臺灣博碩士論文加值系統

本研究以鈣磷比為1.0及0.5之磷酸鈣，藉由熱處理方式進行成核以及成長，使之轉化成磷酸一鈣玻璃陶瓷及磷酸二鈣玻璃陶瓷，再進行機械性質、物理性質之量測。並藉由X-ray分析玻璃陶瓷之相變化以及電子顯微鏡觀察顯微結構。接著以生物適應性測試，以了解材料與骨組織之生物相容性。本研究以紐西蘭大白兔為實驗對象，在股骨（femur）處鑽一孔洞後植入磷鈣系材料，觀察週期為2以及4週，以作為原組織與材料間界面評估。根據實驗結果得知磷酸一鈣玻璃及磷酸二鈣玻璃經由600℃~900℃熱處理後，使得材料有緻密化現象，增強粉體間的鍵結能力，使其抗彎及抗壓強度值會隨著溫度昇高而增加。在動物實驗結果顯示，磷酸一鈣玻璃陶瓷及磷酸二鈣玻璃陶瓷與骨組織間有良好的骨生成，其對骨引導之效果以磷酸一鈣玻璃陶瓷為佳。

The biocompatibility of synthetic calcium phosphate as bone-substitutes specimens was investigated. Calcium phosphates were heat treated in forms of mono-calcium phosphate glass-ceramic and di-calcium phosphate glass-ceramic and analyzed by using X-ray diffraction method and scanning electron microscopy（SEM）. The analysis revealed that mono-calcium phosphate and di-calcium phosphate within heat treatment temperature range of 600-900℃ would result a well mechanical strength of devitrified specimens. The values of bending and compressive strength were increased with the increasing of heated temperatures. The bone-substitutes specimens were then implanted into the medial femoral condyle of the femurs in New Zealand rabbits. In vivo study showed the specimens could be suitable for the repair and replacement of living bone at four-week implantation. In this study, the mono-calcium phosphate glass-ceramic shows better osteo-conduction than that of di-calcium phosphate.

摘　要 I
誌　謝 III
目 錄 IV
表目錄 VI
圖目錄 VII
第一章 緒論 1
1.1 前言 1
1.2 研究背景及目的 2
第二章 理論基礎與文獻回顧 4
2.1 玻璃陶瓷之製造 4
2.1.1 玻璃陶瓷之製造原理 4
2.1.2 燒結之定義與方式 4
2.2 熱分析 8
2.3 結晶化動力學理論 8
2.4 生醫材料之簡介 12
2.5 生醫骨科陶瓷材料之分類 13
2.5.1 生物惰性材料 14
2.5.2 表面活性材料 14
2.5.3 可吸收性材料 15
2.6 生醫玻璃 15
2.7 磷酸鈣及磷酸鈣玻璃 16
2.8 生醫玻璃陶瓷 19
2.9 模擬人工體液 21
2.10 骨組織 22
2.10.1 骨組織學與生長機制 22
2.10.2 具骨引導性之磷酸鈣系材料於骨修復的過程 23
第三章 實驗材料與方法 25
3.1 實驗藥品 25
3.2 實驗儀器 26
3.3 實驗流程 27
3.4 試片之製備 28
3.5 試片分析與檢測 28
3.5.1 示差熱分析 28
3.5.2 掃描電子顯微鏡分析 28
3.5.3 物理性質檢測 29
3.5.4 機械性質檢測 29
3.5.5 X-ray繞射分析 30
3.6 浸漬實驗 30
3.6.1 原子火焰吸收光譜 31
3.7 IN VIVO實驗 31
第四章 結果與討論 35
4.1 示差熱分析 35
4.2 熱處理溫度對材料之影響 42
4.2.1 SEM分析 42
4.2.2 物理性質 47
4.2.3 機械性質 50
4.2.4 X-ray繞射分析 53
4.3 浸漬實驗 55
4.3.1 X-ray繞射分析 55
4.3.2 原子火焰吸收光譜分析 55
4.4 IN VIVO實驗 59
第五章 結論 71
參考文獻 72

[1] G..Georgiou, and J. C. Knowles, “Glass reinforced hydroxyapatite for hard tissue surgery－Part 1: mechanical properties”, Biomaterilas, Vol. 22, 2001, pp. 2811-2815.
[2] K. Toshihiro, H. Yoshimasa, and N. Masayuki, “Apatite formation on calcium phosphate invert glasses in simulated body fluid”, J. Am. Ceram. Soc., Vol.84, no. 2, 2001, pp. 450-452.
[3] SH. Kwon, “Calcium phosphate bioceramics with various porosities and dissolution rates”, J. Am. Ceram. Soc., Vol. 85, no. 12, 2002, pp. 3129-3131.
[4] T. Kasuga, M. Sawada, M. Nogami, and Y Abe, “Bioactive ceramics prepared by sintering and crystallization of calcium phosphate invert glasses”, Biomaterials, Vol. 20, 1999, pp. 1415-1420.
[5] J. Dong, T. Uemura, Y. Shirasaki, and T. Tateishi, “Promotion of bone formation using highly pure porous b-TCP combined with bone marrow-derived osteoprogenitor cells”, Biomaterials, Vol. 23, 2002, pp. 4493-4502.
[6] P. Vincenzini, “Ceramics in substitutive and reconstructive surgery”, Elsevier Science Publishers B. V., 1991.
[7] B. D. Katthagen, “Bone regeneration with bone substitutes”, Springer-Verlag, Berlin, 1987.
[8] 劉典謨，「生醫玻璃/玻璃陶瓷材料」，材料與社會，第75期，82年3月。
[9] L.L. Hench, “Bioactive glasses and glass-ceamics”, Materials science forum, Vol. 293, 1999, pp. 37-64.
[10] H. L. Feng, J. L. Chun, S. C. Ko, S. S. Jui, and P. L. Chun, “Petal-like apatite formed on the surface of tricalcium phosphate ceramic after soaking in distilled water”, Biomaterials, Vol. 22, 2001 pp. 2981-2992.
[11] T. Kokubo, “Novel biomedical materials based on glasses”, Materials science forum, Vol. 293, 1999, pp. 65-82.
[12] Y. Abe, A. Yamaguchi and H. Fuku, “Calcium phosphate glass-ceramics”, Japan , Kokai 76-73-019, Vol. 24, 1976.
[13] W. Vogel, “Chemistry of glass”, The American Ceram. Soc., Inc., Vol. 251, 1985.
[14] Q. Liu, J. R. de Wijn, and C. A. van Blitterswijk, “Covalent bonding of PMMA, PBMA, PBMA, and poly（HEMA）to hydroxyapatite particles”, J. Biomed. Mater. Res., Vol.40, 1998, pp. 257-263.
[15] F.S. Janes, "Bioceramics," 1999, pp. 37-81.
[16] T. Kokubo, HM Kim, and M. Kawashita, “Novel bioactive materials with different mechanical properties”, Biomaterials, Vol. 24, 2003, pp. 2161-2175.
[17] N. Ikeda, “Quantitative comparison of osteoconduction of porous, dense A-W glass-ceramic and hydroxyapatite granules”, Biomaterials, Vol. 20, 1999, pp. 1087-1095.
[18] N. Price, S. P. Bendall, C. Frondoza, R. H. Jinnah, and David S. H., "John Wiley & Sons Inc," Vol. 37, 1997, pp. 394-400.
[19] C. K. Wang, C. P. Ju, and J. H. Chern Lin, “Effect of doped bioactive glass on structure and properties of sintered hydroxyapatite”, Materials Chemistry and Physics, Vol. 53, 1998, pp. 138-149.
[20] A. Ślósarczyk, and J. Piekarczyk, “Ceramic materials on the basis of hydroxyapatite and tricalcium phosphate”, Ceramics International, Vol. 25, 1999, pp. 561-565.
[21] Y. Abe, T. Kasuga, H. Hosono and K. de Groot, “Preparation of high-strength calcium phosphate glass-ceramics by unidirectional crystallization”, J. Am. Ceram. Soc., Vol. 67, 1984, pp. 142-144.
[22] F. Wakai, and F. Aldinger, “Sintering through surface motion by the difference in mean curvature”, Acta Materialia, Vol. 51, 2003, pp. 4013-4024.
[23] G.S. Upadhyaya, “Some issues in sintering science and technology”, Materials chemistry and physics, Vol. 67, 2001, pp. 1-5.
[24] 許國銓，「結晶化玻璃系列之二生醫用結晶化玻璃」，材料與社會，第57期，80年9月。
[25] S. Sato, T. Koshino, and T. Saito, “Osteogenic response of rabbit tibia to hydroxyapatite particle-plaster of paris mixture”. Biomaterials, Vol. 19, 1998, pp. 1895-1900.
[26] 「生物體用的陶瓷人工骨骼及其周邊」，工業技術研究院工業材料研究所編譯資料，No MR058, 1983。
[27] J. B. Park, “Biomaterials science and engineering” Plenum Press, New York, 1984.
[28] P. Vincenzini, “Ceramics in substitutive and reconstructive surgery”, Elsevier Science Publishers B. V., 1991.
[29] B. D. Katthagen, “Bone regeneration with bone substitutes”, Springer-Verlag, 1987.
[30] M. Jarcho, “Calcium phosphate ceramics as hard tissue”, Clin. Orthop. Rel. Res., Vol. 157, 1981, pp. 259-279.
[31] S. F. Hulbert, J. C. Bokros, L. L. Hench, J. W. Wilson and G. Heimke, “Ceramics in clinical applications, past, present and future”, Ceramics in Clinical Applications, 1987, pp. 3-27.
[32] 廖俊仁，「生醫骨科陶瓷材料之發展與應用」，生技醫藥專題。
[33] 洪敏雄，林峰輝，王盈錦，「生醫陶瓷」，陶瓷技術手冊(下)中華民國產業科技發展協進會，第三十一章，1994，第1019-1040頁。
[34] Z. L. Racqual, “Calcium phosphates in oral biology and medicine” 1991, pp. 5-107.
[35] W. H. land, “Biocompatible and bioactive glass-ceramics─state of the art and new directions”, J. Non-crystalline Solids, Vol. 219, 1997, pp. 192-197.
[36] YK Jun, WH Kim, Oh-Kyeong Kweon, and Seong-Hyeon Hong, “The fabrication and biochemical evaluation of alumina reinforced calcium phosphate porous implants”, Biomaterials, Vol. 24, 2003, pp. 3731-3739.
[37] H. Broemer, K. Deutscher, and B. Blencke, “Properties of the bioactive implant material ceravital”, Sci. Ceram., Vol. 9, 1977, pp.219-225.
[38] W. Vogel, “Chemistry of glass”, The American ceramic society, Inc., 1985, pp.251.
[39] T. Kokubo, S. Ito, M. Shigermatsu, S. Sakka and T. Yamamuro, “Mechanical properties of a new type of apatite-containing glass-ceramics for prothetic application”, J. Mater. Sci., Vol. 20, 1985, pp. 2001-2004.
[40] F. H. Lin, and M. H. Hon, “A study on the bioglass ceramics in the Na2O-CaO-SiO2-P2O5 system”, J. Mater. Sci., Vol. 23, 1989, pp. 4295-4299.
[41] I. H. Kalfas, M. D., and F. A. C. S., “Principles of bone healing”, Neurosurf Focus, Vol. 10, no. 4, 2001.
[42] G. A. Rodan, "Control of bone formation and resorption: Biological and clinical perspective," J Cell Biocnem Suppls, Vol. 30, 1998, pp. 55-61.
[43] J. T. Bettany, N. M. Peet, R. G. Wolowacz, T. M Skerry and P. S. Grabowski, "Tetracyclines induce apoptosis in osteoclast," Bone , vol. 27, 2000, pp. 75-80.
[44] Q. Liu, J. R. de Wijn, and C. A. van Blitterswijk, “A study on the grafting reaction of isocyanates with hydroxyapatite particles”, J. Biomed. Mater. Res., Vol. 40, 1998, pp. 358-364.
[45] Q. Liu, J. R. de Wijn, and C. A. van Blitterswijk, “Composite biomaterials with chemical bonding between hydroxyapatite filler particles and PEG/PBT copolymer matrix”, J. Biomed. Mater. Res., Vol. 40, 1998, pp. 490-497.
[46] Q. Liu, J. R. de Wijn, and C. A. van Blitterswijk, “Nono-apatite/polymer composites: mechanical and physicochemical characteristics”, Biomaterials, Vol. 18, 1997, pp. 1263-1270.
[47] A. A. El-Kheshen, and M. F. Zawrah, “Sinterability, microstructure and properties of glass/ceramic composites”, Ceramics International, Vol. 29, 2003, pp. 251-257.