下照式動態光罩快速成型系統製作3D PCL組織工程支架｜國立臺灣科技大學博碩士論文系統

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研究生：	黃孝村 Siao-Cun Huang
論文名稱：	下照式動態光罩快速成型系統製作3D PCL組織工程支架 Research on 3D PCL Tissue Engineering Scaffolds by Upward-Lighting Dynamic Mask Rapid Prototyping System
指導教授：	鄭逸琳 Yih-Lin Cheng
口試委員:	蔡明忠 Ming-Jong Tsai 戴念梓 Niann-Tzyy Dai
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：	120
中文關鍵詞：	快速成型技術、組織工程支架、動態光罩、聚己內酯、數位投影技術
外文關鍵詞：	Rapid prototyping technology, tissue engineering scaffold, Dynamic mask, PCL, DLP
相關次數：	點閱：288 下載：8
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本實驗室先前研究，以快速成型技術概念自行設計生醫動態光罩快速成型系統，將每層2D pattern偏移或旋轉一個角度的方式，光聚合成型PLGA多孔性支架。但製作過程中PLGA支架持續浸泡於有機溶劑中易產生二次溶解，再加上PLGA材料昂貴且分子量分佈範圍大，不容易精準掌控其性質。於是本研究擬直接使用生物相容性佳的PCL，搭配PEG-HEMA、光起始劑及活性單體(HEMA)所混合而成的光聚合生醫材料，製作適合細胞生長的3D立體孔連通組織工程支架。
將原系統由上照式改為下照式，直接採用DLP投影機為光源，針對其光源照射方式、鏡頭成像距離及成型板、成型槽做相關機構的設計變更，並將控制程式與動態光罩產生程式修改整合。用新系統光聚合而成的PCL薄膜，進行靜態降解實驗與細胞(Human adult fibroblasts for foreskin cell)的體外培養(in vitro) 以了解其生物相容性，透過MTT assay及ICC測試評估是否適合細胞生長。從MTT assay測試結果可看出一至十天內的OD值及細胞數量一直都有成長趨勢；而ICC測試及SEM觀察中可以看出細胞在薄膜上有貼附的情況。
藉由製作不同條寬、相同間距之單層支架來測試此系統的加工精度，最小誤差值可達4.6%。然而在製作3D支架時，因已固化材料為白色會反射，會使部分孔洞封閉。透過改變後層的曝光時間，可有效改善此問題。目前已可製作出孔徑形狀為正方形、梯形的3D多孔性支架，以及可用來做大量細胞複製的30°、45°、60°圓錐形結構支架。本研究成功成型數種具生物相容性的3D立體PCL支架，未來不僅可應用於組織工程細胞生長，亦可協助大量細胞複製。

In the previous research in our laboratory, rapid prototyping technology concept was applied to create a Biomedical Dynamic Mask Rapid Prototyping System. PLGA porous scaffolds were fabricated through this system by photo-curing offset or rotated 2D patterns in each layer. The cured PLGA layers encountered re-dissolution issue during the process, and the expensive PLGA has wide molecular weight range, increasing the difficulty in controlling its properties precisely. Therefore, in this research, bio-compatible PCL replaced PLGA and mixed with PEG-HEMA, photo-initiator, and active monomer (HEMA) in chloroform to form the photo-curable biomaterial. Complete 3D scaffolds with interconnected pore network, instead of 2D-pattern offsetting, were fabricated.
The original system was changed from downward-lighting to upward-lighting and DLP (Digital Light Projection) projector was used directly as a light source. The optical path, lens distance, and the material tank were modified. Control program and dynamic mask generation program were revised and integrated. The new system fabricated PCL thin films for static degradation tests and cell culture (human adult fibroblasts for foreskin cell) in vitro to understand its bio-compatibility. In the MTT assay test from 1 to 10 days, the results showed the trend that OD values and cell numbers increased, while the ICC test and the SEM observation indicated that cells had attached to the thin film.
Single-layer scaffolds with identical spacing but different strip width were fabricated to evaluate system’s capability The minimal error may reach 4.6%. However, when fabricating the 3D scaffolds, due to the reflection of the white cured material, some pores were closed. Adjusting exposure time of the later layers can improve this problem effectively. In this study, fabricated pore shapes of 3D scaffolds included square, trapezoid, and cone (30°, 45°, 60°). This research has successfully generated several bio-compatible 3D PCL scaffolds. In the future, it can be not only used in tissue engineering cell growth, but also applicable to mass cell duplication.

摘要...............................................................................................................................I
Abstract......................................................................................................................II
誌謝..............................................................................................................................IV
目錄...............................................................................................................................V
圖目錄.......................................................................................................................VIII
表目錄........................................................................................................................XII
第一章	 緒論..............................................................................................................1
1	前言………………………………………………………………………….1
2	研究背景與動機…………………………………………………………….2
3	研究目的和方法…………………………………………………………….3
4	論文架構……………………………………………………………………..4
第二章	 文獻探討…………………………………………………………………..6
1 組織工程(Tissue Engineering)介紹………………………………………...6
1.1 支架材料之特性……………………………………………………10
1.2 高分子生醫材料……………………………………………………11
1.3 一般支架製作技術…………………………………………………17
2 應用快速原型技術製造組織工程之支架………………………………...22
2.1 快速原型加工原理…………………………………………………22
2.2 快速原型技術應用於組織工程支架之製造………………………24
3 面成型RP系統應用於3D工件之製造…………………………...……..31
第三章系統簡介與機構改善…………………………………………………….….35
1生醫動態光罩快速成型系統……………………………………………....35
1.1先前上照式系統架構……………………………………………….35
1.2 上照式系統與下照式之系統差異比較……………………………37
2下照式生醫動態光罩快速成型系統……………………………………....38
2.1動態光罩控制軟體……………………………………………….…39
2.2 動態光罩產生器……………………………………………………43
3 系統相關機械變更………………………………………………………...46
3.1 動態光罩之光源照射方式變更……………………………………47
3.2 成型板及成型槽變更………………………………………………52
第四章 生醫材料調配與材料性質檢測及細胞培養結果…………………………55
1 實驗藥品與設備…………………………………………………………...55
2 材料系統介紹……………………………………………………………...56
2.1 光起始劑……………………………………………………………56
2.2 光交聯劑……………………………………………………………58
2.3 2-hydroxyethyl mathacrylate (HEMA) 單體.....................................59
2.4 PCL(聚己內酯)—活性寡聚體……………………………………..60
2.5 光聚合生醫材料……………………………………………………61
3 材料性質檢測……………………………………………………………...62
3.1 實驗藥品……………………………………………………………63
3.2 材料性質檢測……………………………………………………....65
3.2.1 材料含水率(Water Absorption Ration)……………………..65
3.2.2 靜態降解測試……………………………………………….67
4 細胞培養與生物相容性檢測……………………………………………...70
4.1 細胞培養……………………………………………………………70
4.2 生物毒性檢測(MTT assay)………………………………………...74
4.3 免疫細胞化學染色法(Immunocytochemistry—ICC)……………..78
4.4 掃描式電子顯微觀察(SEM)……………………………………….81
第五章 製作多孔性3D組織工程支架…………………………………………….84
1 系統加工流程與支架加工參數…………………………………………...84
1.1 加工參數……………………………………………………………85
2 單層支架製作……………………………………………………………...88
2.1 系統製作單層支架最小尺寸測試…………………………………90
3 3D支架設計與製作……..…………………………………………………92
3.1 3D支架設計……..………………………………………………….92
3.2 3D支架製作…………………………………………………………95
第六章 結論與未來工作…………………………………………………………..104
1 結論……………………………………………………………………….104
2 未來工作………………………………………………………………….105
參考文獻……………………………………………………………………………107
附錄一………………………………………………………………………………112
附錄二………………………………………………………………………………113
附錄三………………………………………………………………………………117

                                

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