What might be the effects of titanium debris around the spines of children with scoliosis?

 

One of the BSRF’s research questions is “Can the instrumentation (rods/ implants etc) cause harm in the short or long term?”  The team will set out to answer this question by studying the effect of titanium wear debris on human cells.

Spinal rods are made of metals including titanium, cobalt chromium and stainless steel.  Following NICE guidance in 2014 (1), titanium MAGEC spinal rods have been increasingly used for clinical interventions in early onset scoliosis.  However, issues have been reported including metallosis around explanted MAGEC rods (2, 3).  Explant analysis by our group (4) has found extensive titanium wear debris inside MAGEC rods.  When combined with MAGEC rod seal damage, this likely explains the metallosis seen clinically (4).  The subsequent question is, what is the effect of this titanium wear debris on the growing child?

 

Given high profile concerns regarding metal-on-metal hips, there has been much recent focus on the effects of cobalt and chromium on the human body including work by ourselves (5, 6).  As titanium has not generally formed an articulating surface in joint replacements, so wear debris from it is less common.  Despite this, previous work on titanium wear debris has been done (7, 8).  While it has been suggested that titanium may be less toxic that cobalt chromium (9) it is accepted that titanium causes reactions in human mesenchymal stem cells (10) and titanium debris is known to induce aneuploidy in vitro and in vivo (11).  Moreover, increased titanium ions in the blood of patients with titanium spinal rods has been shown (12).

We wish to add to this body of work.  We have an exceptional combination of clinical, bioengineering and molecular cell biology skills to bring to this project.  Clinical guidance will be provided by Mr Andy Bowey, Consultant Spine Surgeon at the Great North Children’s Hospital in Newcastle upon Tyne.  Bioengineering expertise will be provided by Professor Tom Joyce, Professor of Orthopaedic Engineering at Newcastle University.  Mr Bowey and Prof Joyce have previously and continue to undertake research examining explanted MAGEC rods (4).  Expertise on Molecular Cell Biology with be provided by Dr Alison Tyson-Capper, Reader in Molecular Cell Biology in the Faculty of Medical Sciences at Newcastle University. 

The first stage will be to generate titanium wear debris.  This will be done by articulating titanium test samples against each other using an available wear test rig in the School of Engineering at Newcastle University (13).  The wear debris will then be quantified in terms of particle size and size distribution using an available Nanosight particle analyser (14).  Following this quantification, titanium wear debris will be used to challenge human cells to test biological responses. We will utilise our range of in-vitro cell culture models developed for testing cobalt and chromium wear debris.  Initial endpoint methods will include cell toxicity/viability assays, real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays (ELISA).  These methods will measure any detrimental effects caused by titanium wear debris on cell toxicity, cell invasion/migration and inflammatory responses (5,6).