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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 徐善慧 | |
| dc.contributor.author | Yi-Ting Wen | en |
| dc.contributor.author | 溫苡庭 | zh_TW |
| dc.date.accessioned | 2021-06-17T05:59:13Z | - |
| dc.date.available | 2024-02-20 | |
| dc.date.copyright | 2019-02-20 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-02-14 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71349 | - |
| dc.description.abstract | 3D列印技術在組織工程與再生醫學領域迅速發展，經由生物材料客製化出的軟骨組織工程支架，在和細胞結合以後可以達到修復受損組織的目的，因此成為一個相當有發展性的平台。目前軟骨組織工程支架中使用的細胞多於體外培養後植入體內，具有污染的風險，而無細胞的支架可能沒有足夠的治療效果，因此在臨床應用上仍然具有挑戰性。在本研究中，經由環保水性製程的技術，製作出水性3D列印墨水，以生物降解聚胺酯 (polyurethane, PU) 結合趨化因子SDF-1及載有小分子藥物Y27632的PU微米球，製作出兩階段性藥物釋放的可生物降解軟骨組織工程支架。製備方法是在PU分散液中加入趨化因子SDF-1及含有Y27632的PU微米球製成墨水，目的是利用SDF-1先隨著支架降解而釋出，吸引幹細胞遷移，而後在Y27632作用下，誘導遷移至支架的幹細胞軟骨化；在墨水中輔以聚氧乙烯做為增稠劑後，在低溫下(-40°C)列印成型。含有200 ng/ml的 SDF-1和22 wt% 包Y27632的微球 (微球中含有55 ug/ml 的Y27632)(縮寫為PU/SDF-1/MS_Y支架)的支架具有最佳的性能。支架的結構設計使得SDF-1和Y27632可以在體外依序釋放，並在適當的時間(分別在24小時和62小時)後達到各自的有效濃度(分別為~75 ng/ml和3.38 ug/ ml)，當幹細胞種植在PU/SDF-1/MS_Y支架中7天後，表現出顯著的GAG沉積且能促進幹細胞軟骨化。此外，從PU/SDF-1/MS_Y支架中釋放出的SDF-1也可誘導幹細胞遷移。在兔子關節軟骨缺損實驗中植入此無細胞的PU/SDF-1/MS_Y支架後具有良好的修復效果，說明此3D列印支架於客製化軟骨組織工程上具有可應用性。我們期望此可生物降解的3D列印支架能免去體外組織培養的繁複過程，並解決細胞來源不足的困境，增加組織工程支架在臨床方面應用的可能性。 | zh_TW |
| dc.description.abstract | Three dimensional (3D) printing technology has rapidly developed as a promising technology for manufacturing tissue engineering scaffolds. Cells used in tissue engineering are subjected to the quality management and risk of contamination, while cell-free scaffolds may not have sufficient therapeutic efficacy. In this study, water-based 3D printing ink containing biodegradable polyurethane (PU), chemokine SDF-1, and Y27632 drug-embedding PU microspheres was printed at low temperature (-40 °C) to fabricate tissue engineering scaffolds with sequential drug release function. The scaffolds containing 200 ng/ml SDF-1 and 22 wt% Y27632-encapsulated microspheres (55 ug/ml Y27632 in microspheres) (abbreviated PU/SDF-1/MS_Y scaffolds) had the optimal performance. The structural design of the scaffolds allowed each of SDF-1 and Y27632 to be released sequentially in vitro and reach the effective concentration (~100 ng/ml and 3.38 ug/ml, respectively) after the appropriate time (24 h and 62 h, respectively). Human mesenchymal stem cells (hMSCs) seeded in the scaffolds showed significant GAG deposition in 7 days. Besides, the gradual release of SDF-1 from the PU/SDF-1/MS_Y scaffolds could induce the migration of hMSCs. Implantation of the cell-free PU/SDF-1/MS_Y scaffolds in rabbit articular cartilage defects supported the potential of the scaffolds to promote cartilage regeneration. The 3D printed scaffolds with sequential releases of SDF-1 and Y27632 may have potential in cartilage tissue engineering. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T05:59:13Z (GMT). No. of bitstreams: 1 ntu-108-R05550003-1.pdf: 3546034 bytes, checksum: 330d60ac6096ba6422856d97d388fe18 (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 致謝 I
摘要 II Abstract IV 目錄 VI 表目錄 XIII 第一章 文獻回顧 1 1.1. 軟骨組織修復醫學發展現況 1 1.2. 目前關節軟骨修復方法 1 1.2.1 初期治療 2 1.2.2. 自體軟骨細胞移植法 2 1.3. 軟骨支架材料 3 1.3.1. 天然軟骨支架材料 3 1.3.2. 合成軟骨支架材料 6 1.4. 軟骨組織工程支架 8 1.4.1. 傳統支架製備方法 8 1.4.2. 三維列印支架製程 9 1.5. 軟骨組織工程細胞來源 11 1.5.1. 軟骨細胞作為細胞來源 11 1.5.2. 幹細胞作為細胞來源 12 1.6. 訊息因子對幹細胞的影響 12 1.6.1. 轉化生長因子 13 1.6.2. 小分子抑制劑 13 1.6.3. 基質細胞衍生因子 (Stromal cell derived factor-1, SDF-1) 13 1.7. 研究動機 14 第二章 研究方法 16 2.1. 研究架構 16 2.2. 合成水性生物可降解聚胺酯 18 2.3. PU奈米粒子 (PU nanoparticles, PU NPs) 基本參數分析 20 2.3.1. 衰减全反射傅立葉紅外光譜 (Attenuated total reflection infrared spectroscopy, ATR-IR) 儀 20 2.3.2. 分子量及分子量分佈量測 20 2.3.3. 動態光散射 (Dynamic light scattering, DLS) 分析 20 2.3.4. 穿透式電子顯微鏡 (Transmission electron microscopy, TEM) 21 2.4. PU微球製備與基本性質分析 21 2.4.1. PU微球與載藥PU微球之製備 21 2.4.2. PU微米球表面結構分析 24 2.4.3. 微球體粒徑及尺寸分佈量測 24 2.4.4. Y27632於微球之包覆率分析 24 2.4.5. Y27632於微球之釋放率分析 24 2.5. 3D列印PU支架製程 25 2.5.1. 3D列印PU支架製作 25 2.6. 3D列印支架性質分析 26 2.6.1. 3D列印支架表面型態分析 26 2.6.2. 3D列印支架體外降解性質測試 26 2.6.3. 3D列印支架體外降解壓縮模數測試 26 2.6.4. 3D列印支架控制釋放測試 27 2.7. 細胞培養 27 2.7.1. 人類骨髓間葉幹細胞培養 27 2.7.2. 幹細胞於體外遷移測試 27 2.7.3. 幹細胞於3D列印支架中軟骨分化情形評估 30 2.7.4. 幹細胞於3D列印支架中增生及胞外基質分泌情形評估 33 2.8. 關節軟骨修復實驗 33 2.9. 組織學評估 34 2.10. 統計學分析 34 第三章 實驗結果 36 3.1. 水性生物可降解聚胺酯的合成 36 3.2. 水性生物可降解聚胺酯之物化性分析 36 3.2.1. 表面紅外光圖譜分析 36 3.2.2. 穿透式電子顯微鏡分析 37 3.3. 水性生物可降解聚胺酯微球體之物化性分析 37 3.3.1. 微球體尺寸分佈 37 3.3.2. 掃描式電子顯微鏡分析 38 3.3.3. 微球產率與藥物Y27632包覆率計算 38 3.3.4. 微球藥物釋放 39 3.4. 3D列印支架性質分析 40 3.4.1. 3D列印支架之外觀與掃描式電子顯微鏡分析 40 3.4.2. 支架之蛋白質SDF-1與藥物Y27632控制釋放測試 40 3.4.3. 3D列印支架降解與機械性質測試 41 3.5. 3D列印支架之體外細胞實驗 42 3.5.1. hMSC於體外遷移測試 42 3.5.2 hMSCs於3D列印支架培養之軟骨基因表現評估 42 3.5.3. hMSCs於3D列印支架培養之GAG分泌量評估 43 3.6. 無細胞3D列印支架體內實驗評估 43 3.6.1. 關節軟骨修復評估 43 3.6.2. 組織學分析 44 第四章 討論 45 4.1. 水性生物可降解聚胺酯PU之合成與性質分析 45 4.2. PU微球與包Y27632之PU微球製備 45 4.3. 3D列印支架之製備 46 4.4. 3D列印支架之藥物釋放測試 47 4.5. 3D列印支架之機械性質分析 47 4.6. hMSC於3D列印支架之體外培養測試 48 4.7. 無細胞3D列印支架之關節軟骨修復能力 49 4.8. 未來展望 49 第五章 結論 51 參考文獻 52 | |
| dc.language.iso | zh-TW | |
| dc.subject | 可生物降解聚胺酯 | zh_TW |
| dc.subject | 三維列印支架 | zh_TW |
| dc.subject | 階段性釋放 | zh_TW |
| dc.subject | 組織工程 | zh_TW |
| dc.subject | 軟骨再生 | zh_TW |
| dc.subject | cartilage regeneration. | en |
| dc.subject | Biodegradable polyurethane | en |
| dc.subject | 3D printing osteochondral scaffold | en |
| dc.subject | sequential release | en |
| dc.subject | tissue engineering | en |
| dc.title | 可降解水性聚胺酯之兩階段藥物釋放支架於無細胞軟骨組織工程之應用 | zh_TW |
| dc.title | Biodegradable water-based polyurethane scaffolds with a sequential release function for cell-free cartilage tissue engineering | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 曾清秀,廖昭仰,戴念梓 | |
| dc.subject.keyword | 可生物降解聚胺酯,三維列印支架,階段性釋放,組織工程,軟骨再生, | zh_TW |
| dc.subject.keyword | Biodegradable polyurethane,3D printing osteochondral scaffold,sequential release,tissue engineering,cartilage regeneration., | en |
| dc.relation.page | 76 | |
| dc.identifier.doi | 10.6342/NTU201900540 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-02-14 | |
| 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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