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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 徐善慧 | zh_TW |
| dc.contributor.advisor | Shan-Hui Hsu | en |
| dc.contributor.author | 楊佩旋 | zh_TW |
| dc.contributor.author | Pei-Syuan Yang | en |
| dc.date.accessioned | 2025-02-20T16:19:46Z | - |
| dc.date.available | 2025-02-21 | - |
| dc.date.copyright | 2025-02-20 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-01-21 | - |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/96640 | - |
| dc.description.abstract | 三維 (3D) 生物列印技術可用於製造類癌症組織，以模擬腫瘤微環境中的複雜交互作用。在人類胰腺導管腺癌 (PDAC) 中，其主要涉及了細胞外基質 (ECM)、癌細胞和胰腺星狀細胞之間的交互作用。透明質酸 (HA) 是ECM的主要成分，有利於促進PDAC的腫瘤進展和化療耐藥性。在目前的研究中，通過將多細胞胰腺腫瘤樣球體包封於新型HA-明膠光交聯水凝膠 (即GHP水凝膠) 中，並利用3D生物列印技術在體外創建出類PDAC組織平台。這種最佳化的GHP水凝膠 (含7 wt%明膠和0.2 wt%酚官能基化HA) 達到了與臨床人類PDAC樣本相似的模量 (~5.46 kPa)，其更加緻密且均勻的結構優於純明膠水凝膠 (即GN水凝膠)。於3D生物列印之GHP水凝膠 (GHP 3DP構建體) 內的腫瘤樣球體呈現出顯著的侵襲性和轉移性，伴隨典型上皮-間質轉化 (EMT) 標誌基因的表達上調。此外，其餘基因表達分析顯示CD44基因的表達增加約290倍，而S100A9 (一種用於早期診斷的新型胰腺癌生物標誌物) 則增加了7.3倍的表達。在GHP 3DP構建體的腫瘤樣球體中還觀察到顯著的化療耐藥性，在接受臨床聯合藥物 (吉西他濱和白蛋白結合-紫杉醇) 處理48小時後，其腫瘤樣球體的細胞存活率仍高達98.5%。這與未含水凝膠之單獨培養的腫瘤樣球體和雙細胞類型的共同培養組別所觀察到的較低耐藥性形成鮮明對比 (細胞存活率分别為32.5%和28.9%)。深入研究3D生物列印之類PDAC組織構建體內的HA分布，可發現其分布模式與真實胰腺癌樣本中的結果相似，此展現了於體外再現腫瘤生物學中惡性程度及癌細胞重編程的可能性。綜上所述，該3D生物列印之類PDAC模型具有推動胰腺癌研究和臨床前藥物篩選的巨大潛力。 | zh_TW |
| dc.description.abstract | 3D bioprinting can be utilized to fabricate cancer-like tissue that models complex interactions within the cancer microenvironment. In human pancreatic ductal adenocarcinoma (PDAC), these interactions involve the extracellular matrix (ECM), cancer cells, and pancreatic stellate cells. Hyaluronan (HA) is a major component of ECM supporting tumor progression and chemoresistance in PDAC. In the current study, an in vitro PDAC-like tissue platform was developed by embedding multicellular pancreatic tumor-like spheroids within a novel 3D bioprinting HA-gelatin photocrosslinked hydrogel (GHP). This optimized GHP bioink (7 wt% gelatin and 0.2 wt% phenolic HA) achieved a modulus (~5.46 kPa) closely resembling that of clinical PDAC tissue, with a dense and uniform structure superior to gelatin-only hydrogel (GN). The bioprinted 3D tumor-like spheroids within GHP exhibited distinct invasive and metastatic behavior, along with up-regulated expression of epithelial-mesenchymal transition (EMT) markers. Furthermore, gene expression analysis also revealed a ~290-fold increase in CD44 gene and a 7.3-fold rise in S100A9 (a novel pancreatic cancer biomarker for early diagnosis). These tumor-like spheroids within 3D-bioprinted GHP constructs further demonstrated substantial chemoresistance, maintaining remarkable 98.5% viability after 48 h of exposure to a Gemcitabine and Abraxane combination, in contrast to significantly lower resistance observed in spheroids alone or co-cultured monolayers. An in-depth investigation of HA distribution within the 3D-bioprinted PDAC-like construct revealed a pattern consistent with clinical PDAC, indicating enhanced malignancy and potential tumor reprogramming. This 3D-bioprinted PDAC model holds significant potential for advancing pancreatic cancer research and preclinical drug testing. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-02-20T16:19:46Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-02-20T16:19:46Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員審定書 ............................................................................ I
致謝 .................................................................................... II 摘要 ................................................................................... III Abstract ............................................................................... IV 目次...................................................................................... V 圖次 ................................................................................... VII 表次 ................................................................................... IX 第一章 文獻回顧 .......................................................................... 1 1.1. 三維生物列印技術於腫瘤微環境模擬中的應用價值 ........................................... 1 1.2. 三維細胞培養技術在腫瘤研究中的優勢與進展 ............................................... 1 1.3. 胰腺導管腺癌微環境的挑戰與三維生物列印技術的應用策略 .................................... 2 1.4. 透明質酸對胰腺癌微環境的重要性與其三維生物列印的應用進展 ................................. 2 1.5. 體外三維胰腺癌模型的開發與應用研究 ..................................................... 3 第二章 研究方法 ........................................................................... 5 2.1. 研究架構 ............................................................................ 5 2.2. 透明質酸-苯酚之合成 .................................................................. 6 2.3. 製備明膠/透明質酸-苯酚之澆注或3D生物列印結構 ........................................... 7 2.4. 明膠/透明質酸-苯酚水凝膠之表徵 ........................................................ 8 2.4.1. 原位小角度X光散射分析 .............................................................. 8 2.4.2. 流變性質分析 ....................................................................... 8 2.4.3. 掃描式電子顯微鏡 ................................................................... 9 2.4.4. 動態機械分析 ....................................................................... 9 2.4.5. 體外降解測試 ....................................................................... 9 2.5. 細胞培養 ............................................................................ 9 2.6. 水凝膠包封腫瘤樣球體之澆注和3D生物列印結構 ............................................ 10 2.7. 澆注和3D列印結構中腫瘤樣球體之表徵 ................................................... 11 2.7.1. 細胞螢光標記與腫瘤樣球體之形態觀察 .................................................. 11 2.7.2. 腫瘤樣球體之細胞活性分析 ........................................................... 11 2.7.3. 腫瘤樣球體之共軛焦顯微鏡觀察 ....................................................... 11 2.8. 基因表達分析以評估不同水凝膠結構對於腫瘤樣球體之影響 ................................... 12 2.9. 不同水凝膠結構中腫瘤樣球體之體外化療藥物毒性評估 ....................................... 14 2.10. 不同水凝膠結構中腫瘤樣球體之免疫組織化學染色 ......................................... 14 2.11. 統計學分析 ........................................................................ 15 第三章 實驗結果 .......................................................................... 16 3.1. 透明質酸-苯酚的合成 ................................................................. 16 3.2. 光交聯GHP水凝膠的製備 ............................................................... 18 3.3. 光交聯GHP水凝膠的表徵 ............................................................... 20 3.4. 光交聯GHP水凝膠的流變特性 ........................................................... 23 3.5. 光交聯GHP水凝膠之3D列印 ............................................................ 25 3.6. 包封於不同水凝膠結構中腫瘤樣MIA-PSC共球體之表徵 ...................................... 28 3.7. 包封於水凝膠結構中腫瘤樣MIA-PSC共球體之基因表達 ...................................... 33 3.8. 化療藥物對於水凝膠結構中腫瘤樣MIA-PSC共球體的影響 .................................... 36 3.9. 類胰腺腫瘤3DP建構體的免疫組織化學染色分析 ............................................ 40 第四章 討論 ............................................................................. 43 第五章 結論 ............................................................................. 49 參考文獻 ................................................................................ 50 | - |
| dc.language.iso | zh_TW | - |
| dc.title | 包封多細胞腫瘤球體之可光交聯透明質酸-明膠基質作為3D生物列印體外工程化胰腺癌組織研究 | zh_TW |
| dc.title | 3D bioprinting of multicellular tumor spheroids in photocrosslinkable hyaluronan-gelatin for engineering pancreatic cancer microenvironment | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 田郁文;廖昭仰 | zh_TW |
| dc.contributor.oralexamcommittee | Yun-Wen Tien;Chao-Yaug Liao | en |
| dc.subject.keyword | 3D生物列印,腫瘤樣球體,透明質酸,胰腺導管腺癌,腫瘤微環境, | zh_TW |
| dc.subject.keyword | 3D bioprinting,tumor spheroids,hyaluronan,pancreatic ductal adenocarcinoma (PDAC),tumor microenvironment, | en |
| dc.relation.page | 58 | - |
| dc.identifier.doi | 10.6342/NTU202500241 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2025-01-22 | - |
| dc.contributor.author-college | 工學院 | - |
| dc.contributor.author-dept | 高分子科學與工程學研究所 | - |
| dc.date.embargo-lift | 2025-02-21 | - |
| 顯示於系所單位： | 高分子科學與工程學研究所 | |
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