臺灣博碩士論文加值系統

銅藻（Sargassum Horneri）是一種溫帶性海洋大型褐藻，廣泛分布於中國、韓國和日本沿海等地區。由於台灣處於副熱帶氣候地區，因此並沒有在地的野生銅藻。但是，漂流性銅藻在冬末春初大陸沿岸冷流來到時，會順著冷水團渡過台灣海峽，來到台灣的中、北部海岸及澎湖海岸，成為台灣海洋的廢棄物，甚至造成漁船故障、近海的魚貝類受困死亡，海岸惡臭的環境問題。雖然大量漂流來的銅藻帶來了海洋問題，但銅藻所含有的褐藻醣膠具有多種生物活性，如抗菌、抗氧化、抗病毒、抗炎、抗腫瘤、抗凝血和免疫調節活性等功能。有鑑於褐藻醣膠具有調節與傷口修復相關的轉化生長因子β1的作用，並且能促進新生血管和纖維狀膠原基質的形成等幫助皮膚修復的潛力。因此，本研究結合過去在開發人工真皮的經驗，將台灣海岸銅藻所萃取的褐藻醣膠應用於全皮膚損傷修復之三維海綿敷料的開發。本研究目前已開發含褐藻醣膠的三維海綿敷料的製程及配比，及評估其物理性質及生物相容性。未來將進行組織學及皮膚組織修復能力結果評估。本研究將台灣海域銅藻萃取之褐藻醣膠應用於傷口敷料開發將有助於提升傷口醫療修復的發展，並且幫助提升銅藻的經濟價值，及解決銅藻成為海洋廢棄物的問題。

Sargassum Horneri is a temperate marine macroalgae widely distributed in coastal areas of China, Korea and Japan. Because Taiwan is in a subtropical climate area, there are no wild copper algae in the area. However, the drifting copper algae will cross the Taiwan Strait along the cold water mass when the cold current comes along the coast of the mainland in late winter and early spring, and come to the central and northern coasts of Taiwan and the coast of Penghu. Although a large number of drifting copper algae has brought marine problems, the fucoidan contained in copper algae has a variety of biological activities, such as antibacterial, antioxidant, antiviral, anti-inflammatory, antitumor, anticoagulant and immunomodulatory activities. In view of the potential of fucoidan to regulate transforming growth factor β1 related to wound repair, and to promote the formation of new blood vessels and fibrous collagen matrix, etc., to help skin repair. Therefore, in this study, combined with the experience in the development of artificial, fucoidan extracted from Taiwan's coastal copper algae was used to evaluate the development of a three-dimensional sponge dressing for the repair of total skin damage. In this study, the manufacturing process and proportion of the three-dimensional sponge dressing containing fucoidan have been developed, and its physical properties and biocompatibility have been evaluated. In the future, histological and skin tissue capacity repair results will be evaluated. In this study, the development of fucoidan and dressings extracted from copper algae along the coast of Taiwan will help to improve the development of medical repair, and help to increase the economic value of copper algae, and solve the problem of copper algae being discharged into the ocean.

摘 要 V
ABSTRACT VI
圖次 IX
第一章 緒論 1
1.1研究背景 1
1.2研究動機與目的 2
1.3論文架構 7
第二章 文獻探討 8
2-1組織工程 8
2-2 傷口敷料 10
2-3 3D列印製造技術 11
2.4 DLP列印技術文獻探討 15
2.5 實驗設計法 15
第三章 研究方法與過程 17
3.1 實驗設備與材料 17
3.2設備介紹 26
3.3實驗流程 28
第四章 實驗結果與討論 34
第五章 結果與未來建議 45
第六章 參考文獻 47

圖次
圖一: 馬祖北竿塘后澳沙灘可見被潮水推向岸邊的大量銅藻 3
圖二: 褐藻醣膠的結構 4
圖三:創新細胞積木應用三維人工真皮開發 6
圖四:組織工程流程圖 10
圖五：原膠原（PROCOLLAGEN）的三螺旋結構示意圖 23
圖六：褐藻糖膠的結構 24
圖七：幾丁聚醣的結構 25
圖八：硫酸軟骨素的結構 26
圖九: 本研究製造之用以製成三維海綿敷料之具彈性模具 36
圖十: 本研究製備之三維海綿敷料支成品圖 36
圖十一: 含褐藻醣膠的三維海綿敷料經彎曲(上)及壓縮(下)後之結果 37
圖十二: (A)為第一組正面SEM影像圖; (B)為第二組正面SEM影像圖; (C)為第三組正面SEM影像圖; (D)為第四組正面SEM影像圖; (E)為第五組正面SEM影像圖 38
圖十三: (A)為第一組剖面SEM影像圖; (B)為第二組剖面SEM影像圖; (C)為第三組剖面SEM影像圖; (D)為第四組剖面SEM影像圖; (E)為第五組剖面SEM影像圖 38
圖十四: 膠原蛋白/褐藻醣膠/硫酸軟骨素/幾丁聚醣海綿敷料的XRD分析結果 40
圖十五: 膠原蛋白/褐藻醣膠/硫酸軟骨素/幾丁聚醣海綿敷料的FTIR分析結果 40
圖十六: 膠原蛋白/褐藻醣膠/硫酸軟骨素/幾丁聚醣海綿敷料的體外凝血實驗分析 41
圖十七: 膠原蛋白/褐藻醣膠/硫酸軟骨素/幾丁聚醣海綿敷料的膨潤度分析 42
圖十八: 膠原蛋白/褐藻醣膠/硫酸軟骨素/幾丁聚醣海綿敷料的第1、3、7天降解率 42
圖十九: 膠原蛋白/褐藻醣膠/硫酸軟骨素/幾丁聚醣海綿敷料的第1天細胞存活率 43
圖二十: 膠原蛋白/褐藻醣膠/硫酸軟骨素/幾丁聚醣海綿敷料的第3天細胞存活率 43
圖二十一: 膠原蛋白/褐藻醣膠/硫酸軟骨素/幾丁聚醣海綿敷料的第3天細胞存活率 44

 
表次

表一：各種3D列印技術比較表 13
表二：本研究使用之胺基樹脂 17
表三：本研究使用之甲基丙烯酸羥乙酯 18
表四：本研究使用之三羥甲基胺基甲烷 19
表五：本研究使用之多巴胺 20
表六：本研究使用之2,4,6-三甲基苯甲醯基二苯基氧化膦 21
表七：本研究使用之2-羥基-4-甲氧基-5-磺酸二苯甲酮 21
表八：本研究使用之四甲基哌啶氧化物 22
表九：ELEGOO MARS 3列印機的介紹 26
表十：全波長吸光多功能分析的介紹 27
表十一：掃描電子顯微鏡的介紹 28
表十二: 具生物相容性及彈性的光固化型胺基樹脂的配方表 35
表十三:膠原蛋白/褐藻醣膠/硫酸軟骨素/幾丁聚醣海綿敷料的材料比例配置 36
表十四: 膠原蛋白/褐藻醣膠/硫酸軟骨素/幾丁聚醣海綿敷料的孔隙率分析 39

1.銅藻
Https://Zh.Wikipedia.Org/Wiki/銅藻.
2.海洋環境與保育：外來海藻的生態衝擊 Https://Scitechvista.Nat.Gov.Tw/Article/C000003/Detail?ID=6933fc4d-Cc2b-40cd-A2e1-A1924bc63052.
3.春夏之交銅藻報到，臺灣金山萬里沿岸清運50噸海漂垃圾怎麼處理
Https://Www.Tspweb.Com/Key/铜藻台湾.Html.
4.Hao. Y., Zhao. W., Zhang, L., Zeng, X., Sun, Z., Zhang, D., Shen. P., Li. Z., Han. Y., Li. P., Zhou. Q. Bio-Multifunctional Alginate/Chitosan/Fucoidan Sponges With Enhanced Angiogenesis And Hair Follicle Regeneration For Promoting Full-Thickness Wound Healing. Materials & Design, 2020, 193, 108863.
5.產學研醫攜手 首台慢性傷口癒合治療儀問世 Https://Www.Biomedical.Org.Tw/Webpage/Front_News_View.Aspx?Flag=6ebprj5c078%3D&Id=82f8ba0d-4c44-4627-9583-57e8b268d604.
6.O'Leary. R., Rerek. M., & Wood. E. J. Fucoidan Modulates The Effect Of Transforming Growth Factor (TGF)-Beta1 On Fibroblast Proliferation And Wound Repopulation In In Vitro Models Of Dermal Wound Repair. Biological & Pharmaceutical Bulletin, 2004, 27(2), 266–270.
7.預告馬祖藍眼淚季 澳口沙灘已出現大量銅藻 Https://Www.Cna.Com.Tw/News/Aloc/202002230033.Aspx.
8.有關銅藻(馬尾藻)成災翻身變黃金議題之回應 Https://Www.Namr.Gov.Tw/Ch/Home.Jsp?Id=43&Parentpath=0,6&Mcustomize=Clarification_View.Jsp&Dataserno=127249.
9.Silchenko. A. S., Rasin. A. B., Kusaykin. M. I., Kalinovsky. A. I., Miansong. Z., Changheng. L., Malyarenko. O., Zueva. A. O., Zvyagintseva. T. N., Ermakova. S. P. Structure. Enzymatic Transformation. Anticancer Activity Of Fucoidan And Sulphated Fucooligosaccharides From Sargassum Horneri. Carbohydrate Polymers, 2017, 175, 654–660.
10.Herath. K. H. I. N. M., Cho. J., Kim. A., Kim. H.-S., Han. E. J., Kim. H. J., Kim. M. S., Ahn. G., Jeon. Y.-J., Jee. Y. Differential Modulation Of Immune Response And Cytokine Profiles Of Sargassum Horneri Ethanol Extract In Murine Spleen With Or Without Concanavalin A Stimulation. Biomedicine & Pharmacotherapy, 2019, 110, 930–942.
11.Structure Of Fucoidan - Fucoidan Structure Https://Www.Seekpng.Com/Ipng/U2w7r5u2w7w7t4q8_5-Structure-Of-Fucoidan-Fucoidan-Structure/.
12.Kwak. J.-Y. Fucoidan As A Marine Anticancer Agent In Preclinical Development. Marine Drugs, 2014, 12.
13.Luthuli. S., Wu. S., Cheng. Y., Zheng. X., Wu. M., Tong. H. Therapeutic Effects Of Fucoidan: A Review On Recent Studies. Marine Drugs, 2019, 17.
14.Rioux. L.-E., Turgeon. S. L., Beaulieu. M. Structural Characterization Of Laminaran And Galactofucan Extracted From The Brown Seaweed Saccharina Longicruris. Phytochemistry, 2010, 71, 1586–1595.
15.Pereira. M. S., Mulloy. B., Mourão. P. A. S. Structure And Anticoagulant Activity Of Sulfated Fucans: Comparison Between The Regular, Repetitive, And Linear Fucans From Echinoderms With The More Heterogeneous And Branched Polymers From Brown Algae. Journal of Biological Chemistry, 1999, 274, 7656–7667.
16.Song. Y., Wang. Q., Wang. Q., He. Y., Ren. D., Liu. S., Wu. L. Structural Characterization And Antitumor Effects Of Fucoidans From Brown Algae Kjellmaniella Crassifolia Farmed In Northern China. International Journal of Biological Macromolecules, 2018, 119, 125–133.
17.Sun. X., Duan. M.; Liu. Y., Luo. T., Ma. N., Song. S., Ai. C. The Beneficial Effects Of Gracilaria Lemaneiformis Polysaccharides On Obesity And The Gut Microbiota In High Fat Diet-Fed Mice. Journal of Functional Foods, 2018, 46, 48–56.
18.Ye. J., Chen. D., Ye. Z., Huang. Y., Zhang. N., Lui. E. M. K., Xue. C., Xiao. M. Fucoidan Isolated From Saccharina Japonica Inhibits LPS-Induced Inflammation In Macrophages Via Blocking NF-ΚB, MAPK And JAK-STAT Pathways. Marine Drugs, 2020, 18, 328.
19.先進傷口敷料的全球市場:考察與預測 (2027年) Https://Www.Giichinese.Com.Tw/Report/Qyr1038382-Global-Advanced-Wound-Dressings-Market-Insights.Html.
20.Sen. C. K., Gordillo. G. M., Roy. S., Kirsner. R., Lambert. L., Hunt. T. K., Gottrup. F., Gurtner. G. C., Longaker. M. T. Human Skin Wounds: A Major And Snowballing Threat To Public Health And The Economy. Wound Repair Regen, 2009, 17, 763–771.
21.Gurtner. G. C., Werner. S., Barrandon. Y., Longaker. M. T. Wound Repair And Regeneration. Nature, 2008, 453, 314–321.
22.Mogoşanu. G. D., Grumezescu. A. M. Natural And Synthetic Polymers For Wounds And Burns Dressing. International Journal of Pharmaceutics, 2014, 463, 127–136.
23.Laurienzo. P. Marine Polysaccharides In Pharmaceutical Applications: An Overview. Marine Drugs, 2010, 8.
24.Sezer. A. D., Hatipoglu. F., Cevher. E., Oğurtan. Z., Bas. A. L., Akbuğa. J. Chitosan Film Containing Fucoidan As A Wound Dressing For Dermal Burn Healing: Preparation And In Vitro/In Vivo Evaluation. American Association of Pharmaceutical Scientists, 2007, 8, E94–E101.
25.Murakami. K., Aoki, H., Nakamura, S., Nakamura. S., Takikawa. M., Hanzawa. M.; Kishimoto. S., Hattori. H., Tanaka. Y., Kiyosawa. T., Sato. Y., Ishihara. M. Hydrogel Blends Of Chitin/Chitosan, Fucoidan And Alginate As Healing-Impaired Wound Dressings. Biomaterials, 2010, 31, 83–90.
26.Liu, P., Zhang, Y., Ma, Y., Tan, S., Ren, B., Liu, S., Dai, H., & Xu, Z. Application Of Dental Pulp Stem Cells In Oral Maxillofacial Tissue Engineering. International Journal Of Medical Sciences, 2022, 19(2), 310–320.
27.Geetha Bai, R., Muthoosamy, K., Manickam, S., & Hilal-Alnaqbi, A. Graphene-Based 3D Scaffolds In Tissue Engineering: Fabrication, Applications, And Future Scope In Liver Tissue Engineering. International Journal Of Nanomedicine, 2019, 14, 5753–5783.
28.Jung, K., Covington, S., Sen, C. K., Januszyk, M., Kirsner, R. S., Gurtner, G. C., & Shah, N. H. Rapid Identification Of Slow Healing Wounds. Wound Repair And Regeneration : Official Publication Of The Wound Healing Society [And] The European Tissue Repair Society, 2016, 24(1), 181–188.
29.Tottoli, E. M., Dorati, R., Genta, I., Chiesa, E., Pisani, S., & Conti, B. Skin Wound Healing Process And New Emerging Technologies For Skin Wound Care And Regeneration. Pharmaceutics, 2020, 12(8), 735.
30.Guest, J. F., Fuller, G. W., & Vowden, P. Cohort Study Evaluating The Burden Of Wounds To The UK's National Health Service. BMJ Open, 2020, 10(12), E045253.
31.Hu, Y., Li, H., Lv, X., Xu, Y., Xie, Y., Yuwen, L., Song, Y., Li, S., Shao, J., & Yang, D. Stimuli-Responsive Therapeutic Systems For The Treatment Of Diabetic Infected Wounds. Nanoscale, 2022, 14(36), 12967–12983.
32.Fife, C. E., & Carter, M. J. Wound Care Outcomes And Associated Cost Among Patients Treated In US Outpatient Wound Centers: Data From The US Wound Registry. Wounds : A Compendium Of Clinical Research And Practice, 2012, 24(1), 10–17.
33.Nussbaum, S. R., Carter, M. J., Fife, C. E., Davanzo, J., Haught, R., Nusgart, M., & Cartwright, D. An Economic Evaluation Of The Impact, Cost, And Medicare Policy Implications Of Chronic Nonhealing Wounds. Value In Health : The Journal Of The International Society For Pharmacoeconomics And Outcomes Research, 2018, 21(1), 27–32.
34.Gould, L., Abadir, P., Brem, H., Carter, M., Conner-Kerr, T., Davidson, J., Dipietro, L., Falanga, V., Fife, C., Gardner, S., Grice, E., Harmon, J., Hazzard, W. R., High, K. P., Houghton, P., Jacobson, N., Kirsner, R. S., Kovacs, E. J., Margolis, D., Mcfarland Horne, F., … Schmader, K. Chronic Wound Repair And Healing In Older Adults: Current Status And Future Research. Wound Repair And Regeneration : Official Publication Of The Wound Healing Society [And] The European Tissue Repair Society, 2015, 23(1), 1–13.
35.Globenewswire,Advancedwoundcaremarketworthoverusd13billionby2024,Globalmarketinsights,Inc.,Https://Www.Globenewswire.Com/Fr/News-Release/2018/09/17/1571505/0/En/Advanced-Wound-Care-Market-Worthover-USD-13-Billion-By-2024-Global-Market-Insightsinc.Html,Accessed23nov2022.
36.Heyer, K., Augustin, M., Protz, K., Herberger, K., Spehr, C., & Rustenbach, S. J. Effectiveness Of Advanced Versus Conventional Wound Dressings On Healing Of Chronic Wounds: Systematic Review And Meta-Analysis. Dermatology (Basel, Switzerland), 2013, 226(2), 172–184.
37.Aswathy, S. H., Narendrakumar, U., & Manjubala, I. Commercial Hydrogels For Biomedical Applications. Heliyon, 2020, 6(4), E03719.
38.Nguyen, H. M., Ngoc Le, T. T., Nguyen, A. T., Thien Le, H. N., & Pham, T. T. Biomedical Materials For Wound Dressing: Recent Advances And Applications. RSC Advances, 2023, 13(8), 5509–5528.
39.Cha, C., Piraino, F., Khademhosseini, Ali., Microfabrication Technology In Tissue Engineering. Tissue Engineering, 2014, 283-310.
40.Leong, K. F., Cheah, C. M., & Chua, C. K. Solid Freeform Fabrication Of Three-Dimensional Scaffolds For Engineering Replacement Tissues And Organs. Biomaterials, 2003, 24(13), 2363–2378.
41.KUMAR, Alok, Et Al. Low Temperature Additive Manufacturing Of Three Dimensional Scaffolds For Bone-Tissue Engineering Applications: Processing Related Challenges And Property Assessment. Materials Science And Engineering: R: Reports, 2016, 103: 1-39.
42.Chen, Y. W., Shie, M. Y., Chang, W. C., & Shen, Y. F. Approximate Optimization Study Of Light Curing Waterborne Polyurethane Materials For The Construction Of 3D Printed Cytocompatible Cartilage Scaffolds. Materials (Basel, Switzerland), 2021, 14(22), 6804.
43.Han, L., Mapili, G., Chen, S., And Roy, K. Projection Microfabrication Of Three-Dimensional Scaffolds For Tissue Engineering. ASME. The Journal of Manufacturing Science and Engineering, 2008, 130(2), 021005.
44.Heller, C., Schwentenwein, M., Russmüller, G., Koch, T., Moser, D., Schopper, C., Varga, F., Stampfl, J., & Liska, R. Vinylcarbonates And Vinylcarbamates: Biocompatible Monomers For Radical Photopolymerization. Journal Of Polymer Science Part A: Polymer Chemistry, 2011, 49(3), 650–661.
45.Felzmann, R., Gruber, S., Mitteramskogler, G., Pastrama, M., Boccaccini, A. R., & Stampfl, J. Lithography-based additive manufacturing of customized bioceramic parts for medical applications. In A. R. Boccaccini (Ed.). Proceedings of the IASTED International Conference on Biomedical Engineering, 2013
46.維基百科組織工程學Https://Zh.Wikipedia.Org/Wiki/%E7%BB%84%E7%BB%87%E5%B7%A5%E7%A8%8B%E5%AD%A6#/Media/File:The_Steps_Of_Regenerative_Medicine..Jpg
47.列印常見技術: FDM Vs. SLA Vs. SLS Https://Www.Taiwanteama.Com.Tw/Data_903
48.膠原蛋白Https://Zh.Wikipedia.Org/Wiki/%E8%86%A0%E5%8E%9F%E8%9B%8B%E7%99%BD
49.褐藻糖膠Https://Zh.Wikipedia.Org/Wiki/%E8%A4%90%E8%97%BB%E9%86%A3%E8%86%A0
50.幾丁聚醣Https://Zh.Wikipedia.Org/Wiki/%E5%A3%B3%E8%81%9A%E7%B3%96
51.硫酸軟骨素Https://Zh.Wikipedia.Org/Wiki/%E7%A1%AB%E9%85%B8%E8%BD%AF%E9%AA%A8%E7%B4%A0
52.Elegoo Mars 3
Https://Www.Elegoo.Com/Products/Elegoo-Mars-3-Lcd-3d-Printer
53.TECAN - Infinite M200 Pro 光柵型多功能光譜儀Https://Www.Bio-Cando.Com.Tw/Mainlysale/836
54.場發射掃描式電子顯微鏡 (FE-SEM) Https://Www.Mse.Nchu.Edu.Tw/Zh_Tw/Equipment/Property10/%E5%A0%B4%E7%99%BC%E5%B0%84%E6%8E%83%E6%8F%8F%E5%BC%8F%E9%9B%BB%E5%AD%90%E9%A1%AF%E5%BE%AE%E9%8F%A1-FE-SEM-68837796