Experimental evaluation of tissues, devices and interventions

Total joint replacement simulation and biological evaluation

The iMBE houses one of the largest academic facilities in the world for the pre-clinical testing of artificial joint replacements. Our experimental simulators have in excess of 80 stations for studying tribology of hip, knee, spine and ankle replacement devices

Our hip simulators are capable of simulating both standardised gait conditions, as well as different daily activities such as rising from a chair, stair climbing, and stop-start conditions. We can also simulate a range of adverse conditions including translational and rotational component mal-positioning and joint laxity with varied swing phase loads. Our knee simulators are capable of testing to and beyond the ISO standard. They are capable of testing under different kinematic conditions including high flexion gait, and have been used to study the effects of mal-alignment such as femoral condylar lift off.
We use a range of techniques to study component wear and damage (see characterisation of tissues, materials and surfaces).
We have highly sensitive methodologies to allow the isolation of polymer (e.g. UHMWPE), metal (e.g. cobalt chromium and titanium alloy), ceramic (e.g. Biolox Delta) and ceramic-like coating (e.g. silicon nitride, chromium nitride, DLC) wear particles from simulator lubricants. We employ a toolkit of assays for investigating cell viability, inflammatory cytokine release, production of reactive oxygen species and DNA damage that may go on to have adverse effects in patients in the longer term.

Natural ioint biomechanical and tribological simulation

Methods have been developed to investigate the biomechanical and tribological performance of the natural knee and a range of early repair interventions, such as osteochondral grafts and meniscus repair, in a single-station knee joint simulator. These methods have been applied to the natural porcine knee and on human cadaveric tissue. Simulation methods have also been developed in-house for the evaluation of the natural patella-femoral joint. Our single station hip simulator has six degrees of freedom and can be used to study the natural hip. Friction can be assessed, and changes to the hip following testing can also be characterised. We also have more simple geometrical configuration methods that can be used to investigate the fundamental tribology of early interventions under a range of conditions.
Novel in vitro methods have been developed to test vertebrae, intervertebral discs and full functional spinal units under axial static and cyclic loading. Methods of generating fractures in vertebrae and simulating degeneration in the intervertebral discs have enabled us to evaluate a range of treatments including vertebroplasty and nucleus augmentation.

Characterisation of tissues, materials and surfaces

We use gravimetric analysis alongside 2D contacting profilometry or 3D optical profilometry to determine changes in surface roughness and wear performance. Geometric changes are also measured with bespoke programmes on co-ordinate measurement machines and post-processed to determine wear volumes. We can also measure the surface damage deformation and wear in natural cartilage using replicas and an Alicona optical profiler.
We have a range of single and 2-axis materials testing machines to characterise the properties of natural tissues. We have developed specific methods for testing ligaments and other soft tissues. Bespoke testing jigs have also been designed to undertake indentation testing of cartilage under constrained conditions, to characterise the time-dependent properties of the material. The load/displacement data captured from these tests may be analysed in conjunction with finite element models of the experimental setup to determine key properties such as permeability and modulus.
We undertake histological characterisation of natural tissues, tissue engineered constructs and medical devices. We have capabilities for frozen, paraffin and resin histology of soft and hard materials with a wide range of staining protocols.
We qualitatively characterise specific antigens in tissues and cells using immunohistochemistry and immunocytochemistry, and quantitatively characterise using ELISA.
We use colourimetric assays to quantify cell matrix components, for example to measure the lipid content of bone as an indicator of the efficacy of washing processes.

Functional assessment of cardiovascular devices

In order to predict the in vivo functional performance of replacement biological heart valves/roots it is imperative that appropriate pre-clinical test methods are developed and applied. Although international standards exist for synthetic valves, the viscoelastic behaviour of biological valves and their inherent complexity mean that these methods are not always appropriate. It is also important that the methods consider the performance of the valve/root system, to understand the full structure-function relationships, rather than test parts of the biological heart valves/roots in isolation. At Leeds we are developing appropriate pre-clinical test methods to predict in vivo functional performance. Such methods include assessment of hydrodynamic function, biomechanical properties, and currently under development is a method for predicting the real time wear of biological heart valves/roots.

Orthopaedic retrievals evaluation

Collaborating orthopaedic surgeons send us orthopaedic explants and tissue, retrieved from patients at revision surgery as part of an ethically approved study. These are appropriately stored for future research projects. We have an extensive collection of different designs of hip, knee and ankle replacements.
Orthopaedic retrievals we receive are used to inform research projects. Examples of work in this area to date include characterisation of a series of AES total ankle replacements and assessment of impingement damage on the rim of polyethylene cups. We use a range of advanced metrology techniques (see characterisation of tissues, materials and surfaces).
Techniques to digest tissue and characterise wear particles have been developed (see also Total Joint Replacement simulation and biological evaluation), we can observe different particle type from a single sample (for example: polyethylene, hydroxyapatite and metallic debris).
Oxidation of polyethylene due to degradation over time can be assessed with FTIR. An example of previous work on this was characterisation of the oxidation of a silane cross-linked polyethylene cup that had been shelf-stored for about 20 years.