Biological Effects of Clinically Relevant CoCr Nanoparticles in the Dura Mater: An Organ Culture Study.

Iraklis Papageorgiou,Eileen Ingham,Thomas Abberton,John Fisher,Joanne Tipper,Martin Fuller

doi:10.3390/nano4020485

Abstract

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 of in vitro culture. 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.

Highlights

IntroductionA variety of pathologies can cause low and high back pain including degenerative disc disease
Lower back and neck pain are major health issues in Western countries [1]
The structural arrangement agreed with an ultrastructural study of the human meninges that showed that the dura mater was composed of an outermost loosely arranged fibroelastic layer, a central fibrous layer and an innermost cellular layer [11]

Summary

Introduction

A variety of pathologies can cause low and high back pain including degenerative disc disease. Degenerative disc disease results in abnormal motion leading to biomechanical instability and recurrent pain. Artificial discs include nuclear spacers (e.g., Fernstrom endoprosthesis, Ray prosthetic disc nucleus, Zimmer PEEK Ardis Interbody Inserter), total disc replacement devices (e.g., Charite, ProDisc, Kineflex, Cervicore, Maverick) and elastomeric devices (AcroFlex, Physio-L) [3,4]. All of these devices restore and maintain spinal segment motion while relieving pain. There are, concerns regarding total disc replacements in relation to the generation of wear debris that could lead to osteolysis, as well as other local and systemic effects [1]

Objectives

Results

Conclusion