四乙氧基矽烷與含氟磺酸高分子複合材料塗層之生物相容性研究

一般植入式電子功能器含有電子印刷電路板(Printed circuit board; PCB)和電極，然而電子印刷電路板是須有封裝材料來和生物體組織做隔離，電極部份就需要裸露與生物組織接觸，常被使用的封裝材料即為玻璃，電極則是金屬材料，因為兩者材料性質不同，所以在組裝封裝上就會有材料不相容的問題。 Nafion®有很好的化學防腐蝕性及機械強度，以往Nafion®皆被廣泛應用於一些透析膜，在生物感測器中也被用來做固定生物分子，或做為只讓一些生物分子通過的選擇性膜；而在一些生物陶瓷玻璃中，多含有TEOS這種含矽源的分子，可以水解成SiO2的鍵結，且亦與玻璃基材相結合，這種材料是具有生物相容性。因此本研究提出把Nafion®和TEOS經溶膠-凝膠方式(in situ sol-gel method)的化學反應，製配成複合物，在本研究中，也以不同濃度的Nafion® (5 %；10 %；20 %)，與TEOS混合並作相關的化學及物理特性分析，以及在生物相容性與生物惰性方面，也做了相關探討。在有關改質前後玻璃表面的親疏水性實驗中，我們可以很清楚的了解到有塗覆摻雜Nafion®的溶液，在不同濃度皆有相當低的表面能，意即其相當疏水。而原子力顯微鏡的量測結果可以知道原先無塗覆改質溶液的玻璃表面，相對的平滑(Ra=79.21 nm)，但一有Nafion®的分子存在於表面時，其表面的粗糙度相對地較低；但若Nafion®的濃度攀升到20 %時，其表面粗糙度也相對升高，顯現其材料表面是相當粗糙的。細胞毒性測試方面，複合材料粉末之細胞毒性直接性測試、複合材料塗層之細胞毒性直接性測試、複合材料塗層之細胞毒性間接性測試之三種結果，皆顯示了經sol-gel方式複合而成的溶液，不會對細胞產生毒性反應。在分別測試改質材料上及原培養盤上的細胞相對數量，在含有Nafion®的玻璃改質表面，細胞數目皆小於30 %，意味著此種含氟磺酸高分子材料可以對細胞產生排斥作用，也就是說其分子間的碳氟(C-F)鍵結及帶負電之磺酸根離子(SO3-)，對細胞的影響是產生阻止貼附的效果。在本研究中一系列的測試探討，證明出此種TEOS和Nafion®複合物是不具細胞毒性的生物惰性材料，能應用在植入式功能器中的固定生物分子薄膜，或是封裝基材。而後續的研究探討可以由封裝的應力強度測試、氣體或水氣通透的特性實驗著手，使此複合材料的特性被了解的更多。

關鍵字

TEOS/Nafion®複合物；生物惰性。；封裝材料；細胞毒性；溶膠-凝膠法

並列摘要

An electronic implant device is required to be hermitically packed. In general, the device contains miniaturized electronic printed circuit boards (PCB) and electrodes. The electrodes are usually designed to contact living tissues; contrastly PCB must be properly encapsulated. Thus, the encapsulation materials and the electrodes, which likely are noble metal, are partially contacted. Polydimethylsiloxane (PDMS) and boron silica are commonly used materials in this kind of application for their biocompatible features. To ensure that the contact boundaries between the metal electrodes and the boron silica (or PDMS) are well sealed is a challenge issue. The goal of this study is to develop a biocompatible coating material for sealing the boundaries. Focuses are on synthesizing a coating material that can bind with the boron silica and evaluating the material to be biocompatible. Nafion®, a cationic exchange polymer, is available commercially in a dissolved form. Natures of this polymer include chemistry resistance, thermal stability, high mechanical strength, and non-cytotoxicity. Nafion® has been widely used to immobilize enzymes in biosensor applications. TEOS is a silica based material that is rich with SiO2. One of its characteristics is none cyto-adhesive. More importantly, TEOS can be hydrolyzed and its liquid form can be bonded with glass. Based upon the understanding of Nafion® and TEOS above, an idea of synthesizing a composite using these two materials via in situ sol-gel method is proposed. A series of thorough study were carried out in this course. The feasibility of synthesizing the Nafion®/TEOS composite was first confirmed. Chemical and physical characteristics of the composite with various Nafion® concentrations (5%; 10%; 20%) were analyzed. L-929 cell line was used in our in-vitro studies. Assay such as MTT, cytotoxicity, and agar diffusion followed ISO-10993 to verify the bio-compatible and bio-inert issues of the composites were conducted. The study results are discussed in the following. Contact angle studies on glass substrates with and without the composite coated (or modified) showed that the substrate surfaces with the composite coated on are of low surface energy. This implies that those modified surfaces were hydrophobic. Roughness of glass surface was examined with an atomic force microscope. The roughness of blank glass surfaces (i.e. without the Nafion®/TEOS composite coated) and of glass surfaces with TEOS coated is 79.21 and 198.2 nm, respectively. Surprisingly, the roughness of glass surfaces with the composites 5% and 10% Nafion® coated is 33.2 and 58.65 nm, respectively, which is lower than that of the blank glasses. However, when the composite with 20% Nafion® concentration was examined, its surface roughness increases significantly to 204.7 nm. The results from the cytotoxicity assay using the composites with powder and thin film forms show that the Nafion®/TEOS composites are non-toxic material. The bio-inert studies are for verifying if the composites are bio-inertial materials. In this study, a circular Nafion®/TEOS composite glass plate is placed within a cell culture dish. As a result, the bottom portion of the dish can be divided into two regions. The first region is the Nafion®/TEOS composite glass surface. The second region is the area not covered by the glass. L-929 cells are uniformly seeded onto the dish. MTT tests were conducted at 12, 24, 36 and 48 hours. On average, the cell survival rates are all less than 30% for the first region. On the other hand, the cell survival rates are between 55% and 75% on the second region. This result indicates the L-929 cells do not like to adhere on the Nafion®/TEOS composite surface. This is very likely due to Nafion® because it is a perfluorosulfonic acid polymer whose C-F bonds and SO3- are the main causes. In conclusions, the Nafion®/TEOS composite can be synthesized using in situ sol-gel method. It can be easily coated onto glass substrates and has rather low surface energy. Furthermore, this composite material is non-cytotoxic and bio-inert.

並列關鍵字

Electronic implant device ； Bio-inert ； Hermetic packaging ； In situ sol-gel method. ； Nafion®/TEOS composite ； Cytotoxicity

參考文獻

[1] Tsibouklis, John; Stone, Maureen; Thorpe, Adrian A.; etc. Preventing bacterial adhesion onto surfaces: the low-surface-energy approach. Biomaterials 1999;20:1229-1235

[2] Tsibouklis, John; Graham, Paul; Stone, Maureen; etc. Fluoropolymers with very low surface energy characteristics. Journal of Fluorine Chemistry 2000;104:29-36

[3] Walsh, F. C.; Slade, S.; Campbell, S. A.; Ralph, T. R. Ionic conductivity of an extruded Nafion 1100 EW series of membrane. Journal of The Electrochemical Society 2002;149:A1556-A1564

[4] Hsing, I-Ming; Shao, Zhi-Gang; and Joghee, Prabhuram. Preparation and characterization of hybrid Nafion-silica membrane doped with phosphotungstic acid for high temperature operation of proton exchange membrane fuel cells. Journal of membrane science 2004;229:43-51

[5] Seen Andrew J. Nafion: an excellent support for metal-complex catalysts. Journal of Molecular Catalysis A: Chemical 2001;177:105-112

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四乙氧基矽烷與含氟磺酸高分子複合材料塗層之生物相容性研究

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