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IMMOBILIZATION OF APYRASE CREATES AN ANTITHROMBOTIC BIOMATERIAL SURFACE
University of Kalmar, School of Pure and Applied Natural Sciences.
University of Kalmar, School of Pure and Applied Natural Sciences. (Kristina Nilsson Ekdahl)
Div. Clinical Immunology, Rudbeck Laboratory, University Hospital, Uppsala.
Department of Clinical Chemistry, Laboratory Medicine, University Hospital, Linköping.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Blood incompatibility reactions caused by surfaces often involve platelet activation and subsequent platelet-initiated activation of the coagulation and complement cascades. The goal of this proof-of-principle study was to immobilize apyrase on a biomaterial surface in order to develop an enzymatically active surface that would have the capacity to inhibit platelet activation by degradating ADP. We were able to immobilize apyrase on a polystyrene surface with preservation of the enzymatic activity. We then analyzed the hemocompatibility of the apyrase surface and of control surfaces (serum albumin, avidin, polystyrene, and glass) by incubation with platelet-rich plasma (PRP) or whole blood. Monitoring of markers of platelet, coagulation, and complement activation and staining of the surfaces revealed decreased levels of platelet and coagulation activation parameters on the apyrase surface. The level of complex formation between antithrombin and thrombin or factor XIa and the extent of the platelet loss were significantly lower on the apyrase surface than on any of the control surfaces. No significant differences were seen in complement activation (C3a levels). Staining of the apyrase surface revealed low platelet adherence and no formation of granulocyte-platelet complexes. These results demonstrate that it is possible to create an anti-thrombotic surface targeting the ADP amplification of platelet activation by immobilizing apyrase.

Keywords [en]
Hemocompatibility, biomaterials, platelets, coagulation
National Category
Immunology in the medical area
Research subject
Natural Science, Biomedical Sciences
Identifiers
URN: urn:nbn:se:hik:diva-2790OAI: oai:DiVA.org:hik-2790DiVA, id: diva2:298342
Available from: 2010-04-07 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
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)9789186491017 (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: 2023-01-03Bibliographically approved

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Engberg, Anna

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