Kidane A, Park K
Purdue University, School of Pharmacy, West Lafayette, Indiana 47907, USA.
J Biomed Mater Res. 1999;48(5):640-7. doi: 10.1002/(sici)1097-4636(1999)48:5<640::aid-jbm7>3.0.co;2-x.
Activation of the complement system is one way in which the human body reacts to foreign materials that come in contact with blood. Poly(ethylene oxide) (PEO) has been used quite frequently to modify biomaterial surfaces to prevent protein adsorption and cell adhesion. Despite extensive use of PEO, however, PEO-induced complement activation has not been examined before. We examined the complement activation by PEO chains grafted to glass surfaces. PEO was grafted to trichlorovinylsilane-treated glass (TCVS-glass) by gamma-irradiation using PEO homopolymer, Pluronic F108 (PF108), and PEO-polybutadiene-PEO triblock copolymer (COP5000). Complement activation was assessed by measuring the plasma C3a level. Of the three polymers grafted (PEO, PF108, and COP5000), only PF108 showed significant increases in complement activation over controls. Complement C3a production on PF108-grafted glass was linearly dependent on surface concentration of grafted PF108. The C3a concentration increased from 46 ng/mL to 316 ng/mL as the surface PF108 concentration increased from 0-0.25 microg/cm(2). Kinetics of C3a generation by PF108-grafted surfaces show that 60% of the steady state C3a concentration was generated during the first hour of plasma exposure. When the same PF108-grafted glass surface was repeatedly exposed to fresh plasma, the amount of C3a generated decreased by 70% after the first exposure. This supports the "single-hit" mechanism in complement activation. PEO homopolymer did not activate complement in bulk solution, and, thus, it appears that C3a complement activation by PF108-grafted surfaces is due to the presence of poly(propylene oxide) units. Grafting of PEO using PEO-containing block copolymers requires examination of complement activating properties of the non-PEO segment.
补体系统的激活是人体对与血液接触的外来物质作出反应的一种方式。聚环氧乙烷（PEO）已被频繁用于修饰生物材料表面，以防止蛋白质吸附和细胞黏附。然而，尽管PEO被广泛使用，但此前尚未研究过PEO诱导的补体激活情况。我们研究了接枝到玻璃表面的PEO链引发的补体激活。通过使用PEO均聚物、普朗尼克F108（PF108）和PEO - 聚丁二烯 - PEO三嵌段共聚物（COP5000）进行γ射线辐照，将PEO接枝到三氯乙烯基硅烷处理的玻璃（TCVS - 玻璃）上。通过测量血浆C3a水平评估补体激活情况。在接枝的三种聚合物（PEO、PF108和COP5000）中，只有PF108相对于对照显示出补体激活的显著增加。PF108接枝玻璃上的补体C3a产生与接枝PF108的表面浓度呈线性相关。随着表面PF108浓度从0 - 0.25μg/cm²增加，C3a浓度从46 ng/mL增加到316 ng/mL。PF108接枝表面产生C3a的动力学表明，在血浆暴露的第一小时内产生了稳态C3a浓度的60%。当相同的PF108接枝玻璃表面反复暴露于新鲜血浆时，首次暴露后产生的C3a量减少了70%。这支持了补体激活中的“单次打击”机制。PEO均聚物在本体溶液中不激活补体，因此，PF108接枝表面的C3a补体激活似乎是由于聚环氧丙烷单元的存在。使用含PEO的嵌段共聚物接枝PEO需要研究非PEO链段的补体激活特性。
