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Reduced oxidative stress in primary human cells by antioxidant released from nanoporous alumina
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
2016 (English)In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 104, no 3, 568-575 p.Article in journal (Refereed) Published
Abstract [en]

Nanoporous alumina elicits different inflammatory responses dependent on pore size, such as increased complement activation and reactive oxygen species (ROS) production, on 200 versus 20 nm pores. In this study, we attempt to further modulate inflammatory cell response by loading nanoporous alumina membranes (20, 100, and 200 nm pores), with an antioxidant, Trolox, for controlled drug release. For mononuclear cells (MNC) no difference in cell response, due to pore size, was seen when cultured on nonloaded membranes. However, when exposed to membranes loaded with Trolox, 100 uM was enough to quench ROS by more than 95% for all pore sizes. Polymorphonuclear cells (PMNC) produced significantly more ROS when exposed to 20 versus 100 nm pores. For Trolox loaded membranes, this trend reversed, due to slower release of antioxidant from the 20 nm pores. Furthermore, Trolox exhibited a unique effect on PMNCs that has not previously been reported: It delayed the production of ROS in a manner distinct from antioxidant activity. The present study confirms that nanoporous alumina is a suitable vehicle for drug delivery, and that Trolox can successfully modulate the inflammatory response of both MNC and PMNCs.

Place, publisher, year, edition, pages
2016. Vol. 104, no 3, 568-575 p.
Keyword [en]
nanoporous alumina; Trolox; mononuclear cells; polymorphonuclear cells; reactive oxygen species
National Category
Immunology Biomaterials Science Engineering and Technology
Identifiers
URN: urn:nbn:se:uu:diva-283488DOI: 10.1002/jbm.b.33427ISI: 000372297100016PubMedID: 25952986OAI: oai:DiVA.org:uu-283488DiVA: diva2:919298
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)
Available from: 2016-04-13 Created: 2016-04-13 Last updated: 2017-11-30Bibliographically approved
In thesis
1. Nanofeatures of Biomaterials and their Impact on the Inflammatory Response
Open this publication in new window or tab >>Nanofeatures of Biomaterials and their Impact on the Inflammatory Response
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Nanomaterials offer an advantage over traditional biomaterials since cells naturally communicate via nanoscale interactions. The extracellular matrix, for example, modulates adhesion and cellular functions via nanoscale features. Thus incorporating nanofeatures into biomaterials may promote tissue regeneration, however in certain forms and doses nanomaterials can also cause harm. A thorough understanding of cell-nanomaterial interactions is therefore necessary to better design functional biomaterials. This thesis focuses on evaluating the effect of nanofeatures on inflammation using two different models: nanoporous alumina and hydroxyapatite nanoparticles (HANPs).

The inflammatory response caused by in vitro exposure of macrophages to nanoporous alumina, with pore diameters of 20nm and 200nm, was investigated. In addition in vivo studies were performed by implantation of nanoporous membranes in mice. In both cases the 200nm pore diameter elicited a stronger inflammatory response.

Nanoporous alumina with 20, 100 and 200nm pores were loaded with Trolox, a vitamin E analogue, in order to scavenge ROS produced by primary human polymorphonuclear (PMNC) and mononuclear (MNCs) leukocytes. Unloaded alumina membranes stimulated greater ROS production from PMNCs cultured on 20nm versus 100nm pores. This trend reversed when PMNCs were cultured on Trolox loaded membranes since Trolox eluted slower from 20nm than 100nm and 200nm pores. ROS produced from PMNCs was reduced between 8-30% when cultured on Trolox loaded membranes. For MNCs, ROS production was not affected by pore size. However when the alumina was loaded with Trolox ROS production was quenched by 95%.

HANPs with distinct morphologies (long rods, sheets, dots, and fibers) were synthesized via hydrothermal and precipitation methods. The HANPs were then exposed to PMNCs, MNCs, and the human dermal fibroblast (hDF) cell line. Changes in cell viability, ROS, morphology, and apoptotic behavior were evaluated. PMNC and hDF viability decreased following exposure to fibers, while the dot particles reduced MNC viability. Fibers stimulated greater ROS production from PMNCs and MNCs, and caused apoptotic behavior in all cell types. Furthermore, they also stimulated greater capsule thickness in vivo, suggesting that nanoparticle morphology can significantly influence acute inflammation.

The outcome of this thesis, confirms the importance of understanding how nanofeatures influence inflammation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. 70 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1374
Keyword
Nanofeatures, alumina, hydroxyapatite, inflammation
National Category
Nano Technology Biological Sciences Materials Engineering
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-284402 (URN)978-91-554-9576-3 (ISBN)
Public defence
2016-06-09, Å2001, Lägerhyddsvägen 1, Uppsala, 09:30 (English)
Opponent
Supervisors
Available from: 2016-05-19 Created: 2016-04-18 Last updated: 2016-06-01

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Pujari-Palmer, ShiuliPujari-Palmer, MichaelKarlsson Ott, Marjam

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