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研究生： 史學歡
Hsueh-Huan Shih
論文名稱： 膠原蛋白，三鈣磷酸鹽與生物玻璃牙齒填充複合材料之細胞毒性與降解行為探討
Cytotoxicity and degradation behaviors of collagen, β-TCP and bioglass for dental filler composites
指導教授： 施劭儒
Shao-Ju Shih
口試委員: 林穎志
Ying-Chih Lin
宋振銘
Jenn-Ming Song
周育任
Yu-Jen Chou
施劭儒
Shao-Ju Shih
學位類別： 碩士
Master
系所名稱： 工程學院 - 材料科學與工程系
Department of Materials Science and Engineering
論文出版年： 2019
畢業學年度： 107
語文別： 中文
論文頁數： 101
中文關鍵詞： 生物玻璃 、三鈣磷酸鹽 、膠原蛋白 、牙科填料 、噴霧乾燥法
外文關鍵詞： bioglass, β-tricalcium phosphate, collagen, dental filler, spray drying
相關次數： 點閱：216  下載：0 
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    • 牙周病已成為世界上90％的人口中的主要疾病; 嚴重的牙周炎會導致牙齒脫落和骨缺損且伴隨著出血的情況。為了解決這個問題，本研究在開發一種治療脫落牙齒造成的牙槽骨缺損的牙齒填充材。本實驗設計此填充材含有三種成分：生物活性玻璃（BG），β-三鈣磷酸鹽（β-TCP）和膠原蛋白。 BG具有優異的生物活性，β-TCP具有良好的生物降解性，膠原蛋白使血液凝固良好，並透過冷凍乾燥法在填充材上建立孔洞。基於上述優點，填充材預計可提高了患者牙槽骨的恢復速度，縮短治療骨缺損的時間，從而減輕了患者的疼痛。
    在此研究中，製備了含有0wt%、5wt% 和20wt％生物活性玻璃的填充材，並且在性質上通過X射線繞射（XRD）分析晶體結構，利用掃描電子顯微鏡研究微結構和形貌。接下來，使用XRD和傅里葉轉換紅外光譜測量生物活性。生物活性玻璃粉末皆使用ISO10993-5之濃度標準進行了細胞毒性的測試。陶瓷粉末與膠原蛋白等比例混合完成之填充材進行壓縮測試並依照ISO10993-14之標準進行了降解實驗，探討其降解行為。
    結果表明含有5wt％BG添加的的填充材除了提高24%壓縮強度之外，亦可以通過70%的細胞毒性標準並且具有較長的降解時間，未來可以配合患者的需求來控制填充材的製備。

    Periodontitis has been a major disease among 90% of people in the world; furthermore, severe periodontitis would cause tooth exfoliation and bone defects with bleeding. To solve this problem, this study aims to develop a dental implant to treat bone defects of shed teeth. This dental implant contains three components, bioglass (BG), β-tricalcium phosphate (β-TCP), and collagen. BG exhibits the superior bioactivity, β-TCP provides the good biocompatibility, and collagen makes blood clotted well. Based on these three properties, the dental implant improves the recovered speed of patients’ tooth alveolar bones and further shorten the time of curing bone defects in order to alleviate the pains of patients.
    In this study, 0, 5 and 20 wt % BG-contained fillers were prepared and several characterization techniques were carried out to analyze their properties. Initially, the crystal structures were analyzed by X-ray diffraction (XRD), while the microstructures and morphologies were investigated by scanning electron microscopy. Next, the bioactivities were measured using both XRD and Fourier transform infrared spectroscopy. Cytotoxicity of BG powders were followed ISO10993-5 standard. At last, the degradation behaviors were measured according ISO10993-14 and the mechanical properties of compressive strength are tested.
    In conclusion, the results showed that filler containing 5wt% BG can improve 24% of compressive strength, also pass the 70% cytotoxicity standard and have a longer degradation time. In the future, the preparation of filler can be controlled according to the needs of patients.

    摘要 ............................................................................................................. i Abstract ...................................................................................................... ii 誌謝 ........................................................................................................... iii 目錄 ........................................................................................................... iv 圖目錄 ...................................................................................................... vii 表目錄 ......................................................................................................... x 一、緒論 ..................................................................................................... 1 1.1 研究背景 .......................................................................................... 1 1.2 研究動機 .......................................................................................... 4 二、文獻回顧............................................................................................. 5 2.1 生醫材料簡介 .................................................................................. 5 2.1.1 牙科複合材料 ........................................................................... 6 2.2 生醫材料檢測 .................................................................................. 8 2.3 生醫陶瓷材料 ................................................................................ 11 2.3.1 生物活性玻璃 ......................................................................... 12 2.3.2 生物活性 ................................................................................. 14 2.4 生物活性玻璃合成方式 ................................................................ 17 2.4.1 噴霧乾燥法之簡介 ................................................................. 18 2.4.2 旋風集塵技術 ......................................................................... 19 三、實驗方法........................................................................................... 20 3.1 實驗設計 ........................................................................................ 21 3.2 實驗藥品 ........................................................................................ 26 3.3 實驗儀器 ........................................................................................ 28 3.4 樣品性質及分析方法 .................................................................... 29 3.4.1 X光繞射儀(X-ray diffractometer, XRD) ............................ 29 v 3.4.2 聚焦型離子束顯微鏡系統（Dual beam focused ion beam system, FIB） ................................................................................... 30 3.4.3 傅立葉轉換紅外線光譜儀(Fourier-transform infrared spectroscopy, FTIR) .......................................................................... 32 3.4.4 冷凍乾燥 (Freeze drying) ........................................................ 33 3.4.5 體外生物活性測試 (In Vitro test) .......................................... 35 3.4.6 體外生物相容性測試 (Biocompatible test) ........................... 35 3.2.7 降解實驗 (Degradation test) ................................................... 37 3.2.8 壓縮試驗（Compression test） .............................................. 38 3.2.9 塊材密度測試 (Density test) ................................................... 38 四、實驗結果........................................................................................... 40 4.1 選擇催化劑改善細胞毒性 ............................................................ 40 4.1.1 使用不同催化劑之生物活性玻璃相結構分析 ..................... 41 4.1.2 使用不同催化劑之生物活性玻璃表面形貌分析 ................. 42 4.1.3 使用不同催化劑生物活性玻璃之細胞毒性測試 ................. 45 4.1.4 使用不同催化劑生物活性玻璃之酸鹼度測試 ..................... 47 4.2 利用前驅物醋酸鈣改質生物活性玻璃 ........................................ 49 4.2.1 醋酸鈣改質生物活性玻璃之相結構分析 ............................. 50 4.2.2 醋酸鈣改質生物活性玻璃之表面形貌分析 ......................... 51 4.2.3 醋酸鈣改質生物活性玻璃之生物活性測試 ......................... 54 4.2.4 醋酸鈣改質生物活性玻璃之細胞毒性測試 ......................... 58 4.2.5 醋酸鈣改質生物活性玻璃之酸鹼度測試 ............................. 59 4.3 填充材之分析 ................................................................................ 60 4.3.1 填充材之相結構分析 ............................................................. 61 4.3.2 填充材之巨觀形貌 ................................................................. 62 4.3.3 填充材之表面形貌分析 ......................................................... 63 4.4.4 填充材之細胞毒性測試 ......................................................... 64 4.4.5 填充材之壓縮試驗 ................................................................. 65 4.4.6 填充材之密度測試 ................................................................. 66 vi 4.4.7 填充材之降解實驗 ................................................................. 67 4.4.8 降解實驗填充材之相結構分析 ............................................. 69 4.4.9 降解實驗填充材之形貌分析 ................................................. 70 五、結果討論........................................................................................... 72 5.1 生物活性玻璃之細胞毒性成因 .................................................... 72 5.1.1 酸鹼值與細胞毒性之關聯 ..................................................... 72 5.1.2 組成分與細胞毒性之關聯 ..................................................... 74 5.2 塊材降解行為討論 ........................................................................ 75 5.2.1 膠原蛋白與檸檬酸緩衝液之作用 ......................................... 75 5.2.2 塊材壓縮力與密度關係 ......................................................... 78 5.2.3 塊材降解時間與密度關係 ..................................................... 79 六、結論 ................................................................................................... 81 七、未來工作........................................................................................... 82 八、參考文獻........................................................................................... 83

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