臺灣博碩士論文加值系統

本研究探討聚乙烯吡咯烷酮(Polyvinyl pyrrolidone, PVP )/明膠(Gelatin)/幾丁聚醣(Chitosan)/混摻蛋黃油(Egg Yolk Oil, EYO) 透過戊二醛(Glutaraldehyde, GA)蒸氣交聯製備複合薄膜(簡稱PGC/EYO薄膜)，評估含不同比重蛋黃油之PGC/EYO薄膜其吸水後薄膜性質、機械性質、生物降解度、生物相容性，最後，最適PGC/EYO薄膜試驗於大鼠放射性皮炎(Radiodermatitis)之治療效果。
第一階段試驗不同P：G：C比例之薄膜(簡稱PGC薄膜)，選擇最適合之薄膜基材混摻EYO，其中PGC薄膜比例為1：1：2之薄膜(簡稱PGC112)表現柔軟、有韌性的機械性質且具有穩定的生物降解度，故第二階段欲選擇PGC112混摻EYO製備複合薄膜。
第二階段試驗將EYO以0.25及0.50 wt%混摻於PGC薄膜中，結果顯示含水率皆維持在92%以上，隨著EYO比重增加，薄膜性質越接近PGC/0EYO薄膜；混摻EYO後機械性質整體提升，其中PGC/0.5EYO薄膜具有較佳的延伸率及楊氏模數。ATR-FTIR分析可見因添加EYO而產生新的酯類特徵波峰分別在1744及2926 cm-1。EYO微粒於PGC/EYO薄膜情形由FE-SEM觀察，以PGC/0.5EYO最為顯著。生物相容性實驗中，PGC/EYO薄膜對老鼠成纖維母細胞(L929 cells)於第3天減緩增殖速度，評估後PGC/0.5EYO具有較佳的機械性質、合適的降解性質及生物相容性，選擇其應用於放射性皮炎治療之動物實驗。
最後階段，給予大鼠背部40 Gy使之產生第Ⅲ級放射皮炎，傷口處理30天，結果表明蛋黃油對於放射性皮炎有顯著的修復效果，PGC/0EYO薄膜能夠延遲皮炎發生時間，PGC/0.5EYO具有有良好的放射性皮炎修復能力，組織學表徵觀察到良好的再上皮化，CD68標記物也有顯著降低，具備延遲及修復放射性皮炎之功效。

In this study, we investigated Polyvinylpyrrolidone (PVP)/Gelatin/Chitosan /Egg Yolk Oil (EYO) to prepare composite film (called PGC/EYO film) which cross-linked by glutaraldehyde (GA) vapor, and evaluated film properties after water absorption, mechanical properties, biodegradability, biocompatibility. Finally, evaluating treatment effect of radiodermatitis in rats with the ideal PGC/EYO film .
The first part, the films of different P：G：C ratio (called PGC film) was tested to select the ideal ratio of the film which would blend with EYO. The appropriate ratio of PGC film is 1:1:2 (called PGC112) which has soft and tough mechanical properties, and stable biodegradability. Therefore, PGC112 film would blend with EYO to prepare composite film .
In the second part, the PGC film would blend with 0.25 and 0.50wt% EYO. The results show that the water content rates all high over 92%. With the EYO increased, the mechanical properties of the PGC/EYO film are improved overall, and the PGC/0.5EYO film has the best elongation and Young's modulus. ATR-FTIR analysis shows that the appearance of new peak by adding EYO. The peaks are observed in FE-SEM at 1744 and 2926 cm-1. Observing EYO micro-particles in the PGC/EYO film by FE-SEM, and the most EYO micro-particles distribute over the surface and section of PGC/0.5EYO film. The biocompatibility experiment shows PGC/EYO film has reduction of the proliferation rate of mouse fibroblasts cells (L929 cells) on the third day. After evaluation, PGC/0.5EYO has the ideal mechanical properties, biodegradation and biocompatibility. According to the above results, Selecting PGC/0.5EYO film for the treatment of radiodermatitis.
The final part, Giving 40 Gy to the back of the rats to produce the grade III radiation dermatitis and the wound was treated for 30 days. The results showed that the EYO has a significantly healing effect on radiation dermatitis, and the PGC/0EYO film was able to delay the occurrence of dermatitis. PGC/0.5EYO has a significantly healing effect on radiodermatitis, good re-epithelialization which observed in histological characterization, CD68 reduced significantly, and the effect of delaying and healing radiodermatitis.

誌謝 I
摘要 III
Abstract IV
圖目錄 XI
表目錄 XIV
第一章　前言 1
1-1研究動機 1
1-2研究目的 2
第二章　文獻回顧 4
2-1皮膚構造 4
2-1-1傷口發炎反應 5
2-1-2皮膚傷口修復機制 7
2-2 傷口敷料演進 9
2-3 放射線治療簡介 11
2-3-1 放射線治療之生物效應 12
2-3-2放射性皮炎護理方式 14
2-4 複合薄膜敷料之材料 16
2-4-1 聚乙烯吡咯烷酮 (Polyvinyl pyrrolidone, PVP) 16
2-4-2 明膠 (Gelatin) 18
2-4-3 幾丁聚醣 (Chitosan) 20
2-4-4 蛋黃油(Egg Yolk Oil, EYO) 22
2-5 複合型材料於皮膚組織工程之應用 26
2-5-1 Chitosan/Polyvinyl pyrrolidone (PVP) 26
2-5-2 Gelatin/PVP 27
2-5-3 Chitosan/ Gelatin 28
2-5-4 高分子材料/蛋黃油 29
2-6 幾丁聚醣-明膠與戊二醛交聯機制 31
第三章 材料與方法 34
3-1 實驗藥品 34
3-2 實驗儀器 36
3-3 實驗流程 39
3-3-1　PGC薄膜最適比例選擇與薄膜性質評估 39
3-3-2　PGC/EYO薄膜之性質評估 40
3-3-3　放射皮炎動物實驗流程 41
3-4 實驗方法 42
3-4-1 PGC薄膜製備與交聯 42
3-4-2 PGC薄膜結構穩定性測試及評估 44
3-4-2-1 PGC薄膜交聯度測試 44
3-4-2-2製備磷酸鹽緩衝溶液(Phosphate buffer saline, PBS) 45
3-4-2-3 PGC薄膜降解率測試 45
3-4-2-4 PGC薄膜機械性能測試 - 拉伸測試 46
3-4-2-5 ATR-FTIR測試 46
3-4-3　PGC/EYO複合薄膜之製備與性能評估 47
3-4-3-1 PGC/EYO複合薄膜之製備 47
3-4-3-2 PGC/EYO薄膜之性質測試 49
3-4-3-3 PGC/EYO薄膜之ATR-FTIR測試 49
3-4-3-4 PGC/EYO 生物降解度測試 49
3-4-3-5 PGC/EYO薄膜之機械性能測試 - 拉伸測試 50
3-4-3-6 PGC/EYO薄膜表徵顯微結構觀察 50
3-4-3-7 PGC薄膜表面粒徑分析 51
3-4-4　PGC-EYO複合薄膜生物相容性測試 52
3-4-4-1 細胞培養液之配置 52
3-4-4-2 L929細胞培養與繼代方法 53
3-4-4-3 體外細胞活性測試 54
3-4-4-4 亞甲基藍(Methylene blue)染色觀察 55
3-4-5 放射皮炎動物實驗 56
3-4-5-1 Sprague Dawley大鼠之飼養 56
3-4-5-2 放射皮炎產生方法 56
3-4-5-3 放射皮炎面積分析 63
3-4-5-4 放射皮炎傷口組織切片 63
3-5 統計分析 65
第四章　結果與討論 66
4-1　PGC薄膜之評估 66
4-1-1 不同比例之PGC薄膜性質評估 66
4-1-2 不同比例之PGC薄膜ATR-FTIR分析 72
4-1-3 不同比例之PGC薄膜機械性能分析-拉伸測試 75
4-1-4 不同比例之PGC薄膜生物降解度測試 78
4-2　PGC/EYO薄膜之評估 80
4-2-1 PGC/0EYOPGC/EYO薄膜ATR-FTIR分析 80
4-2-2 PGC/0EYO及PGC/EYO薄膜性質評估 82
4-2-3 PGC/0EYO及PGC/EYO薄膜之機械性質測試 89
4-2-4 PGC/0EYO及PGC/EYO薄膜之生物降解度測試 93
4-2-5 PGC/0EYO及PGC/EYO薄膜之FE-SEM觀察 95
4-2-6 PGC/EYO薄膜之粒徑分析 98
4-2-7 PGC/EYO薄膜之體外細胞測試 102
4-3放射皮炎動物實驗 106
4-3-1放射皮炎面積之比較 106
4-3-2放射皮炎動物實驗-H&E切片染色觀察 113
4-3-3放射皮炎動物實驗- CD68免疫切片染色觀察 119
第五章　結論 124
參考文獻 127
附錄一 138

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