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研究生: 葉宗汶
Zong-Wun Yeh
論文名稱: 光固化生物柔韌材料應用於DLP型3D列印模擬肺泡之研究
Research on application of photocurable flexible biomaterials to DLP-type 3D printing mimic alveoli
指導教授: 鄭逸琳
Yih-Lin Cheng
口試委員: 王潔
Jane Wang
何明樺
Ming-Hua Ho
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: 2022
畢業學年度: 110
語文別: 中文
論文頁數: 131
中文關鍵詞: 肺組織工程柔韌材料維他命E氣體交換模擬肺泡3D列印
外文關鍵詞: Lung tissue engineering, flexible, Vitamin E, Gas Exchange, 3D printing, DLP
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  • 肺臟具重要的氣體交換功能,多數肺損傷患者須透過肺臟移植或氧合器之輔助方能維持生理機能,但移植患者需終身服用免疫抑制藥物,組織工程有機會解決現今之問題。然而,肺組織工程所使用之材料不僅須有生物相容性,亦須具備交換氣體功能,目前文獻研究以細胞培養居多,氣體交換相關者較少,且肺臟組織複雜的血管網路與肺泡為複雜三維結構,一般製程難以生產。因此,本研究擬導入積層製造技術與添加維他命E之生物柔韌材料,以建立模擬肺泡模型,並測試其氣體通透性與模擬肺泡膨脹收縮。
    因應肺泡於呼吸時會產生體積上的膨脹收縮,材料必須擁有適當彈性及機械性質,因此本研究選擇CT2、PUA_L、IC27三種不同性質之柔韌材料進行探討,並於材料中添加抑制劑維他命E,除可提高列印時的品質,亦有助於固化後的材料之氣體交換性質。材料性質測試包括拉伸試驗、接觸角量測 、TGA、DSC、FTIR、降解測試、體外細胞培養與薄膜氣體透測試,並挑選最適合的CT2添加1% 維他命E,以DLP型3D列印製作200 μm模擬肺泡,測試其膨脹收縮與氣體交換功能。所得的模擬肺泡模型,總表面積為0.01 m2,模擬人體單次呼吸的頻率時,可提升受測區域溶氧濃度0.016mg/L,與人體單次呼吸時所通透的氧氣量數據相近。本研究之成果驗證了材料與製程於模擬肺泡模型之可行性,未來將可進一步應用於肺組織工程。


    The lung has an important gas exchange function. Most patients with lung injury require lung transplantation or oxygenator assistance. However, transplant patients need to take immunosuppressive drugs for life. Tissue engineering(TE) has the opportunity to solve the problem. However, the materials used in lung TE must have biocompatibility and the function of exchanging gas. At present, most of the literature studies are based on cell culture, and there are few related to gas exchange. The vascular network and alveoli are complex 3D structures that are difficult to produce in general processes. Therefore, this study intends to introduce additive manufacturing technology and flexible material added with vitamin E to establish a simulated alveoli model and test its gas permeability, expansion, and contraction.
    Due to the volume expansion and contraction of the alveoli during respiration, the material must have appropriate elasticity and mechanical properties. Therefore, this study selected three flexible materials with different properties: CT2, PUA_L, and IC27, and added the inhibitor vitamin E to the material. In addition to improving the quality of printing, it also contributes to the gas exchange properties of the cured material. Material property tests include tensile test, contact angle, TGA, DSC, FTIR, degradation test, in vitro cell culture, and film gas permeation test, and select the most suitable CT2 supplemented with 1% vitamin E, which is produced by DLP type 3D printing 200 μm simulated alveoli to test its expansion, contraction, and gas exchange functions. The obtained simulated alveoli model has a total surface area of 0.01 m2. When simulating the frequency of a single breath of the human body, the dissolved oxygen concentration in the measured area can be increased by 0.016 mg/L, which is similar to the data of the amount of oxygen permeated by a single breath of the human body. The results of this study verified the feasibility of materials and processes in mimic alveoli models and will be further applied to lung tissue engineering in the future.

    第1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 4 第2章 文獻探討 5 2.1 組織工程(TISSUE ENGINEERING)介紹 5 2.2 肺臟相關資訊與肺組織工程 9 2.2.1 肺臟相關資訊 9 2.2.2 脫細胞移植於肺組織工程 10 2.2.3 生物材料支架於肺組織工程 12 2.3 高分子生物柔韌材料 17 2.4 本實驗室歷年研究成果 21 第3章 材料與性質檢測方法 24 3.1 實驗藥品與設備 24 3.1.1 原料與藥品 24 3.1.2 儀器設備 25 3.2 材料系統介紹 26 3.2.1 CT2 26 3.2.2 IC27 26 3.2.3 改質聚氨酯丙烯酸酯L系列(PUA_L) 27 3.2.4 光起始劑 28 3.2.5 Vitamin E 29 3.2.6 材料混合比例 31 3.3 下照式DLP系統與製程介紹 31 3.3.1 下照式DLP成型系統 32 3.3.2 動態光罩控制軟體 33 3.3.3 動態光罩產生器 34 3.3.4 光固化列印 35 3.3.5 後固化 35 3.4 材料性質檢測 36 3.4.1 拉伸試驗 36 3.4.2 接觸角量測 37 3.4.3 交聯密度(Crosslink density)理論推算 40 3.4.4 傅立葉轉換紅外線光譜儀分析(FTIR) 41 3.4.5 熱重量分析(TGA) 42 3.4.6 熱示差掃描(DSC)分析 43 3.4.7 靜態降解重量損失測試 44 3.4.8 體外細胞培養 45 第4章 材料性質檢測結果 48 4.1 拉伸試驗 48 4.2 接觸角量測 52 4.3 傅立葉轉換紅外線光譜儀分析(FTIR) 54 4.4 熱重量分析(TGA) 60 4.5 熱示差掃描(DSC)分析 63 4.6 靜態降解重量損失測試 66 4.7 體外細胞培養 68 4.8 各項性質測試結果探討 70 第5章 通氣薄膜氣體交換與模擬肺泡膨脹收縮測試 71 5.1 通氣薄膜模型建置與列印參數 71 5.1.1 通氣薄膜模型建置 71 5.1.2 DLP光固化3D列印參數 73 5.2 氣體交換測試 76 5.2.1 氣體交換測試系統 77 5.2.2 氣體交換測試結果 83 5.3 3D列印模擬肺泡 90 5.4 模擬肺泡模型建置與列印策略 91 5.4.1 模擬肺泡模型建置 91 5.4.2 DLP光固化3D列印策略 92 5.5 模擬肺泡膨脹收縮測試 94 5.5.1 模擬肺泡膨脹收縮測試系統 95 5.5.2 模擬肺泡膨脹收縮測試結果 97 5.6 模擬肺泡氣體交換測試 97 5.6.1 氣體交換測試系統 97 5.6.2 模擬肺泡氣體交換測試結果 99 5.7 模擬肺泡單次呼吸通氣量測試 100 5.8 總結 102 第6章 結論與未來研究方向 104 6.1 結論 104 6.2 未來研究方向 105 第7章 參考文獻 106

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