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Autoregulation of thromboinflammation on biomaterial surfaces by a multicomponent therapeutic coating
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
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2013 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 34, no 4, 985-994 p.Article in journal (Refereed) Published
Abstract [en]

Activation of the thrombotic and complement systems is the main recognition and effector mechanisms in the multiple adverse biological responses triggered when biomaterials or therapeutic cells come into blood contact. We have created a surface which is auto-protective to human innate immunity by combining three fundamentally different strategies, all developed by us previously, which have been shown to induce substantial, but incomplete hemocompatibility when used separately. In summary, we have conjugated a factor H-binding peptide; and an ADP-degrading enzyme; using a PEG linker on both material and cellular surfaces. When exposed to human whole blood, factor H was specifically recruited to the modified surfaces and inhibited complement attack. In addition, activation of platelets and coagulation was efficiently attenuated, by degrading ADP. Thus, by inhibiting thromboinflammation using a multicomponent approach, we have created a hybrid surface with the potential to greatly reduce incompatibility reactions involving biomaterials and transplantation.

Place, publisher, year, edition, pages
2013. Vol. 34, no 4, 985-994 p.
Keyword [en]
Apyrase, Coagulation, Complement, Factor H-binding peptide, Poly(ethylene glycol) (PEG), Surface modification, Autoregulations, Biological response, Biomaterial surfaces, Blood contact, Complement systems, H-binding, Hemocompatibility, Hybrid surface, Innate immunity, Modified surfaces, Multicomponents, Whole blood, Biological materials, Biomaterials, Peptides, Polyethylene glycols, Surface treatment, Surfaces, 5C6 peptide, biomaterial, complement factor H, macrogol, peptide, unclassified drug, article, autoregulation, biotinylation, endothelium cell, erythrocyte, human, inflammation, multicomponent therapeutic coating, peptide synthesis, porcine aortic endothelial cell, priority journal, protein immobilization, thromboinflammation
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-191995DOI: 10.1016/j.biomaterials.2012.10.040ISI: 000313155800014OAI: diva2:600490
Swedish Research Council, 90293501, A0290401, A0290402

K.N.E., J.D.L., B.N. and Y.T. equally contributed to this paper as a supervisor.

Available from: 2013-01-24 Created: 2013-01-15 Last updated: 2013-02-21Bibliographically approved

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