以鄰苯二酚與金屬離子螯合方式形成抗菌及抗污之表面塗層研究

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姓名

鄭筱彤(Hsiao-Tung Cheng) 查詢紙本館藏

畢業系所

生醫科學與工程學系

論文名稱

以鄰苯二酚與金屬離子螯合方式形成抗菌及抗污之表面塗層研究
(Development of Metal-Phenolic Networks for Antimicrobial and Antifouling Properties)

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摘要(中)

醫療器材裝置通常伴隨著蛋白質，細胞和細菌等大量非特異性吸附。這些問題最終會在醫療上引起不良的致病性，如血栓的形成以及生物材料相關的感染問題。在本研究中，我們利用酚團結構的親水性高分子與二價或三價鐵離子在鹼性溶液中形成複合物 (metal-phenolic complex network, MPN) ，發展出簡單且不受基板大小及化學組成的表面修飾方法，於各種表面進行改質，進而達到抗生物汙染的特性。此篇採用貽貝啟發的鄰苯二酚衍生物—多巴胺甲基丙烯酰胺 (dopamine methacrylamide, DMA)，並利用隨機聚合反應 (free radical polymerization) 將多巴胺甲基丙烯酰胺 (DMA) 與聚乙二醇甲基丙烯酸酯 (polyethylene glycol methacrylate, PEGMA) 形成聚乙二醇甲基丙烯酸酯-多巴胺甲基丙烯酰胺共聚物 (polyethylene glycol methacrylate-co-dopamine methacrylamide, PEGMA-co-DMA)。因鄰苯二酚的結構與二價及三價鐵離子皆能形成複合物 (MPN) ，將能修飾在多種基材表面之上。首先利用1H NMR與凝膠滲透層析儀確定高分子的結構與分子量。接著使用紫外-可見分光光度法計算PEGMA-co-DMA 與二價及三價鐵間的平衡常數。然後使用水接觸角、X射線光電子能譜及原子力顯微鏡 (atomic force microscopy, AFM) 了解表面修飾後的親水性質、表面元素組成及表面粗糙度。最後藉由表皮葡萄球菌及綠膿桿菌進行細菌貼附，再利用纖維母細胞做細胞貼附測試，比較不同價數的鐵離子與PEGMA-co-DMA修飾的薄膜，是否有不同抗生物汙染程度及殺菌的功效。本研究的最終目的是發展出一種新的修飾方法，可於各種基材表面進行改質進而達到抗生物汙染的功能，並期待應用於醫療器材上，以提升生物相容性與安全性。

摘要(英)

Medical devices are often accompanied by large amounts of non-specific adsorption of proteins, cells and bacteria. These problems will eventually cause poor medical pathogenicity, such as the formation of thrombosis and biomaterials associated infection. In this work, we report a facile strategy for preparation of surface-independent and low-fouling coating via coordination of polyphenol with metal ions in aqueous solution. This approach incorporates bio-inspired polymers which containing dopamine methacrylamide (DMA) and poly(ethylene glycol) methacrylate (PEGMA). The product was named polyethylene glycol methacrylate-co-dopamine methacrylamide (PEGMA-co-DMA) for fouling resistance. Herein, metal ions serve as crosslinking agents to react with catechol groups. Film formation was accomplished with the adsorption of the metal-phenolic network (MPN) on various substrates. Here we compared two different charge of metal ions: ferrous ion (Fe2+) and ferric ion (Fe3+). Polymer characterization was carried out with proton nuclear magnetic resonance (1H NMR) spectroscopy and gel permeation chromatography (GPC). The binding constant between iron ions and PEGMA-co-DMA was analyzed by ultraviolet–visible spectroscopy (UV-Vis). The surface hydration, surface elemental composition and the patterns of the modified substrates were confirmed by water contact angle measurements, x-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). For examining the antifouling properties, we immersed the modified substrates into the solutions containing bacteria or cells. Then the adsorbed bacteria or cell was quantified by fluorescence microscopy and cell imaging analysis. This approach provides a deep understanding of a facile way to prepare coating materials biofouling resistance, which can give great inspiration for the design and synthesis of bifunctional coating materials.

關鍵字(中)

★ 抗非特異性吸附
★ 多巴胺
★ 鄰苯二酚
★ 聚乙二醇
★ 金屬離子

關鍵字(英)

論文目次

中文摘要 v
Abstract vi
目錄 viii
圖目錄 xi
表目錄 xiv
簡寫對照表 xv
第一章文獻回顧 1
1-1 生物汙染 (Biofouling) 1
1-1-1 生物膜形成 (Biofilm growth) 1
1-2 抗生物汙染之塗層 (Antifouling coatings) 3
1-2-1 聚乙二醇材料 (PEG) 4
1-2-2 聚乙二醇材料 (PEG) 之應用 5
1-3 自由基聚合反應 (Radical polymerization) 9
1-4 鄰苯二酚衍生物 10
1-4-1 貽貝黏附蛋白 (MAPs) 11
1-4-2 多巴胺 (Dopamine) 12
1-4-3 鄰苯二酚衍生物之應用 13
1-4-4 金屬-酚團網絡 (MPN) 16
1-5 鐵離子殺菌 20
第二章研究目的 22
第三章材料與方法 23
3-1 實驗藥品 23
3-2 實驗設備 25
3-3 材料合成 26
3-3-1多巴胺甲基丙烯酰胺 (DMA) 26
3-3-2 親水性高分子— PEGMA-co-DMA 27
3-4 實驗方法 28
3-4-1 MPN抗汙塗層製備 28
3-4-2 高解析電子能譜儀 (XPS) 30
3-4-3 接觸角測量 30
3-4-4橢圓偏振儀厚度量測 30
3-4-5 UV-VIS吸收光譜分析 31
3-4-6 細胞毒性測試 (MTT) 31
3-4-7 原子力顯微鏡 (AFM) 32
3-4-8 凝膠滲透層析儀 (GPC) 32
3-4-9 細菌貼附實驗 33
3-4-10 細胞貼附實驗 33
第四章結果與討論 34
4-1 材料分析與鑑定 34
4-1-1 DMA之1H-NMR頻譜分析 34
4-1-2 DMA之ESI-MS高效能質譜儀分析 35
4-1-3 PEGMA-co-DMA之1H-NMR頻譜分析 36
4-1-4 PEGMA-co-DMA之GPC分析 37
4-1-5 PEGMA-co-DMA與鐵離子間之平衡常數量測 38
4-1-6 PEGMA-co-DMA材料之細胞毒性試驗 (MTT) 40
4-2 MPN之表面修飾 41
4-2-1 XPS表面元素分析 41
4-2-2 表面修飾厚度測量 45
4-2-3 水接觸角測量 47
4-2-4 AFM表面型態分析 48
4-2-5 酸鹼對於MPN表面之影響 49
4-2-6 MPN表面之抗細菌貼附測試 50
4-2-7 MPN表面之抗細胞貼附測試 53
4-2-8 無表面選擇之MPN抗沾黏修飾 55
4-3 比較不同比例高分子於MPN之表面修飾 57
4-3-1 抗細菌貼附測試 57
4-3-2 抗細胞貼附測試 59
第五章結論與未來展望 61
第六章參考文獻 63

參考文獻

1. Wisniewski, N. and M. Reichert, Methods for reducing biosensor membrane biofouling. Colloids and Surfaces B: Biointerfaces, 2000. 18(3): p. 197-219.
2. Donlan, R.M., Biofilm formation: a clinically relevant microbiological process. Clinical Infectious Diseases, 2001. 33(8): p. 1387-1392.
3. Harding, J.L. and M.M. Reynolds, Combating medical device fouling. Trends in biotechnology, 2014. 32(3): p. 140-146.
4. Mérian, T. and J.M. Goddard, Advances in nonfouling materials: perspectives for the food industry. Journal of agricultural and food chemistry, 2012. 60(12): p. 2943-2957.
5. Almeida, E., T.C. Diamantino, and O. de Sousa, Marine paints: the particular case of antifouling paints. Progress in Organic Coatings, 2007. 59(1): p. 2-20.
6. Anderson, J.M., Biological responses to materials. Annual review of materials research, 2001. 31(1): p. 81-110.
7. Amiji, M. and K. Park, Surface modification of polymeric biomaterials with poly (ethylene oxide), albumin, and heparin for reduced thrombogenicity. Journal of Biomaterials Science, Polymer Edition, 1993. 4(3): p. 217-234.
8. Dunne, W.M., Bacterial Adhesion: Seen Any Good Biofilms Lately? Clinical Microbiology Reviews, 2002. 15(2): p. 155-166.
9. Flemming, H.C. and J. Wingender, The biofilm matrix. Nat Rev Microbiol, 2010. 8(9): p. 623-33.
10. Costerton, J.W., et al., Bacterial biofilms in nature and disease. Annual Reviews in Microbiology, 1987. 41(1): p. 435-464.
11. Mah, T.-F.C. and G.A. O′Toole, Mechanisms of biofilm resistance to antimicrobial agents. Trends in microbiology, 2001. 9(1): p. 34-39.
12. Watnick, P. and R. Kolter, Biofilm, city of microbes. Journal of bacteriology, 2000. 182(10): p. 2675-2679.
13. Stoodley, P., et al., Biofilms as complex differentiated communities. Annu Rev Microbiol, 2002. 56: p. 187-209.
14. Salwiczek, M., et al., Emerging rules for effective antimicrobial coatings. Trends Biotechnol, 2014. 32(2): p. 82-90.
15. Zhong, J., et al., Coating morphology and surface composition of acrylic terpolymers with pendant catechol, OEG and perfluoroalkyl groups in varying ratio and the effect on protein adsorption. Colloids Surf B Biointerfaces, 2016. 140: p. 254-61.
16. Banerjee, I., R.C. Pangule, and R.S. Kane, Antifouling coatings: recent developments in the design of surfaces that prevent fouling by proteins, bacteria, and marine organisms. Adv Mater, 2011. 23(6): p. 690-718.
17. Herold, D.A., K. Keil, and D.E. Bruns, Oxidation of polyethylene glycols by alcohol dehydrogenase. Biochemical pharmacology, 1989. 38(1): p. 73-76.
18. Ryle, A., Behaviour of polyethylene glycol on dialysis and gel-filtration. Nature, 1965. 206(4990): p. 1256-1256.
19. Alcantar, N.A., E.S. Aydil, and J.N. Israelachvili, Polyethylene glycol-coated biocompatible surfaces. Journal of biomedical materials research, 2000. 51(3): p. 343-351.
20. Knop, K., et al., Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew Chem Int Ed Engl, 2010. 49(36): p. 6288-308.
21. Gonias, S.L., M. Einarsson, and S.V. Pizzo, Catabolic Pathways for Streptokinase, Plasmin, and Streptokinase Activator Complex in Mice: IN VIVO REACTION OF PLASMINOGEN ACTIVATOR WITH α2-MACROGLOBULIN. Journal of Clinical Investigation, 1982. 70(2): p. 412.
22. Beauchamp, C.O., et al., A new procedure for the synthesis of polyethylene glycol-protein adducts; effects on function, receptor recognition, and clearance of superoxide dismutase, lactoferrin, and α2-macroglobulin. Analytical biochemistry, 1983. 131(1): p. 25-33.
23. Hunter, C., D. Stevenson, and P. Chambers, Acute and short-term oral toxicity in rats of RD 025, a propylene glycol-ethylene oxide copolymer. Food and cosmetics toxicology, 1967. 5: p. 195-199.
24. Smyth, H.F., C.P. Carpenter, and C.S. Weil, The Chronic Oral Toxicology of thePolyethylene Glycols. Journal of the American Pharmaceutical Association (Scientific ed.), 1955. 44(1): p. 27-30.
25. Weiner, B., et al., Atropine attached to polyethylene glycols. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 1976. 11(6): p. 525-526.
26. Weiner, B.-Z. and A. Zilkha, Polyethylene glycol derivatives of procaine. Journal of medicinal chemistry, 1973. 16(5): p. 573-574.
27. Zalipsky, S., C. Gilon, and A. Zilkha, Attachment of drugs to polyethylene glycols. European Polymer Journal, 1983. 19(12): p. 1177-1183.
28. Mincheva, Z., N. Stambolieva, and I. Rashkov, Preparation and properties of di-, tri-and poly-(ethyleneglycol) esters of 2-benzoxazolon-3-yl-acetic acid. European polymer journal, 1994. 30(7): p. 761-765.
29. Yuan, S., et al., Lysozyme-coupled poly (poly (ethylene glycol) methacrylate)− stainless steel hybrids and their antifouling and antibacterial surfaces. Langmuir, 2011. 27(6): p. 2761-2774.
30. Rundqvist, J., J.H. Hoh, and D.B. Haviland, Poly (ethylene glycol) self-assembled monolayer island growth. Langmuir, 2005. 21(7): p. 2981-2987.
31. Zoulalian, V., et al., Functionalization of titanium oxide surfaces by means of poly (alkyl-phosphonates). The Journal of Physical Chemistry B, 2006. 110(51): p. 25603-25605.
32. Kohler, N., G.E. Fryxell, and M. Zhang, A bifunctional poly (ethylene glycol) silane immobilized on metallic oxide-based nanoparticles for conjugation with cell targeting agents. Journal of the American Chemical Society, 2004. 126(23): p. 7206-7211.
33. Nagaoka, S., et al., Polymers as biomaterials. SW Shalaby, AS Hoffman, BD Ratner and TA Horbett, Ed, 1984. 361.
34. Yuan, S., et al., Lysozyme-coupled poly(poly(ethylene glycol) methacrylate)-stainless steel hybrids and their antifouling and antibacterial surfaces. Langmuir, 2011. 27(6): p. 2761-74.
35. Choi, Y.S., et al., Mussel-inspired dopamine- and plant-based cardanol-containing polymer coatings for multifunctional filtration membranes. ACS Appl Mater Interfaces, 2014. 6(23): p. 21297-307.
36. Kumar, V.M.a.R., Living radical polymerization: A review. Journal of Scientific Research, 2012. 56: p. 141-176.
37. Faure, E., et al., Catechols as versatile platforms in polymer chemistry. Progress in Polymer Science, 2013. 38(1): p. 236-270.
38. Lee, H., N.F. Scherer, and P.B. Messersmith, Single-molecule mechanics of mussel adhesion. Proceedings of the National Academy of Sciences, 2006. 103(35): p. 12999-13003.
39. Ye, Q., F. Zhou, and W. Liu, Bioinspired catecholic chemistry for surface modification. Chemical Society Reviews, 2011. 40(7): p. 4244-4258.
40. TANZER, J.H.W.a.M.L., Polyphenolic Substance of Mytilus edulis: Novel Adhesive Containing L-Dopa and Hydroxyproline. Science, 1981. 212(4498): p. 1038-1040.
41. Waite, J.H., Nature′s underwater adhesive specialist. INTJ.ADHESlON AND ADHESIVES, 1987.
42. Lee, H., et al., Mussel-inspired surface chemistry for multifunctional coatings. science, 2007. 318(5849): p. 426-430.
43. Lee, H., B.P. Lee, and P.B. Messersmith, A reversible wet/dry adhesive inspired by mussels and geckos. Nature, 2007. 448(7151): p. 338-41.
44. Li, L., et al., Mussel-inspired antifouling coatings bearing polymer loops. Chem Commun (Camb), 2015. 51(87): p. 15780-3.
45. Xu, L.Q., et al., Layer-by-layer deposition of antifouling coatings on stainless steel via catechol-amine reaction. RSC Advances, 2014. 4(61): p. 32335.
46. GhavamiNejad, A., C.H. Park, and C.S. Kim, In Situ Synthesis of Antimicrobial Silver Nanoparticles within Antifouling Zwitterionic Hydrogels by Catecholic Redox Chemistry for Wound Healing Application. Biomacromolecules, 2016. 17(3): p. 1213-23.
47. Sanchez, C., H. Arribart, and M.M.G. Guille, Biomimetism and bioinspiration as tools for the design of innovative materials and systems. Nature materials, 2005. 4(4): p. 277-288.
48. Munch, E., et al., Tough, bio-inspired hybrid materials. Science, 2008. 322(5907): p. 1516-1520.
49. Barrett, J., Photo-oxidation of magnesium porphyrins and formation of protobiliviolin. Nature, 1967. 215(5102): p. 733-735.
50. Alben, J., et al., Cytochrome oxidase (a3) heme and copper observed by low-temperature Fourier transform infrared spectroscopy of the CO complex. Proceedings of the National Academy of Sciences, 1981. 78(1): p. 234-237.
51. Ejima, H., et al., One-step assembly of coordination complexes for versatile film and particle engineering. Science, 2013. 341(6142): p. 154-7.
52. Guo, J., et al., Engineering multifunctional capsules through the assembly of metal-phenolic networks. Angew Chem Int Ed Engl, 2014. 53(22): p. 5546-51.
53. Ju, Y., et al., Engineering low-fouling and pH-degradable capsules through the assembly of metal-phenolic networks. Biomacromolecules, 2015. 16(3): p. 807-14.
54. Rahim, M.A., et al., Metal-Phenolic Supramolecular Gelation. Angew Chem Int Ed Engl, 2016. 55(44): p. 13803-13807.
55. Lemire, J.A., J.J. Harrison, and R.J. Turner, Antimicrobial activity of metals: mechanisms, molecular targets and applications. Nat Rev Microbiol, 2013. 11(6): p. 371-84.
56. https://www.gr8potential.ca/news/free-radicals-nutritional-science.
57. Cortes-Cortes, P., et al., Magnetic behavior and antibacterial activity of iron (III) complexes. Journal of the Chilean Chemical Society, 2008. 53(2): p. 1527-1532.
58. http://xpssimplified.com/elements/silicon.php.
59. Kolaylı, S., et al., Does caffeine bind to metal ions? Food chemistry, 2004. 84(3): p. 383-388.
60. http://web1.knvs.tp.edu.tw/AFM/ch4.htm.
61. Xu, L.Q., et al., Antifouling Coatings of Catecholamine Copolymers on Stainless Steel. Industrial & Engineering Chemistry Research, 2015. 54(22): p. 5959-5967.
62. 薛敬和, 高分子設計. 2007.
63. Iffat, A., et al., Interaction of tannic acid with higher oxidation state of iron. JOURNAL-CHEMICAL SOCIETY OF PAKISTAN., 2004. 26: p. 151-156.
64. Theis, T.L. and P.C. Singer, Complexation of iron (II) by organic matter and its effect on iron (II) oxygenation. Environmental Science & Technology, 1974. 8(6): p. 569-573.
65. http://xpssimplified.com/elements/carbon.php.
66. Liu, C.Y. and C.J. Huang, Functionalization of Polydopamine via the Aza-Michael Reaction for Antimicrobial Interfaces. Langmuir, 2016. 32(19): p. 5019-28.
67. http://xpssimplified.com/elements/iron.php.
68. McIntyre, N. and D. Zetaruk, X-ray photoelectron spectroscopic studies of iron oxides. Analytical Chemistry, 1977. 49(11): p. 1521-1529.
69. http://xpssimplified.com/elements/nitrogen.php.
70. http://xpssimplified.com/elements/oxygen.php.
71. Luzinov, I., et al., Polystyrene layers grafted to epoxy-modified silicon surfaces. Macromolecules, 2000. 33(3): p. 1043-1048.
72. Melzak, K.A., et al., Chain Length and Grafting Density Dependent Enhancement in the Hydrolysis of Ester-Linked Polymer Brushes. Langmuir, 2015. 31(23): p. 6463-70.

指導教授

黃俊仁

審核日期

2017-7-26

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