Jahangir A R, McClung W G, Cornelius R M, McCloskey C B, Brash J L, Santerre J P
Department of Biological and Diagnostic Sciences, Faculty of Dentistry, University of Toronto, Toronto, Canada.
J Biomed Mater Res. 2002 Apr;60(1):135-47. doi: 10.1002/jbm.10033.
Polyether-urethanes (PEUs) have been the materials of choice for the manufacture of conventional blood-contacting devices. Nevertheless, biostability and blood compatibility are still among the principal limitations in their long-term application. Studies investigating the development of protective coatings for PEUs have shown that degradation can be reduced with the use of fluorinated surface-modifying macromolecules (SMMs). It has also been hypothesized that SMM-modified PEU surfaces may exhibit improved blood compatibility because other studies have shown a modulation in fibrinogen adsorption onto these surfaces. To determine the blood compatibility of a PEU-containing fluorinated SMMs, a series of in vitro experiments were designed to study the pattern of protein adsorption from plasma and then to assess the nature of platelet adhesion and activation on each substrate. Western blot analysis as well as single protein studies revealed that the dominant "adhesive proteins" [fibrinogen (Fg), fibronectin (Fnc), and vitronectin (Vnc)] were adsorbed on two of the SMM-containing PEUs in lower amounts relative to unmodified base. Platelet adhesion and activation data further highlighted the differences among the various substrates. It was shown that the unmodified base had a higher number of adhered platelets relative to the SMM-modified surfaces, and that of the SMM-containing substrates, which showed the lowest levels of adhesive proteins also, exhibited significantly lower platelet densities. Close morphological examination further revealed that platelets residing on these latter substrates were not appreciably activated. Based on the current evidence, it is believed that the fluorinated SMMs demonstrate good potential for the development of surfaces with minimal thrombogenic character in in vivo applications.
聚醚聚氨酯(PEUs)一直是制造传统血液接触装置的首选材料。然而,生物稳定性和血液相容性仍然是其长期应用的主要限制因素。研究PEUs保护涂层开发的研究表明,使用氟化表面改性大分子(SMMs)可以减少降解。也有人推测,SMM改性的PEU表面可能表现出更好的血液相容性,因为其他研究表明这些表面上纤维蛋白原的吸附有所调节。为了确定含PEU的氟化SMMs的血液相容性,设计了一系列体外实验,以研究血浆中蛋白质吸附的模式,然后评估每种底物上血小板粘附和活化的性质。蛋白质印迹分析以及单一蛋白质研究表明,相对于未改性的基底,主要的“粘附蛋白”[纤维蛋白原(Fg)、纤连蛋白(Fnc)和玻连蛋白(Vnc)]在两种含SMM的PEUs上的吸附量较低。血小板粘附和活化数据进一步突出了各种底物之间的差异。结果表明,相对于SMM改性表面,未改性基底上粘附的血小板数量更多,而含SMM的底物中,其粘附蛋白水平最低,血小板密度也显著较低。仔细的形态学检查进一步表明,位于后一种底物上的血小板没有明显活化。基于目前的证据,相信氟化SMMs在体内应用中具有开发具有最小血栓形成特性表面的良好潜力。