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EVALUATION OF THE HEMOCOMPATIBILITY OF NOVEL POLYMERIC MATERIALS
University of Kalmar, School of Pure and Applied Natural Sciences. (Kristina Nilsson Ekdahl)
University of Kalmar, School of Pure and Applied Natural Sciences.
University of Kalmar, School of Pure and Applied Natural Sciences.ORCID iD: 0000-0002-7192-5794
Department of Oncology, Radiology and Clinical Immunology, Section of Clinical Immunology, Rudbeck Laboratory C5, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

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

Keyword [en]
Polymers, biomaterials, whole blood, complement, coagulation, contact activation, cytokines, hemocompatibility
National Category
Immunology in the medical area
Research subject
Natural Science, Biomedical Sciences
Identifiers
URN: urn:nbn:se:hik:diva-2792OAI: oai:DiVA.org:hik-2792DiVA, id: diva2:298346
Available from: 2010-02-22 Created: 2010-02-22 Last updated: 2018-01-12Bibliographically approved
In thesis
1. Biomaterials and Hemocompatibility
Open this publication in new window or tab >>Biomaterials and Hemocompatibility
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biomaterials are commonly used in the medical clinic today; however, artificial materials can activate the cascade systems in the blood (complement-, coagulation-, contact- and fibrinolytic systems) as well as the platelets to various degrees. When an artificial surface comes in contact with blood, plasma proteins will be adsorbed to the surface within seconds. The composition of the layer of proteins differs between materials and is crucial for the hemocompatibility of the material.

This thesis includes five projects.

In Paper I the anticoagulants heparin and the thrombin inhibitor hirudin were evaluated in a whole blood model. Hirudin was found to be superior to low dose heparin since it did not affect the activation of the complement system nor the leukocytes. The most interesting observation was that expression of TF was seen on surface-attached monocytes in hirudin- treated blood but not heparin blood.

In Paper II peptides from the streptococcal M-protein, which has affinity for the human complement inhibitor C4BP, were attached to a polymeric surface. When being exposed to blood the endogenous complement regulator was enriched at the surface of the material, via the M-peptides. With this new approach we created a self-regulatory surface, showing significant lowered material-induced complement activation.

In Paper III apyrase, an enzyme which hydrolyzes nucleoside ATP and ADP, was immobilized on a polymer surface. Lower platelet activation and platelet-induced coagulation activation was seen for the apyrase-coated surface compared to control surfaces after exposure to whole human blood, due to the enzymes capability to degrade ADP released from activated platelets.

In Paper IV and V we synthesized an array of polymeric materials which were characterized regarding physical-chemical properties, adsorption of plasma proteins, and hemocompatibility. The polymers showed widely heterogeneous protein adsorption. Furthermore, when the polymers were exposed to whole blood, two of the materials showed superior hemocompatibility (monitored as complement- and coagulation activation), compared to the reference poly(vinyl chloride).

Place, publisher, year, edition, pages
Kalmar, Växjö: Linnaeus University Press, 2010. p. 167
Series
Linnaeus University Dissertations ; 2/2010
Keyword
Complement, Coagulation, Whole blood, Biomaterials, Polymers and Hemocompatibility
National Category
Immunology in the medical area
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-5437 (URN)978-91-86491-01-7 (ISBN)
Public defence
2010-01-29, N2007, Smålandsgatan 26, Kalmar, 09:30 (English)
Opponent
Supervisors
Available from: 2010-04-30 Created: 2010-04-29 Last updated: 2018-04-19Bibliographically approved

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Engberg, Anna E.Rosengren-Holmberg, Jenny PNilsson, Per H.Nicholls, Ian A.Nilsson Ekdahl, Kristina

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