Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma
2015 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 36, 55-65 p.Article in journal (Refereed) Published
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-gamma, 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.
Place, publisher, year, edition, pages
2015. Vol. 36, 55-65 p.
Biomaterials, C4 binding protein (C4BP), Complement, Cytokines, Inflammation, In vitro screening
IdentifiersURN: urn:nbn:se:uu:diva-240199DOI: 10.1016/j.biomaterials.2014.09.011ISI: 000345728200006PubMedID: 25292422OAI: oai:DiVA.org:uu-240199DiVA: diva2:776529