可原位聚合人工玻璃體之物化特性與生物相容性之評估

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题名:	可原位聚合人工玻璃體之物化特性與生物相容性之評估
作者:	管哲雍
贡献者:	生物科技研究所
关键词:	玻璃體玻尿酸感溫性水膠生物相容性
日期:	2010
上传时间:	2011-10-27 13:29:39 (UTC+8)
摘要:	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.
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