研究反應誘導分子自組裝於疏水性基材表面之雙離子化改質與其生物惰性之控制

Surface Zwitterionization of hydrophobic substrates via Reaction-induced Molecular Self-assembling for bio-inert control

王俞翔(Yu-Hsiang Wang)

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/cycu201600721

摘要

生物材料常應用在醫療目的，且和人體組織、細胞以及血液有直接的接觸。
人體血液是非常複雜的液體，當生物材料和血液接觸會產生一連串的生物反應，如一開始血漿蛋白吸附，進而造成血小板的貼附、聚集、沾黏，甚至體內血栓的形成，當血栓影響血液流量時，血液無法順利流通體內，造成體內形成缺氧的環境，體內廢物無法代謝且累績，導致組織壞死，對於人體具有極大的危害。為了改善此問題，需設計出理想的生物惰性材料，而此材料需具有抗非特異性蛋白沾黏、抵抗細胞及細菌的貼附。
　本論文研究主軸為於疏水性基材表面之雙離子化改質與其生物惰性之控制，研究中選擇親水性的雙離子性材料硫代甜菜鹼(Sulfobetaine methacrylate; SBMA)和具強疏水性材料苯乙烯(Styrene)進行合成，以前研究嘗試將其進行合成應用，但由於極性差異過大，合成後無法找到溶劑溶解此兩性高分子，因此本研究利用誘導分子自組裝同時反應同時塗佈在表面的方式，解決溶劑之問題，並以苯乙烯和疏水表面形成疏水作用力將此兩性高分子均勻鍵結在表面上，研究中分兩種不同的基材進行表面改質，並分別進行血液相容性及生物相容性之測試。
　　論文第一部分以疏水性矽基材進行表面雙離子化改質及相容性的測試，利用誘導分子自組裝的方式修飾表面，調控單體間的比例控制其生物惰性，並以原子力顯微鏡和掃描式電子顯微鏡觀察到此改質方式可均勻且形成一層薄膜在表面上，在血液相容性，以人體血液之血漿蛋白、全血、白血球、血小板、紅血球、貧血小板血漿以及細胞、細菌進行吸貼附測試，並觀察溶血及凝血之情形。
　　聚偏氟乙烯薄膜在已被廣泛使用在工業上，其優點除具有良好的耐化學腐蝕性、耐高溫、耐氧化性、耐候性、高機械強度，還具有壓電性、介電性、熱電性且具強疏水性等，而強疏水性易造成沾黏的產生，但應用在汙水處理上，當材料沾黏時，需停止作業用特殊藥水清洗，影響工廠的運作，損失昂貴金錢及時間。論文第二部分以聚偏氟乙烯薄膜表面進行表面雙離子化改質及相容性的測試，利用誘導分子自組裝的方式修飾表面，調控單體間的比例控制其生物惰性，並以原子力顯微鏡和掃描式電子顯微鏡觀察到此改質方式均勻塗佈在表面上，且利用熱重分析儀分析材料中各成分的含量比例，在血液相容性以人體血液之血漿蛋白、全血、白血球、血小板、紅血球、貧血小板血漿以及細胞、細菌進行吸貼附測試，並觀察溶血及凝血之情形。
　　並嘗試在不同疏水表面如聚二甲基矽氧烷（Polydimethylsiloxane; PDMS）、聚丙烯薄膜（Propylene；PP）、聚四氟乙烯(Polytetrafluoroethene; PTFE)進行表面修飾，同樣以血液相容性之吸貼附測試，發現誘導分子自組裝可以成功通用在修飾不同疏水表面，利用調控單體間的比例控制其生物惰性，相信此研究在未來表面雙離子化改質發展，可以有極大的助益。

關鍵字

雙離子化 ； 抗沾黏 ； 自組裝改質 ； 生物相容性

並列摘要

Biomaterials are commonly used in medical proposes which needs to be directly in contact with human tissue, cells, and blood. Human blood is a very complex substance, when biomaterials are in contact with blood some phenomena will take effect like blood clotting. When biomaterials experience protein adsorption, platelet adsorption comes next and other bio foulants will also attach to the material. Excessive blood clotting can lead to oxygen deprivations in the tissue cells and may lead to fatal effects to human health. An ideal bioinert material needs to be designed in order to solve this problem. A bioinert material needs to exhibit nonspecific protein adsorption resistance, cell attachment, and bacteria attachment.
This research performs surface modification via zwitterionzation of hydrophobic materials and perform a bio-inert control. In this research chose a zwitterionic material sulfobetaine methacrylate (SBMA), together with styrene which have strong hydrophobic property. In our previous work we try to synthesis a copolymer with these materials for different application, but because of the polarity of the components of the copolymer are very different, it is very hard to find an appropriate solvent to dissolve the copolymer. In this study we use reaction-induced molecular self-assembling for bio-inert control. Utilizing the property of styrene that have a strong hydrophobic force between hydrophobic surfaces hence can bind in the surface. In this study modified two materials and test by blood compatibility and general biocompatibility.
The first part focuses on silicon wafer functionalized with CH3 on the surface. Using reaction-induced molecular self-assembling for bio-inert control we modified the CH3 functionalized wafers. Atomic force microscope (AFM) and scanning electron microscope (SEM) were used to evaluate the surface of the modified substrates. For hemocompatibility, different blood cells like platelets, leukocyte, erythrocytes, and whole blood were put in contact with the modified substrates to check for their attachment. Other general biocompatibility test were also performed like protein adsorption using single protein solution and platelet poor plasma, bacterial attachment, tissue cell attachment, clotting time, and hemolysis.
The second part modifies polyvinylidene fluoride (PVDF) which is widely used in water filtration. It have desirable properties like good mechanical strength, and resistance to solvents, acids, bases and heat, but has a strong hydrophobic property hence will be easy to get fouling. If used in industrial water filtration, they use chemicals to clean the fouled membranes which have high costs and not desirable. The tests for surface morphology, general biocompatibility, and hemocompatibility tests were also done with PVDF. Additionally thermogravimetric analysis (TGA) was performed to evaluate the coating density on the membranes.
We also tried to modify different hydrophobic surfaces like polydimethylsiloxane (PDMS), propylene (PP), polytetrafluoroethene (PTFE) and use reaction-induced molecular self-assembling to modify the surface and change ratio to control bio-inert property, we believe this method can provide development of zwitterionzation in the future

並列關鍵字

Zwitterionization ； Anti-fouling ； in-situ self assembling coating ； biocompatibilty.

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