臺灣博碩士論文加值系統

本實驗室先前研究使用光固化型PCL (PCL-DA)結合光交聯劑PEG-acrylate以及光起始劑，利用直照式動態光罩快速成型系統製作3D組織工程支架，由於材料對光敏感性較高，導至支架疊層至三層時會造成孔徑封閉，故本研究建構反射式動態光罩快速成型系統，來改善這些缺點。此外，利用PEG-diacrylate (PEG-DA)取代PEG-acrylate，可使交聯時的鍵結更穩固藉此特性來提升支架強度。
為了尋找最佳的PCL-DA/PEG-DA混合比例，將材料分為6:4、7:3與8:2三個比例進行性質測試，量測抗拉強度與接觸角。量測結果顯示新材料在抗拉強度的表現上優PEG-acrylate，且材料在親水性的表現上優於未添加PEG-DA之PCL-DA。本研究新建構的反射式動態光罩快速成型系統是將DLP投影機投射的光路反射至材料槽，來降低光照度藉此來改善支架成型精度。利用三種不同比例之材料製作單層支架，其中以比例為8:2之材料，其誤差更可控制在2%以內；利用比例為8:2之材料製作出重現性高的100μm孔徑之單層支架，其誤差可控制在3%以內，並以此利用偏移堆疊的方式製作3D組織工程支架，有效的將堆疊層數由先前的兩層提升至五層。本研究有效的利用PCL-DA/PEG-DA搭配反射式動態光罩快速成型系統使用偏移堆疊方式製作3D組織工程支架

In our previous research, photo-curable PCL (PCL-DA), mixing with PEG-acrylate as a binder and photo-initiator, was photo-polymerized to fabricate tissue engineering scaffolds by a direct Dynamic Masking Rapid Prototyping (DMRP) system. The strong photo-sensitivity of the material system led pores closed in the scaffolds after stacking three layers. Therefore, in this research, a reflective DMRP system was established to improve the above issue. Moreover, PEG-diacrylate (PEG-DA) was used to replace PEG-acrylate to increase the strength of the cured materials.
In order to find suitable composition of PCL-DA to PEG-DA for fabrication, three ratios (6:4, 7:3, 8:2) were investigated. Tensile strength and contact angle were measured. The results showed great strength improvement compared to those use PEG-acrylate as a binder, and the materials are more hydrophilic compared to PCL-DA without PEG-DA. The new reflective DMRP system placed the DLP projector at the side and reflected the light to the material tank by a mirror to reduce illuminance and improve process accuracy. Materials with above ratios were used to fabricate single-layer scaffolds by the new system, and found the ratio of 8:2 has the least error (2%). This best material recipe was further used to generate 3D scaffolds through offsetting grid pattern in the alternating layer, and finally improve the scaffold's stacking layers from two to five. This research has successfully combined PCL-DA and PEG-DA to fabricate 3D tissue engineering scaffolds by reflective DMRP system, and can be applied to more scaffold applications in the future.

摘要 I
致謝 II
目錄 III
圖目錄 VI
表目錄 XII
第一章 緒論 1
1.1 前言 1
1.2 研究動機與目的 2
1.3 研究方法 3
1.4 論文架構 5
第二章 文獻探討 6
2.1 組織工程(Tissue Engineering)介紹 6
2.1.1 支架材料之特性 9
2.1.2 高分子生醫材料 10
2.1.3 傳統支架製備方法 20
2.2 應用快速原型技術製造組織工程支架 25
2.2.1 快速原型加工原理 26
2.2.2 快速原型技術應用於組織工程支架之製造 27
第三章 材料合成與性質檢測 43
3.1 實驗藥品與設備 43
3.2 材料系統介紹與合成系統改善 44
3.2.1 合成PCL-DA 45
3.2.2 合成系統之改善 46
3.2.3 光交聯劑 50
3.2.4 光起始劑 51
3.2.5 光聚合生醫材料 53
3.3 材料性質檢測與設備簡介 54
3.3.1 拉伸試驗 55
3.3.2 接觸角量測 59
3.4 材料性質檢測結果 62
3.4.1 拉伸試驗 62
3.4.2 接觸角量測 66
第四章 系統簡介與機構設計 70
4.1 生醫動態光罩快速成型系統 70
4.1.2 上、下照式成型系統差異 70
4.2 下照式動態光罩快速成型系統 73
4.2.1 動態光罩控制軟體 74
4.2.2 動態光罩產生器 78
4.3 反射式動態光罩快速成型系統設計 83
4.3.1 光學系統設計與改善 85
4.3.2 機構設計與改善 94
4.4 參數設定與精度檢測 99
4.4.1 參數設定 99
4.4.2 系統精度檢測 102
第五章 3D組織工程支架製作 108
5.1 加工流程 108
5.2 單層支架製作 110
5.3 單層小孔徑支架製作 116
5.4 3D支架製作 119
5.4.1 2D圖形設計與3D支架製作流程 119
5.4.2 3D支架精度量測 121
5.5 研究成果比較 126
第六章 結論與未來研究方向 130
6.1 結論 130
6.2 未來工作 131
參考文獻 132

【1】http://textile.iitd.ac.in/highlights/fol8/01.htm
【2】C. Becker and G. Jakse, "Stem Cells for Regeneration of Urological Structures" european urolo g y , Volume 51 (2 0 0 7),1217 – 1228.
【3】宋信文 梁晃千 ，“建立人類的身體工房-組織工程” ，科學發展第362期，2003年2月，6-11
【4】楊婷琪，“組織工程的重要元件-生物分子”，工研院經貿中心生醫組，2002年7月。
【5】廖俊仁，“組織工程用多孔隙骨架材料”，工研院生醫工程中心，2002年。
【6】S. Yang, K. F. Leong, Z. DU, and C. K. Chua, “The design of scaffolds for use in tissue engineering. Part I. Traditional Factors,” Tissue Engineering, Volume 7(2001), 679-689.
【7】http://www.web66.com.tw/web/News?postId=411642.
【8】俞耀庭，生物醫用材料，初版，新文京，2004
【9】D.K. Gilding, and A.M. Reed, “Biodegradable polymers for use in surgery -Poly(glycolic acid)/Poly(lactide acid)homo-and copolymers.2.In vitro degradation, ” Polymer, Volume 22 (1981) 494-498.
【10】工業技術研究院，“生醫材料與組織工程”
【11】張根源，“生物吸收性PLGA材料合成與應用技術”，工業技術與資訊第112 期，2001年2月。
【12】興技生物科技公司, (http://www.bio-invigor.com)
【13】蔡秉宏，”以聚殼醣合成光交聯性衍生物之探討”，國立成功大學化學工程研究所，碩士論文，1999。
【14】D.S, “Medical application of synthetic polymers,” Marcel Dekker, NewYork (1994) 725.
【15】J. S. Park , D. G. Woo , Bo Kyung Sun, “In vitro and in vivo test of PEG/PCL-based hydrogel scaffold for cell delivery application,” Journal of Controlled Release,Volume 124 (2007) 51–59.
【16】許芳豪，“以快速原型技術研究組織工程支架孔徑大小對細胞成長之影響”，國立台灣科技大學機械工程研究所，碩士論文，2006。
【17】H. Y. Kweon, M. K. Yoo, I. K. Park, T. H. Kim, H. C. Lee, H. S. Lee, J. S. Oh, T. Akaike, and C. S. Cho, “A novel degradable poly caprolactone networks for tissue engineering,” Biomaterials,Volume 24 (2003) 801-808.
【18】T. W. Chung , M. C. Yang , C. C. Tseng , S. H. Sheu , S. S. Wang ,Y. Y. Huang , S. D. Chen,“Promoting regeneration of peripheral nerves in-vivo using new PCL-NGF/Tirofiban nerve conduits”Biomaterials ,Volume 32 (2011) 734-743.
【19】Y. Z. Bian , Y. Wang , G. Aibaidoula, “Evaluation of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) conduits for peripheral nerve regeneration, ” Biomaterials, Volume30(2009) 217-225.
【20】K. Whang, C. H. Thomas, K. E. Healy, and G. Nuber, “A novel method to fabricate bioabsorbable scaffolds,” Polymer,Volume 36 (1995), 837-842.
【21】G. Wei and P. X. Ma, “Structure and properties of nano-hydroxyapatite/ polymer composite scaffolds for bone tissue engineering,” Biomaterials 25 (2004) 4749-4757
【22】H. Wang, Y. Lia, Y. Zuoa, J. Lib, S. Mab, L. Cheng,“Biocompatibility and osteogenesis of biomimetic nano-hydroxyapatite/polyamide composite scaffolds for bone tissue engineering,” Biomaterials , ,Volume 28 (2007) 3338–3348
【23】俞耀庭, “生物醫用材料,” 初版 新文京 2004年
【24】D. Yucel, G. T. Kose, V. Hasirci, “Polyester based nerve guidance conduit design, ”Biomaterials,Volume31(2010), 1596-1603
【25】L. Ghasemi-Mobarakeh, M. P. Prabhakaran, M. Morshed, M. H. Nasr-Esfahani, S. Ramakrishna, “Bio-functionalized PCL nanofibrous scaffolds for nerve tissue engineering, ” Materials Science and Engineering C , Volume 30 (2010) 1129–1136
【26】M. S. Widmer, P. K. Gupta, L. Lu, R. K. Meszlenyi ,G. R. Evans, K. Brandt, T. Savel, A. Gurlek, C. W. Patrick Jr. and A. G. Mikos, “Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration,” Biomaterials, Volume 19(1998),1945-1955
【27】M. J. Moore, J. A. Friedman, E. B. Lewellyn, S. M. Mantila, A. J. Krych, S. Ameenuddin, A. M. Knight, L. Lu, B. L. Currier, R. J. Spinner, R. W. Marsh, A. J. Windebank, M. J. Yaszemski, “Multiple-channel scaffolds to promote spinal cord axon regeneration, ” Biomaterials , Volume 27(2006), 419–429
【28】F. P.W. Melchels , J. Feijen , D. W. Grijpma,“A review on stereolithography and its applications in biomedical engineering,”Biomaterials , Volume 31(2010) ,6121-6130
【29】http://www.custompartnet.com/
【30】K.F. Leong, C.M. Cheah, C.K. Chua, “Solid freeform fabrication of 3D scaffolds for engineering replacement tissue and organs,” Biomaterials ,Volume24(2003), 2363–2378
【31】M. J. Mondrinosa, R. Dembzynskib, L. Lub, V. K. C. Byrapogub, D. M. Woottonb, P. I. Lelkesa, Jack Zhoub,123“Porogen-based solid freeform fabrication of polycaprolactone–calcium phosphate scaffolds for tissue engineering,” Biomaterials, Volume 27(2006), 4399-4408
【32】S. Khalil, W. Sun, “Biopolymer deposition for freeform fabrication of hydrogel tissue constructs,”Materials Science and Engineering C, Volume 27(2007), 469–478
【33】L. Shor, S. Guceri, X. Wen, M. Gandhi, W. Sun,“Fabrication of three-dimensional polycaprolactone/hydroxyapatite tissue scaffolds and osteoblast-scaffold interactions in vitr,”Biomaterials, Volume 28(2007),5291-5297
【34】W. Zeng, F. Lin, T. Shi, R. Zhang,Y. Nian, J. Ruan, T. Zhou“Fused deposition modelling of an auricle framework for microtia reconstruction based on CT images,” Rapid Prototyping Journal, Volume14/5 (2008), 280–284
【35】T. Cui, Y. Yan, R. Zhang, “Biomodeling and fabrication of a hybrid PU-collagen nerve regeneration conduit, ” VECIMS,Volume1(2009),3809-3815
【36】http://www.azom.com/article.aspx?ArticleID=1648
【37】J. M. Williams, A. Adewunmi, R. M. Schek, C. L. Flanagan, Paul H. Krebsbach, S. E. Feinberg, S. J. Hollister and S. Das, “Bone tissue engineering using polycaprolactoe scaffolds fabricated via selective laser sintering,” Biomaterials, Volume 26 (2005) 4817-4827.
【38】M. M. Savalani, L. Hao, Y. Zhang, K. E. Tanner, and R. A. Harris，“Fabrication of porous bioactive structures using the selective laser sintering technique”Engineering in Medicine,Volume 221(2007),873-886
【39】C. Mangano, A. D. Rosa, V. Desiderio, R.d’Aquino, A. Piattelli, F. D. Francesco , Virginia Tirino, Francesco Mangano, Gianpaolo Papaccio, “The osteoblastic differentiation of dental pulp stem cells and bone formation on different titanium surface textures,” Biomaterials, Volume 31(2010), 3543-3551.
【40】C. X. F. Lam, X. M. Mo, S.H. Teoh and Hutmacher, “Scaffold development using 3D printing with a starch-based polymer,” Materials Science and Engineering ,Volume 20(2002) 49-56.
【41】M. Lee, J. C.Y. Dunn and B. M. Wu, “Scaffold fabrication by indirect three-dimensional printing,” Biomaterials, Volume 26 (2005), 4281-4289.
【42】M. L. Macdonald, R. E. Samuel, N. J. Shah, R. F. Padera , Y. M. Beben,P. T. Hammond, “ Tissue integration of growth factor-eluting layer-by-layer polyelectrolyte multilayer coated implants” Biomaterials, Volume 32(2011),1446-1453.
【43】H. Jiankang, L. Dichen, L. Yaxiong, Y. Bo, L. Bingheng, L. Qin “Fabrication and characterization of chitosan/gelatin porous scaffolds with predefined internal microstructures,” Polymer, Volume. 48(2007), 4578-4588.
【44】F. P.W. Melchels, J. Feijen, D. W. Grijpma, “A poly(D,L-lactide) resin for the preparation of tissue engineering scaffolds by stereolithography,” Biomaterials, Volume. 30(2009),3801-3809.
【45】J. W. Choi, R. Wicker, S. H. Lee,K. H. Choi, C. S. Ha and I. Chung“Fabrication of 3D biocompatible/biodegradable micro-scaffolds using dynamic mask projection microstereolithography” , Journal of Materials Processing Technology, Volume 209(2009), 5494-5503
【46】李孟龍，“動態光罩快速原型系統製造組織工程支架之研發”，國立台灣科技大學機械工程研究所，碩士論文，2005。
【47】陳俊豪，“光固化快速成型技術製作組織工程支架之研究”，國立台灣科技大學機械工程研究所，碩士論文，2006。
【48】許貽玨，“光聚合生物可分解材料應用於RP技術製作組織工程支架性質之研究”，國立台灣科技大學機械工程研究所，碩士論文，2007。
【49】陳茂揚 “光固化快速成型系統製作3D組織工程支架”國立台灣科技大學機械工程研究所，碩士論文，2008。
【50】曾俊元“動態光罩快速成型系統光聚合PCL-PEG-PCL製作3D組織工程支架”，國立台灣科技大學機械工程研究所，碩士論文，2008。
【51】薛智仁“動態光罩快速成型系統製作3D PCL管狀多孔性組織工程支架之研究”，國立台灣科技大學機械工程研究所，碩士論文，2009。
【52】謝浚雄“光聚合PCL材料系統成份探討及其應用於快速成型3D組織工程支架”，國立台灣科技大學機械工程研究所，碩士論文，2011。
【53】孫凱閔“PCL結合PEG-acrylate透過動態光罩成型系統製作3D多孔性組織工程支架” 國立台灣科技大學機械工程研究所，碩士論文，2011。
【54】sigmaaldrich ( http://www.sigmaaldrich.com/taiwan.html)
【55】ASTM D638-10
【56】Y. Hong, J. Guan, K. L. Fujimoto, R. Hashizume,A. L. Pelinescu, W. R. Wagner “Tailoring the degradation kinetics of poly (ester carbonate urethane) urea thermoplastic elastomers for tissue engineering scaffolds”, Biomaterials, Volume 31(2010),4249-4258.
【57】香港物理協會( http://www.hk-phy.org/ )
【58】Texas Instrument (http://www.dlp.com/tw/)
【59】http://postfiles5.naver.net/data42/2009/1/8/100/noname02_toy327 6.jpg?type=w3
【60】Viviteck (http://www.vivitekusa.com/ )