帶負電荷高分子鏈段之雙離子性嵌段共聚物於可調控之血液相容性質探討

The Study of Zwitterionic Copolymers Containing Polyanion with Tunable Blood Compatibility

賴家榮(Chia-Jung Lai)

指導教授 ： 張雍

中原大學/工學院/化學工程研究所/碩士(2010年)

https://doi.org/10.6840/cycu201000838

摘要

中文摘要
目前對於開發血液相容性材料界面最具挑戰的問題是如何設計有效的
抗血栓之分子結構與穩定的接枝技術，來防止非特定血漿蛋白吸附及血球活
化貼附。於本研究中，我們將九種不同分子量與鏈段比例之雙離子性嵌段共
聚物poly(11-mercaptoundecyl sulfonic acid)-block- poly(sulfobetaine
methacrylate) (PSAm-b-PSBMAn)，以嵌段共聚物中PSA 負電荷鏈段與
polyTMA 刷狀高分子表面進行靜電作用力吸附而形成離子對鍵結，並探討
其血液相容性質之表現。接著利用表面電漿共振儀(Surface Plasmon
Resonance, SPR)來量測人類血漿白蛋白(Human Serum Albumin, HSA)、人類
血漿球蛋白(γ-globulin)及人類血漿纖維蛋白(Fibrinogen)於不同表面的吸附
行為。從實驗結果發現，共聚物表面具有近似於以化學鍵結之polySBMA
刷狀高分子相同的抗蛋白質吸附能力；在血小板貼附實驗中，使用加鈣離子
之血小板濃厚液進行測試，發現血小板的貼附與PSAm-b-PSBMAn 中SA 及
SBMA 的莫耳比例有關，當同時增加SA 及SBMA 的鏈長時，可以有效地
減少血小板的貼附，甚至能完全抵抗血小板的貼附。此外，本研究更進一步
進行全血溶液的貼附測試，實驗結果顯示，當共聚物中SBMA 含量較高時，
可以降低血球的貼附，並且對於血漿蛋白及血小版的貼附都有很好的抗沾黏
能力。而這種獨特的血液相容性質使得帶電之雙離子性嵌段共聚物更有潛力
地應用於新一代血液接觸式生醫材料的開發。

關鍵字

雙離子性嵌段共聚物 ； 表面電漿共振儀 ； 血液相容性

並列摘要

英文摘要
A current challenge in the synthetic biomaterial surface with high blood
compatibility is to design effective antithrombogenic formula and stable grafting
strategy to prevent nonspecific plasma protein adsorption and blood cell
activation. In this work, a novel zwitterionic copolymer containing polyanion
block for ion-pair anchoring to polycation brushes was developed and
investigated as a biomimetic surface with controlled blood compatibility. Nine
well-defined diblock copolymers of poly(11-mercaptoundecyl sulfonic
acid)-block-poly(sulfobetaine methacrylate) (PSA-b-PSBMA) were synthesized
using atom transfer radical polymerization (ATRP) and varying PSA or PSBMA
lengths. Anchoring tests of PSA-b-PSBMA were performed on a gold surface
grafted with polycation brushes of poly(11-mercapto-N,N,Ntrimethylammonium
chloride) (polyTMA) under a range of copolymer
concentrations. Plasma protein adsorption from single protein solutions of
fibrinogen, γ-globulin and HSA onto self-assembled PSA-b-PSBMA copolymer
surfaces was evaluated using a surface plasmon resonance (SPR) sensor. High
plasma protein resistance of copolymer surfaces can be performed to a
comparable nonfouling level to that of a surface chemically grafted with PSBMA
brushes. Platelet adhesion measurements on copolymer surfaces from recalcified
platelet rich plasma solution show that the platelet activation depends on the
ionic and zwitterionic molar mass ratios of PSA-b-PSBMA. Interestingly, the
increase of both ionic SA units and zwitterionic SBMA units in the copolymers
tends to effectively reduce the activation of platelets, even to a level of
non-platelet adhesion. These copolymer surfaces are further challenged by
testing in contact with human whole blood, demonstrating very low blood cell
adhesion on the observed surfaces containing high zwitterionic SBMA units in
IV
the copolymers, as well as its high resistance to plasma protein adsorption and
platelet adhesion. This unique blood compatibility makes the formula of
ionic-zwitteironic copolymer to be potentially appropriate for blood-contacting
biomaterials.

並列關鍵字

diblock copolymer ； Blood Compatibility ； Surface Plasmon Resonance

參考文獻

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11. Iwasaki, Y., et al., Competitive adsorption between phospholipid and plasma