臺灣博碩士論文加值系統

本研究主要目的為利用射頻電漿(13.56MHz)系統對聚乳酸-聚甘醇酸共聚物(PLGA)以及聚甲基丙烯酸甲酯(PMMA)兩種高分子材料進行改質，以觀察表面性質對L929-老鼠纖維母細胞貼附增生情形的影響。藉由溶劑揮發法製成的PLGA及PMMA薄膜，經由O2、CO2、N2、N2/H2、CF4、SF6六種非聚合性氣體電漿改質，依據親疏水性及表面電性，選擇N2/H2以及CF4此兩種具備相反結果的氣體來源作進一步分析探討，前者可使材料表面變為較親水且帶正電荷；後者使材料表面變為疏水且接植帶負電的官能基。
由N2/H2氣體電漿改質，發現調整電漿處理參數(輸出功率；處理時間)對材料表面的親水性及表面界達電位皆帶來影響，而由細胞貼附結果可得知電漿功率影響程度較處理時間更為顯著；而調整N2/H2進料氣體比例對於表面界達電位以及細胞貼附結果，也可間接印證胺基的重要性，說明胺基的存在使得界達電位偏向正電也使得細胞貼附情況獲得改善。此外也探討使用不同溶劑製備出不同表面型態的PLGA及PMMA薄膜，結果顯示在奈米等級(方均根粗糙度<10nm)情況下，改質後的表面化學組成對於細胞貼附的影響遠大於表面物理型態。
由CF4氣體電漿觀察調整電漿功率帶來的影響，不同於N2/H2電漿改質的地方是，CF4氣體電漿不管是對PLGA或PMMA薄膜均有較明顯的蝕刻現象發生，並使高分子薄膜表面變為疏水，但是經由改質後的PLGA及PMMA薄膜細胞相容性也同樣被提升，故推翻親疏水性以及表面電性影響細胞貼附此種說法，須更進一步去探討材料表面化學官能基所帶來的效應。
由XPS分析改質後PLGA以及PMMA薄膜表面，針對N2/H2以及CF4氣體電漿改質，發現C-N鍵結含量以及F/C比例與與細胞貼附結果具有關聯性，而以改質後的PMMA薄膜細胞相容性較PLGA為佳。另外，N2/H2氣體電漿改質後的表面化學組成，與表面界達電位結果相關，顯示材料表面化學官能基對於細胞貼附的重要性，而電漿處理後表面官能基則影響親疏水性及表面電性。

The goal of this work is to investigate the effects of plasma modification on surface properties of polymers and on the interactions between modified surfaces with L929 fibroblast cells. The two polymers used in this study are poly(DL-lactic-co-glycolic acid) (PLGA) and poly(methyl methacrylate) (PMMA). Polymer thin films were fabricated by solvent evaporation technique and treated by 6 different plasma gases (O2, CO2, N2, N2/H2, CF4 and SF6 gas). For the L929 fibroblast cells adhesion, two plasma gases, N2/H2 and CF4, were used to incorporate different functionalities and surface hydrophilicity on the surfaces of PLGA and PMMA. N2/H2 plasma altered the surface to more hydrophilic and caused more positive surface charge. On the other hand, CF4 plasma modified the surface of polymer to become hydrophobic and incorporated negative charged functional groups.
For the surface treatment by using N2/H2 plasma, the effects of operational parameters such as treatment time, applied power on the physical-chemical properties of polymer thin films were evaluated by measuring wettability and zeta potential. The amount of adhered cells on the pristine and plasma modified samples was quantified by LDH assay and the results showed that the effect of applied power was more significant than the treatment time. The feed ratio of N2/H2 gases was also varied to study to examine the importance of the density of amine functionalities on the modulation of surface charge and biocompatibility. Moreover, by directly cultivating the cells on the same polymer with different surface morphology or with varied chemical compositions, it was found that the effect of chemical compositions of surface was more important than the surface topography on the proliferation of L-929 cells.
For the polymers treated with CF4 plasma treatment, the AFM results showed that plasma etching phenomenon occurred and confirmed that the CF4 plasma incorporated hydrophobicity on the surfaces. Interestingly, CF4 plasma also effectively promoted cell adhesion and proliferation which suggested that the cell adhesion and proliferation were independent of the surface wettability and surface charge, while the effect of chemical functional groups incorporated on the surface of material played a more important role.
The XPS results of plasma treated PLGA and PMMA revealed that C-N amount and F/C ratio increased significantly by applying N2/H2 and CF4 plasma, respectively. The trend of the increase of nitrogen or fluorine contents related closely to the cell behaviors and demonstrated that the modified PMMA showed better biocompatibility than the modified PLGA. In summary, we demonstrated an effective method to perform plasma surface modification on PLGA and PMMA. Moreover, the surface chemical functional groups are essential on biocompatibility of materials.

摘要 i
Abstract ii
致謝 iv
總目錄 v
圖目錄 x
表目錄 xix
Abbreviation xxii
第一章 緒論 1
第二章 文獻回顧 3
2-1 高分子材料之特性與應用 3
2-1-1 聚乳酸-甘醇酸共聚合物 3
2-1-2 聚甲基丙烯酸甲酯 6
2-1-3 高分子材料表面改質之方法 7
2-2 電漿的定義 8
2-2-1 低溫電漿的特色 8
2-2-2 電漿於表面處理的反應機制 10
2-2-3 利用低溫電漿進行高分子表面改質 11
2-2-4 含氮電漿與含氟電漿 11
2-2-5 電漿處理增進高分子表面生物相容性 13
2-3 表面界達電位 14
2-3-1 表面界達電位之定義 14
2-3-2 表面界達電位的應用 16
2-4 生物相容性 17
第三章 實驗材料與方法 20
3-1 儀器原理及方法 21
3-1-1 減弱全反射-傅立葉轉換紅外線光譜儀(ATR-FTIR) 22
3-1-2 接觸角 (contact angle) 22
3-1-3 原子力顯微鏡 (Atomic force microscopy, AFM) 23
3-1-4 X-射線光電子能譜儀 (X-ray photoelectron spectroscopy, XPS) 24
3-1-5 薄膜界面電位分析儀 (Electro-kinetic analyzer, EKA) 25
3-1-6 酵素微盤光譜分析系統 (Enzyme-linked immunosorbent assay, ELISA) 26
3-1-7 統計分析方法 28
3-2 實驗藥品 28
3-2-1 高分子材料薄膜製備 28
3-2-2 LDH assay藥品配製 28
3-3 實驗儀器 29
3-4 高分子薄膜製備步驟 29
3-4-1 PLGA薄膜之製備與物性分析 31
3-4-1-1 ATR-FTIR分析 32
3-4-1-2 分子量測定 33
3-4-2 PLGA薄膜熱性質分析 34
3-4-3 PLGA薄膜表面型態分析 35
3-4-4 PMMA薄膜之製備與物性分析 36
3-4-4-1 ATR-FTIR分析 36
3-4-5 PMMA薄膜熱性質分析 38
3-4-6 PMMA薄膜表面型態分析 38
第四章 實驗結果 40
4-1 六種氣體電漿改質高分子薄膜表面特性之研究 40
4-1-1 PLGA薄膜表面改質以及性質分析 40
4-1-2 PMMA薄膜表面改質以及性質分析 41
4-2 N2/H2氣體電漿改質PLGA薄膜表面特性之研究 42
4-2-1 電漿處理條件對PLGA薄膜特性之影響 42
4-2-1-1 電漿參數對於表面水濕性的影響:接觸角測量 42
4-2-1-2 電漿參數對於表面電位的影響:界達電位分析 43
4-2-1-3 電漿參數對於細胞貼附的影響 44
4-2-1-4 電漿參數對於PLGA表面物理化學性質的影響:XPS分析 45
4-2-2 N2/H2氣體組成比例對PLGA薄膜特性之影響 46
4-2-2-1 氣體組成對於表面水濕性的影響:接觸角測量 47
4-2-2-2 氣體組成對於表面電位的影響:界達電位分析 47
4-2-2-3 氣體組成對於細胞貼附的影響 47
4-2-3 薄膜表面型態對PLGA薄膜特性之影響 48
4-2-3-1 薄膜表面型態分析:AFM分析 48
4-2-3-2 薄膜表面型態對於表面水濕性的影響:接觸角測量 49
4-2-3-3 薄膜表面型態對於細胞貼附的影響 49
4-3 N2/H2氣體電漿改質PMMA薄膜表面特性之研究 50
4-3-1 電漿處理條件對PMMA薄膜特性之影響 50
4-3-1-1 電漿參數對於表面水濕性的影響:接觸角測量 50
4-3-1-2 電漿參數對於表面電位的影響:界達電位分析 50
4-3-1-3 電漿參數對於細胞貼附的影響 51
4-3-1-4 電漿參數對於PMMA表面物理化學性質的影響:XPS分析 52
4-3-2 N2/H2氣體組成比例對PMMA薄膜特性之影響 53
4-3-2-1 氣體組成對於表面水濕性的影響:接觸角測量 53
4-3-2-2 氣體組成對於表面電位的影響:界達電位分析 53
4-3-2-3 氣體組成對於細胞貼附的影響 53
4-3-3 薄膜表面型態對PMMA薄膜特性之影響 54
4-3-3-1 薄膜表面型態分析:AFM分析 54
4-3-3-2 薄膜表面型態對於表面水濕性的影響:接觸角測量 54
4-3-3-3 薄膜表面型態對於細胞貼附的影響 55
4-4 CF4氣體電漿改質PLGA薄膜表面特性之研究 55
4-4-1 電漿功率對PLGA薄膜特性之影響 56
4-4-1-1 電漿功率對於表面水濕性及表面電位的影響 56
4-4-1-2 電漿功率對於薄膜表面形態的影響:AFM分析 56
4-4-1-3 電漿功率對於細胞貼附的影響 57
4-4-1-4 電漿功率對於PLGA表面物理化學性質的影響:XPS分析 57
4-5 CF4氣體電漿改質PMMA薄膜表面特性之研究 58
4-5-1 電漿功率對PMMA薄膜特性之影響 58
4-5-1-1 電漿功率對於表面水濕性及表面電位的影響 58
4-5-1-2 電漿功率對於薄膜表面形態的影響:AFM分析 59
4-5-1-3電漿功率對於細胞貼附的影響 59
4-5-1-4 電漿功率對於PMMA表面物理化學性質的影響:XPS分析 59
第五章 討論 104
5-1 高分子材料表面親疏水性對細胞相容性之影響 104
5-1-1 N2/H2氣體電漿改質對PLGA薄膜之影響 104
5-1-2 N2/H2氣體電漿改質對PMMA薄膜之影響 106
5-1-3 CF4氣體電漿改質對PLGA及PMMA薄膜之影響 107
5-2 高分子薄膜表面界達電位對細胞相容性之影響 108
5-2-1 N2/H2氣體電漿功率之影響 108
5-2-2 N2/H2氣體電漿組成比例之影響 109
5-3 高分子薄膜表面化學官能基對薄膜表面界達電位之影響 110
5-3-1 PLGA薄膜表面化學官能基之影響 110
5-3-2 PMMA薄膜表面化學官能基之影響 111
5-4 高分子薄膜表面化學官能基對細胞相容性之影響 112
5-4-1 N2/H2電漿改質後PLGA薄膜表面化學官能基之影響 113
5-4-2 N2/H2電漿改質後PMMA薄膜表面化學官能基之影響 113
5-4-3 PLGA薄膜與PMMA薄膜於N2/H2電漿改質後之比較 114
5-4-4 CF4電漿改質後PLGA薄膜表面化學官能基之影響 115
5-4-5 CF4電漿改質後PMMA薄膜表面化學官能基之影響 116
5-4-6 PLGA薄膜與PMMA薄膜於CF4電漿改質後之比較 116
5-5 高分子薄膜表面型態對細胞相容性之影響 117
5-6 不同氣體電漿來源對細胞相容性之影響 118
5-7 結論 120
5-8 建議 122
第六章 參考文獻 123

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