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

Anna E Engberg, Per H Nilsson, Shan Huang, Karin Fromell, Osama A Hamad, Tom Eirik Mollnes, Jenny P Rosengren-Holmberg, Kerstin Sandholm, Yuji Teramura, Ian A Nicholls, Bo Nilsson, Kristina N Ekdahl

Index: Biomaterials 36 , 55-65, (2014)

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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. Copyright © 2014 Elsevier Ltd. All rights reserved.