Zhang Zheng, Zhang Min, Chen Shengfu, Horbett Thomas A, Ratner Buddy D, Jiang Shaoyi
Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USA.
Biomaterials. 2008 Nov;29(32):4285-91. doi: 10.1016/j.biomaterials.2008.07.039. Epub 2008 Aug 21.
In this work, five self-assembled monolayers (SAMs) and three polymeric brushes with very low fibrinogen adsorption were prepared. The five SAMs are oligo(ethylene glycol) (OEG), phosphorylcholine (PC), oligo(phosphorylcholine) (OPC), and two mixed positively and negatively charged SAMs of SO(3)(-)/N(+)(CH(3))(3) (SA/TMA) and COO(-)/N(+)(CH(3))(3) (CA/TMA). Three polymer brushes were prepared on gold surfaces via surface-initiated atom transfer radical polymerization (ATRP) using three monomers, sulfobetaine methacrylate (SBMA), carboxybetaine methacrylate (CBMA), and oligo(ethylene glycol) methyl ether methacrylate (OEGMA). Surface plasmon resonance (SPR) measurements show that although all of these surfaces are "nonfouling" to fibrinogen adsorption from buffer solution, their protein adsorption from undiluted human blood plasma varies widely. Polymer brushes exhibit much lower protein adsorption from plasma than any of the five SAMs tested. However, platelet adhesion measurements on plasma-preadsorbed surfaces show that all of these surfaces have very low platelet adhesion. Clotting time measurements using recalcified platelet poor plasma (PPP) incubation with the eight types of surfaces show that they do not shorten clotting times. Linear polymers of polySBMA and polyCBMA with similar molecular weights were also synthesized and characterized. In the presence of polyCBMA linear polymers, the clotting time of PPP was prolonged and increased with the concentration of the polymer, while no anticoagulant activity was observed for the polySBMA or PEG polymers. The unique anticoagulant activity of polyCBMA, as well as its high plasma protein adsorption resistance, makes polyCBMA a candidate for blood-contacting applications.
在本研究中,制备了五种自组装单分子层(SAMs)和三种纤维蛋白原吸附率极低的聚合物刷。这五种SAMs分别是聚乙二醇(OEG)、磷酸胆碱(PC)、聚磷酸胆碱(OPC),以及两种带正负混合电荷的SAMs,即SO(3)(-)/N(+)(CH(3))(3)(SA/TMA)和COO(-)/N(+)(CH(3))(3)(CA/TMA)。通过表面引发原子转移自由基聚合(ATRP),使用三种单体,甲基丙烯酸磺酸甜菜碱(SBMA)、甲基丙烯酸羧酸甜菜碱(CBMA)和聚乙二醇甲基醚甲基丙烯酸酯(OEGMA),在金表面制备了三种聚合物刷。表面等离子体共振(SPR)测量表明,尽管所有这些表面对缓冲溶液中的纤维蛋白原吸附都具有“抗污染”性,但其对未稀释人血浆中蛋白质的吸附差异很大。聚合物刷对血浆中蛋白质的吸附比所测试的五种SAMs中的任何一种都低得多。然而,对血浆预吸附表面的血小板黏附测量表明,所有这些表面的血小板黏附率都非常低。使用重新钙化的少血小板血浆(PPP)与这八种类型的表面孵育进行凝血时间测量表明,它们不会缩短凝血时间。还合成并表征了具有相似分子量的聚SBMA和聚CBMA线性聚合物。在聚CBMA线性聚合物存在下,PPP的凝血时间延长,并随聚合物浓度增加而增加,而聚SBMA或聚乙二醇聚合物未观察到抗凝活性。聚CBMA独特的抗凝活性及其高血浆蛋白吸附抗性,使其成为血液接触应用的候选材料。