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研究生:李培榕
研究生(外文):Pei-Rong Li
論文名稱:雙離子共聚物以光化學接枝抗汙塗層於熱塑型聚氨酯導管
論文名稱(外文):Surface Modification of Thermoplastic Polyurethane Catheter by Photografting Zwitterionic Copolymers
指導教授:黃俊仁黃俊仁引用關係
指導教授(外文):Chun-Jen Huang
學位類別:碩士
校院名稱:國立中央大學
系所名稱:生物醫學工程研究所
學門:工程學門
學類:生醫工程學類
論文出版年:2020
畢業學年度:108
語文別:中文
論文頁數:85
中文關鍵詞:雙離子材料2-甲基丙烯酰氧乙基磷酸膽鹼生醫塗層抗沾黏塗層熱塑型聚氨酯
外文關鍵詞:zwitterionic materials2-methacryloyloxyethyl phosphorylcholine (MPC)medical coatingsnon-specific adsorptionthermoplastic polyurethane
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熱塑型聚氨酯(Thermoplastic polyurethane, TPU)因具有良好的生物相容性與機械性質,成為生醫器材的重要材料,如:人工血管、透析幫浦、導管等,但是,導管使用容易引起尿道感染與血液感染。歸究其因,TPU 表面的疏水性質使細菌、蛋白容易貼附,讓醫材的使用效率降低、引發發炎反應及感染等問題,同時,放置導管對病人來說是相當不適與疼痛。
兩性雙離子材料磷脂酰膽鹼具有優異的生物相容性、潤滑與抗汙能力,能有效提高表面親水性質,並降低細菌與蛋白質等貼附,可作為醫療器材的抗汙塗層使用。本實驗嘗試開發一種在大氣環境中,透過浸塗與照射 UV 光源的方式,將兩性雙離子聚合物 2-甲基丙烯酰氧乙基磷酸膽鹼-甲基丙烯酸月桂酯 (poly(2-methacryloyloxyethyl phosphorylcholine-co-dodecyl methacrylate), P(MPC-DMA))以共價接枝上 TPU 導管。在吸收 UV 光源的輻射能量後,光引發劑 4-丙烯酰氧基二苯甲酮 (4-benzoylphenyl acrylate, BPA)被激發,會抓取聚合物及 TPU 導管
碳原子上的氫原子,協助雙離子材料 P(MPC-DMA) 與 TPU 導管共價交聯,得到親水潤滑的表面。第一部分我們使用核磁共振光譜儀 (nuclear magnetic resonance ,NMR) 鑑定高分子的化學結構與轉化率,以及使用全反射-傅立葉轉換紅外線光譜儀 (attenuated total reflection-Fourier-transform infrared spectroscopy, ATR-FTIR )來確認導管表面與雙離子材料 P(MPC-DMA) 的鍵結,利用摩擦力測試、抗蛋白
貼附測試、抗菌貼附測試,檢視改質後的 TPU 導管表面的抗汙潤滑特性,並與具潤滑效果的聚乙烯吡咯烷酮 (Poly(N-vinylpyrrolidone), PVP) 塗布導管比較。第二部分討論三種 P(MPC-DMA)不同分子比例的雙離子共聚物,在不同條件下的表面貼附動力學與粒徑大小關係、抗蛋白能力、溶解度及多種材料上的修飾效果差異。本論文,我們使用簡易操作且有效的改質方式,以雙離子聚合物 P(MPCDMA) 共價鍵結於 TPU 表面,使表面具有抗汙且潤滑的性能,並對表面修飾的機制提出見解,期許未來可以更進一步優化配方與製程技術,以滿足於更多的醫療器材應用。
Thermoplastic polyurethane (TPU) has been widely applied in various medical devices, such as artificial blood vessels, dialysis pumps and catheters, due to its good mechanical and biocompatible properties. However, bacterial infection occurs often in urinary and central venous catheters, which is attributed to the hydrophobic property of TPU, leading to non-specific adsorption of bacteria. Meanwhile, placement of catheters can be uncomfortable and painful for a patient. It has been found that zwitterionic phosphatidylcholine materials possess excellent biocompatible, lubricant and antifouling properties. In this study, we attempt to develop an efficient and facile way to graft zwitterionic polymers on TPU by dip coating and photoreaction in an ambient environment. Amphiphilic copolymers, poly(2-methacryloyloxyethyl phosphorylcholine-co-dodecyl methacrylate), P(MPC-DMA), were covalently grafted onto TPU substrate through photografting of the ketone structure in photoinitiator under UV irradiation. The chemical structures and conversion rate of as-prepared polymers were characterized by nuclear magnetic resonance (NMR) and attenuated total reflection-Fourier-transform infrared spectroscopy (ATR-FTIR). P(MPC-DMA) modified TPU tubes were examined by friction test, UV-Vis spectroscopy, anti-protein adhesion, antibacterial adhesion in comparison with poly(N-vinylpyrrolidone) (PVP) modified tubes. Additionally, we discussed the anti-fouling property and adsorption kinetics of P(MPC-DMA) copolymers with the different molecular ratios to correlate with their colloidal dimensions in solutions with an attempt to explore binding mechanism of polymers. Consequently, we demonstrated a facile and less footprint method to covalently modify P(MPC-DMA) polymeric coatings on TPU surfaces for good lubrication and antifouling capabilities. In the future works, we will dedicate to optimization of the coating process and formulation with an aim to meet the demanded requirements of medical applications.
中文摘要.................................................................................................................i
Abstract................................................................................................................ iii
致謝........................................................................................................................v
目錄.......................................................................................................................vi
圖目錄....................................................................................................................x
表目錄..................................................................................................................xii
化學品名詞簡稱................................................................................................ xiii
一、文獻回顧........................................................................................................1
1-1 生物汙染與醫材設備相關感染 (Device-Associated Infections, DAI)............ 1
1-2 熱塑型聚氨酯的應用與困境............................................................................... 2
1-3 抗菌塗層策略與上市產品回顧........................................................................... 3
1-4 親水塗層的發展性與現有產品........................................................................... 4
1-5 抗沾黏材料........................................................................................................... 5
1-5-1 聚乙二醇材料................................................................................................ 5
1-5-2 乙烯吡咯烷酮 (N-vinylpyrrolidone, NVP) .................................................. 6
1-5-3 雙離子材料.................................................................................................... 7
1-6 表面接枝與光化學接枝..................................................................................... 10
vii
二、研究目的......................................................................................................13
三、實驗藥品與實驗方法..................................................................................14
3-1 實驗藥品與設備................................................................................................. 14
3-1-1 藥品清單...................................................................................................... 14
3-1-2 設備清單...................................................................................................... 15
3-2 材料合成與材料置備......................................................................................... 17
3-2-1 Poly(2-methacryloyloxyethyl phosphorylcholine-co-dodecyl methacrylate),
P(MPC-DMA) 合成 .............................................................................................. 17
3-2-2 聚胺酯導管置備.......................................................................................... 17
3-2-3 鍍金薄片疏水性修飾.................................................................................. 17
3-2-4 玻璃疏水性修飾.......................................................................................... 18
3-2-5 瓊脂平板製備.............................................................................................. 18
3-3 實驗方法............................................................................................................. 19
3-3-1 Poly(2-methacryloyloxyethyl phosphorylcholine-co-dodecyl methacrylate),
P(MPC-DMA) 導管修飾 ...................................................................................... 19
3-3-2 衰減全反射傅立葉轉換紅外線光譜 (Attenuated total reflectance-fourier
transform infrared spectra,ATR-FTIR) 鑑定...................................................... 20
3-3-3 可見光光譜儀 (Ultraviolet–visible spectroscopy,UV-Vis)..................... 20
3-3-4 水下摩擦力測定.......................................................................................... 21
3-3-5 抗蛋白貼附測試.......................................................................................... 21
viii
3-3-6 抗細菌貼附測試.......................................................................................... 22
3-3-7 表面電漿共振抗汙測試.............................................................................. 22
3-3-8 奈米粒徑及介面電位量測儀 (Dynamic light scattering,DLS) .............. 23
3-3-9 水接觸角測定 (Contact angle meter)......................................................... 24
3-3-10 凝膠滲透色譜分析 (Gel Permeation Chromatography,GPC) .............. 24
3-3-11 統計學分析方法........................................................................................ 24
四、結果與討論..................................................................................................25
4-1 氧氣對表面修飾的影響..................................................................................... 25
4-2 除氧劑的選擇..................................................................................................... 28
4-3 Poly(2-methacryloyloxyethyl phosphorylcholine-co-dodecyl methacrylate),
P(MPC-DMA) 鑑定 (
1H NMR) ............................................................................... 31
4-4 Poly(2-methacryloyloxyethyl phosphorylcholine-co-dodecyl methacrylate),
P(MPC-DMA)不同合成比例對聚氨酯導管潤滑度的影響..................................... 32
4-5 Poly(2-methacryloyloxyethyl phosphorylcholine-co-dodecyl methacrylate),
P(MPC-DMA)不同合成比例於 SPR 的抗蛋白貼附效果 ....................................... 34
4-6 空氣烘乾對導管修飾的影響............................................................................. 37
4-7 導管表面 BPA 濃度的重要性 ........................................................................... 38
4-8 輻射波長對 BPA 的使用效率與導管穩定性的影響 ....................................... 40
4-9 導管上聚合物鑑定 (FTIR)................................................................................ 44
4-10 導管於水下的潤滑度測試................................................................................ 46
ix
4-11 導管表面蛋白貼附測試.................................................................................... 48
4-12 導管抗細菌貼附測試........................................................................................ 49
4-13 MD37、MD55、MD73 不同濃度的 SPR 吸附脫附測試............................... 51
4-14 MD37、MD55、MD73 於不同溶劑比例的溶解度........................................ 53
4-15 MD37、MD55、MD73 於 0.5 wt%濃度之 SPR 抗蛋白貼附測試 ................ 54
4-16 MD37、MD55、MD73 修飾於 OTS、PDMS、PET 之接觸角測試 ............ 55
五、結論..............................................................................................................58
六、未來展望......................................................................................................59
七、參考文獻......................................................................................................60
Ortega-Pena, S. and E. Hernandez-Zamora, Microbial biofilms and their
impact on medical areas: physiopathology, diagnosis and treatment. Bol Med
Hosp Infant Mex, 2018. 75(2): p. 79-88.
2. Bixler, G.D. and B. Bhushan, Biofouling: lessons from nature. Philos Trans A
Math Phys Eng Sci, 2012. 370(1967): p. 2381-2417.
3. Darouiche, Rabih O., Device-Associated Infections: A Macroproblem that
Starts with Microadherence. Clinical infectious diseases : an official
publication of the Infectious Diseases Society of America, 2001. 33: p. 1567-
1572.
4. Magill, S.S., et al., Multistate point-prevalence survey of health careassociated infections. N Engl J Med, 2014. 370(13): p. 1198-1208.
5. Francolini, I. and A. Piozzi, Antimicrobial polyurethanes for intravascular
medical devices, in Advances in Polyurethane Biomaterials. 2016. p. 349-385.
6. Xie, D., L. Howard, and R. Almousa, Surface modification of polyurethane with
a hydrophilic, antibacterial polymer for improved antifouling and antibacterial
function. J Biomater Appl, 2018. 33(3): p. 340-351.
7. Osinaga, P.W., et al., Zinc sulfate addition to glass-ionomer-based cements:
influence on physical and antibacterial properties, zinc and fluoride release.
Dent Mater, 2003. 19(3): p. 212-217.
8. Roohpour, N., et al., Development of bacterially resistant polyurethane for
coating medical devices. Biomed Mater, 2012. 7(1): p. 015007-015007.
61
9. Yuan, S., et al., Infection-resistant styrenic thermoplastic elastomers that can
switch from bactericidal capability to anti-adhesion. Journal of Materials
Chemistry B, 2016. 4(6): p. 1081-1089.
10. Guan, J., et al., Functionalizing of polyurethane surfaces by photografting with
hydrophilic monomers. Journal of Applied Polymer Science, 2000. 77: p. 2505-
2512.
11. Jansen, B., L.P. Goodman, and D. Ruiten, Bacterial adherence to hydrophilic
polymer–coated polyurethane stents. Gastrointestinal Endoscopy, 1993.
39(5): p. 670-673.
12. Lee, J.H., H.B. Lee, and J.D. Andrade, Blood compatibility of polyethylene
oxide surfaces. Progress in Polymer Science, 1995. 20(6): p. 1043-1079.
13. Feng, W., et al., Protein resistant surfaces: comparison of acrylate graft
polymers bearing oligo-ethylene oxide and phosphorylcholine side chains.
Biointerphases, 2006. 1(1): p. 50-60.
14. Zhang, H. and M. Chiao, Anti-fouling Coatings of Poly(dimethylsiloxane)
Devices for Biological and Biomedical Applications. J Med Biol Eng, 2015.
35(2): p. 143-155.
15. Zhang, H., et al., Controllable properties and microstructure of hydrogels
based on crosslinked poly(ethylene glycol) diacrylates with different molecular
weights. Journal of Applied Polymer Science, 2011. 121(1): p. 531-540.
16. Dalsin, J.L., et al., Protein Resistance of Titanium Oxide Surfaces Modified by
Biologically Inspired mPEG−DOPA. Langmuir, 2005. 21(2): p. 640-646.
62
17. Lee, S. and J. Vörös, An Aqueous-Based Surface Modification of
Poly(dimethylsiloxane) with Poly(ethylene glycol) to Prevent Biofouling.
Langmuir, 2005. 21(25): p. 11957-11962.
18. Jon, S., et al., Construction of Nonbiofouling Surfaces by Polymeric SelfAssembled Monolayers. Langmuir, 2003. 19(24): p. 9989-9993.
19. Gombotz, W.R., et al., Protein adsorption to poly(ethylene oxide) surfaces. J
Biomed Mater Res, 1991. 25(12): p. 1547-1562.
20. Ding, X., et al., Antibacterial and antifouling catheter coatings using surface
grafted PEG-b-cationic polycarbonate diblock copolymers. Biomaterials, 2012.
33(28): p. 6593-6603.
21. Nejadnik, M.R., et al., Bacterial adhesion and growth on a polymer brushcoating. Biomaterials, 2008. 29(30): p. 4117-4121.
22. Mizrahi, B., et al., Long-lasting antifouling coating from multi-armed polymer.
Langmuir, 2013. 29(32): p. 10087-10094.
23. Perrino, C., et al., A Biomimetic Alternative to Poly(ethylene glycol) as an
Antifouling Coating: Resistance to Nonspecific Protein Adsorption of Poly(llysine)-graft-dextran. Langmuir, 2008. 24(16): p. 8850-8856.
24. Leckband, D., S. Sheth, and A. Halperin, Grafted poly(ethylene oxide) brushes
as nonfouling surface coatings. Journal of Biomaterials Science, Polymer
Edition, 1999. 10(10): p. 1125-1147.
25. Aguirre-Soto, A., et al., On the role of N-vinylpyrrolidone in the aqueous
radical-initiated copolymerization with PEGDA mediated by eosin Y in the
presence of O2. Polymer Chemistry, 2019. 10(8): p. 926-937.
63
26. Husár, B., et al., The formulator's guide to anti-oxygen inhibition additives.
Progress in Organic Coatings, 2014. 77(11): p. 1789-1798.
27. Lorenz, D.H., J.L. Azorlosa, and R.S. Tu, N-vinyl-2-pyrrolidone as a reactive
diluent in radiation curing. Radiation Physics and Chemistry (1977), 1977.
9(4): p. 843-849.
28. Wu, Z., et al., Poly(N-vinylpyrrolidone)-modified poly(dimethylsiloxane)
elastomers as anti-biofouling materials. Colloids Surf B Biointerfaces, 2012.
96: p. 37-43.
29. Kim, S., Y. Jeong, and S.M. Kang, Marine Antifouling Surface Coatings Using
Tannic Acid and Poly(N-vinylpyrrolidone). Bulletin of the Korean Chemical
Society, 2016. 37(3): p. 404-407.
30. Jiang, J., et al., Antifouling and Antimicrobial Polymer Membranes Based on
Bioinspired Polydopamine and Strong Hydrogen-Bonded Poly(N-vinyl
pyrrolidone). ACS Applied Materials & Interfaces, 2013. 5(24): p. 12895-
12904.
31. Le, T.-N., A.-N. Au-Duong, and C.-K. Lee, Facile coating on microporous
polypropylene membrane for antifouling microfiltration using comb-shaped
poly(N-vinylpyrrolidone) with multivalent catechol. Journal of Membrane
Science, 2019. 574: p. 164-173.
32. Wang, X., et al., Integrated antifouling and bactericidal polymer membranes
through bioinspired polydopamine/poly(N-vinyl pyrrolidone) coating. Applied
Surface Science, 2016. 375: p. 9-18.
33. Francois, P., et al., Physical and biological effects of a surface coating
procedure on polyurethane catheters. Biomaterials, 1996. 17(7): p. 667-678.
64
34. Zhang, R., et al., Antifouling membranes for sustainable water purification:
Strategies and mechanisms. Chem. Soc. Rev., 2016. 45 : p. 5888-5294.
35. Chen, S., et al., Surface hydration: Principles and applications toward lowfouling/nonfouling biomaterials. Polymer, 2010. 51(23): p. 5283-5293.
36. Lee, S.Y., et al., Sulfobetaine methacrylate hydrogel-coated anti-fouling
surfaces for implantable biomedical devices. Biomater Res, 2018. 22: p. 1-7.
37. Yang, X., et al., Preparation of antibacterial poly(sulfobetaine methacrylate)
grafted on poly(vinyl alcohol)-formaldehyde sponges and their properties.
Journal of Applied Polymer Science, 2019. 136(6) : p. 47047-47047.
38. Zhang, Z., S. Chen, and S. Jiang, Dual-Functional Biomimetic Materials: 
Nonfouling Poly(carboxybetaine) with Active Functional Groups for Protein
Immobilization. Biomacromolecules, 2006. 7(12): p. 3311-3315.
39. Bretscher, M.S. and M.C. Raff, Mammalian plasma membranes. Nature,
1975. 258(5530): p. 43-49.
40. Ishihara, K., et al., The unique hydration state of poly(2-methacryloyloxyethyl
phosphorylcholine). J Biomater Sci Polym Ed, 2017. 28(10-12): p. 884-899.
41. Zwaal, R.F.A., P. Comfurius, and L.L.M. Van Deenen, Membrane asymmetry
and blood coagulation. Nature, 1977. 268(5618): p. 358-360.
42. Ishihara, K., et al., Hemocompatibility of human whole blood on polymers
with a phospholipid polar group and its mechanism. Journal of Biomedical
Materials Research, 1992. 26(12): p. 1543-1552.
43. Ishihara, K., et al., Reduced thrombogenicity of polymers having phospholipid
polar groups. Journal of Biomedical Materials Research, 1990. 24(8): p. 1069-
1077.
65
44. Ishihara, K., et al., Protein adsorption from human plasma is reduced on
phospholipid polymers. Journal of Biomedical Materials Research, 1991.
25(11): p. 1397-1407.
45. Lewis, A.L., Phosphorylcholine-based polymers and their use in the prevention
of biofouling. Colloids and Surfaces B: Biointerfaces, 2000. 18(3): p. 261-275.
46. Kyomoto, M., T. Moro, and K. Ishihara, 20 - Phospholipid Polymer Grafted
Highly Cross-Linked UHMWPE, in UHMWPE Biomaterials Handbook (Third
Edition), S.M. Kurtz, Editor. 2016, William Andrew Publishing: Oxford. p. 352-
368.
47. Ngo, B.K.D. and M.A. Grunlan, Protein Resistant Polymeric Biomaterials. ACS
Macro Letters, 2017. 6(9): p. 992-1000.
48. Minko, S., Grafting on Solid Surfaces: “Grafting to” and “Grafting from”
Methods, in Polymer Surfaces and Interfaces: Characterization, Modification
and Applications, M. Stamm, Editor. 2008, Springer Berlin Heidelberg: Berlin,
Heidelberg. p. 215-234.
49. Schneider, M.H., Y. Tran, and P. Tabeling, Benzophenone absorption and
diffusion in poly(dimethylsiloxane) and its role in graft photo-polymerization
for surface modification. Langmuir, 2011. 27(3): p. 1232-1240.
50. De Smet, N., M. Rymarczyk-Machal, and E. Schacht, Modification of
polydimethylsiloxane surfaces using benzophenone. J Biomater Sci Polym Ed,
2009. 20(14): p. 2039-2053.
51. Goda, T., et al., Photografting of 2-methacryloyloxyethyl phosphorylcholine
from polydimethylsiloxane: tunable protein repellency and lubrication
property. Colloids Surf B Biointerfaces, 2008. 63(1): p. 64-72.
66
52. Goda, T., et al., Biomimetic phosphorylcholine polymer grafting from
polydimethylsiloxane surface using photo-induced polymerization.
Biomaterials, 2006. 27(30): p. 5151-5160.
53. Leigh, B.L., et al., Antifouling Photograftable Zwitterionic Coatings on PDMS
Substrates. Langmuir, 2019. 35(5): p. 1100-1110.
54. Yu, L., et al., High-Antifouling Polymer Brush Coatings on Nonpolar Surfaces
via Adsorption-Cross-Linking Strategy. ACS Appl Mater Interfaces, 2017.
9(51): p. 44281-44292.
55. Riga, E.K., et al., On the Limits of Benzophenone as Cross-Linker for SurfaceAttached Polymer Hydrogels. Polymers (Basel), 2017. 9(12). p. 685-686.
56. Liu, Q., et al., Covalent Grafting of Antifouling Phosphorylcholine-Based
Copolymers with Antimicrobial Nitric Oxide Releasing Polymers to Enhance
Infection-Resistant Properties of Medical Device Coatings. Langmuir, 2017.
33(45): p. 13105-13113.
57. Lin, X., K. Fukazawa, and K. Ishihara, Photoreactive Polymers Bearing a
Zwitterionic Phosphorylcholine Group for Surface Modification of
Biomaterials. ACS Appl Mater Interfaces, 2015. 7(31): p. 17489-17498.
58. Koc, J., et al., Low-Fouling Thin Hydrogel Coatings Made of Photo-CrossLinked Polyzwitterions. Langmuir, 2019. 35(5): p. 1552-1562.
59. Ligon, S.C., et al., Strategies to reduce oxygen inhibition in photoinduced
polymerization. Chem Rev, 2014. 114(1): p. 557-589.
60. Ohshio, M., K. Ishihara, and S.I. Yusa, Self-Association Behavior of Cell
Membrane-Inspired Amphiphilic Random Copolymers in Water. Polymers
(Basel), 2019. 11(2) : p. 327-327.
67
61. Yanase, Y., et al., Surface Plasmon Resonance for Cell-Based Clinical
Diagnosis. Sensors (Basel, Switzerland), 2014. 14: p. 1823-1835.
62. D’Amelia, R., et al., Quantitative Analysis of Copolymers and Blends of
Polyvinyl Acetate (PVAc) Using Fourier Transform Infrared Spectroscopy (FTIR)
and Elemental Analysis (EA). World Journal of Chemical Education, 2016. 4: p.
25-31.
63. Liu, Y., et al., Durable modification of segmented polyurethane for elastic
blood-contacting devices by graft-type 2-methacryloyloxyethyl
phosphorylcholine copolymer. Journal of biomaterials science. Polymer
edition, 2014. 25: p. 1514-1529
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