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研究生:李憲坤
研究生(外文):Hsien-Kun Lee
論文名稱:應用於顱顏手術之快速塑形智慧支架研發
論文名稱(外文):Development of Fast Shapable Smart Scaffold Applied in Craniofacial Surgery
指導教授:李勝揚李勝揚引用關係楊正昌陳建中陳建中引用關係鄧乃嘉鄧乃嘉引用關係
指導教授(外文):Sheng-Yang LeeJen-Chang YangChien-Chung ChenNai-Chia Teng
學位類別:碩士
校院名稱:臺北醫學大學
系所名稱:口腔科學研究所
學門:醫藥衛生學門
學類:牙醫學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:88
中文關鍵詞:聚乳酸聚己內酯硫酸鈣骨移植物支架
外文關鍵詞:PLAPCLCalcium sulfateBone graftScaffold
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口腔及顱顏外科手術或意外傷害時,倘若造成大範圍之骨缺損,常因癒合不易而需要進行骨移植術加速骨的癒合,目前雖有氫氧磷灰石,磷酸鈣與硫酸鈣合成骨替代物等選擇,但這些產品操作及固化時間長、不易塑形、抗張力與抗剪切力較低,而造成手術時間變長,因此本研究目的在研發一種新型且操作便利,可快速塑形,符合組織工程原理,應用於骨缺損的骨缀補複合材。材料以聚乳酸與聚己內酯為基體,並以硫酸鈣當填充物,利用其在體內可被快速分解吸收的特性,形成具連續性孔洞的支架。結果顯示具最佳機械性質的配比為18:42:40 (wt%),其抗壓強度、三點彎曲強度與彈性模數分別為38.2±1.2 MPa、67.5±7.2 MPa及7.0±0.7 GPa,塑形溫度50 ± 2℃,成形及固化時間不超過6分鐘,細胞毒性及細胞貼附性測試顯示細胞成梭型且外型完整,並無突起變細或細胞凋亡情形且細胞對骨填補材的貼附性良好,MTT test亦顯示細胞存活率高,浸泡於磷酸緩衝溶液經8~12週以掃瞄式電子顯微鏡觀察可見100~300 μm的孔洞結構,符合骨填補材料應用之潛力。
Craniomaxillofacial surgery or accidental injury frequently results in large bony defects requires the bone grafts to enhance the bone healing. Synthetic bone substitutes such as hydroxyapatite, tricalcium phosphate and calcium sulfate have shortcomings in the sense that they have prolonged working and setting time, poor strain, shear strength and not easily shapeable. Therefore, the purpose of this study is to develop a novel, convenient and easily shapeable bone graft that is composed of poly-lactic acid (PLA) and polycaprolactone (PCL) as the matrix and calcium sulfate as the filler. The principle behind is to utilize the material’s distinct characteristic of fast absorption within the body resulting in the formation of a scaffold with interconnective pores. The optimum ratio of the composition with the best mechanical properties as shown in the result is 18% PLA: 42% PCL: 40% CaSO4. The compressive strength, three point bending strength and flexible modulus were 38.2±1.2 MPa, 67.5±7.2MPa and 7.0±0.7 GPa respectively while the shaping temperature was 50±2 ˚C, the hardening time did not exceed 6 minutes. Cytotoxicity test revealed no mutation or apoptosis present. In addition, good cell attachment ability was also observed. MTT test indicated that cell viability observed in the experimental group was very good. After immersion in phosphate-buffered solution (PBS), 100-300µm sized porosities were observed under scanning electron microscope (SEM) and have potential to be a novel bone graft.
致謝…………………………………………………………………………………i
中文摘要……………………………………………………………………………ii
英文摘要……………………………………………………………………………iii
目 錄……………………………………………………………………………iv
圖表目錄……………………………………………………………………………vi
第一章 緒論
第一節 研究動機與重要性…………………………………………………………1
第二節 研究目的……………………………………………………………………2
第三節 研究假設……………………………………………………………………4
第二章 文獻回顧
第一節 骨的組成與構造……………………………………………………………5
第二節 骨折的癒合機制……………………………………………………………6
第三節 骨填補材料的發展…………………………………………………………8
第四節 骨的組織工程學……………………………………………………………10
第五節 支架製備方法及優缺點比較………………………………………………16
第六節 實驗應用的理論基礎………………………………………………………18
第三章 研究材料與方法
第一節 材料與藥品…………………………………………………………………21
第二節 儀器設備……………………………………………………………………21
第三節 研究方法及步驟……………………………………………………………22
第四章 結果與討論
第一節 先期實驗……………………………………………………………………29
第二節 抗壓強度……………………………………………………………………30
第三節 混煉時間……………………………………………………………………31
第四節 熱性質測試…………………………………………………………………32
第五節 軟化溫度……………………………………………………………………34
第六節 固化時間……………………………………………………………………36
第七節 細胞毒性與細胞貼附性測試………………………………………………38
第八節 離體降解實驗………………………………………………………………38
第五章 結論…………………………………………………………………………44
第六章 未來研究方向………………………………………………………………45
參考文獻 ……………………………………………………………………………46
圖表附錄 ……………………………………………………………………………52
圖目錄
圖一.骨折修修復過程中新生骨組織的階段性替代情形…………………………52
圖二.骨組織工程原理與策略………………………………………………………53
圖三.聚乳酸分子結構………………………………………………………………54
圖四.聚己內酯分子結構……………………………………………………………55
圖五.Percolation theory與Lattice Model對照………………………………56
圖六.PLA/PCL/CaSO4複合材先期實驗結果(1)…………………………………57
圖七.PLA/PCL/CaSO4複合材先期實驗結果(2)…………………………………58
圖八.PCL/CaSO4複合材的抗壓強力變化…………………………………………59
圖九.PLA/PCL/CaSO4複合材的抗壓強力變化……………………………………60 圖十.PLA/PCL/CaSO4混煉時塑譜儀的扭力變化…………………………………61
圖十一.PLA/PCL/CaSO4複合材的熱性質分析結果(1)…………………………62
圖十二.PLA/PCL/CaSO4複合材的熱性質分析結果(2)…………………………63
圖十三.PLA/PCL/CaSO4複合材流變性質分析……………………………………64 圖十四.PLA/PCL/CaSO4複合材塑形後的抗壓強力變化…………………………65
圖十五.PLA/PCL/CaSO4複合材塑形後的抗壓強度………………………………66
圖十六.PLA/PCL/CaSO4水浴塑形為二種型態的樣品……………………………67
圖十七.細胞毒性測試結果…………………………………………………………68
圖十八.MTT測試結果………………………………………………………………69
圖十九.PLA/PCL/CaSO4圓片之細胞貼附性實驗結果……………………………70
圖二十.離體降解實驗維持率變化…………………………………………………71
圖二十一. PLA/PCL/CaSO4複合材X-ray繞射測試結果…………………………72
圖二十二.複合材的表面孔洞形成觀察(低倍率)………………………………73
圖二十三.複合材的表面孔洞形成觀察(高倍率)………………………………74
圖二十四.複合材的斷面孔洞形成觀察(低倍率)………………………………75
圖二十五.複合材的斷面孔洞形成觀察(高倍率)………………………………76
圖二十六.PLA/PCL/CaSO4複合材表面碎形分析比較……………………………77
圖二十七.PLA/PCL/CaSO4複合材斷面碎形分析比較……………………………78

表目錄
表一.骨移植物之分類與特性………………………………………………………79
表二.醫用硫酸鈣與普通硫酸鈣比較………………………………………………80
表三.常見之支架製備方法及優缺點比較…………………………………………81
表四.不同重量比PCL/CaSO4摻合程度與抗壓強力與強度………………………82
表五.聚乳酸/聚己內酯/硫酸鈣複合材的熱性質分析結果(一次升溫)………83
表六.聚乳酸/聚己內酯/硫酸鈣複合材的熱性質分析結果(二次升溫)………84
表七.利用菲卡針測試成形時間……………………………………………………85
表八.離體加速實驗不同時間取出的重量變化……………………………………86
表九.離體加速實驗不同時間取出的彎曲強度變化………………………………87
表十.離體加速實驗不同時間取出的彈性模數變化………………………………88
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