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Nanoporesize affects complement activation
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Surface Biotechnology.
2008 (English)In: Journal of biomedical materials research. Part A, ISSN 1552-4965, Vol. 87, no 3, p. 575-81Article in journal (Refereed) Published
Abstract [en]

In the present study, we have shown the vast importance of biomaterial nanotexture when evaluating inflammatory response. For the first time in an in vitro whole blood system, we have proven that a small increase in nanoporesize, specifically 180 nm (from 20 to 200 nm), has a huge effect on the complement system. The study was done using nanoporous aluminiumoxide, a material that previously has been evaluated for potential implant use, showing good biocompatibility. This material can easily be manufactured with different pore sizes making it an excellent candidate to govern specific protein and cellular events at the tissue-material interface. We performed whole blood studies, looking at complement activation after blood contact with two pore size alumina membranes (pore diameters, 20 and 200 nm). The fluid phase was analyzed for complement soluble components, C3a and sC5b-9. In addition, surface adsorbed proteins were eluted and dot blots were performed to detect IgG, IgM, C1q, and C3. All results point to the fact that 200 nm pore size membranes are more complement activating. Significantly, higher values of complement soluble components were found after whole blood contact with 200 nm alumina and all studied proteins adsorbed more readily to this membrane than to the 20 nm pore size membrane. We hypothesize that the difference in complement activation between our two test materials is caused by the type and the amount of adsorbed proteins, as well as their conformation and orientation. The different protein patterns created on the two alumina membranes are most likely a consequence of the material topography.

Place, publisher, year, edition, pages
2008. Vol. 87, no 3, p. 575-81
Keywords [en]
nanotopography, nanoporous alumina, complement, whole blood, protein adsorption
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-88357DOI: 10.1002/jbm.a.31818ISI: 000260984800002PubMedID: 18186072OAI: oai:DiVA.org:uu-88357DiVA, id: diva2:158067
Available from: 2009-01-30 Created: 2009-01-29 Last updated: 2009-07-13Bibliographically 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. p. 74
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 693
Keywords
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: 2018-01-12Bibliographically approved

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