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研究生(外文):Chen, Shih-Jou
論文名稱(外文):Applications of Photocrosslinkable Hydrogel in 3D Bioprinted Microchannel
外文關鍵詞:Hydrogel3D printingPluronic F127MicrochannelWater permeabilityCrosslinkingThermosensitive
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自20世紀末三維層積列印(3D列印)問世以後,此技術的快速便利以及可客製化的優點彷彿為工程領域開啟了另一扇大門,各項新穎設計與應用從此層出不窮。列如學者們可以利用各式材料及列印方式製作出不同大小、形狀的人工血管[1]。隨著科技的進步,在組織工程(Tissue engineering)中利用生物3D列印(3D bioprinting)的技術除了能以更貼近真實生物體內的方式研究細胞發展,人工類器官(Organoid)及人工器官的誕生也已指日可待。而在生物3D列印技術中,生物墨水(Bioink)是最為重要的部分,因此本研究將以3D列印方式製作具良好透水性與生物相容性的微流道。材料方面,先對水溶性且具有生物相容性的材料普朗克尼F127(Pluronic F127)進行末端修飾,使其具有交聯後不溶於水的特性。製程方面,將特定比例的F127-DMA水凝膠以列印方式製作特定三維結構並透過化學交聯維持其結構穩定性,此外也能將未修飾的PF127作為犧牲模板進行微擠出成型列印,以F127-DMA水凝膠包覆犧牲模板同時對其進行光固化,最後再將水溶性的PF127洗去即可獲得微米尺度的流道結構使血液等液體流通進行物質交換。在本篇研究中,以平滑肌細胞對修飾後的F127-DMA進行測試,證實本研究所合成的材料並不具有生物毒性,並可混合細胞作為生物墨水。另外具化學交聯特性的F127-DMA水凝膠不僅可以透過三維層積列印製做出不溶於水的微流道外,也可藉由其交聯後良好的透水性作為供物質交換的透膜、藥物釋放載體等等。
Since the technique of additive manufacture (three-dimensional printing) showed in the late 20th century, by the advantage of creative designs and customization freedom, it is driving significant innovations in the area of engineering, manufacturing, art, etc. For instance, there are many 3D bioprinting strategies for the additive fabrication of artificial blood vessels [1]. In tissue engineering, the appearance of 3D bioprinting allowed bioengineers to observe cells in mimetic in vivo conditions, even leading them closer to the goal of creating artificial organs. Bioink is the most important element in 3D bioprinting; thus, this study aims to used biocompatible hydrogel to fabricate water permeable microchannels. In terms of materials, this research first modified the water-soluble and biocompatible material Pluronic F127 (PF127) into methacrylic anhydride (MA) terminated PF127 (F127-dimethacrylate, F127-DMA). With the crosslinkable terminals, F127-DMA may enhance its mechanical property and became water-insoluble hygroscopic gel after chemical crosslinking upon UV irradiation. In this research, smooth muscle cells (SMCs) were used for the biocompatibility test of synthesized F127-DMA. Moreover, its photocurable properties allowed 3D printed scaffold to maintain the designed architecture in culture medium and other aqueous solutions. Also, the well water permeability gives crosslinked F127-DMA hydrogel the capability of being permeable membrane or drug releasing carriers.
摘要 I
致謝 IV
目錄 V
表目錄 VII
流程目錄 VII
圖目錄 VII
一、緒論 1
1.1 人體中的血管 1
1.1.1 血管的功用與相關疾病 1
1.1.2 血管移植之自體血管與人工廔管 2
1.2 三維層積列印 2
1.2.1 三維層積列印的發展 2
1.2.2 三維層積列印與組織工程 3
1.2.3 生物三維層積列印 4
1.2.3 常用的生物三維層積列印方法 5
1.2.4 生物墨水 7
1.3 水凝膠 7
1.3.1 水凝膠的組成與生醫方面的應用 7
1.3.2 水凝膠交聯反應 8
1.3.3 生物相容性材料帕沙洛姆(Poloxamer)之特性 10
二、研究動機 12
三、研究方法與步驟 13
3.1 實驗藥品清單 13
3.1.1 化學藥品 13
3.1.2 細胞培養藥品與細胞株 14
3.2 研究方法 15
3.2.1 修飾PF127使其具有可交聯性質 15
3.2.2 核磁共振光譜儀(Nuclear magnetic resonance, NMR)樣品配置 16
3.2.3 膠體滲透層析儀(Gel permeation chromatography, GPC)樣品配置 16
3.2.4 溶脹比(Swelling ratio)樣品製備 16
3.2.5 水凝膠之滲透實驗薄膜製備 17
3.2.6 生物相容性樣品製備 17
3.2.7 細胞存活量計數 17
3.2.8 細胞貼附測試樣品製備 18
3.2.9 F127-DMA 列印參數與條件 18
四、結果與討論 19
4.1 PF127水凝膠的修飾 19
4.2 修飾後F127-DMA水凝膠之交聯能力鑑定 24
4.3 F127-DMA水凝膠交聯時間判定 25
4.4探討交聯後水凝膠滲透能力 26
4.5 F127-DMA的生物相容性 28
五、結論 33
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