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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72122完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 徐善慧(Shan-hui Hsu) | |
| dc.contributor.author | Shih-Hsiang Hsiao | en |
| dc.contributor.author | 蕭士翔 | zh_TW |
| dc.date.accessioned | 2021-06-17T06:24:27Z | - |
| dc.date.available | 2018-08-21 | |
| dc.date.copyright | 2018-08-21 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-17 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72122 | - |
| dc.description.abstract | 3D生物列印技術在組織工程與再生醫學領域帶來了革新，經由生物材料與細胞的結合能客製化出組織工程替代物，以達到修復或替換受損組織和器官為目的，因此成為一個相當有吸引力的平台。目前，由於大部分可生物降解的聚合物水凝膠機械穩定性能差，使得在列印的過程中結構傾向於塌陷，因此在開發生物材料上仍然是具有挑戰性。在本研究中，經由環保水性製程的技術，合成出具有雙敏感刺激響應性的可生物降解聚胺酯 (polyurethane, PU) 分散液。製備方法是在PU主鏈的末端引入能紫外線誘導交聯的丙烯酸酯基團，目的是藉由光敏感基團的引入能大幅改善列印性能；在軟鏈段的部分仍然選用混合低聚二醇為熱敏感性的組分。合成出雙刺激性PU分散液通過動態光散射 (dynamic light scattering)、小角X射線散射 (small-angle X-ray scattering) 和流變學測量來驗證PU奈米顆粒的光/熱誘導形態學之變化。結果顯示，這些PU奈米顆粒在經過UV的處理後，顆粒型態多數轉變成棒狀，並且之後在進一步加熱時會形成緻密堆積的結構。藉由其熱敏感性能，固化的PU分散液在接近體溫時能快速的熱凝膠化，並且凝膠模數在0.5–2 kPa範圍內。固化PU水凝膠的流變性能包括動態粘彈性 (dynamic viscoelasticity)，蠕變恢復 (creep recovery) 和剪切變稀行為 (shear thinning behavior) 在37°C下能有利於在列印之前與細胞共混合，並且通過微擠壓的3D列印程序以製造含細胞的建構體。雙刺激型水凝膠建構體顯示出比單刺激型 (熱敏感性) 對照組有更高的列印分辨率、形狀保真度以及有更好的細胞存活率和增殖。此外，具有較低模數 (< 1 kPa) 的軟質水凝膠 (PUA3) 可以提供神經幹細胞具有類似 '豆腐' 和穩定的3D微環境，以利於細胞增殖和分化。我們期望此光/熱敏感可生物降解PU墨水可以提供獨特的流變性質，有助於客製化生物列印軟組織。 | zh_TW |
| dc.description.abstract | 3D bioprinting serves as an attractive platform to fabricate customized tissue-engineered substitutes from biomaterials and cells for the repair or replacement of injured tissues and organs. A common challenge for 3D bioprinting materials is that the structures printed from the biodegradable polymer hydrogels tend to collapse because of the poor mechanical stability. In this study, dual stimuli-responsive biodegradable polyurethane (PU) dispersions (PUA2 and PUA3) were synthesized from an eco-friendly waterborne process. Acrylate group was introduced in the PU chain end to serve as a photo-sensitive moiety for UV-induced crosslinking and improvement of the printability, while mixed oligodiols in the soft segment remained to be the thermo-sensitive moiety. The photo-/thermal-induced morphological changes of PU nanoparticles were verified by dynamic light scattering, small-angle X-ray scattering, and rheological measurement of the dispersions. It was observed that these PU nanoparticles became more rod-like in shape after UV treatment and formed compact packing structures upon further heating. With the thermo-sensitive properties, these UV cured PU dispersions underwent rapid thermal gelation with gel moduli in the range 0.5−2 kPa near body temperature. The rheological properties of the PU hydrogels including dynamic viscoelasticity, creep recovery, and shear thinning behavior at 37°C were favorable for processing by microextrusion-based 3D printing and could be easily mixed with cells before printing to produce cell-laden constructs. The dual-responsive hydrogel constructs demonstrated higher resolution and shape fidelity as well as better cell viability and proliferation than the thermo-responsive control. Moreover, the softer hydrogel (PUA3) with a low modulus (< 1 kPa) could offer neural stem cells a tofu-like, stable, and inductive 3D microenvironment to proliferate and differentiate. We expect that the photo-/thermo-responsive biodegradable polyurethane ink may offer unique rheological properties to contribute toward the custom-made bioprinting of soft tissues. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T06:24:27Z (GMT). No. of bitstreams: 1 ntu-107-R05549013-1.pdf: 4933612 bytes, checksum: e84c1f26905464bc03486f18ebb3a6e5 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 致謝 I
摘要 II Abstract IV 目錄 VI 圖目錄 XII 表目錄 XIV 第一章 文獻回顧 1 1.1. 水凝膠介紹 1 1.2. 可生物降解與環境敏感型水凝膠 2 1.3. 三維列印與三維列印材料 2 1.4. 生物3D列印 4 1.5. 聚胺酯 5 1.5.1. 水性聚胺酯 5 1.5.2. 聚胺酯水凝膠於組織工程應用與作為3D列印材料 6 1.6. 溫感型水凝膠 7 1.6.1. 溫感型聚胺酯水凝膠與其作為3D列印材料 8 1.7. 光感型水凝膠 9 1.7.1. 光感型聚胺酯與其作為3D列印材料 9 1.8. 研究目的 11 第二章 研究方法 12 2.1. 研究架構 12 2.2. L型聚乳酸二元醇與D, L型聚乳酸二元醇之合成與純化 14 2.2.1. PLLA diol或PDLLA diol合成 14 2.2.2 PLLA diol或PDLLA diol純化 15 2.3. 合成聚乳酸二元醇分子量測定 15 2.4. 雙刺激型水性可生物降解聚胺酯合成 16 2.4.1. 雙刺激型聚胺酯之配方設計 16 2.4.2. 雙刺激型聚胺酯合成步驟 18 2.5. 聚胺酯奈米粒子基本參數分析 19 2.5.1. 紫外分光光度計 20 2.5.2. 膠體滲透層析儀 20 2.5.3. 動態光散射 20 2.6. 雙刺激型聚胺酯薄膜性質分析 21 2.6.1. 衰减全反射傅立葉紅外光譜儀 21 2.6.2. 熱性質分析 21 2.6.3. 平衡溶脹法 22 2.7. 聚胺酯奈米顆粒之相變化行為分析 22 2.7.1. 小角度X光散射分析 23 2.7.2. 穿透式電子顯微鏡 23 2.7.3. 衰减全反射傅立葉紅外光譜儀 24 2.7.4. X光繞射儀 24 2.8. 雙刺激型聚胺酯相轉換流變分析 24 2.9. 雙刺激型聚胺酯生物墨水的製備與蠕變測量 25 2.10. 細胞培養 26 2.11. 3D生物列印之應用 26 2.11.1.雙刺激型聚胺酯生物墨水與細胞混合與3D bioprinting 26 2.11.2. 雙刺激型聚胺酯列印建構體之體外降解 27 2.11.3. 細胞於列印建構體之存活率測試與染色標定 27 2.11.4. 基因表現與蛋白質染色 28 2.12. 統計學分析 30 第三章 實驗結果 31 3.1. L與D, L型聚乳酸二元醇之核磁共振分析 31 3.2. 優化合成雙刺激型水性聚胺酯的紫外光照射參數 31 3.2.1. 雙刺激型聚胺酯的基礎光學性能 31 3.2.2. 雙刺激型聚胺酯的官能基團分析 32 3.2.3.雙刺激型聚胺酯最適化光聚合參數 32 3.3. 雙刺激型聚胺酯奈米顆粒分散液的物理化學特性 32 3.4. 雙刺激型聚胺酯奈米顆粒在分散體中的刺激敏感特性 33 3.4.1. 雙刺激型聚胺酯奈米顆粒分散液之動態光散射分析 33 3.4.2. 雙刺激型聚胺酯奈米顆粒分散液之穿透式電子顯微鏡攝影 34 3.5. 雙刺激型聚胺酯奈米顆粒分散液的小角度X射線散射結構分析 34 3.5.1. 聚胺酯奈米顆粒分散液之Guinier method分析 34 3.5.2. 聚胺酯奈米顆粒分散液之Kratky method分子量分析 35 3.6. 雙刺激型聚胺酯相變化機制研究 36 3.6.1. 雙刺激型聚胺酯之熱重性質分析 36 3.6.2. 雙刺激型聚胺酯之結晶學分析 36 3.6.3. 雙刺激型聚胺酯之衰退式全反射傅立葉紅外光譜分析 37 3.6.4. 雙刺激型聚胺酯之交聯度分析 37 3.7. 雙刺激型聚胺酯奈米顆粒分散液之流變性能分析 37 3.7.1. 紫外光固化前後聚胺酯奈米顆粒分散液之流變性能分析 37 3.7.2. 固化聚胺酯水凝膠之流變性能分析 38 3.8. 固化聚胺酯水凝膠之抗蠕變性分析 39 3.9. 紫外光固化聚胺酯水凝膠之3D生物列印 39 3.10. 固化聚胺酯水凝膠建構體之體外降解測定 40 3.11. 雙刺激型聚胺酯水凝膠之組織工程實驗 40 3.11.1. 含纖維母細胞的水凝膠建構體之細胞存活率測定 40 3.11.2. 含神經幹細胞的水凝膠建構體之細胞存活率分析 41 3.11.3. 含神經幹細胞的水凝膠建構體之細胞型態分析 42 3.11.4. 含神經幹細胞的水凝膠建構體之基因表現測定 42 3.11.5. 含神經幹細胞的水凝膠建構體之免疫螢光染色分析 43 第四章 討論 44 4.1. 雙刺激型聚胺酯軟鏈段PLLA diol與PDLLA diol 核磁共振分析 44 4.2. 雙重刺激型聚胺酯奈米顆粒分散液之合成 44 4.3. 雙重刺激型聚胺酯奈米顆粒分散液之基本性質分析 45 4.4. 雙重刺激型聚胺酯光照性能 46 4.5. 溫度對雙重刺激型聚胺酯奈米顆粒分散液性質分析 47 4.6. 電解質對雙重刺激型聚胺酯奈米顆粒分散液性質分析 47 4.7. 雙重刺激型聚胺酯奈米顆粒分散液之光響應性能分析 48 4.8. 雙重刺激型聚胺酯奈米顆粒分散液之相變化分析 49 4.9. 以傅立葉紅外光譜分析雙重刺激型聚胺酯奈米顆粒之相變化行為 49 4.10. 雙重刺激型聚胺酯之熱學性質與結晶學分析 50 4.11. 雙重刺激型聚胺酯水凝膠之流變性質分析 51 4.12. 固化聚胺酯水凝膠之3D列印成果 51 4.13. 細胞於固化聚胺酯水凝膠之存活率測試 52 4.14. 神經幹細胞於固化聚胺酯水凝膠之基因表現與免疫螢光染色分析 53 4.15. 未來展望 54 第五章 結論 56 參考文獻 57 附錄一 藥品清單 87 附錄二 儀器清單 88 | |
| dc.language.iso | zh-TW | |
| dc.title | 雙刺激敏感型可生物降解聚胺酯軟質水凝膠之合成與表徵於細胞共列印應用 | zh_TW |
| dc.title | Synthesis and characterization of dual stimuli–sensitive biodegradable polyurethane soft hydrogels for 3D cell-laden bioprinting | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 張書瑋(Shu-Wei Chang),高震宇(Chen-Yu Kao) | |
| dc.subject.keyword | 3D生物列印,可生物降解聚胺酯,雙重刺激響應性,蠕變性,軟質水凝膠, | zh_TW |
| dc.subject.keyword | 3D bioprinting,biodegradable polyurethane,dual stimuli-responsiveness,creep,soft hydrogel, | en |
| dc.relation.page | 88 | |
| dc.identifier.doi | 10.6342/NTU201803853 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-08-17 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 高分子科學與工程學研究所 | zh_TW |
| 顯示於系所單位： | 高分子科學與工程學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-107-1.pdf 目前未授權公開取用 | 4.82 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。