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研究生:管哲雍
研究生(外文):Kuan, Che-yung
論文名稱:可原位聚合人工玻璃體之物化特性與生物相容性之評估
論文名稱(外文):Evaluation of Physical-chemical Properties andBiocompatibility of in-situ Polymerizable VitreousSubstitute
指導教授:林詠凱
指導教授(外文):Lin, Yung-kai
口試委員:林峯輝陳克華林詠凱
口試委員(外文):Lin, Feng-hueiChen, Ko-huaLin, Yung-kai
口試日期:2011-06-28
學位類別:碩士
校院名稱:中國文化大學
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:中文
論文頁數:68
中文關鍵詞:玻璃體玻尿酸感溫性水膠生物相容性
外文關鍵詞:VitreousHyaluronic acidThermo-responsive hydrogelBiocompatibility
相關次數:
  • 被引用被引用:0
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  • 下載下載:11
  • 收藏至我的研究室書目清單書目收藏:0
白內障併發症中,玻璃體-視網膜病變是導致失明的主要原因。自1960 年以
降,由於矽膠油具有高度安定性、透明度及高介面張力等特性,因此普遍被應用
於玻璃體-視網膜手術過程中填充視網膜的玻璃體替代物。然而,由於矽油的疏
水性與低比重特性導致其無法適當填充玻璃體/視網膜間之介面,患者需於術後
手術取出或反覆注射以避免併發症之發生。有鑑於此,研究者提出一種智慧型原
位聚合玻璃體替代物,利用玻尿酸與Pluronic F-127 共聚合組成。此人工玻璃體
具有於溫度變化下會產生溶液-膠體轉換之特性,在低溫下呈現可注射性,待注
入玻璃體腔時會形成半固態水膠。此種水膠相較於矽油具有較高的親水性、安定
性及生物相容性。本研究將確立玻尿酸/ Pluronic F-127 共聚物之最佳化製程,並
評估其化學特性、動態流變特性、光學特性、生物降解性及生物相容性。實驗結
果指出,H1F20 水膠於於溫度掃描結果指出,H1F20 水膠具有獨特之感溫特性,
其最低液態溫度 (LCST) 約為18℃,其於體溫環境下,其黏彈性為低溫環境下
之40 倍以上。同時H1F20 水膠亦具有良好的透光度及折射率與天然玻璃體相
近。於生物降解性分析指出,H1F20 水膠於含有溶菌酶之磷酸緩衝溶液,反應7
日亦有60%以上之膠體殘留量。於生物相容性試驗中,H1F20 水膠對於ARPE-19
細胞株為最高存活率,且顯著高於控制組。動物試驗指出,將H1F20 水膠進行
玻璃體置換,對於兔眼之角膜厚度及眼壓不會造成影響,於術後5 日進行裂隙燈
分析指出,H1F20 水膠不會造成白內障之產生。以H1F20 水膠進行玻璃體置換
可能導致視網膜電位下降,但藉由組織學檢驗亦驗證H1F20 對於視網膜並無細
胞毒性。綜合上述結果,H1F20 水膠為一種適合的材料可利用於組織工程中。
Vitreouretinal pathologies was one of the complication of cataract and still
remain the leading cause of blindness. Silicone oil has been used in vitreoretinal surgery since 1960s for it suitable properties of stability, transparency and high interfacial surface tension energy of silicone oil at the tamponade into vitreous/retinal interface. Due to the hydrophobic and low density properties of silicone oil lead to a poor contact with the retinal and aqueous fluids, therefore it was necessitate removing or re-injection to avoided life-threatening complication for long period implantation. Authors fabricated a smart in-situ polymerizable vitreous substitute composed of chemical modified HA/Pluronic F-127 copolymer. It was revealed a unique solution-gel transition at different temperature, which is injectable liquid under room temperature and forming hydrogel under physiological temperature within the vitreous cavity. This hydrogel would be more hydrophilic, persistent and providing better biocompatibility than silicone oil. The chemical, rheological, optical properties, biodegradability and biocompatibility will be conducted to investigating the optimal formulation for chemical modified copolymer. Results demonstrated that the H1F20 hydrogel exhibited unique thermoresponsive during temperature increasing, and its LCST was under the 18℃. Under the physical condition, the viscoelastic property of H1F20 hydrogel was 40 folds than 4℃ condition. Futhormore, The H1F20 hydrogel also exhibited high transmission and the refraction index were similar with nature vitreous. The biodegrability analysis indicated H1F20 hydrogel incubating under the lysozyme solution was still remained 60% of resistant for 7 days. The biocompatibility assay for ARPE-19 cell revealed the co-polymer had the highest cell viability, and the viability was significant higher than control (p<0.01) . In animal
study for rabbit eyes, all group after vitrectomy caused slight alteration of corneal thickness and intraocular pressure value, recover in 3 day after post-operation. The slit lamp examination on the post-operated day5, the data indicated the H1F20 hydrogel was not induced the cataract formation. Used H1F20 hydrogel for vitrectomy may cause the alteration of ERG profiles, but the RPE layer still maintain intact of histological properties, which indicated the H1F20 hydrogel did not trigged cytotoxic effect for retina tissue. Summary of the above results, the H1F20 could be a suitable biomaterial application on tissue engineering.
中文摘要
英文摘要
目錄
圖目錄
表目錄
第一章 緒言
1.1 簡介
1.2 玻璃體
1.3 玻璃體置換
1.4 人工玻璃體的發展
1.5 人工玻璃體的應用
1.6 理想的人工玻璃體
1.7 以矽油做為人工玻璃體
1.8 以揭示之人工玻璃體
1.9 目的與動機
第二章 理論基礎
2.1 水膠
2.1.1 水膠的定義
2.1.2 水膠於生醫材料之應用
2.1.3 感溫性水膠
2.2 高分子材料於眼科之應用
2.2.1 玻尿酸
2.2.2 Pluronic F-127
2.3 玻尿酸/Pluronic F-127 水膠之合成理論
2.4 玻尿酸/Pluronic F-127 之開發目標
第三章 材料與方法
3.1 實驗材料
3.2 試驗流程圖
3.3 實驗方法
3.3.1 玻尿酸/Pluronic F-127 共聚物之合成方法
3.3.2 動態流變特性分析
3.3.3 可注射性分析
3.3.4 透光度分析
3.3.5 折射率分析
3.3.6 FTIR 光譜
3.3.7 核磁共振光譜
3.3.8 生物降解性
3.3.9 平衡膨潤率
3.3.10 體外生物相容性評估
3.3.11 動物試驗
第四章 結果
4.1 流變特性分析
4.2 可注射性分析
4.3 光學特性分析
4.4 化學結構分析
4.5 生物降解性
4.6 平衡膨潤率
4.7 體外生物相容性評估
4.8 動物試驗
第五章 討論
第六章 結論
第七章 未來研究
第八章 參考文獻
第九章 致謝
1. 鄭仁豪, 邱弘毅, 羅琇瓊, and 呂大文, 臺灣視網膜病變盛行率與危險因
子研究. 中華民國眼科醫學會雜誌, 2006. 45(3): p. 171-177.
2. Vision Problems in the U.S. Fourth Edition ed. 2008: National Eye Institute
and Prevent Blindness America.
3. Foster, W.J., Vitreous Substitutes. Expert Rev Ophthalmol, 2008. 3(2): p.
211-218.
4. Baino, F., Towards an ideal biomaterial for vitreous replacement: Historical
overview and future trends. Acta Biomater, 2011. 7(3): p. 921-35.
5. Bishop, P.N., Structural macromolecules and supramolecular organisation of
the vitreous gel. Prog Retin Eye Res, 2000. 19(3): p. 323-44.
6. Soman, N. and R. Banerjee, Artificial vitreous replacements. Biomed Mater
Eng, 2003. 13(1): p. 59-74.
7. Suri, S. and R. Banerjee, In vitro evaluation of in situ gels as short term
vitreous substitutes. J Biomed Mater Res A, 2006. 79(3): p. 650-64.
8. Snell, R., Head and neck, in Clinical Anatomy for Medical Students. 1995,
Little, Brown and Co: New York. p. 713-725.
9. Swindle, K.E. and N. Ravi, Recent advances in polymeric vitreous substitutes.
Expert Rev Ophthalmol., 2007. 2(2): p. 255-265.
10. Lee, B., M. Litt, and G. Buchsbaum, Rheology of the vitreous body. Part I:
Viscoelasticity of human vitreous. Biorheology, 1992. 29(5-6): p. 521-33.
11. Lee, B., M. Litt, and G. Buchsbaum, Rheology of the vitreous body: Part 2.
Viscoelasticity of bovine and porcine vitreous. Biorheology, 1994. 31(4): p.
327-38.
12. Lee, B., M. Litt, and G. Buchsbaum, Rheology of the vitreous body: part 3.
Concentration of electrolytes, collagen and hyaluronic acid. Biorheology,
1994. 31(4): p. 339-51.
13. Liu, X.C., P. Wang, and H. Yan, A rabbit model to study biochemical damage
to the lens after vitrectomy: effects of N-acetylcysteine. Exp Eye Res, 2009.
88(6): p. 1165-70.
14. 黃正賢, 糖尿病視網膜病變之治療. 台灣醫學, 1999. 3: p. 564-569.
15. Rosenberg, E.A. and L.C. Sperazza, The visually impaired patient. Am Fam
Physician, 2008. 77(10): p. 1431-6.
16. Constable, I.J. and D.A. Swann, Vitreous substitution with gases. Arch
Ophthalmol, 1975. 93(6): p. 416-9.
17. Sabates, N.R., F.I. Tolentino, M. Arroyo, and H.M. Freeman, The
complications of perfluoropropane gas use in complex retinal detachments.
Retina, 1996. 16(1): p. 7-12.
18. Peyman, G.A., C.M. Vygantas, T.O. Bennett, A.M. Vygantas, and S. Brubaker,
Octafluorocyclobutane in vitreous and aqueous humor replacement. Arch
Ophthalmol, 1975. 93(7): p. 514-7.
19. Guillaubey, A., L. Malvitte, P.O. Lafontaine, N. Jay, I. Hubert, A. Bron, J.P.
Berrod, and C. Creuzot-Garcher, Comparison of face-down and seated
position after idiopathic macular hole surgery: a randomized clinical trial.
Am J Ophthalmol, 2008. 146(1): p. 128-134.
20. Malchiodi-Albedi, F., A. Matteucci, G. Formisano, S. Paradisi, G.
Carnovale-Scalzo, R. Perilli, G. Scorcia, and S. Caiazza, Perfluorohexyloctane
(F6H8) induces structural modifications and increases apoptosis in rat
primary retinal cultures. J Biomed Mater Res B Appl Biomater, 2003. 65(1): p.
133-6.
21. Colthurst, M.J., R.L. Williams, P.S. Hiscott, and I. Grierson, Biomaterials used
in the posterior segment of the eye. Biomaterials, 2000. 21(7): p. 649-65.
22. McCuen, B.W., 2nd, S.P. Azen, W. Stern, M.Y. Lai, J.S. Lean, K.L. Linton,
and S.J. Ryan, Vitrectomy with silicone oil or perfluoropropane gas in eyes
with severe proliferative vitreoretinopathy. Silicone Study Report 3. Retina,
1993. 13(4): p. 279-84.
23. Suzuki, M., T. Okada, S. Takeuchi, Y. Ishii, H. Yamashita, and S. Hori, Effect
of silicone oil on ocular tissues. Jpn J Ophthalmol, 1991. 35(3): p. 282-91.
24. Knorr, H.L., A. Seltsam, L. Holbach, and G.O. Naumann, [Intraocular silicone
oil tamponade. A clinico-pathologic study of 36 enucleated eyes].
Ophthalmologe, 1996. 93(2): p. 130-8.
25. Light, D.J., Silicone oil emulsification in the anterior chamber after
vitreoretinal surgery. Optometry, 2006. 77(9): p. 446-9.
26. Heidenkummer, H.P., A. Kampik, and S. Thierfelder, Experimental evaluation
of in vitro stability of purified polydimethylsiloxanes (silicone oil) in viscosity
ranges from 1000 to 5000 centistokes. Retina, 1992. 12(3 Suppl): p. S28-32.
27. Sternberg, P., Jr., D.L. Hatchell, G.N. Foulks, and M.B. Landers, 3rd, The
effect of silicone oil on the cornea. Arch Ophthalmol, 1985. 103(1): p. 90-4.
28. Karel, I., M. Filipec, and J. Obenberger, Specular microscopy of the corneal
endothelium after liquid silicone injection into the vitreous in complicated
retinal detachments. Graefes Arch Clin Exp Ophthalmol, 1986. 224(2): p.
195-200.
29. Levenson, D.S., F.W. Stocker, and N.G. Georgiade, Intracorneal Silicone Fluid.
Arch Ophthalmol, 1965. 73: p. 90-3.
30. Pritchard, C.D., S. Crafoord, S. Andreasson, K.M. Arner, T.M. O'Shea, R.
Langer, and F.K. Ghosh, Evaluation of viscoelastic poly(ethylene glycol) sols
as vitreous substitutes in an experimental vitrectomy model in rabbits. Acta
Biomater, 2011. 7(3): p. 936-43.
31. Swindle-Reilly, K.E., M. Shah, P.D. Hamilton, T.A. Eskin, S. Kaushal, and N.
Ravi, Rabbit study of an in situ forming hydrogel vitreous substitute. Invest
Ophthalmol Vis Sci, 2009. 50(10): p. 4840-6.
32. Costa, L.G., H. Deng, C.J. Calleman, and E. Bergmark, Evaluation of the
neurotoxicity of glycidamide, an epoxide metabolite of acrylamide: behavioral,
neurochemical and morphological studies. Toxicology, 1995. 98(1-3): p.
151-61.
33. Kim, M.R. and T.G. Park, Temperature-responsive and degradable hyaluronic
acid/Pluronic composite hydrogels for controlled release of human growth
hormone. J Control Release, 2002. 80(1-3): p. 69-77.
34. Drury, J.L. and D.J. Mooney, Hydrogels for tissue engineering: scaffold design
variables and applications. Biomaterials, 2003. 24(24): p. 4337-51.
35. Cosgriff-Hernandez, E. and A.G. Mikos, New biomaterials as scaffolds for
tissue engineering. Pharm Res, 2008. 25(10): p. 2345-7.
36. Hennink, W.E. and C.F. van Nostrum, Novel crosslinking methods to design
hydrogels. Adv Drug Deliv Rev, 2002. 54(1): p. 13-36.
37. Pratt, A.B., F.E. Weber, H.G. Schmoekel, R. Muller, and J.A. Hubbell,
Synthetic extracellular matrices for in situ tissue engineering. Biotechnol
Bioeng, 2004. 86(1): p. 27-36.
38. Nuttelman, C.R., M.A. Rice, A.E. Rydholm, C.N. Salinas, D.N. Shah, and K.S.
Anseth, Macromolecular Monomers for the Synthesis of Hydrogel Niches and
Their Application in Cell Encapsulation and Tissue Engineering. Prog Polym
Sci, 2008. 33(2): p. 167-179.
39. Tan, H., C.M. Ramirez, N. Miljkovic, H. Li, J.P. Rubin, and K.G. Marra,
Thermosensitive injectable hyaluronic acid hydrogel for adipose tissue
engineering. Biomaterials, 2009. 30(36): p. 6844-53.
40. Khattak, S.F., S.R. Bhatia, and S.C. Roberts, Pluronic F127 as a cell
encapsulation material: utilization of membrane-stabilizing agents. Tissue
Eng, 2005. 11(5-6): p. 974-83.
41. Matthew, J.E., Y.L. Nazario, S.C. Roberts, and S.R. Bhatia, Effect of
mammalian cell culture medium on the gelation properties of Pluronic F127.
Biomaterials, 2002. 23(23): p. 4615-9.
42. Lin, H.R., K.C. Sung, and W.J. Vong, In situ gelling of alginate/pluronic
solutions for ophthalmic delivery of pilocarpine. Biomacromolecules, 2004.
5(6): p. 2358-65.
43. Wei, G., H. Xu, P.T. Ding, S.M. Li, and J.M. Zheng, Thermosetting gels with
modulated gelation temperature for ophthalmic use: the rheological and
gamma scintigraphic studies. J Control Release, 2002. 83(1): p. 65-74.
44. Griffiths, P., Hasseth, J.A., Fourier Transform Infrared Spectrometry 2nd ed.
2007, New Jersey: Wiley.
45. Su, W.Y., Y.C. Chen, and F.H. Lin, Injectable oxidized hyaluronic acid/adipic
acid dihydrazide hydrogel for nucleus pulposus regeneration. Acta Biomater,
2010. 6(8): p. 3044-55.
46. McCartney, D.L., K.M. Miller, W.J. Stark, D.L. Guyton, and R.G. Michels,
Intraocular lens style and refraction in eyes treated with silicone oil. Arch
Ophthalmol, 1987. 105(10): p. 1385-7.
47. Kim, J.H., S.B. Lee, S.J. Kim, and Y.M. Lee, Rapid temperature/pH response
of porous alginate-g-poly(N-isopropylacrylamide) hydrogels. Polymer, 2002.
43(26): p. 7549-7558.
48. Wang, L.-Q., K. Tu, Y. Li, J. Zhang, L. Jiang, and Z. Zhang, Synthesis and
characterization of temperature responsive graft copolymers of dextran with
poly(N-isopropylacrylamide). Reactive and Functional Polymers, 2002. 53(1):
p. 19-27.
49. Thompson, J.T., Advantages and limitations of small gauge vitrectomy. Surv
Ophthalmol, 2011. 56(2): p. 162-72.
50. Song, W.K., S.S. Kim, S.E. Kim, and S.C. Lee, Refractive status and visual
acuity changes after oil removal in eyes following phacovitrectomy,
intraocular lens implantation, and silicone oil tamponade. Can J Ophthalmol,
2010. 45(6): p. 616-20.
51. Matteucci, A., G. Formisano, S. Paradisi, G. Carnovale-Scalzo, G. Scorcia, S.
Caiazza, H. Hoerauf, and F. Malchiodi-Albedi, Biocompatibility assessment of
liquid artificial vitreous replacements: relevance of in vitro studies. Surv
Ophthalmol, 2007. 52(3): p. 289-99.
52. Davidorf, F.H., R.B. Chambers, O.W. Kwon, W. Doyle, P. Gresak, and S.G.
Frank, Ocular toxicity of vitreal pluronic polyol F-127. Retina, 1990. 10(4): p.
297-300.
53. Yang, C.S., K.H. Chen, W.M. Hsu, and Y.S. Li, Cytotoxicity of silicone oil on
cultivated human corneal endothelium. Eye (Lond), 2008. 22(2): p. 282-8.
54. Lei, Y., S. Gojgini, J. Lam, and T. Segura, The spreading, migration and
proliferation of mouse mesenchymal stem cells cultured inside hyaluronic acid
hydrogels. Biomaterials, 2011. 32(1): p. 39-47.
55. 陳士軒, 透明質酸之製備與傷口合應用. 1996, 陽明大學碩士論文.
56. 錢宗良, 幹細胞學. 2008: 教育部顧問室「生物及醫學科技人才培育先導型計畫」 幹細胞與組織工程教學資源中心.
57. 陳威, 利用電漿處理及UV 光接枝聚合固定聚丙烯酸藥物釋放水膠並固定
幾丁聚醣/褐藻酸於316L 不鏽鋼表面. 2010, 大同大學碩士論文.
58. Biondi, M., F. Ungaro, F. Quaglia, and P.A. Netti, Controlled drug delivery in tissue engineering. Adv Drug Deliv Rev, 2008. 60(2): p. 229-42.
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1. 古清美:〈劉蕺山對陽明致良知說之繼承與發展〉,《臺大中文學報》第1期,民國74年11月,頁367-396,收錄在古清美著《明代理學論文集》,臺北:大安出版社, 1990年5月,頁209-249。
2. 古清美:〈蕺山學的儒釋之辨〉,《佛學研究中心學報》第2期,民國86年7月,頁179-209。
3. 古清美:〈劉蕺山對周濂溪誠體思想的闡發及其慎獨之學〉,《幼獅學誌》第19卷第2期,民國75年10月,頁79-111。
4. 王瑞昌:〈論劉蕺山的無善無惡思想〉,《鵝湖月刊》第25卷第9期,總第297期,民國89年3月,頁18-32。
5. 王汎森:〈清初思想趨向與「劉子節要」一兼論清初蕺山學派的分裂〉,《中央研究院歷史語言研究所集刊》第68卷第2期,民國86年6月,頁417-448。
6. 王汎森:〈明末清初的人譜與省過會〉,《中央研究院歷史語言研究所集刊》,第63卷第3期,民國82年7月,頁679-712。
7. 王汎森:〈清初的講經會〉,《中央研究院歷史語言研究所集刊》第68卷第3期,民國86年9月,頁503-588。
8. 方祖猷:〈黃宗羲與甬上弟子的學術分歧-兼論蕺山之學的傳播和沒落〉,《香港中文大學中國文化研究所學報》第22期,民國80,頁336-350。
9. 莊溎芬:《王陽明與劉蕺山工夫論之比較》,臺北:國立臺灣師範大學國文所碩士論文,民國81年6月。收錄在《國立臺灣師範大學國文研究所集刊》第38期,民國83年6月,頁735-832。
10. 李明輝:〈劉蕺山對朱子理氣論的批判〉,《漢學研究》第19卷第2期,總第39期,民國90年12月,頁1-32。收錄於李明輝著:《四端與七情-關於道德情感的比較哲學探討》,臺北:臺灣大學出版,2005年6月。
11. 李興源:〈劉蕺山「誠意之學」探析〉,《中國國學》第17期,民國78年11月,頁289-298。
12. 李翔海:〈尋求宗教、哲學與科學精神的統一:論現代新儒學的內在向度〉,孔孟學報第78期,2000年9月,頁283-284。
13. 李中華:〈人類文化變遷中的儒學:仍從儒家的「天人合一」說起〉孔孟月刊 第41卷,第9期,民國92年5月, 頁23-25。
14. 林月惠:〈劉蕺山對《大學》《誠意》章的詮釋〉,「朱子與宋明理學」學術研討會(臺北:鵝湖月刊雜誌社, 2000年12月23 -25日),後再發表於《中國文哲研究集刊》第19期,民國90年9月,頁407-449。
15. 林月惠:〈從宋明理學的「性情論」考察劉蕺山對《中庸》「喜怒哀樂」的詮釋〉,《中國文哲研究集刊》第25期,民國93年9月,頁177-218。