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研究生:張曼蘋
研究生(外文):Man-Ping Chang
論文名稱:摻雜鍶離子之硫酸鈣作為骨替代材之研究
論文名稱(外文):Strontium-Doped Calcium Sulfate Anhydrate as Bone Graft Substitute
指導教授:段維新段維新引用關係
指導教授(外文):Wei-Hsing Tuan
口試委員:王錫福林峯輝劉典謨賴伯亮
口試委員(外文):Sea-Fue WangFeng-Huei LinDean-Mo LiuPo-Liang Lai
口試日期:2017-04-25
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:材料科學與工程學研究所
學門:工程學門
學類:材料工程學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:英文
論文頁數:107
中文關鍵詞:硫酸鈣生物可吸收燒結
外文關鍵詞:calcium sulfatestrontiumbioresorbablesintering
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硫酸鈣 (CaSO4,CS) 作為骨替代材已行之有年,其具備生物相容性、骨融合和骨傳導性,因此硫酸鈣移植物不會引起發炎反應,且可幫助新骨細胞生長。另外,硫酸鈣具備生物可吸收性,可在移植後在體內被完全降解,因此不須經過二次手術移除。
鍶離子具備抗骨質疏鬆的特性,其機制為可促進骨質生成,同時抑制骨質吸收。鍶離子可刺激前成骨細胞複製分化為成骨細胞,且促進膠原蛋白分泌,以此達到促進骨質生成的效果;同時,增加蝕骨細胞抑制因子,以抑制蝕骨細胞的生成及活性,進而抑制骨質流失。
在本研究中,以燒結法製備摻雜鍶之無水硫酸鈣試樣。將10 wt%之硫酸鍶與半水硫酸鈣粉末混合,燒結至1200°C後持溫一小時,此熱處理流程可使鍶離子置換硫酸鈣內的鈣離子,形成一結構緻密的摻雜鍶之無水硫酸鈣試樣。此試樣經過降解測試結果顯示,試樣可在降解的同時釋放鍶離子;另外,在細胞毒性測試上表現出良好的生物相容性,且細胞可在試樣上貼附生長。整體而言,此鍶鈣材料具有良好的潛力作為一可降解並同時抗骨質疏鬆的骨替代材。
Calcium sulfate (CaSO4, CS) has been used as bone graft substitute for more than 100 years. It exhibits well-tolerated and biocompatible properties, osseointegration and osteoconduction. Therefore, calcium sulfate implant induces minimal inflammatory responses in vivo, and can support bone cells to growth over it surface. In addition, calcium sulfate can be resorbed in vivo completely, it is an important property for a bone graft substitute that can avoid additional operation for implant removal.
Strontium ion is known for its antiosteoporotic effect. The mechanism is a dual mode that strontium can enhance bone formation and inhibit bone resorption simultaneously. For bone formation, strontium can stimulate the replication of preosteoblast and induce the secretion of collagen, leading to increase bone matrix. In parallel, strontium can inhibit the differentiation and activity of osteoclasts by upregulation the ratio of osteoprotegerin (OPG) / receptor activator of nuclear factor kappa-B ligand (RANKL) in osteoclast, and leading to the decrease of bone resorption
In the present study, sintering technique is used to prepare calcium sulfate anhydrate specimens incorporating strontium ion. An amount of 10wt% strontium sulfate powder is added into calcium sulfate hemihydrate powder, then sintered at 1200°C for 1 hour to form the strontium-substituted calcium sulfate. The degradation results show that strontium ion release during the specimen degradation simultaneously. In addition, both indirect and direct cytotoxicity results demonstrate the biocompatibility. In conclusion, the strontium-substituted calcium sulfate specimen is a potential material that not only bioresorbable but antiosteoporotic as a novel bone graft substitute.
口試委員會審定書 #
中文摘要 i
ABSTRACT ii
CONTENTS iii
LIST OF FIGURES vi
LIST OF TABLES xi
Chapter 1 Introduction 1
Chapter 2 Literature review 3
2.1 Basics of bone and bone tissue 3
2.2 Resorbable materials as bone graft substitutes 6
2.3 Use of calcium sulfate as bioceramics 8
2.3.1 Chemical and physical properties of calcium sulfate…………..……...8
2.3.2 Biological properties and clinical applications of calcium sulfate…...13
2.4 Biological properties and clinical applications of strontium 14
Chapter 3 Experimental procedures 16
3.1 Calcium sulfate 16
3.1.1 Starting material……………………………………………………..16
3.1.2 Processing…………………………………………………………...16
3.1.3 Characterization……………………………………………………..18
3.1.3.1 Material properties…………………………….……………..18
3.1.3.2 Biological properties…………………………………………19
3.2 Strontium compounds 24
3.2.1 Starting materials 24
3.2.2 Processing 24
3.2.3 Characterization……………………………………………………..24
3.2.3.1 Material properties………………………………………….24
3.2.3.2 Biological properties………………………………………..24
Chapter 4 Results 25
4.1 Calcium sulfate 25
4.1.1 Material properties…………………………………………………..25
4.1.1.1 Phase identification…………………………………………..25
4.1.1.2 Density and weight loss……………………………………...26
4.1.1.3 Microstructure observation…………………………………..28
4.1.2 Biological properties……………………………………………...…29
4.1.2.1 Degradation test……………………………………………...29
4.1.2.2 Cytotoxicity-test on extracts…………………………………34
4.1.2.3 Cytotoxicity-test by direct contact…………………………...35
4.2 Strontium compounds 38
4.2.1 Material properties…………………………………………………..38
4.2.1.1 Phase identification…………………………………………..38
4.2.1.2 Density and weight loss……………………………………...40
4.2.1.3 Microstructure observation…………………………………..44
4.2.1.4 Mechanical property…………………………………………46
4.2.2 Biological properties………………………………….……………..47
4.2.2.1 Degradation test……………………………………………...47
4.2.2.2 Cytotoxicity-test on extracts…………………………………53
4.2.2.3 Cytotoxicity-test by direct contact………………………...…55
4.2.2.4 Animal test – rat calvarial model…………………………….59
Chapter 5 Discussion 62
5.1 Material properties 62
5.1.1 Phase identification………………………………………………….62
5.1.2 Density and weight loss……………………………………………..67
5.1.3 Microstructure observation………………………………………….70
5.1.4 Mechanical property………………………………………………...71
5.2 Biological properties 73
5.2.1 Degradation test……………………………………………………..73
5.2.2 Cytotoxicity-test on extracts………………………………………...81
5.2.3 Cytotoxicity-test by direct contact……………………………….….82
5.2.4 Animal test – rat calvarial model……………………………………85
Chapter 6 Conclusions……………………………………………………………..87
Appendix Precipitates of degradation test…………..……………………..…......88
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