研究羥基與醯胺官能基之分子結構對於抵抗血漿蛋白質吸附與人體血小板貼附的影響

The molecular structure effects of combined hydroxyl and amide group on the resistance of plasma protein adsorption and human platelet adhesion

楊承臻(Cheng-Chen Yang)

指導教授 ： 張雍

中原大學/工學院/化學工程研究所/碩士(2016年)

https://doi.org/10.6840/cycu201600725

摘要

本研究目的為探討羥基和醯胺官能基之分子排列結構對於水膠於抵抗血漿蛋白質吸附與血球貼附之影響。本研究之分子結構設計分為三種類型單體系統，第一類型結構為僅具有羥基官能基單體: (1)甲基丙烯酸羥乙酯 (2-Hdroxyethyl methacrylate, HEMA)與其結構相似物(2)丙烯酸羥乙酯 (2-Hydroxyethyl acrylate, HEA); 第二類型結構為僅具有醯胺官能基單體: (3)丙烯醯胺(Acrylamide, AAm)與其結構衍生物(4)甲基丙烯醯胺(Methacrylamide, MAA); 第三類型結構為同時具有羥基和醯胺官能基單體: (5) N-(2-羥丙基)甲基丙烯醯胺(N-(2-Hydroxypropyl) methacrylamide, HPMA)與(6) N-(2-羥乙基)丙烯醯胺(N-(2-Hyroxyethyl)acrylamide, HEAA)。在製備三種不同類型水膠系統後，比較其不同親水性官能基結構組合對於抵抗血漿蛋白質、血小板和白血球貼附現象的影響。
本研究以微分掃描熱量計(Differential scanning calorimetry, DSC)分別鑑定三種不同類型水膠系統於微觀尺度下之結合水結構型態差異。實驗結果發現醯胺羥基類型之水膠HPMA和HEAA有最佳的水合能力和含量較高的不凍水(non-freezable bound water)。使用酵素連結免疫吸附法分析蛋白質於水膠表面之吸附，分析結果顯示HPMA和HEAA水膠展現優異的抗血漿蛋白質吸附特性。由人體血球貼附於HPMA水膠表面之實驗觀察，結果顯示相當低的血將蛋白吸附進而防止血小板激活與白血球貼附的現象發生。

關鍵字

水膠 ； N-(2-羥乙基)丙烯醯胺 ； N-(2-羥丙基)甲基丙烯醯胺 ； 血漿蛋白質吸附 ； 血小板貼附

並列摘要

The target of this study focuses on the molecular structure effects of hydroxyl and amide groups on the resistance of protein adsorption and blood-cells adhesion. Three types of hydrogel monomer structures were prepared with different hydroxyl and amide functional groups, the first type of monomer structure contains only one hydrophilic hydroxyl group: (1) 2-Hydroxyethyl methacrylate (HEMA) and (2) 2-Hydroxyethyl acrylate (HEA); the second type of monomer structure contains only one hydrophilic amide group: (3) Acrylamide (AAm) and (4) Methacrylamide (MAA); the third type of monomer structure contains both hydroxyl and amide group: (5) N-(2-Hydroxypropyl) methacrylamide (HPMA) and (6) N-(2-Hyroxyethyl)acrylamide (HEAA). After the preparation of three types of monomers into hydrogel systems, the resistance of protein adsorption, platelet adhesion, and leukocyte attachment was evaluated to illustrate the effects of molecular structures combined from different hydrophilic functional groups.
In this study, differential scanning calorimetry (DSC) was used to determine the differences of bound water structures in micro scale from three types of hydrogel systems. It was found that HPMA and HEAA hydrogels have best hydration capability and higher amounts of non-freezable bound water. From the analysis of protein adsorption on the prepared hydrogels by enzyme-linked immunosorbent assay (ELISA), the results showed that HPMA and HEAA hydrogels perform excellent resistance of plasma protein adsorption. From the observation of human blood cells on HPMA hydrogels, the results indicated that extremely low amounts of fibrinogen adsorption resulting the resistance of platelet activation and leukocyte attachment.

並列關鍵字

Hydrogel ； N-(2-Hyroxyethyl)acrylamide ； N-(2-Hydroxypropyl) methacrylamide ； plasma protein adsorption ； platelet adhesion

參考文獻

[1] Lau, K.H.A., C. Ren, T.S. Sileika, S.H. Park, I. Szleifer and P.B. Messersmith, Surface-grafted polysarcosine as a peptoid antifouling polymer brush. Langmuir, 2012. 28(46): p. 16099-16107.

[2] Brash, J.L. and T.A. Horbett, Proteins at Interfaces, Copyright, ACS Symposium Series, Foreword. Journal, 1987. 343(Issue): p. i-iv.

[3] Horbett, T.A. and J.L. Brash, Proteins at Interfaces II, Copyright, 1995 Advisory Board, Foreword. Journal, 1995. 602(Issue): p. i-iv.

[4] Ratner, B.D., A.S. Hoffman, F.J. Schoen and J.E. Lemons, Biomaterials Science. Journal, 2013. p.

[5] Jones, R.G., E.S. Wilks, W.V. Metanomski, J. Kahovec, M. Hess, R. Stepto and T. Kitayama, Compendium of Polymer Terminology and Nomenclature: IUPAC Recommendations, 2008. Journal, 2009. p.