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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 徐善慧(Shan-hui Hsua) | |
dc.contributor.author | Yu-Liang Tsai | en |
dc.contributor.author | 蔡譽良 | zh_TW |
dc.date.accessioned | 2021-06-17T08:24:43Z | - |
dc.date.available | 2021-04-07 | |
dc.date.copyright | 2021-04-07 | |
dc.date.issued | 2021 | |
dc.date.submitted | 2021-03-04 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/74215 | - |
dc.description.abstract | 血管化組織工程中最大的困境在於如何維持人工組織的血液循環,儘管現行已有許多文獻開發不同的血管化組織工程技術,但都各有侷限。在本篇論文中,類血管的組織是透過生醫高分子及工程由葡萄糖敏感及溫度敏感之可3D列印水凝膠犧牲材所製備而成。製備此犧牲材需共聚合溫度敏感的高分子(N-異丙基丙烯醯胺, NIPAM)、活性酯離去基團(丙烯酸五氟苯酯, PFPA),並混合聚乙烯酯(PVA)形成水凝膠網絡,此外,添加少量的奈米纖維素至水凝膠犧牲材中調整其流變學性質以利3D列印。以流變學分析複合水凝膠犧牲材的流動性及熱敏感性可獲得最適合3D列印的比例,優化後的水凝膠犧牲材可透過一般的商用生物3D列印機以30 G(內徑為160 μm)的針頭列印。血管化組織的製程是將生醫高分子溶液澆鑄在3D列印的水凝膠犧牲材上或將水凝膠犧牲材直接列印在生醫高分子中,並利用水凝膠犧牲材葡萄糖敏感的特性,將生醫高分子泡入細胞培養液後,約5分鐘後,便可在生醫高分子內做出客製化的微管道,最後將血管內皮細胞注入生醫高分子內的客製化微管道,讓細胞沿著微管道生長,即可形成類血管網絡。希冀此論文發展出的葡萄糖敏感之可3D列印水凝膠犧牲材能有助於複雜人工組織的列印及血管化組織工程的發展。 | zh_TW |
dc.description.abstract | A major challenge in vascular engineering is to fabricate 3D vascular constructs with proper blood circulation. In spite of the fact that many methods have been reported to generate vascular constructs, there remain some disadvantages. In this study, a hydrogel crosslinked by boronate ester bonds with 3D printability and self-healing ability was prepared as sacrificial materials to tailor tubular microchannels in a non-sacrificial gel. The preparation of the hydrogel involved the copolymerization of N-isopropylacrylamide for thermoresponsiveness, with pentafluorophenyl acrylate for post-modification, and poly(vinyl alcohol) for gel formation. Besides, cellulose nanofibrils was added to facilitate 3D printing of the hydrogel. The thermoresponsiveness and printability of the hydrogel were investigated by rheology. The optimized hydrogel could be successfully printed through a 30 G nozzle (inner diameter= 160 μm) by a commercial 3D bioprinter. To demonstrate the feasibility in fabricating 3D vascularized constructs, the sacrificial hydrogel was printed and a non-sacrificial gel was cast on the sacrificial hydrogel. This combined gel was immersed into culture medium to elute the sacrificial hydrogel. Interconnecting multichannels in the non-sacrificial gel were achieved in 5 min. Vascular endothelial cells (ECs) seeded in the microchannels of the construct were able to proliferate and attach. The glucose-sensitive, 3D printable sacrificial materials may create complex and easily removable 3D structures for the fabrication of precise vascularized constructs. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T08:24:43Z (GMT). No. of bitstreams: 1 U0001-0203202120315500.pdf: 6599925 bytes, checksum: 9976decd2031f18fecee5c1b12164d6a (MD5) Previous issue date: 2021 | en |
dc.description.tableofcontents | 致謝 I 中文摘要 II Abstract III 目錄 IV 圖目錄 VII 表目錄 VIII 第一章 文獻回顧 1 1.1. 水凝膠及其應用 1 1.2. 3D列印的分類及其生醫應用 2 1.3. 研究動機 3 第二章 研究方法 4 2.1. 研究架構 4 2.2. 合成共聚物poly (NIPAM-co-pentafluorophenyl acrylate, poly(NIPAM-PFPA))及表徵 6 2.2.1. 分子量及分子量分布測定 6 2.2.2. 化學組成分析 7 2.3. 改質共聚物poly(NIPAM-co-4-(acrylamidomethyl) phenylboronic acid, poly(NIPAM-4PBA))及表徵 7 2.3.1. 化學組成分析 7 2.4. 製備poly(NIPAM-4PBA)-PVA自癒合水凝膠 7 2.5. CNFs的製備 8 2.5.1. CNFs改質率分析 8 2.5.2. CNFs形貌分析 9 2.6. 製備及表徵poly(NIPAM-4PBA)-PVA-CNFs複合水凝膠 9 2.6.1. poly(NIPAM-4PBA)-PVA-CNFs複合水凝膠的巨觀實驗觀察 10 2.6.2. 傅立葉紅外光光譜(Fourier-Transform infrared spectrometer, FT-IR) 10 2.6.3. 濁度測試(Turbidity measurement ) 11 2.6.4. 差示掃描量熱法(differential scanning calorimetry, DSC) 11 2.6.5. 流變性質檢測(Rheology) 11 2.6.6. 微結構分析 12 2.7. 複合水凝膠3D列印 12 2.8. 製備及表徵非犧牲材內的微孔道 12 2.8.1. 間接孔道製程 12 2.8.2. 直接孔道製程 13 2.8.3. 犧牲材溶解與通透實驗 13 2.8.4. 核磁共振成像(magnetic resonance imaging, MRI) 13 2.8.5. 場發式掃描式電子顯微鏡( field emission scanning electron microscope, FE-SEM) 13 2.9. 細胞培養與製備類血管結構 13 2.9.1. 血管內皮細胞培養 13 2.9.2. 細胞螢光染色 14 2.9.3. 管道內細胞增生 14 2.9.4. 冷凍切片 14 2.10. 統計學分析 14 第三章 實驗結果 15 3.1. poly(NIPAM-PFPA) and poly(NIPAM-4PBA)的合成與分析 15 3.1.1. poly(NIPAM-PFPA)化學成分分析 15 3.1.2. poly(NIPAM-PFPA)產率、分子量及分子量分布 15 3.1.3. poly(NIPAM-4PBA)化學成分分析 15 3.2. CNFs水相分散液表徵 15 3.2.1. CNFs改質率分析 15 3.2.2. CNFs微結構 15 3.3. poly(NIPAM-4PBA)-PVA-CNFs複合水凝膠的表徵 15 3.3.1. 複合水凝膠的製備 16 3.3.2. 複合水凝膠的巨觀實驗觀察 16 3.3.3. 水凝膠與CNFs作用力 16 3.3.4. 濁點實驗 16 3.3.5. 溫度可逆性實驗 16 3.3.6. 流變學實驗 17 3.3.7. 純水凝膠與CNFs的結構分析 17 3.4. 可3D列印的複合水凝膠 18 3.5. 微管道製作 18 3.5.1. 間接孔道製程及表徵 18 3.5.2. 直接孔道製程 18 3.6. 細胞培養與類血管結構 19 3.6.1. 細胞增殖 19 3.6.2. 冷凍切片 19 第四章 討論 20 4.1. 犧牲材研究的比較 20 4.2. PFP活性酯的優勢 20 4.3. 分子量與注射性的關係 20 4.4. 水凝膠與CNFs水相分散液的作用力 21 4.5. 水凝膠的溫度響應 21 4.6. 水凝膠與CNFs水相分散液的流變性質 21 4.7. CNFs水相分散液與水凝膠的結構分析 22 4.8. 複合水凝膠3D列印的限制 22 4.9. 微孔道結構分析 22 4.10. 未來展望 23 第五章 結論及未來展望 24 參考文獻 25 圖目錄 圖2.1. 研究架構圖 5 圖2.2. poly(NIPAM-PFPA)合成結構示意圖 6 圖2.3. poly(NIPAM-4PBA)改質結構示意圖 7 圖2.4. CNFs製備流程示意圖 8 圖2.5. CNFs改質分率計算示意圖 9 圖2.6. 複合水凝膠示意圖 10 圖3.1. 共聚物及改質物的NMR圖譜 30 圖3.2.1. CNFs的滴定曲線。 32 圖3.2.2. CNFs的穿透式電子顯微鏡影像 32 圖3.3.1. poly(NIPAM-4PBA)-PVA-CNFs複合水凝膠。 33 圖3.3.2. 複合水凝膠的巨觀實驗觀察 33 圖3.3.3. 複合水凝膠、純水凝膠及CNFs的FT-IR光譜 34 圖3.3.4. 純水溶液、複合水溶液、純水凝膠及複合水凝膠濁點測試 35 圖3.3.5. 複合水溶液及複合水凝膠的溫度可逆性 36 圖3.3.6.1. 純水凝膠與複合水凝膠的流變性質 37 圖3.3.6.2. CNFs的流變性質 38 圖3.3.7. CNFs、純水凝膠及複合水凝膠的SAXS分析 39 圖3.4.可3D列印的複合水凝膠 40 圖3.5.1.1. 微管道間接孔道製程示意圖 41 圖3.5.1.2. 微管道的電腦設計圖與實際情形 42 圖3.5.1.3. 微管道的SEM影像 43 圖3.5.2.1. 直接孔道製程示意圖 44 圖3.5.2.2. 直接孔道製程所的仿生結構 44 圖3.6.1. ECs在微管道內的增生情況 45 圖3.6.2. ECs在微管道內的冷凍切片 45 表目錄 表3.1. poly(NIPAM-4PBA)-PVA水凝膠最佳化 31 表3.2. 複合水凝膠的最佳化及注射針頭尺寸 34 表3.3. 犧牲材洗出非犧牲材的時間整理表 41 | |
dc.language.iso | zh-TW | |
dc.title | 葡萄糖敏感及溫度敏感之可 3D 列印水凝膠犧牲材用於類血管網絡之應用 | zh_TW |
dc.title | A 3D-printable, glucose-sensitive and thermoresponsive hydrogel as sacrificial materials for constructs with vascular-like channels | en |
dc.type | Thesis | |
dc.date.schoolyear | 109-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 葉伊純(Yi-Cheun Yeh),高震宇(Chen-Yu Kao),莊偉綜(Wei-Tsung Chuang) | |
dc.subject.keyword | 3D 列印,血管化組織工程,自癒合水凝膠,葡萄糖敏感,聚異丙基丙烯醯胺,犧牲材, | zh_TW |
dc.subject.keyword | 3D printing,Vascularized engineering,Self-healing hydrogel,Glucose sensitivity,N-Isopropylacrylamide,Sacrificial material, | en |
dc.relation.page | 56 | |
dc.identifier.doi | 10.6342/NTU202100768 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2021-03-05 | |
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 |
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