的在1.5V-1.1V的范围内调节沉积电压,可调控氢气泡的产生速率,进而调控涂层孔径的平均大小(500nm-5μm)。孔结构为其外层孔洞直径大于内层孔洞直径,贯通性良好。
(2)磷酸钙盐、CS及胶原(Co1)电解液体系电化学沉积制备CC复合涂层。研究表明：当pH=4.9,U=1.3V,T=37.C,Ccs.3.4mg/mL,Ccol=0.16mg/mL, CCa=40mM,CP=13.3mM时,电化学沉积体系中CPC涂层表面满足Col自组装沉积的pH值,Col所成纤维束和膜可沉积于CPC涂层表面构建Col矿化层,与CS、磷酸钙构筑的多孔中间层和CS构筑的致密基层一起形成三明治结构。Col对于磷酸钙的矿化有诱导作用,所以在沉积过程中Col的矿化不可避免。矿化Col层的覆盖程度主要受电解液中的Col浓度影响,而矿化Col层的矿化状态受电解液中的pH值、沉积电压和钙磷浓度共同作用；通过调节以上参数可制备不同Col覆盖度及不同矿化状态的CC复合涂层,进而调控CC复合涂层生物学性能和载药释药特性。
(3)多孔涂层的生物活性及细胞学评价：模拟体液(SBF)浸泡实验表明多孔CPC复合涂层材料和CC复合涂层材料均具有较高的生物活性和矿化功能,其中以CC涂层材料的生物活性和矿化功能更突出；激光共聚焦测试和SEM观察结果均显示MG63细胞初期(4h)在CC涂层表面活性和铺展情况最好,CPC次之碱处理的钛基板效果再次之,较长时间的培养表明三种涂层均具有良好的细胞相容性；MTT结果显示MG63细胞的粘附数目为CC>CPC>Ti;以上结果均显示出Col促进细胞粘附的能力。细胞测试结果同时显示MC3T3-e1细胞在大孔和小孔涂层上的细胞增殖数量上高于中孔涂层,其原因是较大的孔径有利于细胞的伪足伸入其中,增强黏附和增殖；而小孔径涂层表面较平坦,有利于细胞的铺展。评价结果显示Col对矿化和细胞粘附能力有较大贡献,涂层孔径对细胞的粘附和增殖也有较大的影响,同时还显示Col层的矿化状态和磷酸钙的晶相对矿化和体外细胞行为有一定贡献。
(4)多孔复合涂层的药物承载和释放行为研究结果表明：CPC涂层的孔径越大,其药物释放速度越快；相近孔径的CC涂层较CPC涂层的药物缓释速度稍慢；多孔CPC涂层载药后采用CS膜包封可增强药物缓释作用。将不同孔径的CPC涂层加入载药壳聚糖微球,这种多孔CPC涂层既载药又载含药CS微球可达到术后早期释药强度较高,又能满足中后期药物缓释保持一定药物作用强度的要求；且不同孔径载入微球后微球的释药速度不同。评价显示多孔涂层孔径的增大会导致释药速度的增快,但有利于承载含药CS微球；矿化Col层的构建有利于增强缓释的效果,因为矿化层部分延缓了药物的释放速度。
本研究表明碱处理钛基多孔壳聚糖麟酸钙复合涂层材料和胶原／壳聚糖麟酸钙复合涂层材料有良好的生物响应性及一定承载和缓释抗生素的能力,其中多孔胶原／壳聚糖／磷酸钙复合涂层材料性能更优,可期望其在骨修复的过程中能够良好地促进骨整合,在承重骨替代材料方面具有广泛的应用前景。
Biomedical titanium implants can meet the application for bear-loading bone repair, because titanium has good properties such as low density, excellent corrosion resistance, no sensitization response and good biocompatibility. A key issue for implants is to accelerate osteointegration and improve its quality. In this thesis, an approach was adopted by controlling the surface composition and structure for facilitating the attachment and proliferation of cells, as well as to loading and sustained release of antibiotics against for providing a desired environment for bone growth.
Titanium substrate was firstly treated with alkali-heat treatment to form titanium dioxide on th surface. Then, porous chitosan/calcium phosphate (CPC) coating was deposited on the substrate by electrochemical method. Collagen/Chitosan/Calcium phosphate (CC) coating was prepared by electrochemical co-deposition. The composition and surface topography, biological behaviors and drug release behaviors of the coatings were studied. The main results are summarized as:
(1) For electrochemical deposition of porous CPC coating by calcium phosphate and chitosan in the electrolyte, the results showed:The coating with porous structure could be achieved by adjusting deposition potential, the concentration of chitosan and calcium phosphate in the electrolyte. The scratch strength between substrate and the CPC coating was obviously increased with the addition of chitosan. The mechanism of porous CPC coating formation was proposed as hydrogen gas bubble modeling based on the thermodynamics of calcium phosphate systems and the pore formation behavior. When the pH in electrolyte was ranged from4.3to5.5, the deposition potential was crucial for controlling the formation rate of hydrogen gas bubbles, and the average pore size from5um to500nm could be formed if the potential was fixed from1.5V to1.1V. And the outer interconnecting pore size was bigger than the inner ones.
(2) For electrochemical deposition of CC composite coating by calcium phosphate, chitosan and collagen in the electrolyte, the result showed that when the deposition parameters were set as pH=4.9, U=1.3V, T=37℃, CCs=3.4mg/mL, CCol=0.16mg/mL, CCa=40mM, Cp=13.3mM, the collagen could be self-organized to form collagen fibril and mineralized to form a layer, and the mineralized layer existed as the out layer of the coating. During the deposition, the mineralization of collagen was easy to mineralize because the collagen could induce the formation of calcium phosphate, and the mineralization degree could be controlled by the collagen concentration in the electrolyte; the microstructure of the mineralized collagen layer also depended on the pH, electrolyte and the deposition potential.
(3) For evaluation of bioactivity and cell behavior in vitro, soaking in stimulated body fluid (SBF) showed that the porous CPC coating and CC coating both had good bioactivity, and the CC coating was better; The laser scanning confocal microscope (LSCM) and SEM observations of the MG63cell cultured on the coatings indicated that the CC coatings were more favorable for cell spreading at the starting stage (4h) than CPC coatings; the MTT results showed the CC coating> the CPC coating> Ti for cell attachment; these could be attributed to that collagen played a significant role in enhancing mineralization and cell attachment. The MC3T3-el cell culture result indicated that the pore size of the coatings influenced the cell behaviors, and the microstructure of mineralized collagen layer in CC coating and the crystalline phases of calcium phosphate in CPC coating also had impacts on cell behavior.
(4) For the drug loading and release behavior evaluation for the coatings, the release of antibiotic was faster in the coating with larger pores. The drug release rate in CC coating was slower than that in CPC coating. The drug sustained release behavior could be enhanced with coverage of CS membranes. A better approach was suggested to incorporate drug loaded CS nano-particles into the porous coating, and the present porous coatings with larger pore size could provide a platform to accommodate the nano-particles.
Our work demonstrated that the chitosan/calcium phosphate coatings and collagen/chitosan/calcium phosphate coatings on alkali treated titanium substrates had good cytocompatibility and reasonably good drug loading-release behavior, these coatings could be used to enhanced ossteointegration and make significances in bear-loading bone substitution.
引文
[1]张先涛.纳米晶胶原基骨修复材料商业计划[硕士]：清华大学,2004.
[2]陆裕朴.实用骨科学.北京：人民军医出版社,1991
[3]刘昌胜.自固化磷酸钙-人体硬组织修复的新希望：世界科学,1998,(11)：29-31.
[4]席越.骨组织病理解剖学技术.第一版.北京：人民卫生出版社,1997.
[5]S. Zhang, K. Gonsalves. Preparation and characterization of thermally stable nanohydroxyapatite. Journal of Materials Science-Materials in Medicine,1997,8(1): 25-28.
[6]Compact spongy bone. http://en.wikipedia.org/wiki/File:Illu compact spongy bone. jpg.
[7]Bone Structure, http://www.engin.umich.edu/class/bme456/bonestructure/bonestructure. htm2004.
[8]朱振安.骨折内固定的生物力学.医用生物力学,1994,(01)：63-67.
[9]G. Willmann. Coating of implants with hydroxyapatite material connections between bone and metal. Advanced Engineering Materials,1999,1(2):95-105.
[10]Q. Lv, K. Hu, Q. Feng, F. Cui. Preparation of insoluble fibroin/collagen films without methanol treatment and the increase of its flexibility and cytocompatibility. Journal of Applied Polymer Science,2008,109(3):1577-1584.
[11]W. Zhang, Z.L. Huang, S.S. Liao, F.Z. Cui. Nucleation sites of calcium phosphate crystals during collagen mineralization. Journal of the American Ceramic Society,2003, 86(6):1052-1054.
[12]苗顺东.基于缓释锌离子及仿细胞外基质的高生物响应性涂层制备和表征研究[博士]：浙江大学,2009.
[13]N. Ziats, K. Miller, J. Anderson. In vitro and in vivo interactions of cells with biomaterials. Biomaterials,1988,9(1):5-13.
[14]费军.载去甲万古霉素钢板的研制及防治兔胫骨感染的实验研究[博士]：第三军医大学,2008.
[15]R. Gustilo, J. Anderson. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones-Retrospective and prospective analyses. Journal of Bone and Joint Surgery-American Volume,2002,84A(4):682-682.
[16]陈文.氧化铝陶瓷在髋关节置换领域中的应用.生物骨科材料与临床研究,2005,(06)：5-8.
[17]祝云利,吴海山.陶瓷材料在人工关节置换术中的应用现状.国际骨科学杂志,2009,(02)：70-73.
[18]崔福斋,郭牧遥.生物陶瓷材料的应用及其发展前景.药物分析杂志,2010,(07)：1343-1347.
[19]G. Gheysen, P. Ducheyne, L. Hench, P. Meester. Bioglass composites:a potential material for dental application. Biomaterials,1983,4(2):81-84.
[20]S. Hulbert, L. Hench, D. Forbers, L. Bowman. History of bioceramics. Ceramics International,1982,8(4):131-140.
[21]A. Taub, R. Hogri, A. Magal, M. Mintz, Shacham-Diamand Y. Bioactive anti-inflammatory coating for chronic neural electrodes. Journal of Biomedical Materials Research Part A,2012,100A(7):1854-1858.
[22]S. Verrier, J. Blaker, V. Maquet, L. Hench, A. Boccaccini. PDLLA/Bioglass(?) composites for soft-tissue and hard-tissue engineering:an in vitro cell biology assessment. Biomaterials,2004,25(15):3013-3021.
[23]O. Tsigkou, A. Boccaccini, L. Hench, J.M. Polak, Stevens MM. Effect of PDLLA/Bioglass composite films on expression at the mRNA level of collagen type 1 and bone sialoprotein in fetal osteoblasts. Journal of Pharmacy and Pharmacology,2004, 56:S36-S36.
[24]F. Cui, Y. Wang, Q. Cai, W. Zhang. Conformation change of collagen during the initial stage of biomineralization of calcium phosphate. Journal of Materials Chemistry,2008, 18(32):3835-3840.
[25]O. Peitl, E. Zanotto, F. Serbena, L. Hench. Compositional and microstructural design of highly bioactive P2O5-Na2O-CaO-SiO2 glass-ceramics. Acta Biomaterialia,2012,8(1): 321-332.
[26]李保强.壳聚糖／羟基磷灰石仿生骨材料的研究[博士]：浙江大学,2005.
[27]H. Schliephake, C. Botel, A. Forster, B. Schwenzer, J. Reichert, Scharnweber D. Effect of oligonucleotide mediated immobilization of bone morphogenic proteins on titanium surfaces. Biomaterials,2012,33(5):1315-1322.
[28]J. Lincks, B. Boyan, C. Blanchard, C. Lohmann, Y. Liu, D. Cochran. Response of MG63 osteoblast-like cells to titanium and titanium alloy is dependent on surface roughness and composition. Biomaterials,1998,19(23):2219-2232.
[29]R. Flemming, C. Murphy, G. Abrams, S. Goodman, P. Nealey. Effects of synthetic micro-and nano-structured surfaces on cell behavior. Biomaterials,1999,20(6): 573-588.
[30]A. Badami, M. Kreke, M. Thompson, J. Riffle, A. Goldstein. Effect of fiber diameter on spreading, proliferation, and differentiation of osteoblastic cells on electrospun poly(lactic acid) substrates. Biomaterials,2006,27(4):596-606.
[31]A. Travan, E. Marsich, I. Donati, M. Foulc, N. Moritz, H. Aro. Polysaccharide-Coated Thermosets for Orthopedic Applications:From Material Characterization to In Vivo Tests. Biomacromolecules,2012,13(5):1564-1572.
[32]S. Scaglione, V. Guarino, M. Sandri, A. Tampieri, L. Ambrosio, R. Quarto. In vivo lamellar bone formation in fibre coated MgCHA-PCL-composite scaffolds. Journal of Materials Science-Materials in Medicine,2012,23(1):117-128.
[33]U. Ripamonti, L. Roden, L. Renton. Osteoinductive hydroxyapatite-coated titanium implants. Biomaterials,2012,33(15):3813-3823.
[34]M. Rani, A. Agarwal, Y. Negi. Review:Chitosan Based Hydrogel Polymeric Beads-as Drug Delivery System. Bioresources,2010,5(4):2765-2807.
[35]刘相成.人工关节置换术后晚期深部感染的临床分析[博士]：中国人民解放军军医进修学院,2011.
[36]张志斌.骨修复和骨病治疗药物载体CPP/CS复合材料的仿生合成及性能研究[博士]：四川大学,2007.
[37]周健.治疗感染性骨缺损材料的缓释与骨修复的研究[博士]：复旦大学,2011.
[38]W. Xia, K. Grandfield, A. Hoess, A. Ballo, Y. Cai, H. Engqvist. Mesoporous titanium dioxide coating for metallic implants. Journal of Biomedical Materials Research Part B-Applied Biomaterials,2012,100B(1):82-93.
[39]W. Cao, L. Hench. Bioactive materials. Ceramics International,1996,22(6):493-507.
[40]J.E. Lemons. Ceramics:Past, present, and future. Bone,1996,19(1):121-128.
[41]L. Hench. Bioceramics-From Concept to Clinic. Journal of the American Ceramic Society,1991,74(7):1487-1510.
[42]L. Peng, A. Mendelsohn, T. LaTempa, S. Yoriya, C. Grimes, T. Desai. Long-Term Small Molecule and Protein Elution from TiO2 Nanotubes. Nano Letters,2009,9(5): 1932-1936.
[43]J. Holmbom, A. Sodergard, E. Ekholm, M. Martson, A. Kuusilehto, P. Saukko. Long-term evaluation of porous poly(epsilon-caprolactone-co-L-lactide) as a bone-filling material. Journal of Biomedical Materials Research Part A,2005,75A(2): 308-315.
[44]M. Chatzinikolaidou, T. Zumbrink, H. Jennissen. Stability of surface-enhanced ultrahydrophilic metals as a basis for bioactive rhBMP-2 surfaces. Materialwissenschaft Und Werkstofftechnik,2003,34(12):1106-1112.
[45]M. Mohanty, T. Anilkumar, P. Mohanan, C. Muraleedharan, G. Bhuvaneshwar, F. Derangere. Long term tissue response to titanium coated with diamond like carbon. Biomolecular Engineering,2002,19(2-6):125-128.
[46]N. S. Pedro. Titanium Alloys:Preparation, Properties and Applications. Nova Science Pub Incorporated,2010
[47]J. Park, S. Bauer, K. Mark, P. Schmuki. Nanosize and vitality:TiO2 nanotube diameter directs cell fate. Nano Letters,2007,7(6):1686-1691.
[48]C.A. Middleton, C.J. Pendegrass, D. Gordon, J. Jacobs, G.W. Blunn. Fibronectin silanized titanium alloy:A bioinductive and durable coating to enhance fibroblast attachment in vitro. Journal of Biomedical Materials Research Part A,2007,83A(4): 1032-1038.
[49]H. Griesser, K. McLean, G. Beumer, X. Gong, P. Kingshott, G. Johnson. Surface immobilization of synthetic proteins via plasma polymer interlayers. Plasma Deposition and Treatment of Polymers,1999,544:9-20.
[50]C. Lee, A. Singla, Y. Lee. Biomedical applications of collagen. International Journal of Pharmaceutics,2001,221(1-2):1-22.
[51]F. Cui, Y. Li, J. Ge. Self-assembly of mineralized collagen composites. Materials Science & Engineering R-Reports,2007,57(1-6):1-27.
[52]Collagen. http://en.wikipedia.org/wiki/File:Collagentriplehelix.png.
[53]Chitosan. http://en.wikipedia.org/wiki/File:Chitosan2.jpg.
[54]李峻峰,邹琴,赖雪飞.壳聚糖微球药物释放机制研究进展.生物医学工程学杂志,2011,(04)：843-846.
[55]I. Kim, S. Seo, H. Moon, M. Yoo, I. Park, B.C. Kim. Chitosan and its derivatives for tissue engineering applications. Biotechnology Advances,2008,26(1):1-21.
[56]A. Di Martino, M. Sittinger, M. Risbud. Chitosan:A versatile biopolymer for orthopaedic tissue-engineering. Biomaterials,2005,26(30):5983-5990.
[57]L. Ma, C. Gao, Z. Mao, J. Zhou, J. Shen, X. Hu. Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering. Biomaterials,2003,24(26): 4833-4841.
[58]R. Pallela, J. Venkatesan, V. Janapala, S. Kim. Biophysicochemical evaluation of chitosan-hydroxyapatite-marine sponge collagen composite for bone tissue engineering. Journal of Biomedical Materials Research Part A,2012,100A(2):486-495.
[59]R. Wang, M. Hsieh, S. Yang, P. Chuang, J. Lin, C. Yang, et al. Characteristics and cyto-compatibility of Collagen/Ca-P coatings on Ti6A14V substrate. Surface and Coatings Technology,2011,205(19):4683-4689.
[60]刘玲蓉.用于骨组织再生修复的胶原-HA复合材料的应用基础研究[博士]：中国协和医科大学;2007.
[61]D. Campoccia, L. Montanaro, P. Speziale, C. Arciola. Antibiotic-loaded biomaterials and the risks for the spread of antibiotic resistance following their prophylactic and therapeutic clinical use. Biomaterials,2010,31(25):6363-6377.
[62]袁伟永.层层静电自组装技术构建抗菌涂层的研究[硕士]：浙江大学,2006.
[63]方铭中.AZ81镁合金表面微弧氧化改性及涂层的药物释放研究[硕士]：天津大学,2010.
[64]V. Sinha, A. Singla, S. Wadhawan, R. Kaushik, R. Kumria, K. Bansal. Chitosan microspheres as a potential carrier for drugs. International Journal of Pharmaceutics, 2004,274(1-2):1-33.
[65]W. Wei, G. Ma, L. Wang, J. Wu, Z. Su. Hollow quaternized chitosan microspheres increase the therapeutic effect of orally administered insulin. Acta Biomaterialia,2010, 6(1):205-209.
[66]E. Yenilmez, E. Basaran, Y. Yazan. Release characteristics of vitamin E incorporated chitosan microspheres and in vitro-in vivo evaluation for topical application. Carbohydrate Polymers,2011,84(2):807-811.
[67]S. Cafaggi, E. Russo, R. Stefani, R. Leardi, G. Caviglioli, B. Parodi. Preparation and evaluation of nanoparticles made of chitosan or N-trimethyl chitosan and a cisplatin-alginate complex. Journal of Controlled Release,2007,121(1-2):110-123.
[68]Y. Zheng, W. Yang, C. Wang, J. Hu, S. Fu, L. Dong. Nanoparticles based. on the complex of chitosan and polyaspartic acid sodium salt:Preparation, characterization and the use for 5-fluorouracil delivery. European Journal of Pharmaceutics and Biopharmaceutics,2007,67(3):621-631.
[69]李峻峰,张利,李钧甫,邹琴,杨维虎,李玉宝.香草醛交联壳聚糖载药微球的性能及其成球机理分析.高等学校化学学报,2008,(09)：1874-1879.
[70]J. Varshosaz, R. Alinagari. Effect of citric acid as cross-linking agent on insulin loaded chitosan microspheres. Iranian Polymer Journal,2005,14(7):647-656.
[71]A. Wan, Y. Sun, L. Gao, H. Li. Preparation of aspirin and probucol in combination loaded chitosan nanoparticles and in vitro release study. Carbohydrate Polymers,2009, 75(4):566-574.
[72]J. Yu, Y. Li, L. Qiu, Y. Jin. Self-aggregated nanoparticles of cholesterol-modified glycol chitosan conjugate:Preparation, characterization, and preliminary assessment as a new drug delivery carrier. European Polymer Journal,2008,44(3):555-565.
[73]J. Park, G. Saravanakumar, K. Kim, I. Kwon. Targeted delivery of low molecular drugs using chitosan and its derivatives. Advanced Drug Delivery Reviews,2010,62(1): 28-41.
[74]J. Venkatesan, S. Kim. Chitosan composites for bone tissue engineering-An overview. Marine Drugs,2010,8(8):2252-2266.
[75]H. Ho, L. Lin, M. Sheu. Characterization of collagen isolation and application of collagen gel as a drug carrier. Journal of Controlled Release,1997,44(2-3):103-112.
[76]王晓华,鄢立刚,陈芳.甲壳素及其衍生物作为药用辅料的应用进展.药学实践杂志,2000,(02)：86-88.
[77]D. Thacharodi, K. Panduranga. Collagen-chitosan composite membranes for controlled release of propranolol hydrochloride. International Journal of Pharmaceutics,1995, 120(1):115-118.
[78]T. Kokubo, H. Takadama. How useful is SBF in predicting in vivo bone bioactivity? Biomaterials,2006,27(15):2907-2915.
[79]吴波.电化学合成羟基磷灰石涂层及其性能研究[博士]：大连理工大学；2011.
[80]P. Royer, C. Rey. Calcium-phosphate coatings for orthopedic prosthesis. Surface& Coatings Technology,1991,45(1-3):171-177.
[81]M. Okido, K. Nishikawa, K. Kuroda, R. Ichino, Z. Zhao, O. Takai. Evaluation of the hydroxyapatite film coating on titanium cathode by QCM. Materials Transactions,2002, 43(12):3010-3014.
[82]S. Ban, S. Maruno. Deposition of calcium-phosphate on titanium by electrochemical process in simulated body-fluid. Japanese Journal of Applied Physics Part 2-Letters, 1993,32(10B):L1577-L1580.
[83]M. Popa, J. Moreno, M. Popa, E. Vasilescu, P. Drob, C. Vasilescu. Electrochemical deposition of bioactive coatings on Ti and Ti-6A1-4V surfaces. Surface & Coatings Technology,2011,205(20):4776-4783.
[84]F. Bir, H. Khireddine, A. Touati, D. Sidane, S. Yala, H. Oudadesse. Electrochemical depositions of fluorohydroxyapatite doped by Cu2+, Zn2+, Ag+ on stainless steel substrates. Applied Surface Science,2012,258(18):7021-7030.
[85]张柏林.电化学方法制备钛基羟基磷灰石/纳米银复合涂层及其相关性质研究[硕士]：西南交通大学,2010.
[86]X. Pang, I. Zhitomirsky. Electrophoretic deposition of composite hydroxyapatite-chitosan coatings. Materials Characterization,2007,58(4):339-348.
[87]I. Zhitomirsky, A. Hashambhoy. Chitosan-mediated electrosynthesis of orgarlic-inorganic nanocomposites. Journal of Materials Processing Technology,2007, 191(1-3):68-72.
[88]X. Pang, T. Casagrande, I. Zhitomirsky. Electrophoretic deposition of hydroxyapatite-CaSiO3-chitosan composite coatings. Journal of Colloid and Interface Science,2009,330(2):323-329.
[89]F. Sun, X. Pang, I. Zhitomirsky. Electrophoretic deposition of composite hydroxyapatite-chitosan-heparin coatings. Journal of Materials Processing Technology, 2009,209(3):1597-1606.
[90]X. Pang, I. Zhitomirsky. Electrodeposition of hydroxyapatite-silver-chitosan nanocomposite coatings. Surface & Coatings Technology,2008,202(16):3815-3821.
[91]K. Grandfield, I. Zhitomirsky. Electrophoretic deposition of composite hydroxyapatite-silica-chitosan coatings. Materials Characterization,2008,59(1): 61-67.
[92]J. Redepenning, T. Schlessinger, S. Burnham, L. Lippiello, J. Miyano. Characterization of electrolytically prepared brushite and hydroxyapatite coatings on orthopedic alloys. Journal of Biomedical Materials Research,1996,30(3):287-294.
[93]X. Lu, Y. Leng, Q. Zhang. Electrochemical deposition of octacalcium phosphate micro-fiber/chitosan composite coatings on titanium substrates. Surface & Coatings Technology,2008,202(13):3142-3147.
[94]J. Wang, A. Apeldoorn, K. Groot. Electrolytic deposition of calcium phosphate/chitosan coating on titanium alloy:Growth kinetics and influence of current density, acetic acid, and chitosan. Journal of Biomedical Materials Research Part A,2006,76A(3):503-511.
[95]S. Manara, F. Paolucci, B. Palazzo, M. Marcaccio, E. Foresti, G. Tosi. Electrochemically-assisted deposition of biomimetic hydroxyapatite-collagen coatings on titanium plate. Inorganica Chimica Acta,2008,361(6):1634-1645.
[96]A. Roguska, S. Hiromoto, A. Yamamoto, M. Wozniak, M. Pisarek, M. Lewandowska. Collagen immobilization on 316L stainless steel surface with cathodic deposition of calcium phosphate. Applied Surface Science,2011,257(11):5037-5045.
[97]I. Najdovski, P. Selvakannan, A. O'Mullane, S. Bhargava. Rapid Synthesis of Porous Honeycomb Cu/Pd through a Hydrogen-Bubble Templating Method. Chemistry-a European Journal,2011,17(36):10058-10063.
[98]W. Tsai, P. Hsu, Y. Hwu, C. Chen, L. Chang, J. Je. Electrochemistry-Building on bubbles in metal electrodeposition. Nature,2002,417(6885):139-139.
[99]K. Fu, J. Slattery. Coalescence of a bubble at a fluid-fluid interface:Comparison of theory and experiment. Journal of Colloid and Interface Science,2007,315(2): 569-579.
[100]Z. Zhao, H. Li, G. Huo, P. Sun, Li Y., K. Kuroda. Cathodic deposition of hydroxyapatite without H(2) evolution, Surface Engineering:In Materials Science, 2003:169-173.
[101]S. Sirivisoot, R. Pareta, T. Webster. A conductive nanostructured polymer electrodeposited on titanium as a controllable, local drug delivery platform. Journal of Biomedical Materials Research Part A,2011,99A(4):586-597.
[102]朱文菁,金慰芳,张丽丽,张罗修,王洪复.MTT法分析培养成骨细胞的存活和增殖能力.上海医科大学学报,1995,(04)：254-257.
[103]陈卓凡,朱文军,宁成云,曾融生,罗智斌,南开辉,et al纯钛表面酸碱处理及生物矿化的初步研究.中国口腔种植学杂志,2007,(03)：155-158.
[104]M. Takemoto, S. Fujibayashi, M. Neo, J. Suzuki, T. Matsushita, T. Kokubo. Osteoinductive porous titanium implants:Effect of sodium removal by dilute HC1 treatment. Biomaterials,2006,27(13):2682-2691.
[105]胡巧玲,陈中科,陈亮,沈家骢.原位沉析法制备碳酸钙／壳聚糖三维复合材料的研究.高等学校化学学报,2006,(03)：575-578.
[106]仲维卓,罗豪甦,华素坤,许桂生.晶体表面结构和负离子配位多面体生长基元(英文).人工晶体学报,2004,(04)：471-474.
[107]仲维卓,张学华,罗豪甦,华素坤.纳米晶生长习性机理——负离子配位多面体生长基元模型的应用.硅酸盐学报,2004,(03)：239-244.
[108]薛明.新型多孔磷灰石-硅灰石(AW)生物活性玻璃陶瓷支架材料的制备与改性研究[硕士]四川大学,2005.
[109]郑昌琼,冉均国.新型无机材料.北京：科学出版社；2003.
[110]R. Smith, A. Martell. Critical Stability Constants. New York:Plenum Press,1976.
[111]中南矿冶学院分析化学教研室.化学分析手册.北京：科学出版社,1991.
[112]牛宗伟,张建华,李丽,任升峰,孟艳华Sol-gel法合成纳米羟基磷灰石的热力学分析.第五届中国功能材料及其应用学术会议.北京,2004：2401-2404.
[113]王玥华,张云,尹光福,周大利,蒋毅,李勇.用磷酸八钙前驱体法制备β-磷酸三钙.航天医学与医学工程,2004,(04)：266-269.
[114]田一平,杨建华,李晖,郭灵虹.影响α-TCP和HA生物陶瓷表面形成类骨磷灰石的形貌、结构的因素研究.四川大学学报(自然科学版),2007,(01)：135-140.
[115]P. Peng, S. Kumar, N. Voelcker, E. Szili, R. Smart, H. Griesser. Thin calcium phosphate coatings on titanium by electrochemical deposition in modified simulated body fluid. Journal of Biomedical Materials Research Part A,2006,76A(2):347-355.
[116]M. Kuo, S. Yen. The process of electrochemical deposited hydroxyapatite coatings on biomedical titanium at room temperature. Materials Science & Engineering C-Biomimetic and Supramolecular Systems,2002,20(1-2):153-160.
[117]S. Ban, S. Maruno, N. Arimoto, A. Harada, J. Hasegawa. Effect of electrochemically deposited apatite coating on bonding of bone to the HA-G-Ti composite and titanium. Journal of Biomedical Materials Research,1997,36(1):9-15.
[118]胡仁,胡皓冰,林昌健.CaP/壳聚糖复合膜层的电化学共沉积研究.高等学校化学学报,2002,(11)：2142-2146.
[119]唐艳军,李友明,宋晶,潘志东.纳米/微米碳酸钙的结构表征和热分解行为.物理化学学报,2007,(05)：717-722.
[120]孟令科,朱晓丽,叶建东,王迎军.溶胶-凝胶法制备羟基磷灰石及其过程的控制.材料导报材料导报,2002,(11)：75-77.
[121]邬鸿彦,朱明刚,孔令宜,黄立枝.对制备羟基磷灰石粉末工艺条件的再探讨.河北轻化工学院学报,1998,(01)：41-43.
[122]王迎军,宁成云,赵子衷,李尚周,刘正义,卢国辉.HA生物活性陶瓷涂层的爆炸喷涂与等离子喷涂.华南理工大学学报(自然科学版),1998,(07)：124-128.
[123]王迎军,冉炜.高强度生物活性人造齿根的复合制备.华南理工大学学报(自然科学版),1998,(07)：124-128.
[124]肖秀兰,陈志刚.羟基磷灰石涂层制备技术的可行性研究.材料导报,2003,(04)：32-34.
[125]陈晓明,焦玉恒,许传波.电泳沉积制备羟基磷灰石／生物玻璃梯度涂层的研究.材料科学与工程,2002,(04)：545-548.
[126]Y. Li, K. Degroot, J. Dewijn, C. Klein, S. Meer. Morphology and composition of nanograde calcium-phosphate needle-like crystals foed by simple hydrothemal treatment. Journal of Materials Science-Materials in Medicine,1994,5(6-7):326-331.
[127]H. Monma. Electrochemical depostion of calcium-deficient apatite on stainless-steel substrate. Nippon Seramikkusu Kyokai Gakujutsu Ronbunshi-Journal of the Ceramic Society of Japan,1993,101(7):737-739.
[128]M. Wei, A. Ruys, B. Milthorpe, C. Sorrell. Solution ripening of hydroxyapatite nanoparticles:Effects on electrophoretic deposition. Journal of Biomedical Materials Research,1999,45(1):11-19.
[129]L. Cleries, J. Fernandez-Pradas, G. Sardin, J. Morenza. Dissolution behaviour of calcium phosphate coatings obtained by laser ablation. Biomaterials,1998,19(16): 1483-1487.
[130]L. Cleries, J. Fernandez-Pradas, G. Sardin, J. Morenza. Application of dissolution experiments to characterise the structure of pulsed laser-deposited calcium phosphate coatings. Biomaterials,1999,20(15):1401-1405.
[131]L. Cleries, J. Fernandez-Pradas, J. Morenza. Behavior in simulated body fluid of calcium phosphate coatings obtained by laser ablation. Biomaterials,2000,21(18): 1861-1865.
[132]H. Zeng, K. Chittur, W. Lacefield. Dissolution/reprecipitation of calcium phosphate thin films produced by ion beam sputter deposition technique. Biomaterials,1999, 20(5):443-451.
[133]J. Ong, G. Raikar, T. Smoot. Properties of calcium phosphate coatings before and after exposure to simulated biological fluid. Biomaterials,1997,18(19):1271-1275.
[134]J. Vehof, P. Spauwen, J. Jansen. Bone formation in calcium-phosphate-coated titanium mesh. Biomaterials,2000,21(19):2003-2009.
[135]K. Dijk, H. Schaeken, J. Wolke, J. Jansen. Influence of annealing temperature on RF magnetron sputtered calcium phosphate coatings. Biomaterials,1996,17(4):405-410.
[136]I. Lavos-Valereto, B. Konig, C. Rossa, Marcantonio E, Zavaglia AC. A study of histological responses from Ti-6Al-7Nb alloy dental implants with and without plasma-sprayed hydroxyapatite coating in dogs. Journal of Materials Science-Materials in Medicine,2001,12(3):273-276.
[137]S. Sousa, M. Barbosa. Effect of hydroxyapatite thickness on metal ion release from Ti6A14V substrates. Biomaterials,1996,17(4):397-404.
[138]N. Ignjatovic, S. Tomic, M. Dakic, M. Miljkovic, M. Plavsic, D. Uskokovic. Synthesis and properties of hydroxyapatite/poly-L-lactide composite biomaterials. Biomaterials, 1999,20(9):809-816.
[139]D. Ehrenfest, P. Coelho, B. Kang, Y. Sul, T. Albrektsson. Classification of osseointegrated implant surfaces:materials, chemistry and topography. Trends in Biotechnology,2010,28(4):198-206.
[140]C. Reyes, T. Petrie, K. Burns, Z. Schwartz, A. Garcia. Biomolecular surface coating to enhance orthopaedic tissue healing and integration. Biomaterials,2007,28(21): 3228-3235.
[141]M. Lopez-Heredia, P. Weiss, P. Layrolle. An electrodeposition method of calcium phosphate coatings on titanium alloy. Journal of Materials Science-Materials in Medicine,2007,18(2):381-390.
[142]H. Kim, H. Kim, J. Knowles. Fluor-hydroxyapatite sol-gel coating on titanium substrate for hard tissue implants. Biomaterials,2004,25(17):3351-3358.
[143]L. Chen, C. Zhu, D. Fan, B. Liu, X. Ma, Z. Duan. A human-like collagen/chitosan electrospun nanofibrous scaffold from aqueous solution:Electrospun mechanism and biocompatibility. Journal of Biomedical Materials Research Part A,2011,99A(3): 395-409.
[144]S. Ban, S. Maruno. pH distribution around the electrode during electrochemical deposition process for producing bioactive apatite. Japanese Journal of Applied Physics Part 2-Letters,1999,38(5A):L537-L539.
[145]王静梅,姚松年.壳聚糖-氨基酸体系中碳酸钙模拟生物矿化的研究.无机化学学报,2002,(03)：249-254.
[146]黄亚平,赵莹,过梅丽,徐端夫,王笃金.甲壳素和壳聚糖在生物矿化和模拟矿化过程中的调控作用研究进展.高分子通报,2007,(02)：1-7.
[]47]段书源,洪元萍,刘拥军,袁波,蒋峰芝.羟基磷灰石/胶原矿化机理的研究进展.化学通报,2010,(04)：297-301.
[148]S. Rhee, J. Lee, J. Tanaka. Nucleation of hydroxyapatite crystal through chemical interaction with collagen. Journal of the American Ceramic Society,2000,83(11): 2890-2892.
[149]M. Kikuchi, T. Ikoma, S. Itoh, H. Matsumoto, Y. Koyama, K. Takakuda. Biomimetic synthesis of bone-like nanocomposites using the self-organization mechanism of hydroxyapatite and collagen. Composites Science and Technology,2004,64(6): 819-825.
[150]W. Zhang, Z. Huang, S. Liao, F. Cui. Nucleation sites of calcium phosphate crystals during collagen mineralization. Journal of the American Ceramic Society,2003,86(6): 1052-1054.
[151]L. Yang, Y. Zhang, F. Cui. Two types of mineral-related matrix vesicles in the bone mineralization of zebrafish. Biomedical Materials,2007,2(1):21-25.
[152]张克从.晶体生长科学与技术.第二版.北京：科学出版社,1997.
[153]M. Harmand. In-vitro study of biodegradation of a Co-Cr alloy using a human cell-culture model. Journal of Biomaterials Science-Polymer Edition,1995,6(9): 809-814.
[154]和峰,刘昌胜.骨修复用生物玻璃研究进展.玻璃与搪瓷,2004,(04)：54-58.
[155]M. Iijima, Y. Moriwaki. Effects of ionic inflow and organic matrix on crystal growth of octacalcium phosphate; relevant to tooth enamel formation. Journal of Crystal Growth,1999,198:670-676.
[156]Q. Feng, H. Wang, F. Cui, T. Kim. Controlled crystal growth of calcium phosphate on titanium surface by NaOH-treatment. Journal of Crystal Growth,1999,200(3-4): 550-557.
[157]J. Ge, F. Cui, X. Wang, Y. Wang. New evidence of surface mineralization of collagen fibrils in wild type zebrafish skeleton by AFM and TEM. Materials Science & Engineering C-Biomimetic and Supramolecular Systems,2007,27(1):46-50.
[158]Verfaillie CM. Adult stem cells:assessing the case for pluripotency. Trends in Cell Biology,2002,12(11):502-508.
[159]Weissman IL. Translating stem and progenitor cell biology to the clinic:Barriers and opportunities. Science,2000,287(5457):1442-1446.
[160]Jiang YH, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 2002,418(6893):41-49.
[161]M. Reyes, A. Dudek, B. Jahagirdar, L. Koodie, P. Marker, C. Verfaillie. Origin of endothelial progenitors in human postnatal bone marrow. Journal of Clinical Investigation,2008,118(11):3813-3813.
[162]G. Kopen, D. Prockop, D. Phinney. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proceedings of the National Academy of Sciences of the United States of America,1999,96(19):10711-10716.
[163]R. Schwartz, M. Reyes, L. Koodie, Y. Jiang, M. Blackstad, T. Lund. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. Journal of Clinical Investigation,2002,109(10):1291-1302.
[164]J. Mauney, V. Volloch, D. Kaplan. Role of adult mesenchymal stem cells in bone tissue-engineering applications:Current status and future prospects. Tissue Engineering,2005,11(5-6):787-802.
[165]D. Gallego, N. Higuita, F. Garcia, N. Ferrell, D. Hansford. Bioactive coatings on Portland cement substrates:Surface precipitation of apatite-like crystals. Materials Science & Engineering C-Biomimetic and Supramolecular Systems,2008,28(3): 347-352.
[166]P.A. Norowski, J.D. Bumgardner. Biomaterial and Antibiotic Strategies for Peri-implantitis. Journal of Biomedical Materials Research Part B-Applied Biomaterials,2009,88B(2):530-543.
[167]G. Mani, D. Johnson, D. Marton, M. Feldman, D. Patel, A. Ayon. Drug delivery from gold and titanium surfaces using self-assembled monolayers. Biomaterials,2008, 29(34):4561-4573.
[168]H. Akhter, N. Saigal, S. Baboota, S. Faisal, J. Ali. A two pulse drug delivery system for amoxicillin:An attempt to counter the scourge of bacterial resistance against antibiotics. Acta Pharmaceutica,2011,61(3):313-322.
[169]T. Oosegi, H. Onishi, Y. Machida. Novel preparation of enteric-coated chitosan-prednisolone conjugate microspheres and in vitro evaluation of their potential as a colonic delivery system. European Journal of Pharmaceutics and Biopharmaceutics,2008,68(2):260-266.
[2]陆裕朴.实用骨科学.北京：人民军医出版社,1991
[3]刘昌胜.自固化磷酸钙-人体硬组织修复的新希望：世界科学,1998,(11)：29-31.
[4]席越.骨组织病理解剖学技术.第一版.北京：人民卫生出版社,1997.
[5]S. Zhang, K. Gonsalves. Preparation and characterization of thermally stable nanohydroxyapatite. Journal of Materials Science-Materials in Medicine,1997,8(1): 25-28.
[6]Compact spongy bone. http://en.wikipedia.org/wiki/File:Illu compact spongy bone. jpg.
[7]Bone Structure, http://www.engin.umich.edu/class/bme456/bonestructure/bonestructure. htm2004.
[8]朱振安.骨折内固定的生物力学.医用生物力学,1994,(01)：63-67.
[9]G. Willmann. Coating of implants with hydroxyapatite material connections between bone and metal. Advanced Engineering Materials,1999,1(2):95-105.
[10]Q. Lv, K. Hu, Q. Feng, F. Cui. Preparation of insoluble fibroin/collagen films without methanol treatment and the increase of its flexibility and cytocompatibility. Journal of Applied Polymer Science,2008,109(3):1577-1584.
[11]W. Zhang, Z.L. Huang, S.S. Liao, F.Z. Cui. Nucleation sites of calcium phosphate crystals during collagen mineralization. Journal of the American Ceramic Society,2003, 86(6):1052-1054.
[12]苗顺东.基于缓释锌离子及仿细胞外基质的高生物响应性涂层制备和表征研究[博士]：浙江大学,2009.
[13]N. Ziats, K. Miller, J. Anderson. In vitro and in vivo interactions of cells with biomaterials. Biomaterials,1988,9(1):5-13.
[14]费军.载去甲万古霉素钢板的研制及防治兔胫骨感染的实验研究[博士]：第三军医大学,2008.
[15]R. Gustilo, J. Anderson. Prevention of infection in the treatment of one thousand and twenty-five open fractures of long bones-Retrospective and prospective analyses. Journal of Bone and Joint Surgery-American Volume,2002,84A(4):682-682.
[16]陈文.氧化铝陶瓷在髋关节置换领域中的应用.生物骨科材料与临床研究,2005,(06)：5-8.
[17]祝云利,吴海山.陶瓷材料在人工关节置换术中的应用现状.国际骨科学杂志,2009,(02)：70-73.
[18]崔福斋,郭牧遥.生物陶瓷材料的应用及其发展前景.药物分析杂志,2010,(07)：1343-1347.
[19]G. Gheysen, P. Ducheyne, L. Hench, P. Meester. Bioglass composites:a potential material for dental application. Biomaterials,1983,4(2):81-84.
[20]S. Hulbert, L. Hench, D. Forbers, L. Bowman. History of bioceramics. Ceramics International,1982,8(4):131-140.
[21]A. Taub, R. Hogri, A. Magal, M. Mintz, Shacham-Diamand Y. Bioactive anti-inflammatory coating for chronic neural electrodes. Journal of Biomedical Materials Research Part A,2012,100A(7):1854-1858.
[22]S. Verrier, J. Blaker, V. Maquet, L. Hench, A. Boccaccini. PDLLA/Bioglass(?) composites for soft-tissue and hard-tissue engineering:an in vitro cell biology assessment. Biomaterials,2004,25(15):3013-3021.
[23]O. Tsigkou, A. Boccaccini, L. Hench, J.M. Polak, Stevens MM. Effect of PDLLA/Bioglass composite films on expression at the mRNA level of collagen type 1 and bone sialoprotein in fetal osteoblasts. Journal of Pharmacy and Pharmacology,2004, 56:S36-S36.
[24]F. Cui, Y. Wang, Q. Cai, W. Zhang. Conformation change of collagen during the initial stage of biomineralization of calcium phosphate. Journal of Materials Chemistry,2008, 18(32):3835-3840.
[25]O. Peitl, E. Zanotto, F. Serbena, L. Hench. Compositional and microstructural design of highly bioactive P2O5-Na2O-CaO-SiO2 glass-ceramics. Acta Biomaterialia,2012,8(1): 321-332.
[26]李保强.壳聚糖／羟基磷灰石仿生骨材料的研究[博士]：浙江大学,2005.
[27]H. Schliephake, C. Botel, A. Forster, B. Schwenzer, J. Reichert, Scharnweber D. Effect of oligonucleotide mediated immobilization of bone morphogenic proteins on titanium surfaces. Biomaterials,2012,33(5):1315-1322.
[28]J. Lincks, B. Boyan, C. Blanchard, C. Lohmann, Y. Liu, D. Cochran. Response of MG63 osteoblast-like cells to titanium and titanium alloy is dependent on surface roughness and composition. Biomaterials,1998,19(23):2219-2232.
[29]R. Flemming, C. Murphy, G. Abrams, S. Goodman, P. Nealey. Effects of synthetic micro-and nano-structured surfaces on cell behavior. Biomaterials,1999,20(6): 573-588.
[30]A. Badami, M. Kreke, M. Thompson, J. Riffle, A. Goldstein. Effect of fiber diameter on spreading, proliferation, and differentiation of osteoblastic cells on electrospun poly(lactic acid) substrates. Biomaterials,2006,27(4):596-606.
[31]A. Travan, E. Marsich, I. Donati, M. Foulc, N. Moritz, H. Aro. Polysaccharide-Coated Thermosets for Orthopedic Applications:From Material Characterization to In Vivo Tests. Biomacromolecules,2012,13(5):1564-1572.
[32]S. Scaglione, V. Guarino, M. Sandri, A. Tampieri, L. Ambrosio, R. Quarto. In vivo lamellar bone formation in fibre coated MgCHA-PCL-composite scaffolds. Journal of Materials Science-Materials in Medicine,2012,23(1):117-128.
[33]U. Ripamonti, L. Roden, L. Renton. Osteoinductive hydroxyapatite-coated titanium implants. Biomaterials,2012,33(15):3813-3823.
[34]M. Rani, A. Agarwal, Y. Negi. Review:Chitosan Based Hydrogel Polymeric Beads-as Drug Delivery System. Bioresources,2010,5(4):2765-2807.
[35]刘相成.人工关节置换术后晚期深部感染的临床分析[博士]：中国人民解放军军医进修学院,2011.
[36]张志斌.骨修复和骨病治疗药物载体CPP/CS复合材料的仿生合成及性能研究[博士]：四川大学,2007.
[37]周健.治疗感染性骨缺损材料的缓释与骨修复的研究[博士]：复旦大学,2011.
[38]W. Xia, K. Grandfield, A. Hoess, A. Ballo, Y. Cai, H. Engqvist. Mesoporous titanium dioxide coating for metallic implants. Journal of Biomedical Materials Research Part B-Applied Biomaterials,2012,100B(1):82-93.
[39]W. Cao, L. Hench. Bioactive materials. Ceramics International,1996,22(6):493-507.
[40]J.E. Lemons. Ceramics:Past, present, and future. Bone,1996,19(1):121-128.
[41]L. Hench. Bioceramics-From Concept to Clinic. Journal of the American Ceramic Society,1991,74(7):1487-1510.
[42]L. Peng, A. Mendelsohn, T. LaTempa, S. Yoriya, C. Grimes, T. Desai. Long-Term Small Molecule and Protein Elution from TiO2 Nanotubes. Nano Letters,2009,9(5): 1932-1936.
[43]J. Holmbom, A. Sodergard, E. Ekholm, M. Martson, A. Kuusilehto, P. Saukko. Long-term evaluation of porous poly(epsilon-caprolactone-co-L-lactide) as a bone-filling material. Journal of Biomedical Materials Research Part A,2005,75A(2): 308-315.
[44]M. Chatzinikolaidou, T. Zumbrink, H. Jennissen. Stability of surface-enhanced ultrahydrophilic metals as a basis for bioactive rhBMP-2 surfaces. Materialwissenschaft Und Werkstofftechnik,2003,34(12):1106-1112.
[45]M. Mohanty, T. Anilkumar, P. Mohanan, C. Muraleedharan, G. Bhuvaneshwar, F. Derangere. Long term tissue response to titanium coated with diamond like carbon. Biomolecular Engineering,2002,19(2-6):125-128.
[46]N. S. Pedro. Titanium Alloys:Preparation, Properties and Applications. Nova Science Pub Incorporated,2010
[47]J. Park, S. Bauer, K. Mark, P. Schmuki. Nanosize and vitality:TiO2 nanotube diameter directs cell fate. Nano Letters,2007,7(6):1686-1691.
[48]C.A. Middleton, C.J. Pendegrass, D. Gordon, J. Jacobs, G.W. Blunn. Fibronectin silanized titanium alloy:A bioinductive and durable coating to enhance fibroblast attachment in vitro. Journal of Biomedical Materials Research Part A,2007,83A(4): 1032-1038.
[49]H. Griesser, K. McLean, G. Beumer, X. Gong, P. Kingshott, G. Johnson. Surface immobilization of synthetic proteins via plasma polymer interlayers. Plasma Deposition and Treatment of Polymers,1999,544:9-20.
[50]C. Lee, A. Singla, Y. Lee. Biomedical applications of collagen. International Journal of Pharmaceutics,2001,221(1-2):1-22.
[51]F. Cui, Y. Li, J. Ge. Self-assembly of mineralized collagen composites. Materials Science & Engineering R-Reports,2007,57(1-6):1-27.
[52]Collagen. http://en.wikipedia.org/wiki/File:Collagentriplehelix.png.
[53]Chitosan. http://en.wikipedia.org/wiki/File:Chitosan2.jpg.
[54]李峻峰,邹琴,赖雪飞.壳聚糖微球药物释放机制研究进展.生物医学工程学杂志,2011,(04)：843-846.
[55]I. Kim, S. Seo, H. Moon, M. Yoo, I. Park, B.C. Kim. Chitosan and its derivatives for tissue engineering applications. Biotechnology Advances,2008,26(1):1-21.
[56]A. Di Martino, M. Sittinger, M. Risbud. Chitosan:A versatile biopolymer for orthopaedic tissue-engineering. Biomaterials,2005,26(30):5983-5990.
[57]L. Ma, C. Gao, Z. Mao, J. Zhou, J. Shen, X. Hu. Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering. Biomaterials,2003,24(26): 4833-4841.
[58]R. Pallela, J. Venkatesan, V. Janapala, S. Kim. Biophysicochemical evaluation of chitosan-hydroxyapatite-marine sponge collagen composite for bone tissue engineering. Journal of Biomedical Materials Research Part A,2012,100A(2):486-495.
[59]R. Wang, M. Hsieh, S. Yang, P. Chuang, J. Lin, C. Yang, et al. Characteristics and cyto-compatibility of Collagen/Ca-P coatings on Ti6A14V substrate. Surface and Coatings Technology,2011,205(19):4683-4689.
[60]刘玲蓉.用于骨组织再生修复的胶原-HA复合材料的应用基础研究[博士]：中国协和医科大学;2007.
[61]D. Campoccia, L. Montanaro, P. Speziale, C. Arciola. Antibiotic-loaded biomaterials and the risks for the spread of antibiotic resistance following their prophylactic and therapeutic clinical use. Biomaterials,2010,31(25):6363-6377.
[62]袁伟永.层层静电自组装技术构建抗菌涂层的研究[硕士]：浙江大学,2006.
[63]方铭中.AZ81镁合金表面微弧氧化改性及涂层的药物释放研究[硕士]：天津大学,2010.
[64]V. Sinha, A. Singla, S. Wadhawan, R. Kaushik, R. Kumria, K. Bansal. Chitosan microspheres as a potential carrier for drugs. International Journal of Pharmaceutics, 2004,274(1-2):1-33.
[65]W. Wei, G. Ma, L. Wang, J. Wu, Z. Su. Hollow quaternized chitosan microspheres increase the therapeutic effect of orally administered insulin. Acta Biomaterialia,2010, 6(1):205-209.
[66]E. Yenilmez, E. Basaran, Y. Yazan. Release characteristics of vitamin E incorporated chitosan microspheres and in vitro-in vivo evaluation for topical application. Carbohydrate Polymers,2011,84(2):807-811.
[67]S. Cafaggi, E. Russo, R. Stefani, R. Leardi, G. Caviglioli, B. Parodi. Preparation and evaluation of nanoparticles made of chitosan or N-trimethyl chitosan and a cisplatin-alginate complex. Journal of Controlled Release,2007,121(1-2):110-123.
[68]Y. Zheng, W. Yang, C. Wang, J. Hu, S. Fu, L. Dong. Nanoparticles based. on the complex of chitosan and polyaspartic acid sodium salt:Preparation, characterization and the use for 5-fluorouracil delivery. European Journal of Pharmaceutics and Biopharmaceutics,2007,67(3):621-631.
[69]李峻峰,张利,李钧甫,邹琴,杨维虎,李玉宝.香草醛交联壳聚糖载药微球的性能及其成球机理分析.高等学校化学学报,2008,(09)：1874-1879.
[70]J. Varshosaz, R. Alinagari. Effect of citric acid as cross-linking agent on insulin loaded chitosan microspheres. Iranian Polymer Journal,2005,14(7):647-656.
[71]A. Wan, Y. Sun, L. Gao, H. Li. Preparation of aspirin and probucol in combination loaded chitosan nanoparticles and in vitro release study. Carbohydrate Polymers,2009, 75(4):566-574.
[72]J. Yu, Y. Li, L. Qiu, Y. Jin. Self-aggregated nanoparticles of cholesterol-modified glycol chitosan conjugate:Preparation, characterization, and preliminary assessment as a new drug delivery carrier. European Polymer Journal,2008,44(3):555-565.
[73]J. Park, G. Saravanakumar, K. Kim, I. Kwon. Targeted delivery of low molecular drugs using chitosan and its derivatives. Advanced Drug Delivery Reviews,2010,62(1): 28-41.
[74]J. Venkatesan, S. Kim. Chitosan composites for bone tissue engineering-An overview. Marine Drugs,2010,8(8):2252-2266.
[75]H. Ho, L. Lin, M. Sheu. Characterization of collagen isolation and application of collagen gel as a drug carrier. Journal of Controlled Release,1997,44(2-3):103-112.
[76]王晓华,鄢立刚,陈芳.甲壳素及其衍生物作为药用辅料的应用进展.药学实践杂志,2000,(02)：86-88.
[77]D. Thacharodi, K. Panduranga. Collagen-chitosan composite membranes for controlled release of propranolol hydrochloride. International Journal of Pharmaceutics,1995, 120(1):115-118.
[78]T. Kokubo, H. Takadama. How useful is SBF in predicting in vivo bone bioactivity? Biomaterials,2006,27(15):2907-2915.
[79]吴波.电化学合成羟基磷灰石涂层及其性能研究[博士]：大连理工大学；2011.
[80]P. Royer, C. Rey. Calcium-phosphate coatings for orthopedic prosthesis. Surface& Coatings Technology,1991,45(1-3):171-177.
[81]M. Okido, K. Nishikawa, K. Kuroda, R. Ichino, Z. Zhao, O. Takai. Evaluation of the hydroxyapatite film coating on titanium cathode by QCM. Materials Transactions,2002, 43(12):3010-3014.
[82]S. Ban, S. Maruno. Deposition of calcium-phosphate on titanium by electrochemical process in simulated body-fluid. Japanese Journal of Applied Physics Part 2-Letters, 1993,32(10B):L1577-L1580.
[83]M. Popa, J. Moreno, M. Popa, E. Vasilescu, P. Drob, C. Vasilescu. Electrochemical deposition of bioactive coatings on Ti and Ti-6A1-4V surfaces. Surface & Coatings Technology,2011,205(20):4776-4783.
[84]F. Bir, H. Khireddine, A. Touati, D. Sidane, S. Yala, H. Oudadesse. Electrochemical depositions of fluorohydroxyapatite doped by Cu2+, Zn2+, Ag+ on stainless steel substrates. Applied Surface Science,2012,258(18):7021-7030.
[85]张柏林.电化学方法制备钛基羟基磷灰石/纳米银复合涂层及其相关性质研究[硕士]：西南交通大学,2010.
[86]X. Pang, I. Zhitomirsky. Electrophoretic deposition of composite hydroxyapatite-chitosan coatings. Materials Characterization,2007,58(4):339-348.
[87]I. Zhitomirsky, A. Hashambhoy. Chitosan-mediated electrosynthesis of orgarlic-inorganic nanocomposites. Journal of Materials Processing Technology,2007, 191(1-3):68-72.
[88]X. Pang, T. Casagrande, I. Zhitomirsky. Electrophoretic deposition of hydroxyapatite-CaSiO3-chitosan composite coatings. Journal of Colloid and Interface Science,2009,330(2):323-329.
[89]F. Sun, X. Pang, I. Zhitomirsky. Electrophoretic deposition of composite hydroxyapatite-chitosan-heparin coatings. Journal of Materials Processing Technology, 2009,209(3):1597-1606.
[90]X. Pang, I. Zhitomirsky. Electrodeposition of hydroxyapatite-silver-chitosan nanocomposite coatings. Surface & Coatings Technology,2008,202(16):3815-3821.
[91]K. Grandfield, I. Zhitomirsky. Electrophoretic deposition of composite hydroxyapatite-silica-chitosan coatings. Materials Characterization,2008,59(1): 61-67.
[92]J. Redepenning, T. Schlessinger, S. Burnham, L. Lippiello, J. Miyano. Characterization of electrolytically prepared brushite and hydroxyapatite coatings on orthopedic alloys. Journal of Biomedical Materials Research,1996,30(3):287-294.
[93]X. Lu, Y. Leng, Q. Zhang. Electrochemical deposition of octacalcium phosphate micro-fiber/chitosan composite coatings on titanium substrates. Surface & Coatings Technology,2008,202(13):3142-3147.
[94]J. Wang, A. Apeldoorn, K. Groot. Electrolytic deposition of calcium phosphate/chitosan coating on titanium alloy:Growth kinetics and influence of current density, acetic acid, and chitosan. Journal of Biomedical Materials Research Part A,2006,76A(3):503-511.
[95]S. Manara, F. Paolucci, B. Palazzo, M. Marcaccio, E. Foresti, G. Tosi. Electrochemically-assisted deposition of biomimetic hydroxyapatite-collagen coatings on titanium plate. Inorganica Chimica Acta,2008,361(6):1634-1645.
[96]A. Roguska, S. Hiromoto, A. Yamamoto, M. Wozniak, M. Pisarek, M. Lewandowska. Collagen immobilization on 316L stainless steel surface with cathodic deposition of calcium phosphate. Applied Surface Science,2011,257(11):5037-5045.
[97]I. Najdovski, P. Selvakannan, A. O'Mullane, S. Bhargava. Rapid Synthesis of Porous Honeycomb Cu/Pd through a Hydrogen-Bubble Templating Method. Chemistry-a European Journal,2011,17(36):10058-10063.
[98]W. Tsai, P. Hsu, Y. Hwu, C. Chen, L. Chang, J. Je. Electrochemistry-Building on bubbles in metal electrodeposition. Nature,2002,417(6885):139-139.
[99]K. Fu, J. Slattery. Coalescence of a bubble at a fluid-fluid interface:Comparison of theory and experiment. Journal of Colloid and Interface Science,2007,315(2): 569-579.
[100]Z. Zhao, H. Li, G. Huo, P. Sun, Li Y., K. Kuroda. Cathodic deposition of hydroxyapatite without H(2) evolution, Surface Engineering:In Materials Science, 2003:169-173.
[101]S. Sirivisoot, R. Pareta, T. Webster. A conductive nanostructured polymer electrodeposited on titanium as a controllable, local drug delivery platform. Journal of Biomedical Materials Research Part A,2011,99A(4):586-597.
[102]朱文菁,金慰芳,张丽丽,张罗修,王洪复.MTT法分析培养成骨细胞的存活和增殖能力.上海医科大学学报,1995,(04)：254-257.
[103]陈卓凡,朱文军,宁成云,曾融生,罗智斌,南开辉,et al纯钛表面酸碱处理及生物矿化的初步研究.中国口腔种植学杂志,2007,(03)：155-158.
[104]M. Takemoto, S. Fujibayashi, M. Neo, J. Suzuki, T. Matsushita, T. Kokubo. Osteoinductive porous titanium implants:Effect of sodium removal by dilute HC1 treatment. Biomaterials,2006,27(13):2682-2691.
[105]胡巧玲,陈中科,陈亮,沈家骢.原位沉析法制备碳酸钙／壳聚糖三维复合材料的研究.高等学校化学学报,2006,(03)：575-578.
[106]仲维卓,罗豪甦,华素坤,许桂生.晶体表面结构和负离子配位多面体生长基元(英文).人工晶体学报,2004,(04)：471-474.
[107]仲维卓,张学华,罗豪甦,华素坤.纳米晶生长习性机理——负离子配位多面体生长基元模型的应用.硅酸盐学报,2004,(03)：239-244.
[108]薛明.新型多孔磷灰石-硅灰石(AW)生物活性玻璃陶瓷支架材料的制备与改性研究[硕士]四川大学,2005.
[109]郑昌琼,冉均国.新型无机材料.北京：科学出版社；2003.
[110]R. Smith, A. Martell. Critical Stability Constants. New York:Plenum Press,1976.
[111]中南矿冶学院分析化学教研室.化学分析手册.北京：科学出版社,1991.
[112]牛宗伟,张建华,李丽,任升峰,孟艳华Sol-gel法合成纳米羟基磷灰石的热力学分析.第五届中国功能材料及其应用学术会议.北京,2004：2401-2404.
[113]王玥华,张云,尹光福,周大利,蒋毅,李勇.用磷酸八钙前驱体法制备β-磷酸三钙.航天医学与医学工程,2004,(04)：266-269.
[114]田一平,杨建华,李晖,郭灵虹.影响α-TCP和HA生物陶瓷表面形成类骨磷灰石的形貌、结构的因素研究.四川大学学报(自然科学版),2007,(01)：135-140.
[115]P. Peng, S. Kumar, N. Voelcker, E. Szili, R. Smart, H. Griesser. Thin calcium phosphate coatings on titanium by electrochemical deposition in modified simulated body fluid. Journal of Biomedical Materials Research Part A,2006,76A(2):347-355.
[116]M. Kuo, S. Yen. The process of electrochemical deposited hydroxyapatite coatings on biomedical titanium at room temperature. Materials Science & Engineering C-Biomimetic and Supramolecular Systems,2002,20(1-2):153-160.
[117]S. Ban, S. Maruno, N. Arimoto, A. Harada, J. Hasegawa. Effect of electrochemically deposited apatite coating on bonding of bone to the HA-G-Ti composite and titanium. Journal of Biomedical Materials Research,1997,36(1):9-15.
[118]胡仁,胡皓冰,林昌健.CaP/壳聚糖复合膜层的电化学共沉积研究.高等学校化学学报,2002,(11)：2142-2146.
[119]唐艳军,李友明,宋晶,潘志东.纳米/微米碳酸钙的结构表征和热分解行为.物理化学学报,2007,(05)：717-722.
[120]孟令科,朱晓丽,叶建东,王迎军.溶胶-凝胶法制备羟基磷灰石及其过程的控制.材料导报材料导报,2002,(11)：75-77.
[121]邬鸿彦,朱明刚,孔令宜,黄立枝.对制备羟基磷灰石粉末工艺条件的再探讨.河北轻化工学院学报,1998,(01)：41-43.
[122]王迎军,宁成云,赵子衷,李尚周,刘正义,卢国辉.HA生物活性陶瓷涂层的爆炸喷涂与等离子喷涂.华南理工大学学报(自然科学版),1998,(07)：124-128.
[123]王迎军,冉炜.高强度生物活性人造齿根的复合制备.华南理工大学学报(自然科学版),1998,(07)：124-128.
[124]肖秀兰,陈志刚.羟基磷灰石涂层制备技术的可行性研究.材料导报,2003,(04)：32-34.
[125]陈晓明,焦玉恒,许传波.电泳沉积制备羟基磷灰石／生物玻璃梯度涂层的研究.材料科学与工程,2002,(04)：545-548.
[126]Y. Li, K. Degroot, J. Dewijn, C. Klein, S. Meer. Morphology and composition of nanograde calcium-phosphate needle-like crystals foed by simple hydrothemal treatment. Journal of Materials Science-Materials in Medicine,1994,5(6-7):326-331.
[127]H. Monma. Electrochemical depostion of calcium-deficient apatite on stainless-steel substrate. Nippon Seramikkusu Kyokai Gakujutsu Ronbunshi-Journal of the Ceramic Society of Japan,1993,101(7):737-739.
[128]M. Wei, A. Ruys, B. Milthorpe, C. Sorrell. Solution ripening of hydroxyapatite nanoparticles:Effects on electrophoretic deposition. Journal of Biomedical Materials Research,1999,45(1):11-19.
[129]L. Cleries, J. Fernandez-Pradas, G. Sardin, J. Morenza. Dissolution behaviour of calcium phosphate coatings obtained by laser ablation. Biomaterials,1998,19(16): 1483-1487.
[130]L. Cleries, J. Fernandez-Pradas, G. Sardin, J. Morenza. Application of dissolution experiments to characterise the structure of pulsed laser-deposited calcium phosphate coatings. Biomaterials,1999,20(15):1401-1405.
[131]L. Cleries, J. Fernandez-Pradas, J. Morenza. Behavior in simulated body fluid of calcium phosphate coatings obtained by laser ablation. Biomaterials,2000,21(18): 1861-1865.
[132]H. Zeng, K. Chittur, W. Lacefield. Dissolution/reprecipitation of calcium phosphate thin films produced by ion beam sputter deposition technique. Biomaterials,1999, 20(5):443-451.
[133]J. Ong, G. Raikar, T. Smoot. Properties of calcium phosphate coatings before and after exposure to simulated biological fluid. Biomaterials,1997,18(19):1271-1275.
[134]J. Vehof, P. Spauwen, J. Jansen. Bone formation in calcium-phosphate-coated titanium mesh. Biomaterials,2000,21(19):2003-2009.
[135]K. Dijk, H. Schaeken, J. Wolke, J. Jansen. Influence of annealing temperature on RF magnetron sputtered calcium phosphate coatings. Biomaterials,1996,17(4):405-410.
[136]I. Lavos-Valereto, B. Konig, C. Rossa, Marcantonio E, Zavaglia AC. A study of histological responses from Ti-6Al-7Nb alloy dental implants with and without plasma-sprayed hydroxyapatite coating in dogs. Journal of Materials Science-Materials in Medicine,2001,12(3):273-276.
[137]S. Sousa, M. Barbosa. Effect of hydroxyapatite thickness on metal ion release from Ti6A14V substrates. Biomaterials,1996,17(4):397-404.
[138]N. Ignjatovic, S. Tomic, M. Dakic, M. Miljkovic, M. Plavsic, D. Uskokovic. Synthesis and properties of hydroxyapatite/poly-L-lactide composite biomaterials. Biomaterials, 1999,20(9):809-816.
[139]D. Ehrenfest, P. Coelho, B. Kang, Y. Sul, T. Albrektsson. Classification of osseointegrated implant surfaces:materials, chemistry and topography. Trends in Biotechnology,2010,28(4):198-206.
[140]C. Reyes, T. Petrie, K. Burns, Z. Schwartz, A. Garcia. Biomolecular surface coating to enhance orthopaedic tissue healing and integration. Biomaterials,2007,28(21): 3228-3235.
[141]M. Lopez-Heredia, P. Weiss, P. Layrolle. An electrodeposition method of calcium phosphate coatings on titanium alloy. Journal of Materials Science-Materials in Medicine,2007,18(2):381-390.
[142]H. Kim, H. Kim, J. Knowles. Fluor-hydroxyapatite sol-gel coating on titanium substrate for hard tissue implants. Biomaterials,2004,25(17):3351-3358.
[143]L. Chen, C. Zhu, D. Fan, B. Liu, X. Ma, Z. Duan. A human-like collagen/chitosan electrospun nanofibrous scaffold from aqueous solution:Electrospun mechanism and biocompatibility. Journal of Biomedical Materials Research Part A,2011,99A(3): 395-409.
[144]S. Ban, S. Maruno. pH distribution around the electrode during electrochemical deposition process for producing bioactive apatite. Japanese Journal of Applied Physics Part 2-Letters,1999,38(5A):L537-L539.
[145]王静梅,姚松年.壳聚糖-氨基酸体系中碳酸钙模拟生物矿化的研究.无机化学学报,2002,(03)：249-254.
[146]黄亚平,赵莹,过梅丽,徐端夫,王笃金.甲壳素和壳聚糖在生物矿化和模拟矿化过程中的调控作用研究进展.高分子通报,2007,(02)：1-7.
[]47]段书源,洪元萍,刘拥军,袁波,蒋峰芝.羟基磷灰石/胶原矿化机理的研究进展.化学通报,2010,(04)：297-301.
[148]S. Rhee, J. Lee, J. Tanaka. Nucleation of hydroxyapatite crystal through chemical interaction with collagen. Journal of the American Ceramic Society,2000,83(11): 2890-2892.
[149]M. Kikuchi, T. Ikoma, S. Itoh, H. Matsumoto, Y. Koyama, K. Takakuda. Biomimetic synthesis of bone-like nanocomposites using the self-organization mechanism of hydroxyapatite and collagen. Composites Science and Technology,2004,64(6): 819-825.
[150]W. Zhang, Z. Huang, S. Liao, F. Cui. Nucleation sites of calcium phosphate crystals during collagen mineralization. Journal of the American Ceramic Society,2003,86(6): 1052-1054.
[151]L. Yang, Y. Zhang, F. Cui. Two types of mineral-related matrix vesicles in the bone mineralization of zebrafish. Biomedical Materials,2007,2(1):21-25.
[152]张克从.晶体生长科学与技术.第二版.北京：科学出版社,1997.
[153]M. Harmand. In-vitro study of biodegradation of a Co-Cr alloy using a human cell-culture model. Journal of Biomaterials Science-Polymer Edition,1995,6(9): 809-814.
[154]和峰,刘昌胜.骨修复用生物玻璃研究进展.玻璃与搪瓷,2004,(04)：54-58.
[155]M. Iijima, Y. Moriwaki. Effects of ionic inflow and organic matrix on crystal growth of octacalcium phosphate; relevant to tooth enamel formation. Journal of Crystal Growth,1999,198:670-676.
[156]Q. Feng, H. Wang, F. Cui, T. Kim. Controlled crystal growth of calcium phosphate on titanium surface by NaOH-treatment. Journal of Crystal Growth,1999,200(3-4): 550-557.
[157]J. Ge, F. Cui, X. Wang, Y. Wang. New evidence of surface mineralization of collagen fibrils in wild type zebrafish skeleton by AFM and TEM. Materials Science & Engineering C-Biomimetic and Supramolecular Systems,2007,27(1):46-50.
[158]Verfaillie CM. Adult stem cells:assessing the case for pluripotency. Trends in Cell Biology,2002,12(11):502-508.
[159]Weissman IL. Translating stem and progenitor cell biology to the clinic:Barriers and opportunities. Science,2000,287(5457):1442-1446.
[160]Jiang YH, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature, 2002,418(6893):41-49.
[161]M. Reyes, A. Dudek, B. Jahagirdar, L. Koodie, P. Marker, C. Verfaillie. Origin of endothelial progenitors in human postnatal bone marrow. Journal of Clinical Investigation,2008,118(11):3813-3813.
[162]G. Kopen, D. Prockop, D. Phinney. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proceedings of the National Academy of Sciences of the United States of America,1999,96(19):10711-10716.
[163]R. Schwartz, M. Reyes, L. Koodie, Y. Jiang, M. Blackstad, T. Lund. Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. Journal of Clinical Investigation,2002,109(10):1291-1302.
[164]J. Mauney, V. Volloch, D. Kaplan. Role of adult mesenchymal stem cells in bone tissue-engineering applications:Current status and future prospects. Tissue Engineering,2005,11(5-6):787-802.
[165]D. Gallego, N. Higuita, F. Garcia, N. Ferrell, D. Hansford. Bioactive coatings on Portland cement substrates:Surface precipitation of apatite-like crystals. Materials Science & Engineering C-Biomimetic and Supramolecular Systems,2008,28(3): 347-352.
[166]P.A. Norowski, J.D. Bumgardner. Biomaterial and Antibiotic Strategies for Peri-implantitis. Journal of Biomedical Materials Research Part B-Applied Biomaterials,2009,88B(2):530-543.
[167]G. Mani, D. Johnson, D. Marton, M. Feldman, D. Patel, A. Ayon. Drug delivery from gold and titanium surfaces using self-assembled monolayers. Biomaterials,2008, 29(34):4561-4573.
[168]H. Akhter, N. Saigal, S. Baboota, S. Faisal, J. Ali. A two pulse drug delivery system for amoxicillin:An attempt to counter the scourge of bacterial resistance against antibiotics. Acta Pharmaceutica,2011,61(3):313-322.
[169]T. Oosegi, H. Onishi, Y. Machida. Novel preparation of enteric-coated chitosan-prednisolone conjugate microspheres and in vitro evaluation of their potential as a colonic delivery system. European Journal of Pharmaceutics and Biopharmaceutics,2008,68(2):260-266.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |