利用一步驟氨基丙二腈輔助兩性離子之共聚物的塗佈於抗污之應用

Abstract

在高齡人口增加且醫療支出增加的趨勢下，醫療器材產業蓬勃發展，大多數的醫療器材都需要與人類血液抑或是體液接觸，表面容易吸附非特定性蛋白質或微生物的累積，導致器材效能低落、靈敏度下降，因此在表面修飾抗貼附塗層以阻擋非特異性蛋白質吸附，更進一步抵抗細胞貼附。在本研究中，首先藉由自由基聚合合成含有雙離子性的sulfobetaine的共聚物 (pSBMA-co-AEMA)，並開發一步驟AMN 塗佈的方式將兩性分子之共聚物修飾表面，使其能夠達到抗血清蛋白吸附及纖維母細胞 (fibroblast) 貼附的效果。 本研究首先探討共聚物濃度、SBMA/AEMA比例以及反應時間對修飾表面的影響，藉由纖維母細胞(L929)貼附實驗找到最佳抗貼附條件，接著利用石英微量天平測量血清蛋白吸附進行表面分析，本研究中抗貼附表面可減少80%蛋白質吸附量，並將此表面修飾方法運用在PDMS及玻璃上，證明此方法能夠廣泛應用在不同基質上。不僅如此，長期穩定性也是抗貼附表面非常重要的一環，經由穩定性實驗得知，此表面抗貼附功能能維持至少45天，證實此修飾方法能夠在長時間中仍保持穩定。 PDMS是醫療器材中常見的一種生醫材料，為了模擬醫療器材製備流程，因此將PDMS表面修飾之後，進行環氧二烷及高壓釜滅菌以確保其抗貼附的穩定性。從研究結果顯示，相較於未修飾的PDMS，沒有任何細胞貼附在修飾後的表面，由此可知，經滅菌之後的表面仍然表現出高度抗貼附的能力。在未來研究中，欲將此表面進行動物實驗，觀察是否在動物體內產生異物反應。

Due to the increased elderly population and the trend of medical expenses increasing, the medical device industry is growing rapidly. Most of the medical devices need to contact with human blood or body fluids, so the surface is easy to adsorb the nonspecific proteins and cause accumulation of microorganisms, resulting in low efficiency of devices, and the decreased sensitivity. Therefore, surface modification by antifouling coating is necessary to repel protein adsorption, and further resist the cell attachment. In this study, we synthesized the zwitterionic sulfobetaine containing copolymers (P(SBMA-co-AEMA) via free radical polymerization first. One step AMN assisted zwitterionic copolymers coating was developed for surface modification to achieve the resistance to serum protein adsorption and fibroblast adhesion. In our research, we explored the effects of copolymer concentration, SBMA / AEMA ratio and coating time on the modified surface, and found the optimal condition for antifouling performance through L929 cell adhesion experiments. Then, using quartz crystal microbalance (QCM) to measure serum protein adsorption, it reduced 80% of the amount protein adsorbed. Further, the coating is also applied to PDMS and glass, which proved that the method can be widely used on different substrates. Moreover, long-term stability is also a key point of the antifouling surface; through the stability experiments, the antifouling function can be maintained at least 45 days, confirmed that this modified method remains stable for a long time. PDMS is a common used biomaterial for medical devices; in order to mimic the medical device preparation process, thus we sterilized antifouling modified PDMS by ethylene oxide gas and autoclaving to verify its antifouling stability. The results showed that no cell attached on the modified surface compared to unmodified PDMS. We demonstrated that modified surface displayed highly antifouling performance after sterilization. In the future, we will carry on the animal experiments to observe whether modified PDMS induce the foreign body reaction after implanted into rat model or not.