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Validation of an MPC polymer coating to attenuate surface- induced cross-talk between the complement and coagulation systems in whole blood in in vitro and in vivo models
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. (Nilsson)
Department of Bioengineering, The University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo, 113–8656 Japan.
Department of Bioengineering, The University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo, 113–8656 Japan.
Department of Bioengineering, The University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo, 113–8656 Japan.
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2019 (English)In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 19, no 5, article id 1800485Article in journal (Refereed) Published
Abstract [en]

Artificial surfaces that come into contact with blood induce an immediate activation of the cascade systems of the blood, leading to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Heparin coating has been used to improve hemocompatibility, and another approach is 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings. Here, the aim is to evaluate the hemocompatibility of MPC polymer coating by studying the interactions with coagulation and complement systems using human blood in vitro model and pig in vivo model. The stability of the coatings is investigated in vitro and MPC polymer-coated catheters are tested in vivo by insertion into the external jugular vein of pigs to monitor the catheters' antithrombotic properties. There is no significant activation of platelets or of the coagulation and complement systems in the MPC polymer-coated one, which was superior in hemocompatibility to non-coated matrix surfaces. The protective effect of the MPC polymer coat does not decline after incubation in human plasma for up to 2 weeks. With MPC polymer-coated catheters, it is possible to easily draw blood from pig for 4 days in contrast to the case for non-coated catheters, in which substantial clotting is seen.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2019. Vol. 19, no 5, article id 1800485
Keywords [en]
blood compatibility, blood model systems, coagulation system, complement system, heparin coat, MPC polymer coat
National Category
Clinical Laboratory Medicine Biomaterials Science
Identifiers
URN: urn:nbn:se:uu:diva-374785DOI: 10.1002/mabi.201800485ISI: 000471340300015PubMedID: 30786149OAI: oai:DiVA.org:uu-374785DiVA, id: diva2:1282160
Funder
Swedish Research Council, 2016-2075-5.1Swedish Research Council, 2016-04519The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)
Note

Kazuhiko Ishihara har tillkommit som författare sedan posten lades in som manuskript.

Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-07-31Bibliographically approved
In thesis
1. Regulation of thromboinflammation in therapeutic medicine: Special focus on surface coating strategies
Open this publication in new window or tab >>Regulation of thromboinflammation in therapeutic medicine: Special focus on surface coating strategies
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biomaterials are an integral part of modern health care and offer potential treatment modalities to diseases and conditions otherwise intractable. However, the critical issue herein is incompatibility reactions.

Our innate immune system is fundamental in protection against pathogens and foreign intruders and controls the discrimination between self and non-self. Biomaterials come in contact with blood upon implantation where they are sensed by innate immune mediators which through a cascade of complex, multifaceted reactions induce inflammation as well as thrombosis which may induce biomaterial dysfunction and rejection. This explains why patients undergoing haemodialysis therapy exhibit an increased incidence of whole-body inflammation and other thrombotic events. Similarly, therapeutic cells such as hepatocytes upon implantation initiate an instant blood mediated inflammatory reaction, responsible for cell damage and death via apoptosis.

In order to achieve safer and more efficient therapeutic interventions,  engineering of materials and cells that can avoid these adverse reactions is essential. Fabrication of biomaterials consisting of  coating of bioinert polymers to avoid immune recognition and activation is a promising approach to modulate immune reactions.

In this thesis, we have employed a PEG-lipid polymer coating, which intercalates in to biomembranes via hydrophobic interactions and thus shields from immune rejection. Treatment with PEG-lipid not only makes the surface “invisible” to immune cells but it also acts as a filter which prevents entry of immune cells without inducing cytotoxicity. Results from this thesis illustrate that fabrication of bio-surfaces by bio-inert PEG-lipid polymer is a harmless procedure which not  only attenuates thrombo-inflammation but also assist in design of self-tailored materials for a wide range of biomedical applications.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 71
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1536
National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-374157 (URN)978-91-513-0563-9 (ISBN)
Public defence
2019-03-14, Rudbecksalen, C11, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2019-02-19 Created: 2019-01-24 Last updated: 2019-03-18

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