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Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma
Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB). Region Skåne.
Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB). Oslo Univ Hosp, Rikshosp, Norway;Univ Oslo, Norway.ORCID-id: 0000-0002-7192-5794
Linnéuniversitetet, Fakulteten för Hälso- och livsvetenskap (FHL), Institutionen för kemi och biomedicin (KOB).
Uppsala University.
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2015 (Engelska)Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 36, s. 55-65Artikel i tidskrift (Refereegranskat) 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. (C) 2014 Elsevier Ltd. All rights reserved.

Ort, förlag, år, upplaga, sidor
2015. Vol. 36, s. 55-65
Nyckelord [en]
Biomaterials, C4 binding protein (C4BP), Complement, Cytokines, Inflammation, In vitro screening
Nationell ämneskategori
Immunologi Biomaterialvetenskap
Forskningsämne
Kemi, Organisk kemi; Naturvetenskap, Biomedicinsk vetenskap
Identifikatorer
URN: urn:nbn:se:lnu:diva-39124DOI: 10.1016/j.biomaterials.2014.09.011ISI: 000345728200006Scopus ID: 2-s2.0-84921965003OAI: oai:DiVA.org:lnu-39124DiVA, id: diva2:781034
Tillgänglig från: 2015-01-15 Skapad: 2015-01-15 Senast uppdaterad: 2018-11-02Bibliografiskt granskad
Ingår i avhandling
1. Interaction between biomaterials and innate immunity with clinical implications
Öppna denna publikation i ny flik eller fönster >>Interaction between biomaterials and innate immunity with clinical implications
2015 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Today there is an increasing clinical demand and expectation of patients for biomaterials, which underscores the importance of discovering the correlations between biomaterials and biological systems, especially blood. When an artificial material makes contact with blood, the first event is a rapid adsorption of plasma protein on the material surface, on top of which the innate immune system is triggered, with potentially detrimental consequences. The work presented in this thesis, reported in four papers, was designed to investigate complications associated with (a) biomaterial-induced immune systems, including activation mechanisms and crosstalk between cascades on the biomaterial surface, and with (b) clinical investigations.

In Paper I and Paper II, a series of studies led to the development of a direct prediction of the subsequent biological events based on the pattern of initially bound proteins. A reciprocal relationship was demonstrated between activation of the contact system and the complement system when they were induced on artificial material surfaces. Based on these studies, a robust and simple method for biocompatibility testing was proposed and validated, yielding high specificity and sensitivity when compared to today’s gold standard. Paper III investigated biomaterial-induced activation of complement and leukocytes in dialysis treatment-related conditions. The results suggested that citrate is more biocompatible than the conventionally used acetate. This reduction in activation could be further enhanced with higher citrate concentrations, suggesting that dialysis fluid containing citrate is a promising alternative to acetate dialysis fluid. Paper IV investigated complement initiation mechanisms with clinical implications. An experimental system was set up to revisit the initiation of the complement alternative pathway, and correlations were found between chaotropic or nucleophilic agents and iC3 generation under physiologically relevant conditions. A clinical study of hepatic encephalopathy patients indicated a direct correlation between elevated plasma ammonia and iC3 formation, as well as with complement activation in vivo

Taken together, these studies have provided a model for a robust biomaterial test and have investigated biomaterial-induced complications in the fluid phase in clinically related conditions; furthermore, the basic mechanisms of complement activation have been dissected in relation to disease symptoms.

Keywords: Complement system, contact system, blood, biomaterials, biocompatibility, in vitro screening, iC3, dialysis

Ort, förlag, år, upplaga, sidor
Växjö: Linnaeus University Press, 2015
Serie
Linnaeus University Dissertations ; 236/2015
Nyckelord
Complement system, contact system, blood, biomaterials, biocompatibility, in vitro screening, iC3, dialysis
Nationell ämneskategori
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
Identifikatorer
urn:nbn:se:lnu:diva-47391 (URN)978-91-87925-87-0 (ISBN)
Disputation
2015-12-18, N2007, Smålandsgatan 24, Kalmar, 09:30 (Engelska)
Opponent
Handledare
Tillgänglig från: 2015-11-26 Skapad: 2015-11-24 Senast uppdaterad: 2015-11-26Bibliografiskt granskad

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Engberg, Anna E.Nilsson, Per H.Huang, ShanRosengren-Holmberg, Jenny P.Sandholm, KerstinNicholls, Ian A.Nilsson Ekdahl, Kristina

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Engberg, Anna E.Nilsson, Per H.Huang, ShanRosengren-Holmberg, Jenny P.Sandholm, KerstinNicholls, Ian A.Nilsson Ekdahl, Kristina
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