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研究生: NUR HASANAH
NUR HASANAH
論文名稱: 具物理性質及生物相容性之TRIS-NVP-PEGMA-MAA 複合水凝膠於眼部之應用
Physical properties and biocompatibility of TRIS-NVP-PEGMA-MAA hydrogel for ophthalmic application2019
指導教授: 楊銘乾
MING-CHIEN YANG
口試委員: 劉定宇
TING-YU LIU
鄭詠馨
Yung-Hsin Cheng
學位類別: 碩士
Master
系所名稱: 工程學院 - 材料科學與工程系
Department of Materials Science and Engineering
論文出版年: 2019
畢業學年度: 107
語文別: 英文
論文頁數: 62
中文關鍵詞: TRISNVPPEGMAMAA矽水凝膠隱形眼鏡
外文關鍵詞: TRIS, NVP, PEGMA, MAA, silicone hydrogel, contact lens
相關次數: 點閱:447下載:22
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本論文經由光起始自由基聚合方法合成有機矽水凝膠,其單體為3- [三(三甲基甲矽烷氧基)甲矽烷基]丙基甲基丙烯酸酯(3-[tris(trimethylsiloxy)silyl]propyl methacrylate,TRIS),N-乙烯基吡咯烷酮(N-vinylpyrrolidone,NVP),甲基丙烯酸(methacrylic acid, MAA),以及聚(乙二醇)甲基丙烯酸酯(poly(ethylene glycol) methacrylate, PEGMA),交聯劑為乙二醇二甲基丙烯酸酯(ethylene glycol dimethacrylate, EGDMA),並以2-羥基-2-甲基苯丙酮(2-hydroxy-2-methylpropiophenone,PI-1173)為光起始劑,1-己醇(1-hexanol)作為溶劑。隨著PEGMA含量之增加,凝膠之合成率由70%逐步下降,平衡含水率(EWC)上升,拉伸強度及楊氏模數增加。由於PEGMA的抗垢特性,溶菌酶及人血清蛋白(HSA)的吸附量極低。此外,根據體外L929纖維母細胞之測定,證實這些矽水凝膠無細胞毒性。根據以上實驗結果,顯示TRIS-NVP-PEGMA-MAA共聚物由於高含水量,優異的光學透明度,低蛋白質吸收和生物相容性,成為隱形眼鏡的良好候選材料。


A silicone hydrogel was synthesized through photoinitiated free radical polymerization process using 3-[tris(trimethylsiloxy)silyl]propyl methacrylate (TRIS), N-vinylpyrrolidone (NVP), poly(ethylene glycol) methacrylate (PEGMA), methacrylic acid (MAA), ethylene glycol dimethacrylate (EGDMA) as cross-linker, 2-hydroxy-2-methylpropiophenone (PI-1173) as photoinitiator, and 1-hexanol as solvent. The gel fraction values are around 70 % and decrease with the increase of PEGMA content in the formulation due to the poor copolymerization of methacrylate functional monomers and NVP. Increase the content of PEGMA led the higher EWC. This is due to the changes in hydrophilic and hydrophobic monomer ratio in the formula. The tensile strength and Young’s modulus of hydrogels were higher with the addition of PEGMA. The adsorbed amount of lysozyme and HSA was very small due to nonfouling properties of hydrogels. In addition, these silicone hydrogels were confirmed non-cytotoxic according to an in-vitro L929 fibroblast assay. In summary, the results illustrated that TRIS-NVP-PEGMA-MAA copolymer was a good candidate for contact lens material due to the high water content, excellent optical transparency, low protein adsorption, and biocompatibility.

ABSTRACT i 摘要 ii ACKNOWLEDGEMENTS iii List of Content iv List of Figures vii List of Tables viii Chapter 1 Introduction 1 1.1 Background of study 1 1.2 Motivation and the objectives of study 2 Chapter 2 Literature Review 4 2.1 Hydrogels 4 2.2 Hydrogel classification 5 2.2.1 Chemical hydrogel 5 2.2.2 Physical Hydrogel 6 2.3 Cross-linking in hydrogel 6 2.4 Contact lens 8 2.5 Classification of Contact Lenses 9 2.5.1 Rigid contact lens 9 2.5.2 Soft Contact Lens 9 2.6 Properties of soft Contact lens material 10 2.6.1 Water content 11 2.6.2 Surface wetting 12 2.6.3 Oxygen permeability 13 2.6.4 Mechanical Properties 15 2.6.5 Surface roughness 16 2.6.6 Biocompatibility 16 2.7 Materials introduction 18 2.7.1 3-Methacryloyloxypropyltris(trimethylsilyloxy)silane(TRIS) 18 2.7.2 N-vinyl pyrrolidone (NVP) 19 2.7.3 Poly(ethylene glycol) methacrylate (PEGMA) 20 2.7.4 Methacrylic acid (MAA) 20 2.7.5 Ethylene glycol dimethacrylate (EGDMA) 21 Chapter 3 Materials and Methods 22 3.1 Experimental process 22 3.2 Experimental Principle 23 3.3 Materials 23 3.4 Analyzers 24 3.5 Experimental Steps 24 3.6 Physical Characterization Testing 25 3.6.1 Gel fraction 25 3.6.2 Equilibrium water content 25 3.6.3 Contact Angle Measurement 26 3.6.4 Light Transmittance 26 3.6.5 Mechanical strength 27 3.7 Biocompatibility testing 28 3.7.1 Protein Adsorption 28 3.7.2 Cell toxicity 29 Chapter 4 Result and discussion 31 4.1 Gel fraction 31 4.2 Equilibrium water content (EWC) 32 4.3 Contact Angle 34 4.4 Light Transmittance 35 4.5 Mechanical Strength 36 4.6 In vitro cytotoxicity 39 4.7 Protein adsorption 41 4.8 Preliminary comparison with conventional contact lens 42 References 47

1. Augst AD, Kong HJ, Mooney DJ. Alginate Hydrogels as Biomaterials. Macromolecular Bioscience. 2006;6(8):623-33.
2. El-Sherbiny IM, Yacoub MH. Hydrogel scaffolds for tissue engineering: Progress and challenges. Global Cardiology Science and Practice. 2013;2013(3):38.
3. Ragauskas AJ, Williams CK, Davison BH, Britovsek G, Cairney J, Eckert CA, et al. The Path Forward for Biofuels and Biomaterials. Science. 2006;311(5760):484.
4. Shoichet MS. Polymer Scaffolds for Biomaterials Applications. Macromolecules. 2010;43(2):581-91.
5. Zhao Z, Xie H, An S, Jiang Y. The Relationship between Oxygen Permeability and Phase Separation Morphology of the Multicomponent Silicone Hydrogels. The Journal of Physical Chemistry B. 2014;118(50):14640-7.
6. Wang J-j, Li X-s. Improved oxygen permeability and mechanical strength of silicone hydrogels with interpenetrating network structure. Chinese Journal of Polymer Science. 2010;28(6):849-57.
7. Samsom M, Korogiannaki M, Subbaraman LN, Sheardown H, Schmidt TA. Hyaluronan incorporation into model contact lens hydrogels as a built-in lubricant: Effect of hydrogel composition and proteoglycan 4 as a lubricant in solution. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2018;106(5):1818-26.
8. Lin C-H, Cho H-L, Yeh Y-H, Yang M-C. Improvement of the surface wettability of silicone hydrogel contact lenses via layer-by-layer self-assembly technique. Colloids and Surfaces B: Biointerfaces. 2015;136:735-43.
9. Lin M, Svitova T. Contact Lenses Wettability In Vitro: Effect of Surface-Active Ingredients2010. 440-447 p.
10. Goda T, Ishihara K. Soft contact lens biomaterials from bioinspired phospholipid polymers. Expert Review of Medical Devices. 2006;3(2):167-74.
11. Kirchhof S, Goepferich AM, Brandl FP. Hydrogels in ophthalmic applications. European Journal of Pharmaceutics and Biopharmaceutics. 2015;95:227-38.
12. Singh A, Li P, Beachley V, McDonnell P, Elisseeff JH. A hyaluronic acid-binding contact lens with enhanced water retention. Contact Lens and Anterior Eye. 2015;38(2):79-84.
13. Lira M, Santos L, Azeredo J, Yebra-Pimentel E, Real Oliveira ME. The effect of lens wear on refractive index of conventional hydrogel and silicone-hydrogel contact lenses: A comparative study2008. 89-94 p.
14. Xu C, Ruiyu H, Xie B, Ismail M, Yao C, Luan J, et al. Improved Protein Resistance of Silicone Hydrogels by Grafting Short Peptides for Ophthalmological Application2017.
15. Zhang H, Chiao M. Anti-fouling Coatings of Poly(dimethylsiloxane) Devices for Biological and Biomedical Applications. Journal of Medical and Biological Engineering. 2015;35(2):143-55.
16. Zhao Z-B, An S-S, Xie H-J, Han X-L, Wang F-H, Jiang Y. The Relationship between the Hydrophilicity and Surface Chemical Composition Microphase Separation Structure of Multicomponent Silicone Hydrogels. The Journal of Physical Chemistry B. 2015;119(30):9780-6.
17. Xu C, He R, Xie B, Ismail M, Yao C, Luan J, et al. Improved protein resistance of silicone hydrogels by grafting short peptides for ophthalmological application. International Journal of Polymeric Materials and Polymeric Biomaterials. 2017;66(12):618-25.
18. Jaya Maitra VKS. Cross-linking in Hydrogels - A Review. American Journal of Polymer Science. 2014;Vol. 4 No. 2:25-31.
19. Hoffman AS. Hydrogels for biomedical applications. Advanced Drug Delivery Reviews. 2012;64:18-23.
20. Kopeček J. Hydrogel biomaterials: A smart future? Biomaterials. 2007;28(34):5185-92.
21. Wichterle O, LÍM D. Hydrophilic Gels for Biological Use. Nature. 1960;185:117.
22. Chai Q, Jiao Y, Yu X. Hydrogels for Biomedical Applications: Their Characteristics and the Mechanisms behind Them. Gels. 2017;3(1):6.
23. Zhao Z-b, An S-s, Xie H-j, Jiang Y. Copolymerization and properties of multicomponent crosslinked hydrogels. Chinese Journal of Polymer Science. 2015;33(1):173-83.
24. Park S-E, Nho Y-C, Kim H-I. Preparation of poly(polyethylene glycol methacrylate-co-acrylic acid) hydrogels by radiation and their physical properties. Radiation Physics and Chemistry. 2004;69(3):221-7.
25. Caló E, Khutoryanskiy VV. Biomedical applications of hydrogels: A review of patents and commercial products. European Polymer Journal. 2015;65:252-67.
26. Xu J, Xue Y, Hu G, Lin T, Gou J, Yin T, et al. A comprehensive review on contact lens for ophthalmic drug delivery. Journal of Controlled Release. 2018;281:97-118.
27. Paradiso P, Chu V, Santos L, Serro AP, Colaço R, Saramago B. Effect of plasma treatment on the performance of two drug-loaded hydrogel formulations for therapeutic contact lenses. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2015;103(5):1059-68.
28. Chen J-S, Liu T-Y, Tsou H-M, Ting Y-S, Tseng Y-Q, Wang C-H. Biopolymer brushes grown on PDMS contact lenses by in situ atmospheric plasma-induced polymerization2017. 69 p.
29. Méijome JM, González ‐ Pérez, J. , Fernandes, P. R., Ferreira, D. P., Mollá, S. and Compañ, V. Silicone Hydrogels Materials for Contact Lens Applications. In Concise Encyclopedia of High Performance Silicones (eds A. Tiwari and M. D. Soucek). Wiley Online Library. 2014.
30. McMahon TT, Zadnik K. Twenty-five Years of Contact Lenses: The Impact on the Cornea and Ophthalmic Practice. Cornea. 2000;19(5):730-40.
31. Bhamra TS, Tighe BJ. Mechanical properties of contact lenses: The contribution of measurement techniques and clinical feedback to 50 years of materials development. Contact Lens and Anterior Eye. 2017;40(2):70-81.
32. Nicolson PC, Vogt J. Soft contact lens polymers: an evolution. Biomaterials. 2001;22(24):3273-83.
33. Jones L, May C, Nazar L, Simpson T. In vitro evaluation of the dehydration characteristics of silicone hydrogel and conventional hydrogel contact lens materials. Contact Lens and Anterior Eye. 2002;25(3):147-56.
34. Yuan Y, Lee TR. Contact Angle and Wetting Properties. In: Bracco G, Holst B, editors. Surface Science Techniques. Berlin, Heidelberg: Springer Berlin Heidelberg; 2013. p. 3-34.
35. Kim E, Saha M, Ehrmann K. Mechanical Properties of Contact Lens Materials. Eye Contact Lens. 2018;44 Suppl 2:S148-S56.
36. Naahidi S, Jafari M, Edalat F, Raymond K, Khademhosseini A, Chen P. Biocompatibility of engineered nanoparticles for drug delivery. Journal of Controlled Release. 2013;166(2):182-94.
37. Muratore LM, Heuts JPA, Davis TP. Synthesis of 3-[tris(trimethylsilyloxy)silyl]propyl methacrylate macromers using catalytic chain transfer polymerization: a kinetic and mechanistic study. Macromolecular Chemistry and Physics. 2000;201(9):985-94.
38. L.M. Muratore MLC, T.P. Davis. Determination of the propagation rate coefficient for 3-[tris(trimethylsilyloxy)silyl] propyl methacrylate by pulsed-laser polymerization. Polymer. 2000;41:1441–7.
39. Saricilar S, Robert Knott R, Barner-Kowollik C, Davis T, Heuts J. Reversible addition fragmentation chain transfer polymerization of 3-[tris(trimethylsilyloxy) silyl] propyl methacrylate2003. 5169-76 p.
40. Tranoudis I, Efron N. Water properties of soft contact lens materials. Cont Lens Anterior Eye. 2004;27(4):193-208.
41. López-Alemany A, Compañ V, F Refojo M. Porous structure of Purevision (TM) versus Focus (R) night & day (TM) and conventional hydrogel contact lenses2002. 319-25 p.
42. Balaraman M, PonnanEttiyappan J, Agarwal M. Role of N-vinyl-2-pyrrolidinone on the thermoresponsive behavior of PNIPAm hydrogel and its release kinetics using dye and vitamin-B12 as model drug2013.
43. Hwang JW, Noh SM, Kim B, Jung HW. Gelation and crosslinking characteristics of photopolymerized poly(ethylene glycol) hydrogels. Journal of Applied Polymer Science. 2015;132(22).
44. Dai X, Chen X, Yang L, Foster S, Coury AJ, Jozefiak TH. Free radical polymerization of poly(ethylene glycol) diacrylate macromers: Impact of macromer hydrophobicity and initiator chemistry on polymerization efficiency. Acta Biomaterialia. 2011;7(5):1965-72.
45. Cao Z, Sun X, Yeh C-K, Sun Y. Effects of Methacrylic Acid on Physical/Mechanical Properties and Biocompatibility of Urethane-Based Denture Biomaterials. Materials Sciences and Applications. 2011;Vol.02No.08:6.
46. Qu Z, Xu H, Gu H. Synthesis and Biomedical Applications of Poly((meth)acrylic acid) Brushes. ACS Applied Materials & Interfaces. 2015;7(27):14537-51.
47. Tarducci C, Schofield WCE, Badyal JPS, Brewer SA, Willis C. Synthesis of Cross-Linked Ethylene Glycol Dimethacrylate and Cyclic Methacrylic Anhydride Polymer Structures by Pulsed Plasma Deposition. Macromolecules. 2002;35(23):8724-7.
48. Zhao D, Jiao X, Zhang Y, An D, Shi X, Lu X, et al. Polymerization mechanism of poly(ethylene glycol dimethacrylate) fragrance nanocapsules. RSC Advances. 2015;5(116):96067-73.
49. Gang L, Ting W, Maofang H, Tianming G, Xin F. Effect of ethyleneglycol dimethacrylate crosslinker on the performance of core-double shell structure poly(vinyl acetate-butyl acrylate) emulsion. Journal of Applied Polymer Science. 2015;132(17).
50. Lin C-H, Yeh Y-H, Lin W-C, Yang M-C. Novel silicone hydrogel based on PDMS and PEGMA for contact lens application. Colloids and Surfaces B: Biointerfaces. 2014;123:986-94.
51. Matthew JE, Nazario YL, Roberts SC, Bhatia SR. Effect of mammalian cell culture medium on the gelation properties of Pluronic® F127. Biomaterials. 2002;23(23):4615-9.
52. Soltys-Robitaille CE, Ammon DM, Valint PL, Grobe Iii GL. The relationship between contact lens surface charge and in-vitro protein deposition levels. Biomaterials. 2001;22(24):3257-60.

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