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研究生: 陳茂揚
Mao-Yang Chen
論文名稱: 光固化快速成型系統製作3D組織工程支架
Fabrication of Tissue Engineering 3D Scaffolds by Photo-Curing Rapid Prototyping System
指導教授: 鄭逸琳
Yih-lin Cheng
口試委員: 李振綱
Cheng-Kang Lee
謝明發
Ming-Fa hsieh
學位類別: 碩士
Master
系所名稱: 工程學院 - 機械工程系
Department of Mechanical Engineering
論文出版年: 2008
畢業學年度: 96
語文別: 中文
論文頁數: 96
中文關鍵詞: 光固化快速成型技術組織工程支架動態光罩
外文關鍵詞: photo-curing rapid prototyping technique, tissue engineering scaffold, Dynamic Mask
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  • 在傳統組織工程支架製備方法,普遍有著孔洞分佈不均勻、無法確保孔洞連通性、低再現性、機械強度不足及有機溶劑揮發不完全等問題,製造出的支架無法取得品質均一且符合需求的支架來源;這裏利用光固化快速成型技術,使多孔性支架以’面’方式成型,可避免規劃加工路徑、成型速度不一的缺點,並可解決傳統支架製作問題。
    本研究將延續實驗室先前所研發的生醫動態光罩快速成型系統(Dynamic Mask Rapid Prototyping System),針對光源變更以及風扇加裝後,製作支架時無法控制支架尺寸精度與保持支架製作穩定度,故進行相關機構改善,再利用數種水準的曝光時間(45秒、60秒、75秒與90秒)進行一系列成型加工測試,並規劃檢測支架條寬、間距與層厚,藉以評估成型系統製作支架精度與穩定性之提昇,在此檢測過程中,評估出2D薄膜支架製作最佳曝光時間為60秒,層厚約為0.272mm,有助後續應用於3D多孔性支架製作。
    在3D多孔性支架製作中,舊系統由於製作誤差過大,以不同條
    寬而言,最大誤差可達370%,最小也有37.5% ,在實際堆疊過程中,
    因條寬變大而導致孔洞變小,支架至多堆疊到三層,便難以沖洗出孔
    洞;新系統製作支架,條寬誤差最小可降至10%,已能成功堆疊製作
    出五層多孔性支架,已可算具有3D多孔性支架之雛形。
    以3T3纖維母細胞進行體外培養,經由倒立式顯微鏡、掃描式電子顯微鏡以及生物毒性測試檢測細胞生長於支架上的形態,細胞培養在支架上顯示出正常生長的狀態,且由生物毒性測試得到吸光值有明顯增加,代表細胞活性不會受到植入支架培養產生負面影響,呈現正常成長。


    We find issues of uneven pores, unensured pore connect, low representation, insufficient mechanical strength and incomplete organic solvent evaporation in the traditional tissue engineering making of scaffolds. The quality of the scaffolds is not in consistence and source of scaffolds can not be met. In this research, the photo-curing rapid prototyping technique is used to form porous scaffolds in “surface” to avoid defects of planning processing paths and different forming speeds and solve the issues of traditional scaffolds.
    Further to Dynamic Mask Rapid Prototyping System developed before in the laboratory, the research improves mechanism aiming at light source change and fan installation where control pore size precision and scaffold fabrication stability can not be kept. Later, a series of forming processing tests are made with several standards of exposure time(45 second、60 second、75 second and 90 second). Scaffold dimensions are planned to evaluate the improvement of forming system in making scaffold precision and stability. In this test, the best exposure time of 2D membrane scaffold is 60 second and the layer thickness is around 0.272 mm, helping making of 3D porous scaffolds.
    In making of 3D porous scaffolds, the maximum deviation of different strip widths is 370% and the smallest is 37.5%. In actual stacking, increased strip width leads to smaller pores. Scaffolds are stacked to maximum 3 layers to be washed out of the pores. In the new system, the strip width is minimized to 10% and five-layer porous scaffolds can be successfully made, showing the embryo of 3D porous scaffolds. In vitro is made with 3T3 fibroblasts cell. After inspection of cell growth on the scaffolds via Hoffman Phase Contrast microscope, scanning electron microscope and MTT assay, cells grow normally on the scaffolds. O.D value is increased from MTT assay, meaning that cell activity is not negatively affected by implanted scaffolds.

    摘要 I Abstract II 目錄 V 圖目錄 VII 表目錄 XI 第一章 緒論 1 1.1研究背景與動機 1 1.2 研究目的和方法 2 1.3 論文撰寫架構 3 第二章 文獻探討 4 2.1 組織工程(Tissue Engineering)介紹 4 2.1.1 支架材料特性 7 2.1.2 高分子生醫材料 8 2.1.3傳統支架製作方法 13 2.2快速原型技術 16 2.2.1快速原型技術原理 17 2.2.2 快速原型技術應用於組織工程支架之製造 18 第三章 系統介紹與相關機構改善 26 3.1 生醫動態光罩快速成型系統 27 3.2 動態光罩控制軟體 28 3.2.1 光罩輪廓資料之輸入與處理 29 3.2.2 動態光罩圖案的產生 30 3.3 動態光罩產生器 32 3.4 系統相關機構改善 34 3.4.1 機台相關機構變更設計 34 3.4.2 光學透鏡組變更設計 42 第四章 支架檢測與系統比較分析 46 4.1實驗藥品與設備 46 4.2材料與成型系統加工 48 4.2.1 光聚合生醫材料 48 4.2.2 成型系統加工流程 50 4.3支架製作與相關尺寸檢測 51 4.3.1 支架條寬與間距量測 52 4.3.2 層厚量測 56 4.4 系統比較分析 59 第五章 3D支架製作與細胞培養 62 5.1 實驗藥品與儀器 62 5.1.1 原料與藥品 62 5.1.2 細胞培養相關儀器 62 5.1.3 實驗藥品配置(由台大化工所提供) 63 5.2 3D多孔性支架製作 65 5.2.1 支架設計 65 5.2.2 3D多孔性支架製作 71 5.3 細胞培養與細胞活性測試 76 5.3.1 細胞培養 76 5.3.2 生物毒性測試(MTT assay) 79 5.3.3 細胞培養結果 80 第六章 結論與未來研究方向 86 6.1 結論 86 6.2未來工作 87 參考文獻 88 附錄一 94

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