Geelhood Steven J, Horbett Thomas A, Ward W Kenneth, Wood Michael D, Quinn Matthew J
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, USA.
J Biomed Mater Res B Appl Biomater. 2007 Apr;81(1):251-60. doi: 10.1002/jbm.b.30660.
The long-term function of implantable biosensors is limited by the foreign-body reaction (FBR). Since the acute phase of the FBR involves macrophage attachment mediated by adsorbed fibrinogen, preadsorption, and retention of other proteins might reduce the FBR. The retention of preadsorbed albumin, hemoglobin, von Willebrand's factor, and high-molecular-weight kininogen was therefore measured after exposure to plasma. The retention of preadsorbed proteins after incubation with monocyte cultures and implantation in rats was also measured. Fibrinogen adsorption from plasma to the preadsorbed surfaces was also measured. Hemoglobin adsorption was higher than that for other proteins, and it also had the greatest retention after exposure to blood plasma. When surfaces preadsorbed with hemoglobin were incubated with monocytes, more of the hemoglobin was displaced than that after incubation in plasma, while still more hemoglobin was displaced when the surfaces were implanted in vivo. Protein preadsorption on polystyrene greatly reduced fibrinogen adsorption. However, polyurethane surfaces used for glucose sensors had low fibrinogen adsorption compared with polystyrene, and this low level was not further reduced by preadsorption with other proteins. Preadsorbed proteins on polymers appear to be removed by passive exchange and/or displacement by plasma proteins and by proteases released by monocytes.
可植入生物传感器的长期功能受到异物反应(FBR)的限制。由于FBR的急性期涉及由吸附的纤维蛋白原介导的巨噬细胞附着,其他蛋白质的预吸附和保留可能会减少FBR。因此,在暴露于血浆后测量了预吸附的白蛋白、血红蛋白、血管性血友病因子和高分子量激肽原的保留情况。还测量了与单核细胞培养物孵育并植入大鼠后预吸附蛋白质的保留情况。还测量了从血浆到预吸附表面的纤维蛋白原吸附情况。血红蛋白的吸附高于其他蛋白质,并且在暴露于血浆后其保留量也最大。当预吸附有血红蛋白的表面与单核细胞孵育时,被置换的血红蛋白比在血浆中孵育后更多,而当表面植入体内时,被置换的血红蛋白更多。聚苯乙烯上的蛋白质预吸附极大地降低了纤维蛋白原的吸附。然而,与聚苯乙烯相比,用于葡萄糖传感器的聚氨酯表面的纤维蛋白原吸附较低,并且通过其他蛋白质的预吸附并没有进一步降低这种低水平。聚合物上预吸附的蛋白质似乎通过被动交换和/或血浆蛋白以及单核细胞释放的蛋白酶的置换而被去除。