有機/無機添加矽酸鈣生醫用混凝土之開發與應用研究

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研究生：	牛慈伶 Tzu-ling Niu
論文名稱：	有機/無機添加矽酸鈣生醫用混凝土之開發與應用研究 Development and application of biomedical concrete with organic/inorganic additives
指導教授：	金重勳 Tsung-Shune Chin
口試委員:
學位類別：	碩士 Master
系所名稱：	工學院 - 材料科學工程學系 Materials Science and Engineering
論文出版年：	2008
畢業學年度：	96
語文別：	中文
論文頁數：	97
中文關鍵詞：	三鈣矽酸鹽、生醫用混凝土、氫氧基磷灰石、三鈣磷酸鹽、膠原蛋白、海藻酸鈉、老鼠纖維母細胞株、紐西蘭大白兔
外文關鍵詞：	Tricalcium silicate, bioconcrete, HAp, -TCP, collagen, alginate, L929, Newland white rabbits
相關次數：	點閱：2 下載：0
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工業用的混凝土主要為由水、水泥及粒料(如:砂及小碎石等)組成的混合物。而本實驗研究目的即製備醫藥級的人工混凝土，應用於修復骨頭缺陷。
本實驗生醫用混凝土設計方面，以Zn0.075Ca2.925SiO5、氫氧基磷灰石( HAp )及□-三鈣磷酸鹽( □-TCP )分別替代水泥、砂及小碎石的角色。Zn0.075Ca2.925SiO5由試藥級的CaCO3、SiO2 及ZnO於1400 oC經固態反應煆燒製備，將所得的Zn0.075Ca2.925SiO5粉末再利用高速球磨細化使粒徑達10 □m以下，並以10 wt% NaH2PO4 溶液為連結劑進一步混合其它無機成份HAp及□-TCP。此外，添加生物用膠原蛋白( Collagen )及海藻酸鈉( Alginate )改善其生物相容性。此生醫混凝土無機成份比例選用Zn0.075Ca2.925SiO5 : HAp: □-TCP為1: 2: 4，並添加collgen及alginate各1 wt% (簡稱: G1)。此材料成分具有適當的操作性質、工作及固化時間，分別為11及90分鐘，且平均壓縮強度達30~40 MPa。並以純Zn0.075Ca2.925SiO5添加同G1含量高分子作為對照組(簡稱: O1)做深入研究。
生物性質測試方面，使用老鼠纖維母細胞( L929 )進行體外細胞實驗。細胞毒性測試方面，G1相對於O1顯示優越的生物相容性，且可刺激細胞分裂成長。在動物實驗方面，由一個月的骨頭外觀照片顯示G1具有不錯的骨骼修補能力。綜合上述生物實驗結果，皆顯示G1為一具有良好生物相容性的生醫混凝土材料，可用於骨骼填補。

Technological concrete is a construction material commonly composed of water, cement and aggregate such as sand and gravel . The purpose of this study is to fabricate biomedical concrete for bone defect repair.
In this research, the roles of the cement, sand and gravel are respectivly Zn0.075Ca2.925SiO5, hydroxylapatite( HAp ) and□□-tricalcium phosphate (□-TCP). Zn doped tricalcium silicate powders (Zn0.075Ca2.925SiO5) are prepared by calcining reagent-grade CaCO3, SiO2 and ZnO at 1400 oC through the solid-state reaction. And then the Zn0.075Ca2.925SiO5 powders are milled by high-energy ball milling to lower the particle size under 10 □m. 10 wt% NaH2PO4 used as binder, furthermore, biological polymers, collagen and alginate, are added to improve the bio-compatibility of the biomedical concrete. The inorganic component ratio of the biomedical concrete is 1 : 2 : 4, and organic additives were 1 wt% collagen and 1 wt% alginate (named : G1). The biomedical concrete mixed with NaH2PO4 solution has proper 11 minutes working time and 90 minutes setting time. The compressive strength of the biomedical concrete is averagely 30~40 MPa. Pure Zn0.075Ca2.925SiO5 added with the same polymer content is prepared and serving as relative ( named : O1). G1 and O1 are further studied.
Mice fibroblast cell line ( L929 ) is cultured for in vitro test. In the cytotoxicity tests, G1 shows excellent bio-compatibility comparing to O1. In addition, for Animal test for Newland white rabbits in vivo, G1 shows good repairing ability.

中文摘要………………………………………………………………Ι
總目錄…………………………………………………………………V
圖目錄………………………………………………………………...VΙΙΙ表目錄…………………………………………………………………X
第一章 前言…………………………………………………………… 1
1-1 研究動機………………………………………………………… 1
1-2 研究目的………………………………………………………… 3

第二章 文獻及理論回顧……………………………………………… 4
2-1骨科植入材料特性………………………………………………. 4
  2-1-1生醫材料簡介………………………………………………4
  2-1-2 骨水泥的發展、種類及應用………………………………7
2-2     生醫用混凝土的成分特性………………………….………… 11
    2-2-1 無機成份-雙相磷酸鈣材料及三鈣矽酸鹽.………………11
2-3-2有機成分-膠原蛋白及海藻酸鈉…………………………15
2-3 煆燒、燒結及混凝土強度………………………………………19
  2-3-1 煆燒與燒結原理…………………………………………...19
  2-3-2 影響混凝土的強度因素…………………………………..20
2-4 體外生物相容性試驗……………………………...……………22
  2-4-1 人工模擬體液……………………………………………...22
  2-4-2 MTT測試…………………………………………………....25

第三章 實驗方法………………………………………………………27
3-1 材料準備………………………………………………………28
  3-1-1製備ZnxCa3-xSiO5及生醫混凝土之材料準備…………….28
3-1-2 細胞貼附及毒性測試之材料備…………………………...30
3-1-3 動物實驗之材料準備...........................................................32
3-2製備微米ZnxCa3-xSiO5粉末…………………………………34
3-3 混凝土的操作、表面形貌結構及強度分析……………………35
  3-3-1 工作、操作時間及pH值變化的量測……………………...35
  3-3-2 X光繞射儀………………………………………………….36
  3-3-3 場發式電子顯微鏡………………………………………37
  3-3-4 萬能壓縮測試機…………………………………..……….38
3-4細胞生物相容性測試( in vitro )…………………………………39
3-4-1膠原蛋白去免疫端的製程…………………………………39
  3-4-2 L929細胞貼附骨水泥表面形貌之實驗……………………40
    3-4-3 不同天數骨水泥離子釋出對L929細胞毒性測試法..........41
  3-5 動物實驗( in vivo ).......................................................................43

第四章 結果與討論……………………………………………………45
4-1選擇ZnxCa3-xSiO5粉體中之Zn摻雜量…………………………45
4-1-1不同的Zn摻雜量對煆燒後ZnxCa3-xSiO5粉體的影響……45
4-1-2 不同的冷卻方式對Zn0.075Ca2.925SiO5粉體的影響………...49
4-2 細化ZnxCa3-xSiO5及□-TCP、HAp粒徑大小評估………………51
  4-2-1球磨Zn0.075Ca2.925SiO5參數及粒徑大小................................51
4-2-2 TCP、HAp粒徑大小分析…………………………………...54
4-3 生醫混凝土成份選擇…………………………………………...56
4-3-1不同無機成分比例選擇與性質…………………………….56
    4-3-2  添加膠原蛋白之含量選擇與性質分析…………….……58
4-3-3 添加海藻酸鈉之含量選擇與性質分析……….......………61
4-4 生醫混凝土的性質分析……………………………………...…62
4-4-1 生醫混凝土養護於飽和水蒸汽之水合性質分析….......…62
4-4-2 生醫混凝土的pH值變化及壓縮強度分析……………….66
    4-4-3 生醫混凝土浸泡於SBF中性質分析……………………...71
4-4-4 生醫混凝土模擬體內植入情形…………………...………75
 4-5 老鼠纖維母細胞L929生物相容性測試……………………….77
4-5-1 表面貼附測試……….…………………...…..…………….77
4-5-2 材料短期浸泡於培養液對於L929細胞毒性分析………..81
4-5-3材料長期浸泡於SBF對於L929細胞毒性分析及離子釋出
     情形………………………………………………………....82
 4-6 紐西蘭大白兔體內動物實驗…………………………………...86
    4-6-1 血液檢查評估……….…………………...…..…………….86
4-6-2 骨頭照片評估…………………………………...………..89

第五章 結論……………………………………………………………91
第六章 參考文獻………………………………………………………93

                                

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