Complement activation by PEO-grafted glass surfaces

Activation of the complement system is one way in which the human body reac ts to foreign materials that come in contact with blood, Poly(ethylene oxid e) (PEO) has been used quite frequently to modify biomaterial surfaces to p revent protein adsorption and cell adhesion. Despite extensive use of PEG, however, PEG-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 gam ma-irradiation using PEO homopolymer, Pluronic(R) F108 (PF108), and PEO-pol ybutadiene-PEO triblock copolymer (COP5000), Complement activation was asse ssed 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 con centration increased from 0-0.25 mu g/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 o f C3a generated decreased by 70% after the first exposure. This supports th e "single-hit" mechanism in complement activation. PEO homopolymer did not activate complement in bulk solution, and, thus, it appears that C3a comple ment activation by PF108-grafted surfaces is due to the presence of poly(pr opylene oxide) units. Grafting of PEO using PEG-containing block copolymers requires examination of complement activating properties of the non-PEG se gment. (C) 1999 John Wiley & Sons, Inc.