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In vivo and in vitro evaluation of hydroxyapatite nanoparticle morphology on the acute inflammatory response
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.
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2016 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 90, 1-11 p.Article in journal (Refereed) Published
Abstract [en]

Biomedical implants have been widely used in bone repair applications. However, nanosized degradation products from these implants could elicit an inflammatory reaction, which may lead to implant failure. It is well known that the size, chemistry, and charge of these nanoparticles can modulate this response, but little is known regarding the role that the particle's morphology plays in inducing inflammation. The present study aims to investigate the effect of hydroxyapatite nanoparticle (HANPs) morphology on inflammation, in-vitro and in-vivo. Four distinct HANP morphologies were fabricated and characterized: long rods, dots, sheets, and fibers. Primary human polymorphonuclear cells (PMNCs), mononuclear cells (MNCs), and human dermal fibroblasts (hDFs) were exposed to HANPs and alterations in cell viability, morphology, apoptotic activity, and reactive oxygen species (ROS) production were evaluated, in vitro. PMNCs and hDFs experienced a 2-fold decrease in viability following exposure to fibers, while MNC viability decreased 5-fold after treatment with the dots. Additionally, the fibers stimulated an elevated ROS response in both PMNCs and MNCs, and the largest apoptotic behavior for all cell types. Furthermore, exposure to fibers and dots resulted in greater capsule thickness when implanted subcutaneously in mice. Collectively, these results suggest that nanoparticle morphology can significantly impact the inflammatory response.

Place, publisher, year, edition, pages
2016. Vol. 90, 1-11 p.
Keyword [en]
Hydroxyapatite nanoparticles; Morphology; Mononuclear cells; Polymorphonuclear cells; Reactive oxygen species; In vivo
National Category
Immunology Biomaterials Science Engineering and Technology
URN: urn:nbn:se:uu:diva-283555DOI: 10.1016/j.biomaterials.2016.02.039ISI: 000374618100001PubMedID: 26974703OAI: diva2:919301
VINNOVA, 2010-01907
Available from: 2016-04-13 Created: 2016-04-13 Last updated: 2016-07-11Bibliographically 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.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1374
Nanofeatures, alumina, hydroxyapatite, inflammation
National Category
Nano Technology Biological Sciences Materials Engineering
Research subject
Engineering Science with specialization in Materials Science
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)
Available from: 2016-05-19 Created: 2016-04-18 Last updated: 2016-06-01

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