臺灣博碩士論文加值系統

有鑑於鎂合金具生物可降解性、優良的生物相容性及接近骨頭的楊氏系數，故被視為理想的生醫及牙科植入材。然而鎂合金的易腐蝕性卻限制了其在生醫領域的進一步應用；本實驗中，利用電解沉積氧化鋯韌化氧化鋁與氫氧基磷灰石鍍層不僅明顯地將在模擬體液(Hank’s solution)中測得的腐蝕電流由24 μA/cm2 降低到 1.6 μA /cm2 ，也增加了生物活性。接著為了治療及降低手術中感染骨髓炎的風險，再次藉由電解沉積將chitosan-vancomycin-gelatin-calcium phosphate (Chi-Van-Gel-Cap)複合鍍層批覆在試片表面，可得之總載藥量超過2000 μg/cm2並同時呈現兩個月持續釋放的含藥鍍層。考慮到由於骨頭與植入材之間楊氏系數差異所造成的應力遮蔽效應，這種經過以上表面修飾的鎂合金將會是生醫材料在未來一個有潛力的選項。

Magnesium alloys can be ideal materials for medical and dental implants due to their excellent biocompatibility, and degradability. Besides, their Young’s modulus is very close to nature bone. However, the poor corrosion resistance restricts their further applications in medical device. In this study, an electrolytic Al2O3-ZrO2 composite (zirconia toughened alumina, ZTA) coating as the bonding layer for hydroxyapatite (HA) coating, not only obviously improving the corrosion current density from 24μA/cm2 to 1.6μA /cm2 in Hank’s solution by potentiodynamic curves, but also enhancing the bioactivity, is introduced on the surface of AZ91. Furthermore, in order to reduce the probability of osteomyelitis or to treat the related, the chitosan-vancomycin-gelatin-calcium phosphate (Chi-Van-Gel-Cap) composite is also deposited by electrolysis, revealing the drug loading more than 2000 μg/cm2 and the period of sustaining release longer than two months in Hank’s solution. Considering the stress shielding effects resulting from the great difference of Young’s modulus between bone and clinical implants, the surface modified Mg alloys by the above method will be one of the better biomaterials in the future.

摘要 I
Abstract II
1. Introduction 1
2. Materials and methods 4
2-1 Materials 4
2-2 Cathodic polarization tests and electrolytic depositions 4
2-3 Coating characterization 5
2-4 Corrosion evaluation 5
2-5 Drug loading and in vitro release tests 5
2-6 Cell culture 6
3. Results and discussion 8
3-1 Cathodic reactions 8
3-2 Coatings characterization 13
3-2.1 X-ray diffraction 13
3-2.2 FE-SEM 16
3-2.3 Cross-section observations by focused ion beam (FIB) system 19
3-2.4 corrosion evaluation 22
3-2.5 Weight gain & Drug loading 24
3-3 In vitro tests 29
3-3.1 Drug release study 29
3-3.2 MTT test 34
4. Summary and Conclusions 36
5.References 38

[1]T.E. B.L. Mordike, , Materials Science and Engineering A, (2001) 37-45.
[2]M.K. Kulekci, Magnesium and its alloys applications in automotive industry, The International Journal of Advanced Manufacturing Technology, 39 (2007) 851-865.
[3]M.P. Staiger, A.M. Pietak, J. Huadmai, G. Dias, Magnesium and its alloys as orthopedic biomaterials: a review, Biomaterials, (2006) 1728-1734.
[4]R. Zeng, W. Dietzel, F. Witte, N. Hort, C. Blawert, Progress and Challenge for Magnesium Alloys as Biomaterials, Advanced Engineering Materials, (2008) B3-B14.
[5]H. Waizy, J.-M. Seitz, J. Reifenrath, A. Weizbauer, F.-W. Bach, A. Meyer-Lindenberg, B. Denkena, H. Windhagen, Biodegradable magnesium implants for orthopedic applications, Journal of Materials Science, (2012).
[6]G. Song, S. Song, A possible biodegradable magnesium implant material, Advanced Engineering Materials, (2007) 298-302.
[7]Stanislav Antolin, Alan S. Nagelberg, David K. Creber, Formation of Al2O3/Metal Composites by the Directed Oxidation of Molten Aluminum-Magnesium-Silicon Alloys: Part I, Microstructural Development, Journal of the American Ceramic Society, (1994).
[8] R. Arrabal, E. Matykina, P. Skeldon, G. E. Thompson, Incorporation of zirconia particles into coatings formed on magnesium by plasma electrolytic oxidation, Journal of material science, (2008).
[9]A.D. Dobrzanska-Danikiewicz, K. Golombek, D. Pakula, J. Mikula, M. Staszuk, L.W. Zukowska, Long-term development directions of PVD/CVD coatings deposited onto sintered tool materials, Archives of Materials Science and Engineering, (2011) 69-96.
[10] S. Hori, M. Yoshimura, S. So_miya, Al2O3–ZrO2 Ceramics Prepared from CVD Powders, Advances in Ceramics, Vol. 12, Science and Technology of Zirconia II, (1984).
[11]H. Luo, Q. Cai, J. He, B. Wei, Preparation and properties of composite ceramic coating containing Al2O3-ZrO2-Y2O3 on AZ91D magnesium alloy by plasma electrolytic oxidation, Current Applied Physics, (2009) 1341-1346.
[12] H. Duan, K. Du, C. Yan, F. Wang, Electrochemical corrosion behavior of composite coatings of sealed MAO film on magnesium alloy AZ91D, Electrochimica Acta, (2006) 2898-2908.
[13] S.V. Lamaka, G. Knornschild, D.V. Snihirova, M.G. Taryba, M.L. Zheludkevich, M.G.S. Ferreira, Complex anticorrosion coating for ZK30 magnesium alloy, Electrochimica Acta, (2009) 131-141.
[14] W. Shang, B. Chen, X. Shi, Y. Chen, X. Xiao, Electrochemical corrosion behavior of composite MAO/sol–gel coatings on magnesium alloy AZ91D using combined micro-arc oxidation and sol–gel technique, Journal of Alloys and Compounds, (2009) 541-545
[15]S.K. Yen, S.W. Hsu, Electrolytic Al2O3 coating on Co-Cr-Mo implant of hip prosthesis, Journal of Biomedical Materials Research, (2000).
[16]S.K. Yen, M.J Guo, H.Z Zan, Characterization of electrolytic ZrO2 coating on Co–Cr–Mo implant alloys of hip prosthesis, Biomaterials, (2001).
[17]R.Chaim, I.Zhitomirsky, L. Gal-OR, Electrochemical Al2O3-ZrO2 composite coatings on non-oxide ceramic substrates, Journal of Materials Science, (1997) 389-400.
[18]S.K. Yen, C.M. Lin. Cathodic reactions of electrolytic hydroxyapatite coating on pure titanium, Materials Chemistry and Physics, (2003) 70-76.
[19]D.P. Lew, F.A. Waldvogel, Osteomyelitis, The Lancet, (2004) 369-379.
[20]F.A. Waldvogel, G. Medoff, M.N. Swartz, Osteomyelitis: a review of clinical features, therapeutic considerations and unusual aspects, New England Journal Medicine, (1970) 198-206.
[21]M. Bohner, J. Lemaitre, P. VanLanduyt, P.Y. Zambelli, H.P. Merkle, B. Gander, Gentamicin-loaded hydraulic calcium phosphate bone cement as antibiotic delivery system, Journal of Pharmaceutical Sciences., (1997) 565-572.
[22]C.L Nelson, The current status of material used for depot delivery of drugs, Clinical Orthopaedics and Related Research, (2004) 72-8.
[23]S Radin, P Ducheyne, T Kamplain, B.H. Tan. Silica sol–gel for the controlled release of antibiotics, I. Synthesis, characterization, and in vitro release, Journal of Biomedical Materials Research, (2001) 313–20.
[24]L. Vodna, S. Bubenikova, D. Bakos, Chitosan based hydrogel microspheres as drug carriers, Macromolecular Bioscience, (2007) 629-34.
[25]K. Vandenbulcke, L.I. Horvat, De Mil M, G. Slegers, H. Beele, Evaluation of the antibacterial activity and toxicity of 2 new hydrogels: a pilot study, The International Journal of Lower Extremity Wounds, (2006) 109-14.
[26] M. Lucke, G. Schmidmaier, S. Sadoni, B. Wildemann, R. Schiller, N.P. Haas, et al, Gentamicin coating of metallic implant reduces implant-related osteomyelitis in rats, Bone, (2003) 521-531.
[27]C.C. Yang, C.C. Lin, S.K. Yen, Electrochemical Deposition of Vancomycin/Chitosan Composite on Ti Alloy, Journal of The Electrochemical Society, (2012) 152-158.
[28]M. Stigter, J. Bezemer, K. de Groot, and P. Layrolle, Incorporation of different antibiotics into carbonated hydroxyapatite coatings on titanium implants, release and antibiotic efficacy, Journal of Controlled Release, (2004) 127-137.
[29]R.U. Light, H.R. Prentice, Gelatin sponge: Surgical investigation of a new matrix used in conjunction with thrombin in hemostasis, Archives of Surgery, (1945) 69-77.
[30]C. Pilcher, W.F. Meacham, Absorbable gelatin sponge and thrombin for hemostasis in neurosurgery, Experimental and clinical observations, Surgery Gynecology & Obstetrics, (1945) 365-369.
[31]R. Lattes, V.K. Frantz, Absorbable gauze in bone surgery: Experimental studies suggesting clinical application in reconstruction of joints, Annals of Surgery, (1946) 28-39.
[32]W.C. Guralinick, B. Mass, L. Berg, Gelform in oral surgery-A repory of two hundred fifty case, Oral surgery Oral Medicine Oral Pathology, (1948) 632-639.
[33]Z.E. Taheri, Thhe use of gelform paste in anterior cervical fusion, Journal of Neurosurgery, (1971) 438.
[34]R.H. Cobden, E.L. Thrasher, W.M. Marris, Topical hemostatic agents to reduce bleeding from cancellous bone, Journal of Bone & Joint Surgery, (1976) 70-73.
[35]M.B. Yaylaoglu, P. Korkusuz, U. Ors, F. Kokusuz, V. Hasirci, Development of a calcium phosphate-gelatin composite as a bone substitute and its use in drug release, Biomaterials, (1999) 711-719.
[36]Majeti N.V Ravi Kumar, A review of chitin and chitosan applications, Reactive and Functional Polymers, (2000).
[37]Chun-Yi Lo The deposition of chitosan/gelatin/vancomycin/calcium phosphate composite on titanium alloy, Unpublished master dissertation, National Chung Hsing University, Taichung, 2011.
[38] ASTM: E 2149-01
[39] K. L. Kirkwood, R. Dziak and P. G. Beadford, Inositol trisphosphate receptor gene expression and hormonal regulation in osteoblast-like cell lines and primary osteoblastic cell cultures, Journal of Bone and Mineral Research, (1996) 1889-1896.
[40]S.K. Yen, C.C.Chang, The mechanism of electrolytic Al2O3 coating on MAR-M247 superalloy, Institute of Material Engineering, (1999) 779-783.
[41]H.C.H., S.K. Yen, Nano- crystallization and surface analysis of electrolytic ZrO2 coating on Co-Cr alloy, Journal of Materials Science: Materials in Medicine, (2001) 497-501.
[42]S.K. Yen, Characterization of electrolytic ZrO2 Coating on AISI 316L stainless steel, Journal of the Electrochemical Society, (1999) 1392-1396.
[43]J.Y. Lai, The Study of Electrolytic Alumina Toughened Zirconias and Zirconia Toughened Aluminas Ceramic Coatings on Co-Cr-Mo Alloy, Unpublished master dissertation, National Chung Hsing University, Taichung, (2007).
[44]H.C.H., S.K. Yen, Nano- crystallization and surface analysis of electrolytic ZrO2 coating on Co-Cr alloy, Journal of Materials Science: Materials in Medicine, (2001) 497-501.
[45]Yanfeng Gao, Toshitake Masuda, A.K.K. Hiromichi Ohta, Room-temperature preparation of ZrO2 precursor thin, Chemistry of Materials, (2004) 2615-2622.
[46]D. Doni Jayaseelan, D. Amutha Rani, Tadahiro Nishikawa, Hideo Awaji, F.D. Gnanam, Power characteristics, sintering behavior and microstructure of sol-gel derived ZTA composites, Journal of the European Ceramic Society, (2000) 267-275.
[47]Haihe Luo, Qizhou Cai, Jian He, Bokang Wei, Preparation and properties of composite ceramic coating containing Al2O3-ZrO2-Y2O3 on AZ91D magnesium alloy by pasma electrolytic oxidation, Current Applied Physics, (2009) 1341-1346.
[48]R.J. Samuels, Solid state characterization of the structure of chitosan films, Journal of Polymer Science: Polymer Physics Edition, (1981) 1081-1105.
[49]Chun-Yi Lo The deposition of chitosan/gelatin/vancomycin/calcium phosphate composite on titanium alloy, Unpublished master dissertation, National Chung Hsing University, Taichung, (2011).
[50] http://www.lsbu.ac.uk/water/hygel.html
[51] http://www.chm.bris.ac.uk/motm/glycine/glycineh.htm
[52]G.S. Stein, J.B. Lian, J.L. Stein, A.J. Van Wijnen and M. Montecino, Transcriptional control of osteoblast growth and differentiation, Physiological Reviews (1996) 593-629.
[53]H. Rubin, Degrees and kinds of delection in spontaneous neoplastic transformation: an operational analysis, Proceedings of the National Academy of Sciences, (2005) 9276-9281.
[54]H. Rubin, Magnesium: the missing element in molecular views of cell proliferation control, BioEssays, (2005) 311-320.
[55]H. Rubin, Degrees and kinds of delection in spontaneous neoplastic transformation: an operational analysis, Proceedings of the National Academy of Sciences, (2005) 9276-9281.
[56]Frank Witte, Norbert Hort, Carla Vogt, Smadar Cohen, Karl Ulrich Kainer, Regine Willumeit, Frank Feyerabend, Degradable biomaterials based on magnesium corrosion, Current Opinion in Solid State and Materials Sciencem (2008) 63-72.
[57]Edin, Matthew L., Miclau, Theodore, lester, Gayle E., Lindsey, Ronald W., Dahners, Laurence E., Effect of cefazolin and vancomycin on osteoblasts in vitro, Clinical Orthopaedics & Related Research, (1996) .