Development of defect models for the ankle to evaluate changes in joint geometry and tribology as a predictor for degeneration

The aim of this project is to develop clinically relevant experimental and/or computational models to represent bony defects of the ankle, in order to explore the influence on mechanics and tribology to identify a potential degeneration pathway.

Objectives:
1)To identify the geometric changes in the ankle relating to bony defects
identify typical 'normal' talar geometry
Identify changes in geometry relating:
Haemophilia related defects (typically joint surface geometry)
Osteochondral defect (location and size/shape)

2)To identify changes in mechanical properties of the bone.
Mechanical characterisation of tissues (where available)
Computational modelling based on medical imaging

3)Development of representative defect models (using data from 1 & 2)
Investigation of methods for developing 'degraded bone'
Biochemical degeneration of cadaveric bone tissue
3D printing of talar models with representative defects and bony structure
Computational FE models of the ankle joint

4)To investigate the effect of defects on the tribology of the ankle joint under a range of appropriate conditions(experimentally and/or computationally)
static loading (contact pressure e.g. Tekscan)
experimental testing in a natural joint simulator (fatigue, friction, wear)
Finite element models to investigate range of parameters

Characterisation of the geometry of the natural ankle
Development of novel experimental and/or computational methods focussed on the ankle joint
Limited natural ankle modelling either experimentally or computationally has been undertaken to date, and therefore this project represents a significant bioengineering advance in the ability to develop a model for predicting degeneration.
Potential platform for future treatment development

Regenerative Medicine been defined as "an interdisciplinary approach, spanning tissue
engineering, stem cell biology, gene therapy, cellular therapeutics, biomaterials (scaffolds and matrices),nanoscience, bioengineering and chemical biology that seeks to repair or replace damaged or diseased human cells or tissues to restore normal function, (UK Strategy for Regenerative Medicine). CDT TERM will focus on acellular therapies, scaffolds,autologous cells and regenerative devices, which can be delivered to patients as class three device interventions, thus reducing the time and cost of translation and which provide an opportunity to deliver economic growth and benefits to health in the next decade. The primary beneficiaries of CDT TERM are patients, the health service, UK industry, as well as the academic community and the students themselves. Recognising that the impact and benefit from CDT TERM will arise in the future, the statements describing impact below are supported by evidence of actual impact from our existing research and training.

Patients will benefit from regenerative interventions, which address unmet clinical needs, have improved safety and reliability, have been stratified to meet patients needs and manufactured in a cost effective manner. An example of impact arising from previous students work is a new acellular scaffold for young adult heart valve repair, which has demonstrated improved clinical outcomes at five years.

The Health Service will benefit from collaborations on research, development and evaluation of technologies, through existing partnerships with National Health Service Blood and Transplant NHSBT and the Leeds Biomedical Musculoskeletal Research Unit LMBRU. NHSBT will benefit through collaborative projects, through technology transfer, through enhancement of manufacturing processes, through pre-clinical evaluation of products and supply of trained personnel. We currently collaborate on heart valves, skin, ligaments and arteries, have licensed patents on acellular bioprocesses, and support product and process developments with pre-clinical testing and simulation. LMBRU and NHS clinicians will benefits from our collaborative research and training environment and access to our research expertise, facilities and students. Existing collaborative projects include, delivery devices for minimally manipulated stem cells and applied imaging for early OA.

Industry will benefit from supply of highly trained multidisciplinary engineers and scientists, from collaborative research and development projects, from creation and translation of IP, creation of spinout companies and through access to unique equipment, facilities and expertise. We have demonstrated: successful spin outs in form of Tissue Regenix and Credentis; successful commercialisation of a novel biological scaffolds for vascular patch repair; sustainable long term R and D and successful licensing of technology with DePuy; collaborative research with Invibio, partnering with Simulation Solutions to develop new pre-clinical simulation systems, which been adopted by regulatory agencies such as China FDA. Our graduates and researchers are employed by our industry partners.

The academic community will benefit through collaborative research and access to our facilities. We have funded collaborations with over 30 academic institutions in UK and internationally. The CDT TERM will support these collaborations and the academic partners will support student research and training. The CDT students will benefit from enhanced integrated multidisciplinary training and research, a cohort experience focused on research innovation and translation, access to our research partners, industry and clinicians. Feedback from existing students has identified the benefit of the multidisciplinary experience, the depth and breadth of excellence in our research base, the outstanding facilities and the added value of the cohort training.