title: The profile of adsorbed plasma and serum proteins on methacrylic acid copolymer beads: Effect on complement activation.
abstract: Polymer beads made of 45% methacrylic acid co methyl methacrylate (MAA beads) promote vascular regenerative responses in contrast to control materials without methacrylic acid (here polymethyl methacrylate beads, PMMA). In vitro and in vivo studies suggest that MAA copolymers induce differences in macrophage phenotype and polarization and inflammatory responses, presumably due to protein adsorption differences between the beads. To explore differences in protein adsorption in an unbiased manner, we used high resolution shotgun mass spectrometry to identify and compare proteins that adsorb from human plasma or serum onto MAA and PMMA beads. From plasma, MAA beads adsorbed many complement proteins, such as C1q, C4-related proteins and the complement inhibitor factor H, while PMMA adsorbed proteins, such as albumin, C3 and apolipoproteins. Because of the differences in complement protein adsorption, follow-up studies focused on using ELISA to assess complement activation. When incubated in serum, MAA beads generated significantly lower levels of soluble C5b9 and C3a/C3adesargin comparison to PMMA beads, indicating a decrease in complement activation with MAA beads. The differences in adsorbed protein on the two materials likely alter subsequent cell-material interactions that ultimately result in different host responses and local vascularization.
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Canada.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Wells
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Canada.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Guo
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Emili
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Canada. Electronic address: michael.sefton@utoronto.ca.
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sefton
mesh_terms: D000327:Adsorption; D001798:Blood Proteins / Q000737:chemistry* / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D003165:Complement System Proteins / Q000737:chemistry / Q000276:immunology*; D008422:Materials Testing; D008863:Microspheres; D010949:Plasma / Q000737:chemistry* / Q000276:immunology*; D011109:Polymethacrylic Acids / Q000737:chemistry*
chemical_list: D001798:Blood Proteins; D011109:Polymethacrylic Acids; D003165:Complement System Proteins
keywords: Complement activation; Mass spectrometry; Methacrylic acid; Polymer beads; Protein adsorption