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Time sequence of blood activation by nanoporous alumina: Studies on platelets and complement system
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology. (Nano-biomaterial research and Tissue Culturing)
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology. (Nano-biomaterial research and Tissue Culturing)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
2010 (English)In: Microscopy research and technique (Print), ISSN 1059-910X, E-ISSN 1097-0029, Vol. 73, no 12, 1101-1109 p.Article in journal (Refereed) Published
Abstract [en]

In the present work the time sequence of blood activation by alumina membranes with different porosities (20 and 200 nm in diameter) was studied. The membranes were incubated with whole blood from 2 min to 4 h. Platelet adhesion and activation in addition to complement activation were monitored at different time points. Evaluation of platelet adhesion and activation was done by determining the change in platelet number and the levels of thrombospondin-1 in the fluid phase. Scanning electron microscopy studies were done to further evaluate platelet adhesion and morphology. Immunocytochemical staining was used to evaluate the presence of CD41 and CD62P antigens on the material surface. Complement activation was monitored by measuring C3a and sC5b-9 in plasma samples by means of enzyme immunoassays. Both alumina membranes displayed similar complement activation time profiles, with levels of C3a and sC5b-9 increasing with incubation time. A statistically significant difference between the membranes was found after 60 min of incubation. Platelet activation characteristics and time profile were different between the two membranes. Platelet adhesion increased over time for the 20 nm surface, while the clusters of microparticles on the 200 nm surface did not appreciably change during the course of the experiment. The release of thrombospondin-1 increased with time for both membranes, however much later for the 200 nm alumina (240 min) as compared to the 20 nm membrane (60 min). The surface topography of the alumina most probably influence protein transition rate, which in turn affects material-platelet activation kinetics.

Place, publisher, year, edition, pages
Wiley-Liss Inc. , 2010. Vol. 73, no 12, 1101-1109 p.
Keyword [en]
nanotopography, biomaterial, whole blood, thrombospondin-1, platelet microparticles
National Category
Other Basic Medicine
Research subject
Immunology; Materials Science
Identifiers
URN: urn:nbn:se:uu:diva-110620DOI: 10.1002/jemt.20854ISI: 000284063800005OAI: oai:DiVA.org:uu-110620DiVA: diva2:277462
Available from: 2009-11-18 Created: 2009-11-18 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Effect of Surface Nanotopography on Blood-Biomaterial Interactions
Open this publication in new window or tab >>Effect of Surface Nanotopography on Blood-Biomaterial Interactions
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Biologically inspired materials are being developed with the aim of improving the integration of medical implants and minimizing non-desirable host reactions. A promising strategy is the design of topographically patterned surfaces that resemble those found in the extracellular environment.

Nanoporous alumina has been recognized as a potential biomaterial and as an important template for the fabrication of nanostructures.

In this thesis in vitro studies were done to elucidate the role of alumina nanoporosity on the inflammatory response. Specifically, by comparing alumina membranes with two pore sizes (20 and 200 nm in diameter). Complement and platelet activation were evaluated as well as monocyte/macrophage behaviour.

Whole blood was incubated with the alumina membranes and thereafter the biomaterial surfaces were evaluated in terms of protein and platelet adhesion as well as procoagulant properties. The fluid phase was analyzed for complement activation products and platelet activation markers. Besides, human mononuclear cells were cultured on the alumina membranes and cell adhesion, viability, morphology and release of pro-inflammatory cytokines were evaluated.

The results indicated that nanoporous alumina with 200 nm pores promotes higher complement activation than alumina with 20 nm pores.

In addition, platelet response to nanoporous alumina was found to be highly dependent on the material porosity, as reflected by differences in adhesion, PMP generation and procoagulant characteristics.

A clear difference in monocyte/macrophage adhesion and activation was found between the two pore size alumina membranes. Few but highly activated cells adhered to the 200 nm membrane in contrast to many but less activated monocytes/macrophages on the 20 nm surface.

The outcome of this work emphasizes that nanotopography plays an important role in the host response to biomaterials.

Better understanding of molecular interactions on nano-level will undoubtedly play a significant role in biomaterial implant development and will contribute to design strategies for controlling specific biological events.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 74 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 693
Keyword
nanoporous alumina, nanotopography, biomaterial, platelets, complement system, macrophages, whole blood, inflammatory response
National Category
Other Basic Medicine Immunology in the medical area
Research subject
Immunology; Materials Science
Identifiers
urn:nbn:se:uu:diva-110614 (URN)978-91-554-7668-7 (ISBN)
Public defence
2010-01-20, B21, BMC, Husarg. 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2009-12-16 Created: 2009-11-18 Last updated: 2010-12-21Bibliographically approved

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Ferraz, NataliaHong, Jaan

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