title: Biomaterials trigger endothelial cell activation when co-incubated with human whole blood.
abstract: Endothelial cell activation resulting from biomaterial contact or biomaterial-induced blood activation may in turn also affect hemostasis and inflammatory processes in the blood. Current in vitro hemocompatibility assays typically ignore these modulating effects of the endothelium. This study describes a co-incubation system of human whole blood, biomaterial and endothelial cells (ECs) that was developed to overcome this limitation. First, human endothelial cells were characterized in terms of their expression of coagulation- and inflammation-relevant markers in response to various activators. Subsequently, their capacity to regulate hemostasis as well as complement and granulocyte activation was monitored in a hemocompatibility assay. After blood contact, quiescent ECs exhibited anticoagulant and anti-inflammatory properties. When they were co-incubated with surfaces exhibiting pro-coagulant or pro-inflammatory characteristics, the ECs down-regulated coagulation but not complement or leukocyte activation. Analysis of intracellular levels of the endothelial activation markers E-selectin and tissue factor showed that co-incubation with model surfaces and blood significantly increased the activation state of ECs. Finally, the coagulation- and inflammation-modulating properties of the ECs were tested after blood/biomaterial exposure. Pre-activation of ECs by biomaterials in the blood induced a pro-coagulant and pro-inflammatory state of the ECs, wherein the pro-coagulant response was higher for biomaterial/blood pre-activated ECs than for TNF-α-pre-activated cells. This work provides evidence that biomaterials, even without directly contacting the endothelium, affect the endothelial activation state with and have consequences for plasmatic and cellular reactions in the blood.
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Herklotz
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Hanke
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hänsel
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Drichel
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Germany.
authors.forename: Monique
authors.initials: M
authors.lastname: Marx
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Germany. Electronic address: maitz@ipfdd.de.
authors.forename: Manfred F
authors.initials: MF
authors.lastname: Maitz
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Werner
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry*; D001769:Blood / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D016207:Cytokines / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology*; D008422:Materials Testing
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D018836:Inflammation Mediators
keywords: Blood; Coagulation; Endothelial cells; Hemocompatibility test; Inflammation