Biological Effects of Clinically Relevant CoCr Nanoparticles in the Dura Mater: An Organ Culture Study.
Medical interventions for the treatment of spinal disc degeneration include total disc replacement and fusion devices. There are, however, concerns regarding the generation of wear particles by these devices, the majority of which are in the nanometre sized range with the potential to cause adverse biological effects in the surrounding tissues. The aims of this study were to develop an organ culture model of the porcine dura mater and to investigate the biological effects of CoCr nanoparticles in this model. A range of histological techniques were used to analyse the structure of the tissue in the organ culture. The biological effects of the CoCr wear particles and the subsequent structural changes were assessed using tissue viability assays, cytokine assays, histology, immunohistochemistry, and TEM imaging. The physiological structure of the dura mater remained unchanged during the seven days ofin vitroculture. There was no significant loss of cell viability. After exposure of the organ culture to CoCr nanoparticles, there was significant loosening of the epithelial layer, as well as the underlying collagen matrix. TEM imaging confirmed these structural alterations. These structural alterations were attributed to the production of MMP-1, -3, -9, -13, and TIMP-1. ELISA analysis revealed that there was significant release of cytokines including IL-8, IL-6, TNF-α, ECP and also the matrix protein, tenascin-C. This study suggested that CoCr nanoparticles did not cause cytotoxicity in the dura mater but they caused significant alterations to its structural integrity that could lead to significant secondary effects due to nanoparticle penetration, such as inflammation to the local neural tissue.
IMBE (Institute of Medical & Biological Engineering), School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. I.papageorgiou@leeds.ac.uk.
Iraklis
I
Papageorgiou
IMBE (Institute of Medical & Biological Engineering), School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. thomasabberton@gmail.com.
Thomas
T
Abberton
IMBE (Institute of Medical & Biological Engineering), School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. M.J.G.Fuller@leeds.ac.uk.
Martin
M
Fuller
IMBE (Institute of Medical & Biological Engineering), School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. J.L.Tipper@leeds.ac.uk.
Joanne L
JL
Tipper
IMBE, School of Mechanical Engineering, University of Leeds, Leeds LS2 9JT, UK. J.Fisher@leeds.ac.uk.
John
J
Fisher
IMBE (Institute of Medical & Biological Engineering), School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. E.Ingham@leeds.ac.uk.
Eileen
E
Ingham
cytokines; dura mater; immunohistochemistry; matrix metalloproteinases; meninges; nanoparticles; total disc replacement