Enhanced stratified pre-clinical simulation of the natural knee

The clinical need for this project is in the ability to develop and translate safe and reliable medical device technology in the tibio-femoral joint for treatment of degenerative joint disease. Current options for young and active patients with degenerative joint disease - such as mosaicplasty or MACI - are limited, with very limited success, and can be costly. Further, such interventions have not been pre-clinically tested. Surgeons are reluctant to carry out total joint replacement in younger patients, leaving them in pain and for the condition to worsen before any intervention takes place. There is a clinical need both for improved interventions, and for stratified pre-clinical simulation methods to assess the intervention before it is offered to the patient. Such pre-clinical simulation methods will ultimately be adopted by companies developing tissue repair interventions to support their product development process and to reduce risk of costly failures both to them and patients.


The research challenge is to develop experimental simulation methods that can be used to pre-clinically assess and predict biomechanical and tribological function of tissue repair interventions in the natural tibio-femoral joint.

The specific research questions are as follows:
1. Can knee experimental simulation models be developed that mimic knee conditions from patients with different knee diseases and pathology (e.g. cartilage defect, ligament defect, meniscus defect, bone defect)?
2. Can enhanced pre-clinical experimental simulation methods be developed that can evaluate different knee therapies and interventions? And differentiate between different interventions (of the same type)?

Addressing these questions will guide the stratification and development of enhanced experimental simulation methods for biomechanical/tribological function.

Currently scaffolds or other tissue repair interventions move directly into animal studies without functional tribological or biomechanical studies, which can lead to costly failures in animals as well as in the clinic. Projects to commercially develop and get CE mark for early repair interventions such as scaffolds cost of the order of £1 to 3m, followed by similar investments to support clinical trials and post market activity. Pre-clinical simulation will support this activity and reduce the risk of unsuccessful outcomes in clinical studies.

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.