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Procoagulant behavior and platelet microparticle generation on nanoporous alumina
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.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology. (Nano-biomaterial research and Tissue Culturing)
2010 (English)In: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 24, no 8, 675-692 p.Article in journal (Refereed) Published
Abstract [en]

In the present work, we have investigated platelet microparticle(PMP) generation in whole blood after contact with nanoporous alumina.Alumina membranes with pore sizes of 20 and 200nm in diameter were incubated with whole blood and the number of PMP in the fluid phase was determined by flow cytometry. The role of the complement system in PMP generation was investigated using an analog of the potent complement inhibitor compstatin. Moreover, the procoagulant activity of the two pore size membranes were compared by measuring thrombin formation. Results indicated that PMP were not present in the fluid phase after whole blood contact with either of the alumina membranes. However, scanning electron microscope micrographs clearly showed the presence of PMP clusters on the 200nm pore size alumina, while PMP were practically absent on the 20nm membrane. We probed no influence of complement activation in PMP generation and adhesion and we hypothesize that other specific material-related protein–platelet interactions are taking place. A clear difference in procoagulant activity between the membranes could also be seen, 20nm alumina showed 100% higher procoagulant activity than 200nm membrane. By combining surface evaluation and flow cytometry analyses of the fluid phase, we are able to conclude that 200nm pore size alumina promotes PMP generation and adhesion while the 20nm membrane does not appreciably cause any release or adhesion of PMP, thus indicating a direct connection between PMP generation and nanoporosity.

Place, publisher, year, edition, pages
SAGE , 2010. Vol. 24, no 8, 675-692 p.
Keyword [en]
nanoporous alumina, nanotopography, platelets, platelet microparticles, procoagulant activity, compstatin
National Category
Chemical Sciences
Research subject
Immunology; Materials Science
Identifiers
URN: urn:nbn:se:uu:diva-130496DOI: 10.1177/0885328209338639ISI: 000277806100001PubMedID: 19581322OAI: oai:DiVA.org:uu-130496DiVA: diva2:349812
Available from: 2010-09-08 Created: 2010-09-08 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, JaanKarlsson Ott, Marjam

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