臺灣博碩士論文加值系統

鈦金屬是經常被用在生醫相關應用的輕金屬材料，主要是因為鈦具有良好的生醫相容性與化學穩定性；而鈦金屬在生醫上的應用又會因材料表面的形貌、氧化物的結構、氧化層的厚度、化學組成不同，而有很大的差異；為了使鈦金屬更適合金屬植入相關的生醫應用，往往需要在材料的表面進行氧化層的改質或是被覆氫氧基磷灰石（Hydroxyapatite, HA），除了可以加快骨整合的速度之外，也可以增加鈦金屬材料與骨組織之間的接合強度。
電漿電解氧化法（plasma electrolytic oxidation, PEO）是自1930年代就有的技術，但是近年來，隨著輕金屬材料在工業界、航太工程與生醫材料上的應用越來越廣，電漿電解氧化法成為越來越常被應用在輕金屬表面改質的技術。電漿電解氧化法是一種設備簡便、成膜迅速的製程，在適當的電解溶液環境中，加上數百伏特的外加電壓，金屬的表面會產生局部的電漿與火花反應，短時間內，金屬的表面便形成緻密且多孔的氧化層，同時也能將溶液中的元素併入氧化層當中。此氧化層具有極佳的接合強度、大的接觸面積、耐高溫、高強度、高磨耗、抗腐蝕等優良的特性，相當適合生醫上的使用。
在鈦金屬上以醋酸鈣（Ca(CH3COO)2）、β-甘油磷酸鈉（C3H7Na2O6P•5H2O）為電解液進行電漿電解氧化反應，可以在試片上迅速的被覆二氧化鈦膜，且膜層當中有鈣與磷的併入，經過適當的熱處理，可以成為具有高度生醫活性的試片。本實驗使用田口實驗法，以電解液組成、反應時間、反應電壓為因子，各因子在三種水準下分別執行電漿電解氧化試驗，然後量測試片的粗糙度與銳鈦礦相的相對強度，使用田口實驗法的L9直交表找出以生醫適用性為目的的優選反應參數。以此參數進行電漿電解氧化反應，反應後的試片不需要經過高溫水熱處理，室溫下，將試片浸泡在2M的K2HPO4水溶液下10分鐘，再以此浸泡過的試片進行活體外試驗。活體外試驗是使用模擬人體體液（Simulate body fluid, SBF）浸泡試片1-15天，再分析其性質；試片浸泡SBF 3天後，在試片的表面即有氫氧基磷灰石的生成，7天後試片的表面覆滿氫氧基磷灰石。以FE-SEM、XRD分析試片的微結構與組成，並以傅立葉轉換紅外線光譜儀（FT-IR）分析試片的化學組成。

Titanium, a kind of light metal material, is widely applicated in biomedical field, mainly because of good bio-compatibility and chemical stability. Generally various applications of titanium depend on the characteristic such as surface property, oxide structure, thickness of oxide layer and chemical composition. The oxide layer of the material surface or coated hydroxyapatite of titanium often was modifies for the purpose of usage in implantation. By this kind modification, not only the bonding process could be strength between the titanium materials and also speed up the osteointegration of bone tissue.
Plasma electrolytic oxidation (PEO) is an oxidation technology that was developed since the 1930s. Light metal material was more and more broadly used in the different industries, including material industry, aerospace engineering and biomedical industry. Thus the application of PEO in light metal surface modification technology was widely used recently.
PEO is a fast film-forming process with simple device. Metal surface could induce local spark and plasma reactions by hundreds voltage in suitable electrolytic solution. Under this condition, the formation of dense and porous oxide layer was induced shortly on metal surface. This oxide layer has excellent characteristics of good bonding strength, large contact area, high temperature tolerance, high durability, better corrosion resistance and so on. It is very suitable in biomedical field due to its excellent properties.
Titanium metal using the calcium acetate （Ca(CH3COO)2), β-glycerophosphate (C3H7Na2O6P • 5H2O) as the electrolyte for plasma electrolytic oxidation, and we can rapidly get specimens which coated with titanium dioxide films dope calcium and phosphorous. Greatly bioactivite materials will complete after suitable thermal process. In this study, we perform PEO process under three levels of each factor (electrolyte composition, reaction time, reaction voltage factor) by using Taguchi method, and measured roughness of the sample and the relative intensity of anatase. We implement PEO reaction by some optimal reaction parameters which from L9 orthogonal array table in Taguchi method and is for the purpose of applicability of biomedical. Specimen after the reaction without under hydrothermal treatment, the sample immersed in 2 M of K2HPO4 solution for 10 minutes, and then soaked specimen is performed some in vitro tests. In vitro studies are analyzing the specimens immersed in Simulate body fluid (SBF) for 1-15 days. Hydroxyapatite-containing coatings on titanium substrates were formed after 3 days’ immersion. And the sample surface covered with hydroxyapatite after 7 days’ immersion. The microstructures and compositions of the obtained films were analyzed by field-emission scanning electron microscopy and X-ray diffraction. The chemical states were also analyzed by Fourier transform infrared spectroscopy.

目錄
誌謝 Ⅰ
摘要 Ⅱ
目錄 Ⅴ
表目錄 VIII
圖目錄 IX
第一章 緒論 1
1.1 研究背景 1
1.2 研究動機 2
1.3 研究目的 3
第二章 理論背景與文獻回顧 4
2.1生醫材料 4
2.1.1 鈦 5
2.1.2二氧化鈦 5
2.1.3氫氧基磷灰石 8
2.2電漿電解氧化法簡介 10
2.2.1 電漿電解氧化法原理 10
2.2.2 以電漿電解氧化法製備二氧化鈦膜 13
2.3 金屬上被覆氧基磷灰石 17
2.3.1 電漿電解氧化法製備之二氧化鈦膜上被覆氧基磷灰石 17
2.3.2 以其他方法在鈦金屬上被覆氫氧基磷灰石 20
2.4田口實驗法簡介 22
第三章 研究方法 23
3.1 實驗流程 23
3.2基材前處理與反應溶液配置 23
3.3以電漿電解氧化法制備二氧化鈦膜的方法 25
3.4設計田口實驗法的參數 27
3.5試片進行浸泡SBF之體外試驗 29
3.5.1磷酸氫二鉀溶液的製備 29
3.5.2模擬人體體液（Simulated body fluid, SBF）製備 30
3.5.3試片浸泡模擬人體體液1-15天 32
3.6分析儀器 32
3.6.1 試片外觀與氧化層膜厚分析 32
3.6.2 氧化層結晶相、相對強度與晶粒尺寸分析 32
3.6.3 試片表面形貌與元素定量分析 33
3.6.4 試片表面粗糙度分析 33
3.6.5 試片表面元素的化學鍵結分析 33
第四章 結果與說明 35
4.1 Ti原始基材之外觀與結晶相分析 35
4.2 以電漿電解氧化法在鈦基材上製備二氧化鈦膜 36
4.2.1 電壓與電流隨反應時間變化曲線 36
4.2.2 試片外觀與結晶相分析 39
4.2.3 試片表面形貌之分析 40
4.2.4 試片膜厚之分析 41
4.2.5 試片表面粗糙度之分析 42
4.3 以田口實驗法分析實驗參數 42
4.3.1實驗參數與粗糙度關係性之分析 43
4.3.2實驗參數與anatase對試片相對強度之分析 47
4.3.3 實驗參數綜合討論 50
4.3.4 以優化實驗參數執行田口法之確認實驗 52
4.4 體外試驗 53
4.4.1 試片浸泡SBF後之XRD分析 53
4.4.2 試片浸泡SBF後之FE-SEM分析 54
4.4.3 試片浸泡SBF後之FT-IR分析 58
第五章 討論 60
5.1設定田口實驗的參數區間與目標性質的討論 60
5.1.1設定反應電壓區間 60
5.1.2設定粗糙度望大為生醫材料目標性質 62
5.1.3設定anatase相的相對強度望大為生醫材料目標性質 64
5.2氫氧基磷灰石是否生成 65
5.3氫氧基磷灰石的成核機制 66
5.4 PEO反應後試片不同之後處理對試片HA成核影響的比較 68
5.5 綜合討論 71
第六章 結論 73
參考文獻 74

[1] Clemson Advisory Board for Biomaterials, Definition of the word biomaterial, Thc 6th Annnal Intermalionel Biomaterial Symposium, April (1974).
[2] N. Huang, P. Yang, Y.X. Leng, J.Y. Chen, H. Sun, J. Wang, G.J. Wang, P.D. Ding and Y. Leng, “Hemocompatibility of titanium oxide films,” Biomaterials, Vol.24, Issue 13 (2003) 2177-2187.
[3] J.S. Sun, H.C. Liu, H.S Chang, J. Li, F.H. Lin and H.C. Tai, “The influence of hydroxyapatite particle size on bone cell activities: an in vitro study,” J. Biomed. Mater., Res, Vol.3, Issue 3 (1998) 390-397.
[4] S.D. Bruck, Properties of biomaterials in the physiological environment, CRC Press. Inc., Boca Raton, Florida (1980).
[5] J. Lausma, L. Mattsson, U. Rolander and B. Kasemo, “Chemical composition and morphology of titanium surface oxides,” Mater Res Soc Symp Proc., 55 (1986) 351.
[6] A.L. Yerokhin, X. Nie, A. Leyland and A. Matthews, “Characterisation of oxide films produced by plasma electrolytic oxidation of a Ti6Al4V alloy,” Surf. Coat. Technol., 130 (2000) 195-206.
[7] Y.T. Sul, “The significance of the surface properties of oxidized titanium to the bone response: special emphasis on potential biochemical bonding of oxidized titanium implant,” Biomaterials, 24 (2003) 3893-3907.
[8] H.S. Ryu, W. H. Song and S. H. Hong, “Biomimetic apatite induction on Ca-containing titania,” Current Applied Physics, 5 (2005) 512-515.
[9] Y. Han , S.H. Hong and K. Xu, “Structure and in vitro bioactivity of titania-based films by micro-arc oxidation,” Surface and Coatings Technology, 168 (2003) 249–258.
[10] 鄭智文，化學氣相沉積二氧化鈦薄膜及添加雜質效應，國立成功大學材料科學(工程)研究所，1991，碩士論文。
[11] X. Bokhimia, A. Moralesa, M. Aguilara, J.A. Toledo-Antoniob and F. Pedrazab, “Local order in titania polymorphs,” International Journal of Hydrogen Energy, 26 (2001) 1279–1287.
[12] M.J. Herrmann, C. Guillard and P. Pichat, Catalyst Today, 17, 7 (1993).
[13] N. Huang, P. Yang and X. Cheng, “Blood compatibility of amorphous titanium oxide films synthesized by ion beamenhanced deposition,” Biomaterials, 19 (1998) 771.
[14] K. Hayasho, T. Mashima and K. Uenoyama, “The effect of hydroxyapatite coating on bony ingrowth into grooved titanium implants,” Biomaterials, 20 (1999) 111.
[15] K. de Groot, Bioceramics of calcium phosphate, CRC Press. Inc., Boca Raton, Florida, (1983)79-97.
[16] P. Bristowe, ”Studies in Materials Science Reader in Materials Science,” Clare College, Cambridge.
[17] 李易聲，利用不同CeO2 觸媒降解苯胺之濕式過氧化反應之研究，嘉南藥理科技大學環境工程與科學系，2010，碩士論文。
[18] G.P. Wirtz, S.D. Brown and W. M. Kriven, “Ceramic coatings by anodic spark deposition,” Mater. Manuf. Processes, 6 (1991) 87-115.
[19] M. Fini, A. Cigada, G. Rondelli, R. Chiesa and R. Giardino, “In vitro and in vivo behaviour of Ca- and P-enriched anodized titanium,” Biomaterials, 20 (1999) 1587-1594.
[20] A.L. Yerokhin, X. Nie, A. Leyland, A. Matthews and S.J. Dowey, “Plasma electrolysis for surface engineering,” Surf. Coat. Technol., 122 (1999) 73-93.
[21] P. Gupta, G. Tenhundfeld, E.O. Daigle and D. Ryabkov, “Electrolytic plasma technology: Science and engineering-An overview,” Surf. Coat. Technol., 201 (2007) 8746-8760.
[22] L.Wan, J.F. Li and J.Y. Feng, “Anatase TiO2 films with 2.2 eV band gap prepared by micro-arc oxidation,” Materials Science and Engineering, 139, (2007), 216-220.
[23] Y. Han, S.H. Hong and K. Xu, “Synthesis of nanocrystalline titania films by micro-arc oxidation,” Materials Letters, 56 (2002) 744–747.
[24] T.H. Teh, A. Berkani , S. Mato and P. Skeldon, “Initial stages of plasma electrolytic oxidation of titanium” Corrosion Science, 45 (2003) 2757–2768.
[25] D. Wei, Y. Zhou, D. Jia and Y. Wang, “Effect of applied voltage on the structure of microarc oxidized TiO2-based bioceramic films,” Materials Chemistry and Physics., 104 (2007) 177–182.
[26] F. Jin, P..K. Chu, K. Wang and J. Zhao, “Thermal stability of titania films prepared on titanium by micro-arc oxidation,” Materials Science and Engineering, 476 (2008) 78–82.
[27] T. Kokubo, H. M. Kim and M. Kawashita, “Novel bioactive materials with different mechanical properties,” Biomaterials, 24 (2003) 2161.
[28] Y. Han, J. Sun and X. Huang, “Formation mechanism of HA-based coatings by micro-arc oxidation,” Electrochemistry Communications, 10 (2008) 510–513.
[29] M. Fini, A. Cigada, G. Rondelli, R. Chiesa and R. Giardino, “In vitro and in vivo behaviour of Ca- and P-enriched anodized titanium,” Biomaterials, 20 (1999) 1587-1594.
[30] X. Nie , A. Leyl and A. Matthews, “Deposition of layered bioceramic hydroxyapatite/ TiO2 coatings on titanium alloys using a hybrid technique of micro-arc oxidation and electrophoresis,” Surface and Coatings Technology, 125 (2000) 407–414.
[31] Y. Han, S.H. Hong and K. Xu, “Structure and in vitro bioactivity of titania-based films by micro-arc oxidation,” Surface and Coatings Technology, 168 (2003) 249-258.
[32] W.H. Songa, Y.K. Juna,Y. Hana and S.H. Hong, “Biomimetic apatite coatings on micro-arc oxidized titania,” Biomaterials, 25 (2004) 3341-3349.
[33] D. Wei, Y. Zhou, D. Jia and Y. Wang, “Chemical treatment of TiO2-based coatings formed by plasma electrolytic oxidation in electrolyte containing nano-HA, calcium salts and phosphates for biomedical applications,” Applied Surface Science, 254 (2008) 1775–1782.
[34] X.J. Tao, S.J. Li, C.Y. Zheng, J. Fu, Z. Guo, Y.L. Hao, R. Yang and Z.X. Guo, “Synthesis of a porous oxide layer on a multifunctional biomedical titanium by micro-arc oxidation,” Materials Science and Engineering C, 29 (2009) 1923-1934.
[35] S. Limin, C.B. Christopher, A.G. Karlis and K. Ahmet, “Material Fundamentals and Clinical Performance of Plasma-Sprayed Hydroxyapatite Coatings: A Review,” J. Biomed Mater Res., Vol. 58 ( 2001) 570-592.
[36] 吳佳昌、曾婉榕、張浩陞、曾麗玲、謝耀東, “人工植體覆蓋式義齒之存活率：高雄榮總14年回溯性研究,” 牙醫學雜誌(J Dent Sci)., Vol.2 Issue.29 (2009) 1-6.
[37] R.D. Bloebaum, D. Beeks and L.D. Dorr, “Complications with hydroxyapatite particulate
separation in total hiparthroplasty,” Clin Orthop., 298 (1994) 19-26.
[38] M.S. Kim, J.J. Ryu and Y.M. Sung, “One-step approach for nano-crystalline hydroxyapatite coating on titanium via micro-arc oxidation,” Electrochemistry Communications, 9 (2007) 1886–1891.
[39] 李輝煌，田口方法-品質設計的原理與實務，高立圖書有限公司，民國八十九年。
[40] T. Kokubo and H. Takadama, “How useful is SBF in predicting in vivo bone bioactivity?” Biomaterials, 27 (2006) 2907.
[41] R.A. Spurr and H. Myers. “Quantitative Analysis of Anatase-Rutile Mixtures with an X-Ray Diffractometer” Anal. Chem., 29 (1957) 760-762.
[42] B. D. Cullity and S. R. Stock. Elements of X-ray Diffraction, Third Edition. Prentice, New York, (2001).
[43] M. Jevitc, M. Mitric, S Skapin, B. Jancar, N. Ignjatovic and D. Uskokovic, “Crystal Structure of Hydroxyapatite Nanords Synthesized by Sonochemical Homogeneous Precipitation,”Crystal Growth and Design, 8(2003) 2217-2222.
[44] P. Thomeen, C. Larsson, L.E. Ericson, L. Sennerby, J. Lausmaa and B. Kasemo,“Structure of the interface between rabbit cortical bone and implants of gold, zirconium and titanium,”Journal of Materials Science: Materials in Medicine, 8(1997) 653.
[45] K. Kieswetter, Z. Schwartz, D.D. Dean and B.D. Boyan, “The Role of Implant Surface Characteristics in the Healing of Bone,” Critical Reviews in Oral Biology & Medicine, 7 (1996) 329-345.
[46] A. Wennerberg, T. Albrektsson and B. Andersson, “An animal study of c.p. titanium screws with different surface topographies,” Journal of Materials Science: Materials in Medicine, 6 (1995) 302-309.
[47] 黃何雄、何俊德、游惠婷, “Effect of Surface Roughness of Ti and Ti-6A1-4V Alloy on the Initial Adhesion and Proliferation of osteoblast-like U-2 OS Cells,” 中華牙醫學雜誌, vol.23, Issue 3 (2004).
[48] B. Chehroudi, T.R.L. Gould and D.M. Brunette. “Effects of grooved titanium coated implant surface on epithelial cell behavior in vitro and in vivo,” J. Biomed Mater Res., 23 (1989) 1067-1085.
[49] M.Uchida, H.M. Kim, T. Kokubo, S. Fujibayashi and T. Nakamura, “Structural dependence of apatite formation on titania gels in a simulated body fluid,” J. Biomed Mater Res., Vol. 64A (2003) 164– 170.
[50] R. Rohanizadeh, M. Al-Sadeq and R.Z. LeGeros, “Preparation of different forms of titanium oxide on titanium surface: Effects on apatite deposition,” J. Biomed Mater Res., Vol. 71 (2004) 343–352.
[51] D. Elwell and H.J. Schell, “Crystal Growth from High-Temperature Solutiona,” Academic Press, Inc., 150 (1975)
[52] 崔廣宇，藉由仿生浸泡法在體外鍍製氫氧基磷灰石趨勢之探討，國立成功大學製造工程研究所，碩士論文
[53] H. S. Ryu, W.H. Song and S.H. Hong R, “Biomimetic apatite induction of P-containing titania formed by micro-arc oxidation before and after hydrothermal treatment,” Surface & Coatings Technology, 202 (2008) 1853-1858.