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- Engberg, Anna E., et al.
(författare)
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Blood protein-polymer adsorption : Implications for understanding complement-mediated hemoincompatibility
- 2011
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Ingår i: Journal of Biomedical Materials Research - Part A. - : Wiley. - 1549-3296. ; 97A:1, s. 74-84
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to create polymeric materials with known properties to study the preconditions for complement activation. Initially, 22 polymers were screened for complement activating capacity. Based on these results, six polymers (P1-P6) were characterized regarding physico-chemical parameters, for example, composition, surface area, pore size, and protein adsorption from human EDTA-plasma. P2, P4, and reference particles of polystyrene and polyvinyl chloride, were hydrophobic, bound low levels of protein and were poor complement activators. Their accessible surface was limited to protein adsorption in that they had pore diameters smaller than most plasma proteins. P1 and P3 were negatively charged and adsorbed IgG and C1q. A 10-fold difference in complement activation was attributed to the fact that P3 but not P1 bound high amounts of C1-inhibitor. The hydrophobic P5 and P6 were low complement activators. They selectively bound apolipoproteins AI and AIV (and vitronectin), which probably limited the binding of complement activators to the surface. We demonstrate the usefulness of the modus operandi to use a high-throughput procedure to synthesize a great number of novel substances, assay their physico-chemical properties with the aim to study the relationship between the initial protein coat on a surface and subsequent biological events. Data obtained from the six polymers characterized here, suggest that a complement-resistant surface should be hydrophobic, uncharged, and have a small available surface, accomplished by nanostructured topography. Additional attenuation of complement can be achieved by selective enrichment of inert proteins and inhibitors.
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- Engberg, Anna E., 1982-, et al.
(författare)
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EVALUATION OF THE HEMOCOMPATIBILITY OF NOVEL POLYMERIC MATERIALS
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- When a biomaterial surface comes in contact with blood an immediate adsorption of plasma proteins to the surface will occur, and the cascade systems in the blood, such as the complement, coagulation and contact system, will be activated to various degrees. The intensity of this reaction will determine the hemocompatibility of the materials. Here we present an evaluation of the link between the composition, the physico-chemical properties and the protein adsorption properties of six newly synthesized polymers (P1-P6) and the hemocompatibility.The hemocompatibility of the polymeric surfaces was evaluated in human blood plasma and whole blood. Commercially available polyvinylchloride (PVC) was used as reference material. The hemocompatibility of the polymeric surfaces was evaluated with regard to complement activation (C3a and sC5-9 generation) and coagulation activation (platelet loss and TAT-formation) and cytokine productions (27 analytes in multiplex assay) after contact with whole blood. Contact activation was quantified by analyses of FXIIa-C1INH, FXIa-C1INH, and kallikrein-C1INH complexes.Polymers P2 (p<0.05 for C3a), P3, P5 and P6 showed less complement activation, and polymers P1 and P4 (p<0.05 for platelet loss), as well as P5 and P6 showed less coagulation activation compared with reference PVC. Polymers P1-P3 induced activation of the contact system, P3 being the most potent. Secretion of 17 cytokines including chemokines and growth factors were differentially influenced by the polymers, P1 and P3 being significantly (p<0.05) more compatible for five of the analytes.Collectively these data demonstrate that the composition of the polymers clearly leads to different biological properties as a consequence of distinctive physico-chemical properties and protein adsorption patterns.1
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- Engberg, Anna E., et al.
(författare)
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Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma
- 2015
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 36, s. 55-65
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Tidskriftsartikel (refereegranskat)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-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.
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