Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma

• Published in: Biomaterials 2015-01, Vol.36, p.55-65
• Main Authors: Engberg, Anna E, Nilsson, Per H, Huang, Shan, Fromell, Karin, Hamad, Osama A, Mollnes, Tom Eirik, Rosengren-Holmberg, Jenny P, Sandholm, Kerstin, Teramura, Yuji, Nicholls, Ian A, Nilsson, Bo, Ekdahl, Kristina N
• Format: Article
• Language: English
• Subjects: Activation; Advanced Basic Science; Biocompatible Materials - adverse effects; Biomaterials; Biomedical materials; Biomedical Sciences; Biomedicinsk vetenskap; Blood; C4 binding protein (C4BP); Complement; Complement Activation - drug effects; Complement C4b-Binding Protein - immunology; Complement Membrane Attack Complex - immunology; Complement System Proteins - immunology; Correlation; Cytokines; Dentistry; Humans; In vitro screening; Inflammation; Inflammation - blood; Inflammation - chemically induced; Inflammation - immunology; Inhibitors; Interferon-gamma - immunology; Interleukin-17 - blood; Interleukin-17 - immunology; Interleukin-6 - blood; Interleukin-6 - immunology; In vitro screening; Organic Chemistry; Organisk kemi; Polymers - adverse effects; Surgical implants
• ISSN: 0142-9612; 1878-5905; 1878-5905
• DOI: 10.1016/j.biomaterials.2014.09.011

Abstract Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-γ, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard.