臺灣博碩士論文加值系統

藉由層積冷凍成型(Deposition Freezing Manufacturing, DFM)來製造具特定結構與外型的三維支架時，會因為製作環境溫度、噴嘴尺寸、噴頭移動速度、及材料噴擠壓力等因素，影響支架製作的品質，造成製作出的支架有坍塌、變形、孔洞不一的問題，所以本研究將探討影響支架製作品質的因素並加以控制，來達到精確地製作出三維支架，以及解決支架懸空變形的問題。
本研究藉由固定製作參數來控制製備材料的品質；設計新型圓筒型製作平台，提升更大範圍且溫度穩定的製作環境，可製作2.5公分高的支架；觀測噴擠材料凝固速度，得知材料凝固時間在6~10秒間，支架不會產生翹曲或坍塌；分析固定材料噴擠壓力下，噴頭直線與轉彎速度對線徑的影響，發現當噴頭直線速度與轉彎速度為1:1.67時，支架直線與轉彎處線徑將最相近。並藉由嘗試各種水溶性支撐材料，配合以雙噴頭分別噴擠支架與支撐材料的製作方式，製作出具懸空斜面的三維支架。
製程的改善，讓300個支架製作良率提升為90%。由SEM觀察，所製作的支架結構與外型更接近預先設定的模型、支架線徑誤差小於3μm、孔洞大小更接近設計值，也因此支架含水率也增加。

Use the Deposition Freezing Manufacturing(DFM) to fabricate the purposive structure of the scaffolds, we know the working temperature, the size of nozzle, the movement speed of nozzle, and the pressure of deposition will affect the quality of scaffold, to cause the scaffold collapsing, changing shape, and hard to control the pore size. So the study will confer and control these factors let the 3D scaffold can be accurately fabricated and solve the problem of the suspended in midair scaffold changing shape.
The study fixes the fabricating parameter to control the quality of material; to design a new cylindrical production platform to promote the low temperature production environment of large range and stable temperature to fabricate a scaffold high then 2.5cm; to observe the clotting speed of the deposition material knows the clotting speed at 6-10 seconds, the scaffolds will not effect warpage and collapse; to analyze the influence of the pressure and speed on fiber size, when the straight and turn speed ratio is 1:1.67, the straight and turn fiber size is the most close. And we try many kinds of water-soluble support materials to cooperate with two-nozzle spurting scaffold and support materials to fabricate the suspended in midair 3D scaffold of an inclined plane.
The improving of the process let the fabricating yield of 300 piece scaffolds be 90%. The structure and appearance of the scaffolds are more close the design model in advance, the fiber size error less than 3μm, the pore size is more close the design, so the scaffold moisture content is increasing.

摘　　　　要 I
A b s t r a c t II
致　　　　謝 III
目　　　　錄 IV
圖 目 　錄 VII
表 目 　錄 IX
第一章 緒論 1
1-1 研究動機與目的 1
1-2 研究方法簡介 3
1-3 論文流程 4
第二章 文獻回顧 5
2-1 組織工程簡介 5
2-2 支架材料 5
2-2-1 支架的材料特性 5
2-2-2 支架製作的考量 6
2-2-3 材料介紹 7
2-3 支架製備的方法 9
2-3-1 傳統支架製備的方法 9
2-3-2 快速成型支架製作簡介 9
第三章 材料與系統架構 12
3-1 實驗材料 12
3-2 實驗儀器與器材設備 13
3-2-1 支撐與支架材料製備 13
3-2-2 支架的製備 13
3-2-3 支架型態的觀察 13
3-3 硬體架構 14
3-4 軟體架構 16
3-4-1 支架設計 16
3-4-2 支架製作 17
3-4-3 溫度記錄 18
第四章 系統作業流程 20
4-1 作業流程 20
4-2 路徑的規劃 23
4-3 材料製備 24
4-4 冷凍真空乾燥 25
第五章 製程改善之研究 27
5-1 影響支架製作品質不良的因素 27
5-2 支架製作的改良 30
5-2-1 材料噴擠量 30
5-2-2 恆低溫製作環境 33
5-2-3 材料凝固速度 38
5-2-4 噴頭移動速度與轉彎處殘料的關係 44
5-2-5 支架孔洞的設計 48
5-2-6 支架製作之相關應用 54
5-3 需支撐之特定形狀的三維支架製作 54
5-3-1 雙噴頭的影響 56
5-3-2 支撐材料的決定 58
5-3-3 支撐材料應用在特定形狀支架上的相關評估 58
5-4 支架含水率測定 63
第六章 結論與未來展望 66
參 考 文 獻 68

[1]Hutmacher D. W., Scaffolds in tissue engineering bone and cartilage, Biomaterials, Vol. 21, pp.2529–2543, 2000.
[2]Hutmacher D. W., Zein I., Teoh S. H., et al., Design and fabrication of a 3D scaffold for tissue engineering bone, In: Agrawal C. M., Parr J. E., Lin S. T., editors., Synthetic bioabsorbable polymers for implants, STP 1396., West Conshohocken, PA, American Society for Testing and Materials, pp. 152–167, 2000.
[3]Lanza R. P., Langer R., Vacanti J., Principles of Tissue Engineering, 2nd Ed, Academic, 2000.
[4]Hutmacher D. W., Sittinger M., Risbud M. V., Scaffold-based tissue engineering: rationale for computer-aided design and solid free-form fabrication systems, Trends in Biomaerial, Vol. 22, No.7, pp.354-62, July 2004.
[5]Chen V. J., Smith L. A., Ma P. X., Bone Regeneration on Computer-Designed Nano-Fibrous Scaffolds, Biomaterials, Vol. 27, pp.3973-3979, 2006.
[6]Yang, S., Leong, K. F., Du, Z., et. al., The design of scaffolds for use in tissue engineering. Part I. Traditional Factors, Tissue Engineering, Volume 7(6), pp. 679-689. 2001.
[7]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，民95。
[8]黃學惠，骨細胞支架之電腦輔助設計與製造，國立成功大學醫學工程研究所碩士論文, 民94。
[9]Hutmacher D. W., Schantz T., Zein I., et al., Mechanical properties and cell cultural response of polycaprolactone scaffolds designed and fabricated via fused deposition modelling, Journal of Biomedical Materials Research, Vol. 55, pp.203–216, 2001.
[10]Kim S. S., Utsunomiya H., Koski J. A., et al., Survival and function of hepatocytes on a novel 3D synthetic biodegradable polymer scaffold with intrinsic network of channels, Ann. Surg., Vol. 228, pp.8–13, 1998.
[11]Xiong Z., Yan Y. N., Wang S. , et al., Fabrication of porous scaffolds for bone tissue engineering via low-temperature deposition, Scripta Materialia, Vol. 46, No. 11, pp.771-776, 2002.
[12]黃仁波，以冷凍式快速原型法製作組織工程支架，國立中央大學機械工程研究所碩士論文，民94。
[13]吳瑞祥，組織工程用三維支架支製成路徑規劃，國立中央大學機械工程研究所碩士論文，民97。
[14]陳彥霖，“組織工程用三維支架之電腦輔助製程設計，國立中央大學機械工程研究所碩士論文，民96。
[15]Bryant F. D., Sui G., Leu M. C., A study on effects of process parameters in rapid freeze prototyping, Rapid Prototyping Journal, Vol. 9, No.1, pp.19-23, 2003.
[16]Edwards S., Mitchell W., Matthews J. , et al., Design of nonwoven scaffold structures for tissue engineering of the anterior cruciate ligament, AUTEX Research Journal, Vol. 4, No. 2, pp.86-94, 2004.
[17]Khalil, S. and Sun, W., Biopolymer Deposition for Freeform Fabrication of Hydrogel Tissue Constructs, J. of Materials Science and Engineering C, Vol. 27, No. 3, pp.469-478, 2007.
[18]Yaszemski M. J., Payne R. G., Hayes W. C., et al., Evolution of bone transplantation molecular, cellular and tissue strategies to engineer human bone, Biomaterials, Vol. 17, No. 2, pp.175-185, 1996.
[19]Mooney D. J., Langer R., in The Biomedical Engineering Handbook (Brozino J. D. ed.), pp.1609-1618.
[20]黃偉春等，軟骨組織工程進展，國外醫學生物醫學工程分冊第22卷第5期，民88。
[21]楊志明主編，組織工程，九州圖書文物有限公司，400-405頁，台北市，民94。
[22]King E., Cameron R. E., Effect of hydrolytic degradation on the microstructure of poly(glycolic acid): an X-ray scattering and ultraviolet spectrophotometry study of wet sample ultraviolet, J. Appl. Polym. Sci., Vol. 66, pp.1681-1690, 1997.
[23]You Y., Min B. M., Lee T. S., et al., In vitro degradation behavior of electrospun polyglycolide, polylactide, and poly(lactide- co-glycolide), J. Appl. Sci., Vol. 95 , pp.193-200, 2005.
[24]徐 丹等，聚丙烯酸鈉增稠劑的特性及用途，河南科學，第23卷，第6期，810-812頁，民94。
[25]Yarlagadda. P. K., Chandrasekharan. M., Shyan. J. Y., Recent advances and current developments in tissue scaffolding, Biomed Mater Eng, Vol. 15, No. 3, pp.159-177, 2005.
[26]Widmer M. S., Gupta P. K., Lu L., et al., Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration, Biomaterials, Vol. 19, issue 21, pp.1945-1955, 1998.
[27]Yeong W., Chua C., Leong K. , et al., Rapid prototyping in tissue engineering:challenges and potential(Review), Trends Biotechnol, Vol. 22, No.12, pp.643-52, 2004.
[28]Hutmacher D. W., Scaffold design and fabrication technologies for engineering tissues-state of the art and future perspectives, J. Biomater. Sci. Polymer Edn., Vol. 12, pp.107-124, 2001.
[29]Zein I., Hutmacher D. W., Tan K. C. , et al., Fused deposition modelling of novel scaffold architectures for tissue engineering applications, Biomaterials, Vol. l23, pp.1169–85, 2002.
[30]Landers R. and. Mülhaupt R., Desktop manufacturing of complex objects, prototypes and biomedical scaffolds by means of computer-assisted design combined with computer-guided 3D plotting of polymers and reactive oligomers, Macromol. Mater. Eng., Vol. 282, pp.17–21, 2000.
[31]Landers R., Hubner U., Schmelzeisen R., et al., Rapid prototyping of scaffolds derived from thermoreversible hydrogels and tailored for applications in tissue engineering, Biomaterials, vol. 23, pp.4437–4447, 2002.
[32]Landers R., Pfister A., Hubner U., et al., Fabrication of soft tissue engineering scaffolds by means of rapid prototyping techniques, Journal of Materials Science, Vol. 37, pp.3107-16, 2002.
[33]Xiong Z., Yan Y., Zhang R. , et al., Fabrication of porous poly(L-lactic acid) scaffolds for bone tissue engineering via precise extrusion, Scripta Mater., Vol. 45, pp.773–779, 2001.
[34]Wang F., Shor L., Darling A., et al., Precision Extruding Deposition and Characterization of Cellular Poly- -Caprolactone Tissue Scaffold, Rapid Prototyping Journal, Vol. 10, pp.42-49, 2004.
[35]Darling A. L., Sun W., 3D Microtomographic Characterization of Precision Extruded Poly- -Caprolactone Scaffolds, Journal of Biomedical Materials Research Part B, Applied Biomaterials, Vol. 70, Issue 2, 2004.
[36]呂桓綜，組織工程精密支架之製造，國立中央大學機械工程研究所碩士論文，民91。
[37]Woodfield T.B.F., Malda J., Wijn J. de, et al., Design of porous scaffolds for cartilage tissue engineering using a three-dimensional fibre-deposition technique, Biomaterials, Vol. 25, pp.4149-4161, 2004.
[38]Leu M. C., Zhang W., Sui G., An experimental and analytical study of ice part fabrication with rapid freeze prototyping, CIRP Annals, Vol. 49, No. 1, pp.147-150, 2000.
[39]Xiong Z., Yan Y. N., Yunyu H., et al., Layered manufacturing of tissue engineering scaffolds via multi-nozzle deposition, Mater. Lett. 57, pp. 2623–2628, 2003.
[40]Pang L., Hu Y. Y., Yan Y. N., et al., Surface modification of PLGA/β-TCP scaffold for bone tissue engineering: hybridization with collagen and apatite, Surface Coat. Tec., Vol. 201, pp.9549-9557. 2007.
[41]王 琴等，聚丙烯酸鈉低濃度時的流變特性及其影響因素，食品與發酵工業，第30卷，第1期，42-44頁，民93。