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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 何佳安(Ja-An Annie Ho) | |
dc.contributor.author | Yi-Te Chou | en |
dc.contributor.author | 周易德 | zh_TW |
dc.date.accessioned | 2021-06-07T18:04:23Z | - |
dc.date.copyright | 2021-02-22 | |
dc.date.issued | 2021 | |
dc.date.submitted | 2021-02-04 | |
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J Biomater Appl 28, 1151-1163, doi:10.1177/0885328213499272 (2014). 171 Alfonso-Garcia, A. et al. Label-free identification of macrophage phenotype by fluorescence lifetime imaging microscopy. J Biomed Opt 21, doi:Artn 046005 10.1117/1.Jbo.21.4.046005 (2016). 172 Galvan-Pena, S. O'Neill, L. A. Metabolic reprograming in macrophage polarization. Front Immunol 5, 420, doi:10.3389/fimmu.2014.00420 (2014). 173 Alfonso-Garcia, A. et al. Label-free identification of macrophage phenotype by fluorescence lifetime imaging microscopy. J Biomed Opt 21, 46005, doi:10.1117/1.JBO.21.4.046005 (2016). 174 Rayahin, J. E., Buhrman, J. S., Zhang, Y., Koh, T. J. Gemeinhart, R. A. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16189 | - |
dc.description.abstract | 根據中華民國骨質疏鬆症學會的統計數字,台灣民眾髖關節骨折發生率在國際間名列前茅。而目前臨床醫學並無針對骨折癒合修復的專屬用藥,因此本研究的目標是開發生物相容性的奈米粒子促進骨折的修復速度,加速病患斷骨的癒合,減低病患生理、心理的壓力和經濟負擔。針對改善骨折患處局部的微環境,以加速骨折癒合。本研究的策略包括:(1)緩解骨折初期產生之急性發炎反應。(2)調節骨折微環境中巨噬細胞的極化。本研究利用兩種劑型:(1)生物可降解的奈米載體(PLGA)包覆抗發炎藥物,用以緩解發炎;(2)PLGA包覆免疫調節藥物,在骨折微環境增加M2巨噬細胞數量達到加速癒合目的。同時,在奈米粒子外層修飾玻尿酸,增加極化巨噬細胞效率。抗炎藥物選擇上,設計篩藥平台用篩選適合骨折修復的抗炎藥物,條件包括了LPS處理RAW264.7細胞株模擬發炎環境,加入臨床使用的抗發炎藥物進行測試,DCFDA偵測自由基、Griess試劑檢測一氧化氮等發炎指標的產物來確認藥物的效力,同時也利用MTT測試細胞存活率確認有效劑量。使用alizarin rad s染色,偵測抗發炎藥物是否影響造骨細胞的分化,並使用TRAP染色,偵測抗發炎藥物是否影響蝕骨細胞的分化能力,經由篩藥平台的篩選,阿斯匹靈是適合骨折使用之抗炎藥物。本研究亦使用巨噬細胞株,經由QPCR、Flow cytometry等技術建立並鑑定辛伐他汀成功介導M2-like巨噬細胞數量,並且於巨噬細胞轉換的過程中成功觀察到造骨細胞分化。接著,將辛伐他汀進行奈米劑型合成,該載體經證實有效介導M2-like巨噬細胞數量進而促進造骨細胞活化。本研究成功藉由核磁共振成像觀察到本研究開發的奈米載體可使骨傷位置呈現消炎狀態,並開創雙光子共軛焦顯微鏡即時觀察動物骨質上巨噬細胞極化狀態。綜合以上,本研究之奈米劑型極具潛力應用於促骨癒合。 | zh_TW |
dc.description.abstract | According to statistics released by the Taiwanese Osteoporosis Association, the incidence of hip bone fracture in Taiwan ranks at top in Asia. Traditional repair of fracture remains to be anatomic reduction and rigid internal fixation. Bone fracture may be costly, in terms of direct medical costs and lost productivity. Up to now, there is no clinical medication available that is specifically designed for fractures. Hence, in this study is to develop bio-compatible nanoparticles to promote the bone repair, leading to the acceleration in the rehabilitation of the patients, and shortening of the recovery time. One of our strategies in promoting bone fracture is to improve the inflammatory microenvironment of fracture site. The other strategy is related to the manipulation of macrophages (toward M2-like) involving in fracture repair. We herein design two nano-formulations for achieving our specific aims. The utilization of bio-degradable PLGA nanoparticles, carrying anti-inflammatory drugs is to relieve inflammation. While immunomodulatory drugs were encapsulated in hyaluronic acid-modified PLGA nanoparticles, the switch of M0 macrophage to M2-like macrophage become feasible. Recently, we have proved that nanoformulations can improve bone fracture healing via in vitro/in vivo experiment. This experimental evidence can make our nanoformulations as potential medicine for bone fracture in clinical. | en |
dc.description.provenance | Made available in DSpace on 2021-06-07T18:04:23Z (GMT). No. of bitstreams: 1 U0001-0402202112340500.pdf: 5413798 bytes, checksum: 70ae4725ffd959fb6976226efe77e768 (MD5) Previous issue date: 2021 | en |
dc.description.tableofcontents | 目錄 口試委員審定書 I 謝誌 II 中文摘要 III Abstract IV 縮寫表 V 第一章 緒論 1 1.1 前言 1 1.2 骨骼 1 1.2.1 骨骼構造 1 1.2.2 骨折類型 3 1.2.3 骨折修復階段 5 1.2.4 骨折治療 8 1.2.5 造骨細胞(Osteoblast)和骨細胞(Osteocyte) 9 1.2.6 蝕骨細胞(Osteoclast) 10 1.3 巨噬細胞在骨折修復環境的角色 11 1.4 奈米技術在骨再生的應用 13 1.4.1 聚乳酸聚乙醇酸(PLGA)奈米載體 14 1.5 玻尿酸(Hyaluronic acid) 15 1.6 抗發炎藥物(Anti-inflammation drugs) 16 1.6.1 布洛芬(Ibuprofen) 17 1.6.2 萘普生(Naproxen) 17 1.6.3 阿斯匹靈(Aspirin) 18 1.6.4 美洛昔康(Meloxicam) 18 1.6.5 塞來昔布(Celecoxib) 19 1.6.6 依托考昔(Etoricoxib) 19 1.7 抗氧化藥物(Anti-oxidant drugs) 20 1.7.1 抗壞血酸(Ascorbic acid) 21 1.7.2 乙醯半胱氨酸(N-acetyl-cysteine;NAC) 21 1.8 他汀類藥物 (Stain drugs) 22 1.8.1 辛伐他汀(Simvastatin) 23 第二章 研究目的與策略 24 第三章 材料與方法 27 3.1 細胞培養及細胞株 (Cell lines and Cell culture) 27 3.2 細胞mRNA萃取與反轉錄 (mRNA extraction and Reverse Transcription) 28 3.2.1 mRNA萃取 28 3.2.2 mRNA定量 28 3.2.3 反轉錄 29 3.3 聚合酶鏈鎖反應 (Polymerase Chain Reaction, PCR) 29 3.4 即時定量聚合酶鏈鎖反應 (Real-time PCR;Quantitative PCR;QPCR) 31 3.5 西方墨點法 (Western blotting assay) 31 3.5.1 蛋白質萃取液之取得 31 3.5.2 蛋白質定量 32 3.5.3 蛋白質電泳凝膠(SDS-PAGE)之配置 32 3.5.4 SDS-PAGE蛋白質膠體電泳 33 3.5.5 蛋白質樣本轉印 33 3.5.6 免疫墨點法 (Immuno-blotting) 34 3.6 細胞存活率測定(MTT cell viability assay) 34 3.7 台盼藍染色(Trypan blue staining) 35 3.8 細胞分化 (Cell differentiation) 35 3.9 茜紅素S染色(Alizarin Rad S Staining assay;ARS) 36 3.10 抗酒石酸酸性磷酸酶染色(Tartrate-resistant acid phosphatase stain;TRAP) 37 3.11 一氧化氮累積量偵測(Griess Assay) 38 3.12 細胞內自由基偵測(Intracellular reactive oxygen species;ROS) 38 3.13 免疫螢光染色(Immunofluorescence assay;IFA) 39 3.14 流式細胞儀分析(Flow cytometric analysis) 40 3.15 In vitro雙光子共軛焦顯微鏡(Two-Photon Confocal Microscopy)觀察 40 3.16 脂質PLGA複合奈米粒子合成(Lipid-PLGA) 40 3.17 玻尿酸透析(Dialysis) 41 3.18 樣品冷凍乾燥(Freeze drying;Lyophilisation) 42 3.19 玻尿酸修飾脂質PLGA複合奈米粒子(HA-Lipid-PLGA) 42 3.20 動態光散射粒徑分析及電位分析(Dynamic Light Scattering/Zeta Potential Analyzer) 43 3.21 紫外光/可見光光譜儀(UV-VIS)定量 43 3.22 奈米粒子釋放曲線(Release Profile)測定 44 3.23 動物骨傷模型建立 45 3.24 建立分辯率核磁共振特殊影像 45 3.25 In vivo雙光子共軛焦顯微鏡(Two-Photon Confocal Microscopy)觀察 46 第四章 現有結果與討論 47 4.1 建立蝕骨細胞及造骨細胞分化和鑑定平台 47 4.2 確認各種抗發炎、抗氧化候選藥物對單核球細胞的存活率影響 52 4.3 確認各種抗發炎、抗氧化候選藥物對抗氧化指標之有效劑量 54 4.4 建立巨噬細胞極化以及鑑定系統 57 4.5 確認各種抗發炎候選藥物是否具有促M1至M2極化能力 60 4.6 確認各種抗發炎候選藥物是否具有抑制蝕骨細胞分化能力 62 4.7 確認各種抗發炎候選藥物是否具有抑制造骨細胞分化能力 65 4.8 極化巨噬細胞型態對造骨細胞之影響 69 4.9 辛伐他汀對巨噬細胞極化狀態之影響 71 4.10 包覆辛伐他汀之脂質PLGA複合奈米粒子之合成結果與型態鑑定 78 4.11 包覆辛伐他汀之脂質PLGA複合奈米粒子修飾玻尿酸之合成結果與型態鑑定 81 4.12 奈米粒子藥物釋放曲線(Release profile) 85 4.13 奈米粒子包覆辛伐他汀對巨噬細胞極化狀態之影響 87 4.14 奈米粒子包覆辛伐他汀極化巨噬細胞對造骨細胞之影響 90 4.15 特殊MRI影像對骨傷動物微環境檢測 93 4.16 雙光子共軛焦顯微鏡對骨傷動物模型M1/M2巨噬細胞影像測試 95 第五章 總論與未來展望 99 第六章 參考文獻 104 | |
dc.language.iso | zh-TW | |
dc.title | 發展具生物可利用性的奈米粒子以促進骨折癒合 | zh_TW |
dc.title | Development of bio-applicable nanoparticles for the promotion of fracture healing | en |
dc.type | Thesis | |
dc.date.schoolyear | 109-1 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 周必泰(Pi-Tai Chou),徐士蘭(Shih-Lan Hsu),吳立真(Li-Chen Wu),曾崇育(Chugn-Yuh Tseng),楊家銘(Chia-Min Yang) | |
dc.subject.keyword | 骨折癒合,奈米藥物傳輸系統,M1型態巨噬細胞,M2型態巨噬細胞,抗發炎,抗氧化,核磁共振成像,雙光子共軛焦顯微鏡, | zh_TW |
dc.subject.keyword | bone fracture healing,nanodrug delivery system,M1 type macrophage,M2 type macrophage,anti-inflammatory,anti-oxidative stress,MRI,Two-photon microscopy, | en |
dc.relation.page | 118 | |
dc.identifier.doi | 10.6342/NTU202100504 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2021-02-04 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科技學系 | zh_TW |
顯示於系所單位: | 生化科技學系 |
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