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Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
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2015 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 36, 55-65 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
Biomaterials, C4 binding protein (C4BP), Complement, Cytokines, Inflammation, In vitro screening
National Category
Biomaterials Science
URN: urn:nbn:se:uu:diva-240199DOI: 10.1016/j.biomaterials.2014.09.011ISI: 000345728200006PubMedID: 25292422OAI: oai:DiVA.org:uu-240199DiVA: diva2:776529
Available from: 2015-01-07 Created: 2015-01-06 Last updated: 2015-01-07Bibliographically approved

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Fromell, KarinHamad, Osama A.Teramura, YujiNilsson, BoEkdahl, Kristina N.
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Clinical ImmunologyDepartment of Chemistry - BMC
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