Applications for this PhD have now closed.
Location University of Technology Sydney, Faculty of Engineering and Information Technology
Discipline
App. deadline 10/12/2018
Funding
  • Scholarship available
Eligibility Australian and New Zealand residents

Spinal devices and instrumentation, wear particles, neural cells, 3D bioprinting

Value: $27,596

Duration: 3 yrs 

Topic: Spinal devices and instrumentation, wear particles, neural cells, 3D bioprinting

Enquiries:  Professor Joanne Tipper - please contact before applying

School/Centre: School of Biomedical Engineering

Closing date: Monday, 10 December 2018

Domestic candidates only. 

Neural cell responses to wear debris from spinal instrumentation and devices

Our recent research has shown that metal-on-UHMWPE TDR devices wear at similar if not higher levels compared to modern hip and knee replacements. The wear manifests as microscopic wear particles that lead to osteolysis, as described for hip replacements. Metallic spinal fusion devices also generate significant debris and/or corrosion products. Adverse responses have been observed recently in association with total disc replacements, including recent reports describing metallosis and the formation of pseudotumours around metal-on-metal TDRs. Furthermore, there is substantial evidence documenting the release of metallic particulates from spinal fusion instrumentation and the associated inflammatory responses that ensue, in terms of cellular infiltrates and cytokine release (predominantly TNF-α). Clinically there are reports that describe delayed neurological symptoms, including radiculopathy and paraparesis, in patients with metallosis associated with spinal fusion devices. Other reports describe late operative site pain.

The effects of ions and metal debris, which have such a devastating influence on connective tissues in the hip, remain unknown for the neural structures in the spine. Cells of the central nervous system (CNS) are protected by the meninges and the cerebrospinal fluid (CSF). Disruption of these anatomical features makes the spinal cord and adjacent neural structures particularly vulnerable to exposure to tribo-corrosive products. There is evidence that particles in the spine have the ability to cross both the dural barrier and the blood spinal cord barrier. Furthermore, nanoparticles are known to cross the blood brain barrier (BBB); a feature that is currently being exploited as a means to deliver nervous system drugs systemically. There are clear implications for the entry of nanoscale wear particles. This has led to the hypothesis that the barrier functions protecting the spinal cord will be compromised by exposure to metal wear particles and/or ions and that subsequent adverse responses to these species by neural cell populations will result in neurotoxicity, leading to complications such as pseudotumours in the spine and subsequent failure of the implant.

This project will address the following objectives:

    1. Characterisation of tribo-corrosion products (ions and debris) from explanted components and tissues.

      2. Determination of the responses of mixed populations of neural cells to particles and corrosion products in advanced 3D bioprinted tissue culture models.

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