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研究生: 鐘瑜庭
Yu-Ting Chung
論文名稱: DLP型3D列印光固化彈性暨韌性生醫材料應用於仿生氣管支架之研究
Research on DLP-type 3D printing photocurable flexible and resilient biomaterials for biomimetic tracheal scaffold application
指導教授: 鄭逸琳
Yih-Lin Cheng
口試委員: 鄭逸琳
張復瑜
陳盈君
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: 2023
畢業學年度: 111
語文別: 中文
論文頁數: 119
中文關鍵詞: 氣管組織工程仿生氣管支架彈性材料3D列印
外文關鍵詞: tracheal tissue engineering, biomimetic tracheal scaffold, elastic materials, 3D printing
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  • 氣管是呼吸過程中不可或缺的重要通道,對於人體的呼吸功能至關重要。目前氣管損傷患者須以接合手術或氣管移植以維持正常呼吸功能。組織工程為氣管治療提供了新的解決方法。然而,氣管組織工程所使用的材料需要具備生物相容性,並須在呼吸和外力作用下保持管腔的機械強度,且能夠在移植過程中保持結構的完整性。目前的研究主要集中在材料的選擇與改性和支架結構設計,對結構設計和材料搭配對整體支架力學性能和軟骨細胞培養的影響較少討論。
    因此,本研究的目標是引入積層製造技術和具有機械強度和可回復特性的生物彈性材料,製造仿生氣管支架,並測試其受力性能和細胞培養表現。考慮到氣管在呼吸過程中的膨脹收縮和管腔尺寸的維持特性,材料必須具有適當的彈性和機械性質。因此,本研究設計了兩組具有彈性和回復力的材料系統,分別為UA-HEMA和UA-PCLDA-HEMA。進行材料性質的測試,以確保兩組材料系統的機械和生物性質符合仿生氣管支架的需求。支架結構設計通過填滿3/4環形孔洞來模仿原生氣管組織的C型軟骨環。有限元素分析(FEA)和實際測試用於評估仿生氣管支架在受力下的拉伸壓縮應力。本研究透過具彈性及韌性生醫高分子的材料組合與仿生的設計,以及針對移植需求設計之縫合區域,成功列印出15%應變下2.0±0.35分鐘可回復原狀、縫合與切段可保持結構完整、於2倍拉伸長度及完全壓縮下不會破壞,同時具有良好軟骨細胞貼附性之仿生氣管支架。


    The trachea serves as an essential pathway for respiratory gas exchange and is crucial for human respiratory function. Currently, patients with tracheal injuries rely on anastomosis or tracheal transplantation to maintain normal breathing. Tissue engineering offers a new approach for tracheal treatment. However, materials used in tracheal tissue engineering must possess biocompatibility and maintain mechanical strength within the respiratory and external force environment, while preserving structural integrity during transplantation. Current research primarily focuses on material selection, modification, and scaffold structure design, with limited discussion on the combined effects of structure and material on overall scaffold mechanical performance and chondrocyte cultivation.
    Therefore, the objective of this study is to introduce additive manufacturing techniques and biologically elastic materials with mechanical strength and recoverable properties to fabricate biomimetic tracheal scaffolds, and evaluate their mechanical performance and cell culture characteristics. Considering the trachea's characteristics of expansion, contraction, and maintenance of lumen size during respiration, materials must possess appropriate elasticity and mechanical properties. To achieve this, two sets of elastic and recoverable material systems, UA-HEMA and UA-PCLDA-HEMA, are designed. Material properties are tested to ensure that both systems meet the mechanical and biological requirements of biomimetic tracheal scaffolds. Scaffold structure design involves filling 3/4 circular holes to mimic the C-shaped cartilaginous rings of native tracheal tissue. Finite element analysis (FEA) and practical testing are employed to assess the tensile-compressive stress of the biomimetic tracheal scaffold under loading.
    This study successfully prints a biomimetic tracheal scaffold with elastic and resilient biomedical polymers, incorporating a biomimetic design and suturing area tailored for transplantation requirements. The scaffold exhibits a recovery time of 2.0±0.35 minutes under 15% strain, maintains structural integrity during suturing and segmenting, and withstands 2-fold elongation and complete compression without damage. Additionally, it demonstrates favorable chondrocyte adhesion. These findings contribute to the field of tracheal tissue engineering.

    摘要 I ABSTRACT II 致謝 IV 目錄 V 圖目錄 X 表目錄 XIV 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 氣管相關資訊與氣管組織工程 9 2.2.1 氣管相關資訊 9 2.2.2 脫細胞移植於氣管組織工程 11 2.2.3 生物材料支架於氣管組織工程 12 2.3 高分子生物彈韌材料 16 2.4 拉脹結構(AUXETIC STRUCTURE) 22 2.5 本實驗室歷年研究成果 23 第3章、 材料、設備及性質檢測 26 3.1 實驗藥品與設備 26 3.1.1 原料與藥品 26 3.1.2 儀器設備 27 3.2 本研究所使用之材料介紹 28 3.2.1 聚氨酯丙烯酸酯(Urethane acrylate , UA) 28 3.2.2 聚己內酯雙丙烯酸酯(Polycaprolactone diacrylate, PCL-DA) 29 3.2.3 甲基丙烯酸羥乙酯(2-Hydroxyethyl methacrylate, HEMA) 29 3.2.4 光起始劑 30 3.2.5 Vitamin E 31 3.2.6 蘇丹黑 32 3.3 本研究所使用之下照式DLP系統 33 3.3.1 下照式DLP成型系統 33 3.3.2 動態光罩控制軟體 34 3.3.3 動態光罩產生器 35 3.3.4 光固化列印 36 3.3.5 後固化 37 3.4 材料性質檢測 37 3.4.1 交聯密度理論推算 37 3.4.2 傅立葉轉換紅外線光譜儀分析(FTIR) 38 3.4.3 拉伸試驗 40 3.4.4 接觸角量測 40 3.4.5 膨脹試驗(Swelling test) 42 3.4.6 初步體外軟骨細胞培養 42 3.4.7 寡聚物之靜態降解重量損失速率 43 第4章、 材料性質檢測結果 45 4.1 交聯密度理論值推算 45 4.2 傅立葉轉換紅外線光譜儀分析(FTIR) 46 4.3 拉伸試驗 49 4.4 接觸角量測 50 4.5 膨脹試驗(SWELLING TEST) 51 4.6 初步體外細胞培養 52 4.7 各項性質測試結果探討 55 第5章、 氣管支架設計與性質測試 56 5.1 有限元素分析受力預測 57 5.1.1 氣管支架模型設計 57 5.1.2 有限元素分析前處理 59 5.1.3 氣管支架徑向拉伸模擬 64 5.1.4 氣管支架徑向壓縮模擬 65 5.2 機械性質測試 66 5.2.1 支架徑向拉伸測試 67 5.2.2 支架徑向壓縮測試 68 5.2.3 支架三點彎曲測試 70 5.2.4 支架回復力測試 71 5.2.5 與原生兔氣管機械性質之比較 74 5.3 臨床可行性測試 76 5.3.1 縫針測試 76 5.3.2 切段測試 77 5.3.3 軟骨細胞培養 78 5.4 與過去成果之比較 81 5.4.1 抗拉與抗壓之模擬比較 81 5.4.2 材料比較 85 5.4.3 氣管支架設計比較 87 5.4.4 氣管支架設計對管腔維持能力之比較 89 5.5 總結 91 第6章、 結論與未來研究展望 93 6.1 結論 93 6.2 未來研究方向 94 第7章、 參考文獻 95

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