title: Inflammatory response induced by candidate biomaterials of an implantable microfabricated sensor.
abstract: The implantation of synthetic medical devices is known to generate an immediate and complex material-related inflammatory response. Consequently, 15 candidate materials for a new microfabricated sensor were investigated. A human whole blood model that permits the interaction of all the putative inflammatory systems was used. The experiments were performed by administering 500 μL of lepirudin-anticoagulated blood in each well of a 24-well polystyrene microtiter plate preloaded with the respective materials. The degree of inflammation was evaluated by assessing four complement activation markers, six proinflammatory cytokines, and chemokines, the expression of monocyte tissue factor (TF), as well as platelet activation. The complement system was inhibited with the C5-inhibitor eculizumab. Three of the materials distinctly activated complement through the alternative pathway, whereas the rest of the materials were virtually inert. Notably, the same three materials induced a marked and selective expression of TF as well as the release of five of the six cytokines. All these increases were statistically significant (p < 0.05). Inhibition of complement by the C5-inhibitor virtually abolished TF expression and markedly reduced several of the cytokines, suggesting that complement is a particularly useful tool to reveal the immediate inflammatory-inducing properties of these biomaterials.
authors.affiliation: Institute of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, Oslo, Norway. andrey.sokolov@medisin.uio.no
authors.forename: A
authors.initials: A
authors.lastname: Sokolov
authors.forename: B C
authors.initials: BC
authors.lastname: Hellerud
authors.forename: E A
authors.initials: EA
authors.lastname: Johannessen
authors.forename: T E
authors.initials: TE
authors.lastname: Mollnes
mesh_terms: D001672:Biocompatible Materials / Q000009:adverse effects*; D015374:Biosensing Techniques / Q000295:instrumentation*; D018925:Chemokines / Q000378:metabolism; D003167:Complement Activation; D005947:Glucose / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D055616:Microtechnology / Q000295:instrumentation*; D015539:Platelet Activation; D019736:Prostheses and Implants / Q000009:adverse effects*; D013925:Thromboplastin
chemical_list: D001672:Biocompatible Materials; D018925:Chemokines; D013925:Thromboplastin; D005947:Glucose