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BLOOD PROTEIN-POLYMER ADSORPTION FINGERPRINTING:IMPLICATIONS FOR UNDERSTANDING HEMOCOMPATIBILITYAND FOR BIOMATERIAL DESIGN
University of Kalmar, School of Pure and Applied Natural Sciences. (Kristina Nilsson Ekdahl)
University of Kalmar, School of Pure and Applied Natural Sciences.
Department of Pathology, University of Pennsylvania, 401 Stellar Chance, Philadelphia, PA 19104, USA.
Department of Pathology, University of Pennsylvania, 401 Stellar Chance, Philadelphia, PA 19104, USA.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Within seconds after an artificial material has been implanted into the blood thesurface will be covered by adsorbed plasma proteins. The composition of theprotein layer is determined by the physical-chemical properties of the surface. Asthe layer itself will become the new interface between the material and blood, itis of major importance for the hemocompatibility. In this project we have studiedthe adsorption of proteins to a model material (polystyrene, PS) with the peptidemass fingerprint technique (PMF) analyzed on a Matrix Assisted LaserDesorption/Ionization Time-of-Flight (MALDI-TOF). To further be able to studythe adsorption of plasma proteins to polymer surfaces, we have synthesized 33new polymer compositions with variable surface properties. Six of thosepolymers were selected and their protein binding ability was determined as wellas quantification of adsorption of 20 plasma proteins to the surface of thepolymers. Our results showed that fourteen high abundant plasma proteins werepositively identified on the PS-surface by MALDI-TOF. Further, the resultsshowed that the synthesized polymers had very distinctive adsorption patterns,with enrichment of different proteins after incubation in plasma and serum. Oneof the polymers was shown to adsorb large amounts of the complementactivating recognition protein C1q, which makes this polymer to a potentialactivating surface. Two of the polymers showed a clear enrichment of thecomplement regulating protein vitronectin as well as two apolipoproteins (AI andAIV) to the surface of the polymers, while some of the polymers bound proteinsapproximately in correlation to the concentration found in plasma.

Keywords [en]
Polymers, biomaterials, plasma proteins, protein adsorption hemocompatibility
National Category
Immunology in the medical area
Research subject
Natural Science, Biomedical Sciences
Identifiers
URN: urn:nbn:se:hik:diva-2791OAI: oai:DiVA.org:hik-2791DiVA, id: diva2:298345
Available from: 2010-03-22 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
Keywords
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

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