title: The RGD coupling strategy determines the inflammatory response of human primary macrophages in vitro and angiogenesis in vivo.
abstract: Surface modifications of implants are frequently done using bioactive peptides. However, immune cells such as macrophages might evoke a rejection of an implant due to an undesired activation by the materials. Here, the influence of different strategies for peptide immobilization onto (poly)-vinylidene fluoride (PVDF) on inflammation and angiogenesis is studied. The inflammatory response of human primary macrophages is investigated by analyzing inflammatory cytokine expression. Surface roughness and adsorptive coupling have only minor effects on macrophage activation. Acrylic acid (AAc)-based covalent RGD-coupling leads to the most favorable cellular reaction, indicated by increased VEGF release. Chemical vapor deposition treated surfaces are inert, but additional covalent coupling of RGD induces a pronounced proinflammatory reaction. An in vivo angiogenesis study reveals that covalent coupling of RGD results in delayed but increased angiogenesis. It is concluded that for implant decoration with peptides, the substrate material has to be selected carefully to prevent inflammatory immune responses.
authors.affiliation: Medical Faculty, Interdisciplinary Centre for Clinical Research Aachen (IZKF Aachen), RWTH Aachen, Aachen, Germany; Medical Faculty, Department of Medicine III, RWTH Aachen, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bartneck
authors.forename: Claudia
authors.initials: C
authors.lastname: Skazik
authors.forename: Nora E
authors.initials: NE
authors.lastname: Paul
authors.forename: Jochen
authors.initials: J
authors.lastname: Salber
authors.forename: Doris
authors.initials: D
authors.lastname: Klee
authors.forename: Gabriele
authors.initials: G
authors.lastname: Zwadlo-Klarwasser
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials; D002448:Cell Adhesion; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D011145:Polyvinyls / Q000737:chemistry; D061251:Primary Cell Culture; D013499:Surface Properties / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D005465:Fluorocarbon Polymers
chemical_list: D000179:Acrylates; D001672:Biocompatible Materials; D055767:Immobilized Proteins; D053583:Interleukin-1beta; D009842:Oligopeptides; D011145:Polyvinyls; D042461:Vascular Endothelial Growth Factor A; C467484:VEGFA protein, human; C024865:polyvinylidene fluoride; D005465:Fluorocarbon Polymers; C047981:arginyl-glycyl-aspartic acid; C036658:acrylic acid
keywords: PVDF; cytokine release; gene expression; human primary macrophages; peptides