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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 黃義侑 | |
| dc.contributor.author | Yong-Shi Chan | en |
| dc.contributor.author | 陳詠欣 | zh_TW |
| dc.date.accessioned | 2021-06-17T06:13:04Z | - |
| dc.date.available | 2023-10-12 | |
| dc.date.copyright | 2018-10-12 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-10-05 | |
| dc.identifier.citation | [1] Prausnitz, M. R., & Langer, R. (2008). Transdermal drug delivery. Nature biotechnology, 26(11), 1261-1268.
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Side-opened out-of-plane microneedles for microfluidic transdermal liquid transfer. Journal of Microelectromechanical systems, 12(3), 296-301. [12] Wang, P. M., Cornwell, M., Hill, J., & Prausnitz, M. R. (2006). Precise microinjection into skin using hollow microneedles. Journal of investigative dermatology, 126(5), 1080-1087. [13] Martanto, W., Moore, J. S., Kashlan, O., Kamath, R., Wang, P. M., O'neal, J. M., & Prausnitz, M. R. (2006). Microinfusion using hollow microneedles. Pharmaceutical research, 23(1), 104-113. [14] Gualeni, B., Coulman, S. A., Shah, D., Eng, P. F., Ashraf, H., Vescovo, P., ... & Birchall, J. C. (2017). Minimally‐invasive and targeted therapeutic cell delivery to the skin using microneedle devices. British Journal of Dermatology. [15] Kim, Y. C., Park, J. H., & Prausnitz, M. R. (2012). Microneedles for drug and vaccine delivery. Advanced drug delivery reviews, 64(14), 1547-1568. [16] Wang, P. M., Cornwell, M., Hill, J., & Prausnitz, M. R. (2006). Precise microinjection into skin using hollow microneedles. Journal of investigative dermatology, 126(5), 1080-1087. [17] Chandrasekaran, S., Brazzle, J. D., & Frazier, A. B. (2003). Surface micromachined metallic microneedles. Journal of microelectromechanical systems, 12(3), 281-288. [18] Sammoura, F., Kang, J., Heo, Y. M., Jung, T., & Lin, L. (2007). Polymeric microneedle fabrication using a microinjection molding technique. Microsystem Technologies, 13(5-6), 517-522. [19] Lindvall, O., Kokaia, Z., & Martinez-Serrano, A. (2004). Stem cell therapy for human neurodegenerative disorders–how to make it work. [20] Lee, K. O., Gan, S. U., & Calne, R. Y. (2012). Stem cell therapy for diabetes. Indian journal of endocrinology and metabolism, 16(Suppl 2), S227. [21] Segers, V. F., & Lee, R. T. (2008). Stem-cell therapy for cardiac disease. Nature, 451(7181), 937-942. [22] Rosenberg, S. A., Restifo, N. P., Yang, J. C., Morgan, R. A., & Dudley, M. E. (2008). Adoptive cell transfer: a clinical path to effective cancer immunotherapy. Nature Reviews Cancer, 8(4), 299-308. [23] Iliescu, F. S., Teo, J. C. M., Vrtacnik, D., Taylor, H., & Iliescu, C. (2018). Cell therapy using an array of ultrathin hollow microneedles. Microsystem Technologies, 24(7), 2905-2912. [24] Harper, C. A. (2006). Handbook of plastic processes. John Wiley & Sons. [25] M.C. Hacker, A.G. Mikos, in Principles of Regenerative Medicine (2011), 587–622 [26] Wang, Q. L., Zhu, D. D., Chen, Y., & Guo, X. D. (2016). A fabrication method of microneedle molds with controlled microstructures. Materials Science and Engineering: C, 65, 135-142. [27] Larrañeta, E., Moore, J., Vicente-Pérez, E. M., González-Vázquez, P., Lutton, R., Woolfson, A. D., & Donnelly, R. F. (2014). A proposed model membrane and test method for microneedle insertion studies. International journal of pharmaceutics, 472(1-2), 65-73. [28] Kheir, E., Stapleton, T., Shaw, D., Jin, Z., Fisher, J., & Ingham, E. (2011). Development and characterization of an acellular porcine cartilage bone matrix for use in tissue engineering. Journal of biomedical materials research Part A, 99(2), 283-294. [29] Chen, R. N., Ho, H. O., Tsai, Y. T., & Sheu, M. T. (2004). Process development of an acellular dermal matrix (ADM) for biomedical applications. Biomaterials, 25(13), 2679-2686. [30] Del Marmol, V., & Beermann, F. (1996). Tyrosinase and related proteins in mammalian pigmentation. FEBS letters, 381(3), 165-168. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71875 | - |
| dc.description.abstract | 微針是以微米等級的針穿透過皮膚表皮製造出微通道，並以無痛、微創的方式進行藥物傳遞。利用該微通道，可以克服經皮吸收所面臨傳遞的藥物的限制，其必須是脂溶性且小分子藥物才可透過皮膚角質層的屏障。微針的優點是可以避免藥物在通過體內時受到肝臟腸胃等的代謝、減少感染的風險、以無痛且微創的方式以增加患者使用上的依從性，並且可以延長藥物釋放。微針又分為固體微針、藥物塗層微針，中空微針、可降解微針以及水膠微針。其中中空微針具有夾帶物質進行傳送的優勢，但因結構相較於其他類型微針較為複雜，也因此在製程上產生的成本高、步驟繁瑣、無法進行量產等等的限制。細胞療法為藥物治療外的一種治療方式，用以恢復體內受損及缺失的細胞及組織。目前，該療法主要以針劑注射的方式將細胞傳遞到體內。該方法除了會面臨傳統針劑所面臨到的限制，以針劑進行細胞注射也會造成細胞聚集，無法有足夠空間進行生長。因此在綜合上述兩者優缺點，本研究以聚二甲基矽氧烷(Polydimethylsiloxane, PDMS)做為材料，利用雷射雕刻機在聚二甲基矽氧烷上進行雕刻，製作出可調控微結構的中空微針陣列之模具。利用聚丙烯酸甲酯(Polymethylmethacrylate, PMMA)成功製作出不同微結構之中空微針陣列。接著將不同種類之細胞培養於中空微針陣列之上，利用MTT Assay測試細胞培養於中空微針上的細胞活性，且利用Live/Dead染色測試材料之生物相容性並觀察細胞於中空微針上的貼附情況。結果顯示PMMA中空微針具有良好的生物相容性，且在電子顯微鏡的照射觀察下，貼附於中空微針上的細胞仍可保持原本的細胞型態。同時，將此中空微針作為細胞傳遞之載體，針對依序以凍融、洗滌劑及生物酶的綜合去細胞處理程序所製備的去細胞支架，進行細胞傳遞。並證實細胞經由中空微針載體可有效傳遞並且生長。 | zh_TW |
| dc.description.abstract | Microneedles are micro-scale needles that pierce into epidermis of skin to create micro-channel for drug delivery in a painless, minimally invasive way. With this micro-channel, we can address the limitation of transdermal method, which is the molecule of the drug must be small and oil-soluble to penetrate the stratum corneum barrier. The advantages of microneedles are avoiding drug degradation in stomach and liver, reducing the risk of infection, improving patient compliance due to minimal skin trauma, less pain, and sustaining drug release. The current types of microneedles include solid microneedles, coated microneedles, hollow microneedles, degradable microneedles, and hydro-forming microneedles. Cellular therapy is one of therapeutic medical therapy, which involves culturing and modifying cells in an in vitro sterilized environment. The cells will deliver to the body to restore damaged or missing cells and tissues in the body. Nowadays, the therapy mainly delivers the cells to the body by injection. In addition, there are some limitations by traditional injection. For example, the injection has a risk of infection, the patient's compliance is low due to pain at injection, and injections could also cause cells are no room for growth. Therefore, in combining the advantages and disadvantages of the above two, in this study, polydimethylsiloxane (PDMS) was used as a material, engraved by laser engraving machine, to produce a hollow microneedle array mold. Polymethylmethacrylate (PMMA) was then used for filling, polymerization and demolding. Hollow microneedle arrays with different microstructures were successfully fabricated. The cells were cultured on the hollow microneedles. We used MTT Assay to test cell viability and the biocompatibility of the material. Then we used Live/Dead Staining to test the survival rate of the cells and we also observed the attachment of the cells on the hollow microneedles. The results show that PMMA hollow microneedles have good biocompatibility and the cells can be successfully attached to the microstructure of hollow microneedles. At the same time, the hollow microneedles were used as a carrier for cell delivery, and the cells were delivered to acellular tissue scaffolds prepared by a comprehensive acellular processing program in sequence of freeze-thaw, detergent and biological enzyme. This study confirmed that the cells can effectively enter the tissue via hollow microneedle carrier and growth well. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T06:13:04Z (GMT). No. of bitstreams: 1 ntu-107-R05548056-1.pdf: 3051892 bytes, checksum: eac2e66bf2b999ab1d1f4df1656d7881 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 致謝 I
摘要 II Abstract III 目錄 V 圖目錄 VIII 表目錄 IX 第一章、序論 1 1.1 經皮吸收(Transdermal) 1 1.2 微針陣列(Microneedle Array) 2 1.3 中空微針(Hollow Microneedle) 4 1.4 細胞療法(Cell Therapy) 7 1.5 聚丙烯酸甲酯(Polymethylmethacrylate, PMMA) 8 1.6 聚二甲基矽氧烷(Polydimethylsiloxane, PDMS) 9 1.7 雷射雕刻(Laser Engraving) 9 第二章、研究動機與目的 11 2.1 研究背景與動機 11 2.2 實驗方法描述 12 2.3 研究實驗架構 13 第三章、材料與方法 14 3.1 實驗藥品 14 3.2 實驗儀器 16 3.3 中空微針的製備 18 3.3.1 PDMS中空微針模具的製作 18 3.3.2 設計中空微針之構型 18 3.3.3 PMMA中空微針的製作 21 3.4 中空微針結構量測 22 3.5 中空微針穿透力測試 22 3.5.1 利用皮膚模擬物進行穿透力測試 23 3.5.2 利用新生豬皮(Neonatal porcine skin)進行穿透力測試 24 3.6 細胞於中空微針貼附情況 24 3.6.1 培養之細胞種類 24 3.6.2 細胞存活率分析 25 3.6.3 細胞活性染色 26 3.6.4 電子顯微鏡(SEM)觀察表面結構及細胞貼附 26 3.7 細胞轉移材料 27 3.7.1 海藻酸(Alginate)的製備 27 3.7.2 去細胞支架製備 28 3.8 中空微針為載體進行細胞轉移率測試 31 3.9 以共聚焦顯微鏡觀察中空微針之細胞傳遞 31 3.10 以組織切片觀察中空微針之細胞傳遞 32 3.10.1 蘇木紫-伊紅染色(Hematoxylin and Eosin stain, H&E stain) 32 3.10.2 免疫螢光染色(Immunocytochemistry, IHC) 34 3.10.3 DAPI螢光染色 36 第四章、結果與討論 37 4.1 中空微針微結構量測 37 4.1.1 平口中空微針 37 4.1.2 斜口中空微針 39 4.2 中空微針穿透力測試 41 4.2.1 利用皮膚模擬物進行穿透力測試 41 4.2.2 利用新生豬皮進行穿透力測試 41 4.3 細胞於中空微針貼附情況 44 4.3.1 細胞存活率分析 44 4.3.2 細胞活性染色 45 4.3.3 電子顯微鏡(SEM)觀察表面結構及細胞貼附 46 4.4 中空微針為載體進行細胞轉移率測試 48 4.5 以共聚焦顯微鏡觀察中空微針之細胞傳遞 49 4.5.1 利用中空微針將細胞傳遞至去細胞化豬角膜 49 4.5.2 比較以中空微針與傳統細胞傳遞之差異 50 4.5.3 觀察經中空微針傳遞後細胞增生狀況 51 4.6 以組織切片觀察中空微針之細胞傳遞 53 第五章、結論 56 第六章、參考資料 57 | |
| dc.language.iso | zh-TW | |
| dc.subject | 聚丙烯酸甲酯 | zh_TW |
| dc.subject | 微針陣列 | zh_TW |
| dc.subject | 雷射雕刻 | zh_TW |
| dc.subject | 細胞傳遞 | zh_TW |
| dc.subject | 中空微針 | zh_TW |
| dc.subject | Cell delivery | en |
| dc.subject | Microneedle arrays | en |
| dc.subject | Polymethylmethacrylate | en |
| dc.subject | Laser Engraving | en |
| dc.subject | Hollow microneedles | en |
| dc.title | 製備可調控微結構之中空微針陣列於細胞傳遞之應用 | zh_TW |
| dc.title | The Fabrication of Hollow Microneedle Array with Controlled Microstructure for Cell Delivery | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 鐘次文,黃意真 | |
| dc.subject.keyword | 微針陣列,中空微針,細胞傳遞,雷射雕刻,聚丙烯酸甲酯, | zh_TW |
| dc.subject.keyword | Microneedle arrays,Hollow microneedles,Cell delivery,Laser Engraving,Polymethylmethacrylate, | en |
| dc.relation.page | 60 | |
| dc.identifier.doi | 10.6342/NTU201804174 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2018-10-05 | |
| dc.contributor.author-college | 工學院 | zh_TW |
| dc.contributor.author-dept | 醫學工程學研究所 | zh_TW |
| 顯示於系所單位： | 醫學工程學研究所 | |
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