臺灣博碩士論文加值系統

組織工程結合工程與生命科學的原理與方法，發展活組織的取代物，修復、維持與改善人體組織的功能。組織工程支架為組織工程的三要素之一，利用層加工（積層製造）堆疊成型的方式，可解決傳統支架製造方法的孔洞不易控制、特定形狀難以製作等問題。本實驗室發展的生醫動態光罩快速成型系統，已可利用可見光固化PCL 類的生物可分解材料，惟PCL較屬疏水性，容易降低細胞的貼附效果。
而Chitosan是生物相容性非常高、親水性佳的天然生醫材料。本研究添加Chitosan於原先已掌握的可光固化PCL 材料系統中，並測試材料性質之改善情況，以決定適當之添加量與快速成型系統之成型參數，並評估細胞於該材料上生長貼附之情形，最後透過動態光罩快速成型系統製作出組織工程支架。結果發現添加Chitosan可以有效的增加材料的親水性以及生物相容性，又其中以添加10%Chitosan的材料組合擁有優良的親水性且精度、強度也可維持在所需要的水準，細胞培養也顯示出極佳的生長效果，本研究經由添加Chitosan有效的改善原先材料系統的疏水性缺點，並且使得材料擁有更佳的生物相容性，可以更廣泛的應用於生醫組織工程支架。

Tissue Engineering combines the principles and methods of engineering and life science to develop biological substitutes to restore, maintain and improve human tissue functions. Scaffold is one of the three key elements in Tissue Engineering. Layered manufacturing techniques, also known as Additive manufacturing (AM) processes, provide a great opportunity to fabricate 3D scaffolds without problems such as limited control of pore-size and restricted geometric shapes in traditional methods. The Biomedical Maskless Rapid Prototyping System developed in our previous research, utilizing the visible light to cure photo-curable PCL-type biodegradable material, has proven the feasibility of building 3D scaffolds with several layers. However, PCL is more hydrophobic.
On the other hand, chitosan is great natural biomaterials with high biocompatibility and hydrophilic property. Therefore, in this research, we plan to add chitosan individually into the photo-curable PCL material system and utilize Biomedical Maskless Rapid Prototyping System to fabricate tissue engineering scaffolds. Tests will be conducted to understand the improvement of scaffold properties after addition of chitosan. The results has shown that adding Chitosan can effectively increase the hydrophilicity and biocompatibility. We find that addition of 10% Chitosan material composition has good hydrophilicity and precision. Also, the strength can be maintained at the required level. The other hand, cell culture also shows outstanding growth effect. In this study, we improve the shortcomings of the original hydrophobic by adding Chitosan, and we make the material has excellent biocompatibility that can be widely used in biomedical tissue engineering scaffolds.

摘要 I
ABSTRACT II
致謝 IV
縮寫表(ABBREVIATIONS) VI
目錄 VII
表目錄 XIX
第一章 緒論 1
1.1 前言 1
1.2 研究動機與目的 2
1.3 研究方法 3
1.4 論文架構 5
第二章 文獻探討 6
2.1 組織工程(TISSUE ENGINEERING)介紹 6
2.1.1 支架材料之特性 9
2.1.2 高分子生醫材料 10
PCL與幾丁聚醣相關： 17
2.1.3 傳統支架製備方法 18
2.2 應用積層製造 (ADDITIVE MANUFACTURING，AM)技術製造組織工程支架 23
2.2.1 快速原型加工原理 23
2.2.2 積層製造 (additive manufacturing，AM)技術應用於組織工程支架之製造 25
2.2.3 幾丁聚醣在生醫的應用 33
2.2.4 研究回顧 35
第三章 材料合成與性質檢測 40
3.1 實驗藥品與設備 40
3.2 材料系統介紹 41
3.2.1 PCL-DA合成 43
3.2.2 幾丁聚醣(Chitosan) 45
3.2.3 PEG-DA 48
3.2.4 光起始劑 49
3.2.5 混合方式 52
3.2.6 光聚合生醫材料 54
3.3 材料鑑定與性質檢測 56
3.3.1 傅立葉轉換紅外線光譜儀(Fourier Transform Infrared Rays spectroscopy ,FTIR)分析 56
3.3.2 熱示差掃描分析儀(DSC) 57
3.3.3 熱重量分析測試(TGA) 58
3.3.4 拉伸試驗 59
3.3.5 接觸角量測 63
3.4 材料性質檢測結果 66
3.4.1 傅立葉轉換紅外線光譜儀(Fourier Transform Infrared Rays spectroscopy ,FTIR)分析 66
3.4.2 熱示差掃描分析儀(DSC) 73
3.4.3 熱重量分析測試(TGA) 74
3.4.4 拉伸試驗 75
3.4.5 接觸角量測 80
第四章 系統簡介與參數調整 85
4.1 生醫動態光罩快速成型系統 85
4.1.2 下照式反射動態光罩成型系統 85
4.2 下照式動態光罩快速成型系統 88
4.2.1 動態光罩控制軟體 88
4.2.2 動態光罩產生器 92
4.3 加工流程 97
4.4 參數設定與精度檢測 98
4.4.1 參數設定 98
第五章 支架檢測與細胞培養結果 101
5.1 實驗藥品 101
5.2 材料性質測試 104
5.2.1 酸鹼值量測 105
5.2.2 重量損失量測 107
5.3 細胞培養與生物相容性檢測 110
5.3.1 細胞培養 110
5.3.2 倒立式顯微鏡觀察細胞生長情況 113
5.3.3 生物毒性檢測(MTT assay) 116
5.3.4 電子顯微鏡觀察(SEM) 120
第六章 系統精度檢測 125
6.1 系統精度量測 125
第七章 結論與未來研究方向 135
7.1 結論 135
7.2 未來研究方向 136
參考文獻 137

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