臺灣博碩士論文加值系統

目錄
中文摘要 i
Abstract ii
致謝iv
圖目錄viii
表目錄xii
第一章緒論 1
1.1. 載藥型隱形眼鏡 1
1.1.1乾眼症 1
1.1.2乾眼症常見療法 4
1.1.3眼藥水的缺點及不便 7
1.1.4含眼藥物之隱形眼鏡 9
1.2人工血管 12
1.2.1簡介 12
1.2.2 3D列印與大量客製化技術之比較 13
1.2.3 3D列印技術及其分類 15
1.2.4自由基光聚合 20
1.2.5動靜脈人工血管 21
第二章具大分子藥物隱形眼鏡之藥物釋放特性 23
2.1前言 23
2.2藥品與儀器 25
2.2.1實驗藥品 25
2.2.2生物實驗所需之細胞及試劑 26
2.2.3實驗所需儀器 27
2.3實驗方法 28
2.3.1隱形眼鏡的製備 28
2.3.2藥物釋放實驗 28
2.3.3 UV-Vis 可見光分譜儀析 29
2.3.4溶脹測試(Swelling test) 29
2.3.5含水量測試(Equilibrium water content) 30
2.3.6水分散失測試(Water retention test) 30
2.3.7掃描式電子顯微鏡分析(Scanning Electron Microscope, SEM) 31
2.3.8隱形眼鏡透明度測試(Transparency test) 31
2.3.9細胞培養 32
2.3.10細胞毒性測試(MTT assay) 32
2.3.11接觸角樣品製備 33
2.3.12 Bradford protein assay 33
2.4結果與討論 34
2.4.1標準曲線定量 34
2.4.2去離子水與甲基丙烯酸羥乙酯(HEMA)比例對於載藥型隱形眼鏡的影響 35
2.4.3不同分子量的玻尿酸(HA)對於釋放的影響 37
2.4.4 [2-(甲基丙烯酰基氧基)乙基]二甲基-(3-磺酸丙基)氫氧化銨 (SBMA)對隱形眼鏡的影響 40
2.4.5 甲基丙烯酸的添加對於隱形眼鏡的影響 44
2.4.6 二甲基丙烯酸乙二醇酯的添加對隱形眼鏡的影響 46
2.4.7（2,4,6-三甲基苯甲酰基）二苯基氧化膦的添加對於隱形眼鏡的影響 48
2.4.8 SEM觀察隱形眼鏡的表面結構 50
2.4.9生物毒性測試 54
2.4.10隱形眼鏡之優化配方及其性質 56
2.5結論 61
第三章 人工血管 62
3.1前言 62
3.2藥品與器材 64
3.2.1 3D列印所需之藥品 64
3.2.2各藥品名稱及縮寫 65
3.2.3生物實驗所需之細胞及試劑 66
3.2.4實驗所需之儀器設備 66
3.3實驗步驟 68
3.3.1 PEGDMA2000 及PEGDMA6000的合成 68
3.3.2 3D列印機台操作 69
3.3.4 3D列印墨水配製 70
3.3.5 3D列印機台操作 70
3.3.6 3D列印材料 70
3.3.7材料後處理 73
3.3.8微拉力試驗測試 73
3.3.8穿針微拉力試驗測試 74
3.3.9溶脹實驗 74
3.3.10透明度測試 75
3.3.11流水實驗 75
3.3.12掃描式電子顯微鏡分析(Scanning Electron Microscope, SEM) 75
3.3.13細胞培養 76
3.3.14細胞毒性測試(MTT assay) 76
3.3.15抗沾黏實驗 77
3.4結果與討論 78
3.4.1不同配方之材料的微拉力測試 78
3.4.2穿針實驗微拉力測試 94
3.4.3材料彈力恢復測試 97
3.4.4材料穿透度 99
3.4.5材料毒性測試 100
3.4.6血管之機械性質基本鑑定 101
3.4.7血管之穿針實驗 102
3.4.8 SEM觀察材料的表面結構 103
3.4.9抗細胞沾黏測試 104
3.5總結 109
第四章附錄 110
第四章文獻參考 111

[1] J. L. Gayton, "Etiology, prevalence, and treatment of dry eye disease," Clinical ophthalmology (Auckland, NZ), vol. 3, p. 405, 2009.
[2] P. D. O’Brien and L. M. Collum, "Dry eye: diagnosis and current treatment strategies," Current allergy and asthma reports, vol. 4, no. 4, pp. 314-319, 2004.
[3] D. Definition, "classification. The definition and classification of dry eye disease: Report of the Definition and Classification Subcommittee of International Dry Eye Workshop," Ocul Surf, vol. 5, no. 2, pp. 75-92, 2007.
[4] S. E. Moss, R. Klein, and B. E. Klein, "Prevalence of and risk factors for dry eye syndrome," Archives of ophthalmology, vol. 118, no. 9, pp. 1264-1268, 2000.
[5] P.-Y. Lin, S.-Y. Tsai, C.-Y. Cheng, J.-H. Liu, P. Chou, and W.-M. Hsu, "Prevalence of dry eye among an elderly Chinese population in Taiwan: the Shihpai Eye Study," Ophthalmology, vol. 110, no. 6, pp. 1096-1101, 2003.
[6] D. A. Schaumberg, D. A. Sullivan, and M. R. Dana, "Epidemiology of dry eye syndrome," in Lacrimal Gland, Tear Film, and Dry Eye Syndromes 3: Springer, 2002, pp. 989-998.
[7] A. Lee et al., "Prevalence and risk factors associated with dry eye symptoms: a population based study in Indonesia," British Journal of Ophthalmology, vol. 86, no. 12, pp. 1347-1351, 2002.
[8] F. A. Maulvi, T. G. Soni, and D. O. Shah, "Extended release of hyaluronic acid from hydrogel contact lenses for dry eye syndrome," Journal of Biomaterials Science, Polymer Edition, vol. 26, no. 15, pp. 1035-1050, 2015.
[9] G. Uncu, R. Avci, Y. Uncu, C. Kaymaz, and O. Develioğlu, "The effects of different hormone replacement therapy regimens on tear function, intraocular pressure and lens opacity," Gynecological Endocrinology, vol. 22, no. 9, pp. 501-505, 2006.
[10] N. A. McNamara, K. A. Polse, R. J. Brand, A. D. Graham, J. S. Chan, and C. D. McKenney, "Tear mixing under a soft contact lens: effects of lens diameter," American journal of ophthalmology, vol. 127, no. 6, pp. 659-665, 1999.
[11] J. A. Smith et al., "Dry eye signs and symptoms in women with premature ovarian failure," Archives of Ophthalmology, vol. 122, no. 2, pp. 151-156, 2004.
[12] K. Tsubota et al., "New perspectives on dry eye definition and diagnosis: a consensus report by the Asia Dry Eye Society," The ocular surface, vol. 15, no. 1, pp. 65-76, 2017.
[13] S. Mishima, A. Gasset, S. Klyce, and J. Baum, "Determination of tear volume and tear flow," Investigative Ophthalmology & Visual Science, vol. 5, no. 3, pp. 264-276, 1966.
[14] M. B. Abelson, G. W. Ousler, L. A. Nally, D. Welch, and K. Krenzer, "Alternative reference values for tear film break up time in normal and dry eye populations," in Lacrimal Gland, Tear Film, and Dry Eye Syndromes 3: Springer, 2002, pp. 1121-1125.
[15] M. Fagnola, M. P. Pagani, S. Maffioletti, S. Tavazzi, and A. Papagni, "Hyaluronic acid in hydrophilic contact lenses: spectroscopic investigation of the content and release in solution," Contact Lens and Anterior Eye, vol. 32, no. 3, pp. 108-112, 2009.
[16] R. Gaudana, H. K. Ananthula, A. Parenky, and A. K. Mitra, "Ocular drug delivery," The AAPS journal, vol. 12, no. 3, pp. 348-360, 2010.
[17] J. W. Shell, "Pharmacokinetics of topically applied ophthalmic drugs," Survey of ophthalmology, vol. 26, no. 4, pp. 207-218, 1982.
[18] H. Zhu and A. Chauhan, "A mathematical model for ocular tear and solute balance," Current eye research, vol. 30, no. 10, pp. 841-854, 2005.
[19] M. A. Watsky, M. M. Jablonski, and H. F. Edelhauser, "Comparison of conjunctival and corneal surface areas in rabbit and human," Current eye research, vol. 7, no. 5, pp. 483-486, 1988.
[20] K.-H. Hsu, S. Gause, and A. Chauhan, "Review of ophthalmic drug delivery by contact lenses," Journal of Drug Delivery Science and Technology, vol. 24, no. 2, pp. 123-135, 2014.
[21] J. Dart, "Corneal toxicity: the epithelium and stroma in iatrogenic and factitious disease," Eye, vol. 17, no. 8, p. 886, 2003.
[22] J. Brown, M. McGeown, B. Conway, and C. Hill, "Chronic renal failure associated with topical application of paraphenylenediamine," British medical journal (Clinical research ed.), vol. 294, no. 6565, p. 155, 1987.
[23] A. Guzman-Aranguez, B. Fonseca, G. Carracedo, A. Martin-Gil, A. Martinez-Aguila, and J. Pintor, "Dry eye treatment based on contact lens drug delivery: a review," Eye & Contact Lens: Science & Clinical Practice, vol. 42, no. 5, pp. 280-288, 2016.
[24] C. White, A. Tieppo, and M. Byrne, "Controlled drug release from contact lenses: a comprehensive review from 1965-present," Journal of drug delivery science and technology, vol. 21, no. 5, pp. 369-384, 2011.
[25] Y. Kapoor, J. C. Thomas, G. Tan, V. T. John, and A. Chauhan, "Surfactant-laden soft contact lenses for extended delivery of ophthalmic drugs," Biomaterials, vol. 30, no. 5, pp. 867-878, 2009.
[26] M. E. Byrne, K. Park, and N. A. Peppas, "Molecular imprinting within hydrogels," Advanced drug delivery reviews, vol. 54, no. 1, pp. 149-161, 2002.
[27] X. Hu et al., "Hydrogel contact lens for extended delivery of ophthalmic drugs," International Journal of Polymer Science, vol. 2011, 2011.
[28] Y.-K. Son, Y. P. Jung, J.-H. Kim, and D. J. Chung, "Preparation and properties of PEG-modified PHEMA hydrogel and the morphological effect," Macromolecular research, vol. 14, no. 3, pp. 394-399, 2006.
[29] B. C. Gross, J. L. Erkal, S. Y. Lockwood, C. Chen, and D. M. Spence, "Evaluation of 3D printing and its potential impact on biotechnology and the chemical sciences," ed: ACS Publications, 2014.
[30] S.-J. Yoo et al., "3D printing in medicine of congenital heart diseases," 3D printing in medicine, vol. 2, no. 1, p. 3, 2015.
[31] H. N. Chia and B. M. Wu, "Recent advances in 3D printing of biomaterials," Journal of biological engineering, vol. 9, no. 1, p. 4, 2015.
[32] B. Berman, "3-D printing: The new industrial revolution," Business horizons, vol. 55, no. 2, pp. 155-162, 2012.
[33] J. W. Stansbury and M. J. Idacavage, "3D printing with polymers: Challenges among expanding options and opportunities," Dental Materials, vol. 32, no. 1, pp. 54-64, 2016.
[34] J. Jakubiak et al., "Camphorquinone–amines photoinitating systems for the initiation of free radical polymerization," Polymer, vol. 44, no. 18, pp. 5219-5226, 2003.
[35] Z. Ji et al., "3D Printing of Photocuring Elastomers with Excellent Mechanical Strength and Resilience," Macromolecular rapid communications, vol. 40, no. 8, p. 1800873, 2019.
[36] G. Donati et al., "PTFE grafts versus tunneled cuffed catheters for hemodialysis: which is the second choice when arteriovenous fistula is not feasible?," Artificial organs, vol. 39, no. 2, pp. 134-141, 2015.
[37] A. F. Schild, E. Perez, E. Gillaspie, C. Seaver, J. Livingstone, and A. Thibonnier, "Arteriovenous fistulae vs. arteriovenous grafts: a retrospective review of 1,700 consecutive vascular access cases," The journal of vascular access, vol. 9, no. 4, pp. 231-235, 2008.
[38] A. Yin et al., "Electrospinning collagen/chitosan/poly (L‐lactic acid‐co‐ϵ‐caprolactone) to form a vascular graft: Mechanical and biological characterization," Journal of biomedical materials research Part A, vol. 101, no. 5, pp. 1292-1301, 2013.
[39] M. Shin et al., "Endothelialized networks with a vascular geometry in microfabricated poly (dimethyl siloxane)," Biomedical microdevices, vol. 6, no. 4, pp. 269-278, 2004.
[40] P. Roy-Chaudhury, V. P. Sukhatme, and A. K. Cheung, "Hemodialysis vascular access dysfunction: a cellular and molecular viewpoint," Journal of the American Society of Nephrology, vol. 17, no. 4, pp. 1112-1127, 2006.
[41] E. Andrzejewska, "Free radical photopolymerization of multifunctional monomers," in Three-Dimensional Microfabrication Using Two-photon Polymerization: Elsevier, 2016, pp. 62-81.
[42] R. A. Hoshi, R. Van Lith, M. C. Jen, J. B. Allen, K. A. Lapidos, and G. Ameer, "The blood and vascular cell compatibility of heparin-modified ePTFE vascular grafts," Biomaterials, vol. 34, no. 1, pp. 30-41, 2013.
[43] K. Konner, B. Nonnast-Daniel, and E. Ritz, "The arteriovenous fistula," Journal of the American Society of Nephrology, vol. 14, no. 6, pp. 1669-1680, 2003.
[44] J. H. Lawson et al., "Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials," The Lancet, vol. 387, no. 10032, pp. 2026-2034, 2016.
[45] P. B. Morgan et al., "International contact lens prescribing in 2015," Contact Lens Spectrum, vol. 31, no. 1, pp. 24-29, 2016.
[46] J. Creech, A. Chauhan, and C. Radke, "Dispersive mixing in the posterior tear film under a soft contact lens," Industrial & engineering chemistry research, vol. 40, no. 14, pp. 3015-3026, 2001.
[47] J. Kim, C.-C. Peng, and A. Chauhan, "Extended release of dexamethasone from silicone-hydrogel contact lenses containing vitamin E," Journal of Controlled Release, vol. 148, no. 1, pp. 110-116, 2010.
[48] C. Karlgard, N. Wong, L. Jones, and C. Moresoli, "In vitro uptake and release studies of ocular pharmaceutical agents by silicon-containing and p-HEMA hydrogel contact lens materials," International journal of pharmaceutics, vol. 257, no. 1-2, pp. 141-151, 2003.
[49] D. Gulsen and A. Chauhan, "Dispersion of microemulsion drops in HEMA hydrogel: a potential ophthalmic drug delivery vehicle," International Journal of Pharmaceutics, vol. 292, no. 1-2, pp. 95-117, 2005.
[50] D. Gulsen, C.-C. Li, and A. Chauhan, "Dispersion of DMPC liposomes in contact lenses for ophthalmic drug delivery," Current eye research, vol. 30, no. 12, pp. 1071-1080, 2005.
[51] Y. Kapoor and A. Chauhan, "Drug and surfactant transport in Cyclosporine A and Brij 98 laden p-HEMA hydrogels," Journal of colloid and interface science, vol. 322, no. 2, pp. 624-633, 2008.
[52] H. Hiratani and C. Alvarez-Lorenzo, "Timolol uptake and release by imprinted soft contact lenses made of N, N-diethylacrylamide and methacrylic acid," Journal of Controlled Release, vol. 83, no. 2, pp. 223-230, 2002.
[53] H. Hiratani and C. Alvarez-Lorenzo, "The nature of backbone monomers determines the performance of imprinted soft contact lenses as timolol drug delivery systems," Biomaterials, vol. 25, no. 6, pp. 1105-1113, 2004.
[54] H. Hiratani, A. Fujiwara, Y. Tamiya, Y. Mizutani, and C. Alvarez-Lorenzo, "Ocular release of timolol from molecularly imprinted soft contact lenses," Biomaterials, vol. 26, no. 11, pp. 1293-1298, 2005.
[55] A. Weeks, L. N. Subbaraman, L. Jones, and H. Sheardown, "The competing effects of hyaluronic and methacrylic acid in model contact lenses," Journal of Biomaterials Science, Polymer Edition, vol. 23, no. 8, pp. 1021-1038, 2012.
[56] I. Tranoudis and N. Efron, "Tensile properties of soft contact lens materials," Contact Lens and Anterior Eye, vol. 27, no. 4, pp. 177-191, 2004.
[57] D. Groß, M. Childs, and J.-M. Piaton, "Comparative study of 0.1% hyaluronic acid versus 0.5% carboxymethylcellulose in patients with dry eye associated with moderate keratitis or keratoconjunctivitis," Clinical ophthalmology (Auckland, NZ), vol. 12, p. 1081, 2018.
[58] A. Fallacara, S. Vertuani, G. Panozzo, A. Pecorelli, G. Valacchi, and S. Manfredini, "Novel artificial tears containing cross-linked hyaluronic acid: an in vitro re-epithelialization study," Molecules, vol. 22, no. 12, p. 2104, 2017.
[59] P. Aragona, V. Papa, A. Micali, M. Santocono, and G. Milazzo, "Long term treatment with sodium hyaluronate-containing artificial tears reduces ocular surface damage in patients with dry eye," British Journal of Ophthalmology, vol. 86, no. 2, pp. 181-184, 2002.
[60] A. Fallacara, E. Baldini, S. Manfredini, and S. Vertuani, "Hyaluronic acid in the third millennium," Polymers, vol. 10, no. 7, p. 701, 2018.
[61] M. E. Johnson, P. J. Murphy, and M. Boulton, "Effectiveness of sodium hyaluronate eyedrops in the treatment of dry eye," Graefe's Archive for Clinical and Experimental Ophthalmology, vol. 244, no. 1, pp. 109-112, 2006.
[62] G. Camillieri, C. Bucolo, S. Rossi, and F. Drago, "Hyaluronan-induced stimulation of corneal wound healing is a pure pharmacological effect," Journal of Ocular Pharmacology & Therapeutics, vol. 20, no. 6, pp. 548-553, 2004.
[63] P. Troiano and G. Monaco, "Effect of hypotonic 0.4% hyaluronic acid drops in dry eye patients: a cross-over study," Cornea, vol. 27, no. 10, pp. 1126-1130, 2008.
[64] J. Wu et al., "Importance of zwitterionic incorporation into polymethacrylate-based hydrogels for simultaneously improving optical transparency, oxygen permeability, and antifouling properties," Journal of Materials Chemistry B, vol. 5, no. 24, pp. 4595-4606, 2017.
[65] W. Zhang, G. Li, Y. Lin, L. Wang, and S. Wu, "Preparation and characterization of protein-resistant hydrogels for soft contact lens applications via radical copolymerization involving a zwitterionic sulfobetaine comonomer," Journal of Biomaterials science, Polymer edition, vol. 28, no. 16, pp. 1935-1949, 2017.
[66] Y.-H. Zhao, K.-H. Wee, and R. Bai, "Highly hydrophilic and low-protein-fouling polypropylene membrane prepared by surface modification with sulfobetaine-based zwitterionic polymer through a combined surface polymerization method," Journal of Membrane Science, vol. 362, no. 1-2, pp. 326-333, 2010.
[67] J. Deng, S. Chen, J. Chen, H. Ding, D. Deng, and Z. Xie, "Self-reporting colorimetric analysis of drug release by molecular imprinted structural color contact lens," ACS applied materials & interfaces, vol. 10, no. 40, pp. 34611-34617, 2018.
[68] D. M. McElroy, L. M. Geever, C. L. Higginbotham, and S. M. Devery, "The Effect of Photoinitiator Concentration on the Physicochemical Properties of Hydrogel Contact Lenses," in Applied Mechanics and Materials, 2014, vol. 679: Trans Tech Publ, pp. 118-127.
[69] E. A. Kamoun, A. El-Betany, H. Menzel, and X. Chen, "Influence of photoinitiator concentration and irradiation time on the crosslinking performance of visible-light activated pullulan-HEMA hydrogels," International journal of biological macromolecules, vol. 120, pp. 1884-1892, 2018.
[70] B. Cheng, Y.-M. Xing, N.-C. Shih, J.-P. Weng, and H.-C. Lin, "The formulation and characterization of 3D printed grafts as vascular access for potential use in hemodialysis," RSC advances, vol. 8, no. 28, pp. 15471-15479, 2018.