Biomaterials. 2014 Oct 4. pii: S0142-9612(14)01009-6. doi: 10.1016/j.biomaterials.2014.09.011. [Epub ahead of print]
Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma.
Engberg AE1, Nilsson PH2, Huang S3, Fromell K4, Hamad OA4, Mollnes TE5, Rosengren-Holmberg JP6, Sandholm K3, Teramura Y7, Nicholls IA8, Nilsson B4, Ekdahl KN9.
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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-?, 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.
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