Particulate toxicology and characterisation relating to metal-on-metal hip replacements

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The aim of the project is to characterise the size, composition and number of wear particles in vivo that are produced in poorly performing metal-on-metal (MoM) hip replacements and to investigate how these particles interact with cellular systems in-vitro.The work programme will consist of three inter-related parts:1) The effect of metal particles containing chromium, cobalt and molybdenum on different cells. For example this could include red blood cells, osteoblasts (bone making cells), chondroblasts (cartilage making cells) and macrophages (white blood cells used for immune defence). It will focus on cellular viability, toxicity and whether apoptosis induction (programmed cell death) takes place. Cellular uptake studies will look at preferential cellular ionic uptake location (cytosol or cellular membrane) and the driving forces for such phenomena. This will be examined using techniques such as inductively coupled plasma mass spectrometry (ICP-MS) and immunofluorescence, to locate and potentially quantify the ionic distribution.2) The development of methods for the characterisation of the size, composition and number of wear-metal particles in hip-patient samples. This will involve the development of methods based on the use of single particle (sp) ICP-MS and will involve the optimisation of methods to isolate the particles from the sample matrix using enzymatic digestion and centrifugation.3) Particle imaging electron microscopy. Further characterisation of particulate material to confirm the spICP-MS results will use imaging methods such as scanning electron microscopy (SEM) or transmission electron microscopy (TEM). The analysis of sub-micron particles by electron microscopy will involve optimisation of the SEM system and the application of software used for forensic purposes, that allows for the automatic analysis of particles using low energy lines.The host Supra-Regional Assay Service Trace Element Laboratory has a dedicated research laboratory, instrumentation and research staff for the project. It has considerable experience in the measurement of trace elements and elemental species in human samples and has the facilities to handle human pathological samples.