以仿生錨定結構固定化雙離子硫代甜菜鹼共聚物於多樣性基材產生通用型生物惰性表面

General Bioinert Surfaces via Biomimetic Formula Anchoring of Zwitterionic Sulfobetaine Copolymers on Versatile Substrates

賈維森(Gian Vincent Dizon)

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/cycu201600321

摘要

3, 4-二羟苯丙氨酸(DOPA)與離氨基酸(lysine)是兩種由貽貝分泌出的蛋白質中所發現的胺基酸結構，此兩成分可使貽貝擁有極佳的黏附能力。 另一材料多巴胺，具有與DOPA和離氨基酸相似的結構，同時也具有良好的黏附特性。在此研究中，多巴胺的衍生物，3-甲基丙烯醯胺多巴胺被合成用來作為錨定試劑，因為其具有良好的黏附能力。 從貽貝優秀的黏附特性所得到的啟發，本實驗將合成含有DMA之雙離子共聚高分子，來改質生醫材料使其具有生物惰性性質。本實驗的基板是利用一種簡易的外部接枝方式，將基材浸泡於共聚高分子溶液中16小時，以進行基材表面修飾。並藉由調整DMA與SBAA莫爾比例、共聚高分子溶液濃度和添加劑，以調控出改質矽晶片之最佳化塗佈參數。從實驗結果發現，DMA的莫爾比例只需占共聚高分子含量之30%就能成功地固定在矽晶片上，並且提供良好之生物惰性，展現材料表面的親水性以及抗蛋白質能力之特性。此外，乙二胺(ethylenediamine，EDA)於塗佈溶液中的存在，能使共聚高分子與基材緊密交聯進而提升修飾基材的生物相容性。為了進一步證明其生物惰性特性，本實驗選用血小板和紅血球進行血球細胞貼附實驗。實驗結果可發現改質過後的矽晶片其表面對於兩種血球細胞貼附量皆明顯降低。接著為了展現該共聚高分子塗佈的普遍性，將此共聚高分子溶液塗佈於表面已被修飾成CH3官能基之不鏽鋼和聚苯乙烯盤。經過共聚高分子溶液修飾後的不鏽鋼或聚苯乙烯盤表面其親水性有所提升，進而降低蛋白質的吸附量。另一方面，從結果得知表面改質成CH3官能基之基材，不需加入EDA即可展現出良好的塗佈效果。故本實驗成功的合成出共聚物高分子，並藉由塗佈參數的調整，可於不同疏水性質的基材表面獲得最佳塗佈效果。

關鍵字

仿生錨定試劑； 雙離子共聚物； 生物惰性； 甲基丙烯醯胺多巴胺

並列摘要

3,4-dihydroxy-L-phenylalanine (DOPA) and lysine are amino acids found on the protein secreted by mussels which possesses very good adhesive capabilities. Another material which contains the characteristics of both DOPA and lysine within its similar structure is dopamine, which is also regarded as a well adhesive material. In this research a dopamine derivative, dopamine metharylamide (DMA), was synthesized to make use of its impressive adhesive capabilities as an anchoring agent. Inspired by mussel’s great adhesive capabilities, a zwitterionic copolymer containing the biomimetic structure of DMA was synthesized to modify biomaterials for a general bioinert property. The substrates were modified using a simple grafting unto approach, immersing the substrates in the copolymer solution for 16 hours. The coating procedure was optimized for silicon wafer varying the molar ratios of DMA to SBAA, the concentration of the copolymer solution, and the presence of an additive to the copolymer solution. It was found out that the copolymer containing a minimum mole content of 30% DMA was already able to successfully anchor on the silicon wafer and still provide a general bioinert property seen in the significant increase in hydrophilicity and reduction in protein adsorption. Additionally, the presence of ethylenediamine (EDA) in the coating solution showed enhanced biocompatibility by promoting the crosslinking of the copolymer to the substrate. To further demonstrate its bioinert property, blood cell adhesion experiments was performed using thrombocytes and red blood cells. The modified silicon wafer showed significant reduction in the attachment of both blood cells. Then to demonstrate the universality of the copolymer coating, it was used to modify various substrates namely CH3 modified substrates, stainless steel, and polystyrene plates. The various substrates all exhibited reduction in protein adsorption and increase in hydrophilicity. However, with the results from the CH3 modified substrates it showed that the copolymer coating performed better without the addition of EDA. Thus it was concluded that the copolymer synthesized was able to modify various substrates however variations for the coating parameters is necessary for optimum performance.

並列關鍵字

Biomimetic Anchoring ； Zwitterionic Copolymer ； Bioinert ； Dopamine Methacrylamide

參考文獻

1. Dayicioglu, D., J.C. Oeltjen and K.L. Fan, Plastic Reconstructive and Aesthetic Surgery. 2012.

2. Ratner, B.D., A.S. Hoffman, F.J. Schoen and J.E. Lemons, Introduction - Biomaterials Science: An Evolving, Multidisciplinary Endeavor. 2013. p. xxv-xxxix.

3. Migonney, V., History of Biomaterials. 2014. p. 1-10.

4. Santin, M. and G. Phillips, History of Biomimetic, Bioactive and Bioresponsive Biomaterials. 2012. p. 1-34.

8. Castner, D.G. and B.D. Ratner, Biomedical surface science: Foundations to frontiers. Surface Science, 2002. 500(1–3): p. 28-60.