以表面誘導聚合技術製備含甲基丙烯酸聚乙二醇酯之聚氟化乙二烯薄膜與其低生物結垢性之探討

Preparation and characterization of poly(vinylidene fluoride) membrane grafted with poly(ethylene glycol) methacrylate via surface-initiated copolymerization and investigation of their low-biofouling property

柯朝寅(Chao-Yin Ko)

指導教授 ： 張雍

中原大學/工學院/化學工程研究所/碩士(2009年)

https://doi.org/10.6840/cycu200900973

摘要

對於使用於人體體內與人體組織接觸之生醫材料，表面抗非特定性生物分子吸附為非常重要的一個環節，當材料表面具有良好的抗生物分子沾黏特性及高效的穩定性，其可有效減少可能對人體產生的危害。在本研究中將選用已被認定具抗生物分子沾黏特性之甲基丙烯酸聚乙二醇酯(poly(ethylene glycol) methacrylate, PEGMA)單體，並使用表面誘導聚合技術將PEGMA接枝於聚氟化乙二烯(poly(vinylidene fluoride), PVDF)薄膜表面。本研究將系統性的探討PEGMA表面接枝之物理及化學結構對於抗生物沾黏特性之表現，於本論文中分成兩部分來進行討論。

本研究第一部份內容主要以探討不同表面誘導聚合方法來製備抗蛋白質沾黏之PVDF超過濾薄膜。製備方式使用表面起始熱誘導、表面自由基誘導及低壓電漿誘導聚合三種表面改質方法將PEGMA接枝共聚合於PVDF薄膜表面。研究中透過紅外線光譜儀、親疏水接觸角量測儀及生物原子力顯微鏡，觀察分析薄膜表面物理性質及化學特性。研究中亦對於不同之聚合改質方式進行比較及分析，探討表面聚合之PEGMA接枝度及表面物理構形與蛋白質吸附現象之關聯性，並進一步探討改質後薄膜於蛋白質溶液之過濾效能。研究結果顯示，藉由表面誘導聚合方法的控制，PVDF薄膜表面之PEGMA接枝量可控制於0.05 mg/cm2 至 1.05 mg/cm2的範圍中。經改質後之PVDF薄膜表面，會產生兩種不同之PEGMA接枝結構: 刷狀(brush-like)構形及網狀(network-like)構形。研究結果發現，網狀構形之PEGMA接枝層之含水量較刷狀構形高，但網狀構形之PEGMA接枝層會產生較低的蛋白質吸附量與較佳的蛋白質抗沾黏之過濾效能。透過第一部份的研究工作，不僅成功使用三種不同的表面改質技術將親水性之PEGMA接枝於疏水性之PVDF薄膜，也將PEGMA接枝結構對於PVDF薄膜抗生物沾黏特性之關連性提供基礎的了解。

本研究第二部份內容主要以常壓電漿誘導聚合改質方法將PEGMA接枝於疏水性之商業化PVDF微過濾薄膜表面，並系統性的探討改質後之PVDF薄膜與其人體血液相容特性之表現。研究中透過紅外線光譜儀、親疏水接觸角量測儀、電子顯微鏡及生物原子力顯微鏡，觀察分析薄膜表面物理性質及化學特性。研究中使用酵素連結免疫吸附分析(enzyme-linked immunosorbent assay, ELISA)來評估人體血漿蛋白於薄膜表面之吸附行為。研究結果顯示，藉由常壓電漿處理時間的控制，在2分鐘的改質時間範圍內，可有效率的調整表面聚合之PEGMA接枝度及改變PVDF薄膜表面之親水程度。隨著PEGMA接枝度及表面含水量的提高，可顯著的降低血漿蛋白於表面吸附量及消除表面血小板貼附及活化情形。由血漿蛋白吸附及血小板貼附測試結果可指出，使用常壓電漿改質法可有效率的製備出高親水性及具高度血液相容性之PVDF薄膜。

關鍵字

低生物結垢性 ； 聚氟化乙二烯 ； 甲基丙烯酸聚乙二醇酯

並列摘要

The first part of this work describes the antifouling property of poly(vinylidene fluoride) (PVDF) membrane associated with surface grafting structures of poly(ethylene glycol) methacrylate (PEGMA) controlled via three different modification approaches of surface-initiated radical graft copolymerization, including thermal-induced radical polymerization, surface-initiated atom transfer radical polymerization (ATRP), and plasma-induced graft-polymerization. The chemical composition and microstructure of the various surface-modified PEGylated PVDF membranes were characterized by Fourier transform infrared spectroscopy (FT-IR), contact angle and atomic force microscopy (AFM) measurements. Antifouling property of the modified PVDF membranes was evaluated according to the amount of protein adsorption and the filtration test for BSA solution in this study. The physical structures of PEGMA coverage on the PVDF membranes can be controlled with a wide range of grafting amount from 0.05 mg/cm2 to 1.05 mg/cm2. Two different physical and chemical structures of PEGylated grafting layers, brush-like PEGMA and network-like PEGMA, on PVDF membrane surface were achieved. Results show that the amount of adsorbed proteins on the modified PVDF membranes depends on the structures of PEGylated grafting layers. Hydration capacity of water molecules in the grafting structure of network-like PEGMA is more than that of brush-like PEGMA. However, it appears that grafting layer of brush-like PEGMA lead to lower protein adsorption and better anti-fouling for BSA filtration than that of network-like PEGMA on PVDF membrane surface. This study not only introduces different practical modification approaches to achieve a hydrophobic PVDF membrane grafting hydrophilic PEGMA, but also provides a fundamental understanding of various PEGylated structures governing the performance of anti-fouling properties.

The second part of this work describes that hydrophobic poly(vinylidene fluoride) (PVDF) microporous membranes grafted with hemocompatible poly(ethylene glycol) methacrylate (PEGMA) were prepared by a highly efficient surface modification via plasma-induced graft-polymerization at atmospheric pressure. The chemical composition, hydrophilicity and morphology of the surface-modified PVDF membranes were characterized by Fourier transform infrared spectroscopy (FT-IR), contact angle, scanning electron microscope (SEM) and bio-atomic force microscopy (bio-AFM) measurements. The plasma protein adsorption on the prepared membranes was evaluated using the method of enzyme-linked immunosorbent assay (ELISA). The grafting coverage of the copolymerized PEGMA and hydrophilicity on the surface of PVDF membranes can be precisely controlled via different plasma jet treating time in the range of 120 sec at atmospheric pressure. The relative nonspecific protein adsorption and platelet adhesion on the resulting membranes from human blood plasma was effectively reduced with increasing of the grafting coverage, as well as hydration capacity, of the PEGMA chain grafted on the PVDF membrane surface. From blood compatible evaluation of plasma protein adsorption and platelet adhesion test in vitro, it is concluded that plasma-induced graft-polymerization at atmospheric pressure provides a potential surface modification approach for the efficient preparation of controllable hydrophilic PVDF membranes with good hemocompatibility.

並列關鍵字

poly(ethylene glycol) methacrylate ； low-biofouling ； poly(vinylidene fluoride)

參考文獻

1. Williams, D. F., The Williams Dicuionary of Biomaterials. Liverpool: Livepool University Press: 1999.

2. Ratner, B. D., Biomaterials Science: An Introduction to Materials in Medicine. 2nd ed.; Elsevier Academic Press: 2004; p 10-19.

4. Hubbel J.A. , L. R., Tissue Engineering. Chem. Eng. New: 1995.

8. Temenoff, J. S.; Mikos, A. G., Biomaterials:The Intersection of Biology and Materials Science. Pearson Education Hall: 2008; p 10.

10. Park, J. B., Biomaterials science and enginerring. Plenum: 1984.