According to the National Joint Registry, Total Knee Replacement (TKR) is generally a successful elective operation, with more than 100,000 primary TKR procedures performed every year in England and Wales alone. However 5-10% require reoperation and replacement within 10 years of initial surgery, with the cost of some procedures reaching £75,000 per patient. Additionally, up to 30% of recipients report little or no symptom improvement and/or dissatisfaction with the results. The increasing cost of current product materials and globally decreasing market prices, together with an ageing population, changing patient expectations and increasing population BMI, creates the opportunity. A PEEK knee product can be manufactured with a 6 minute, one shot moulding process at a significant cost reduction over incumbent materials that can take 6 weeks to manufacture, offering opportunities for supply chain improvements. A first iteration of a PEEK femoral knee component has been developed and has been implanted into a small number of patients in a pre-market, global feasibility study designed to assess safety and efficacy. This device comprises a cemented femoral component used in conjunction with an all polyethylene tibia and patellar replacement. To optimise clinical outcomes for different groups of patients, additional variants of this TKR will be required, such as modular tibial components and cementless fixation options. This research programme is set to revolutionise knee replacement, using advanced materials technology combined with enhanced preclinical evaluation simulation methods to develop an affordable all polymer knee replacement that fixes securely into bone and minimises wear. The research will create a platform from which further medical treatment options could be developed, to meet other currently unmet needs (for example, long term soft tissue repair, facial reconstruction, metal sensitive orthopaedic patients).

Orthopaedic surgeons treat a wide variety of patients with cartilage damage, from young athletes with cartilage injury to elderly patients with advanced osteoarthritis. There are a variety of treatment options, and these are chosen based on the age of the patient. For patients under the age of 35, biological repair is successful. Biological repair includes techniques that try and make the cartilage heal itself by stimulating regenerative cells from the underlying bone (microfracture) or removing healthy cartilage cells from a non load bearing part of the joint, growing them in the laboratory, and re-implanting in the defect. For older patients, total or partial joint replacement is more reliable. The average age of total hip and knee replacement patients in the UK is 69 and 70 years respectively, and these have remained constant over the past five years indicating no trend for surgeons to replace joints of younger patients. There is therefore a wide gap in the treatments available for patients in the 35 to 60 year age bracket who are considered too old for biological repair, but too young to be considered ideal candidates for joint replacement. The aim of the fellowship is to develop the technology for patients in this age group that can replace the cartilage surface without removing bone stock such that any future partial or total joint replacements can be performed as a normal index procedure. To achieve this aim, the fellowship will use advanced materials and manufacturing techniques to create the technology required for cartilage substitution implants with ultra low friction and wear properties that will protect the device from the service loads it will experience in use. In addition to providing the orthopaedic surgeon with a treatment option for the 35-60 year old patient, developing this technology will have application across the whole orthopaedic field. It will generate the mechanical boundary conditions and test methods for further development of biological repair scaffolds and repair material (currently mostly fibrocartilage rather than the desired hyaline cartilage) for patients under 35 years old. The development of polymer technology will provide the information required for low cost all polymer implants that would be suitable for less functionally demanding patients. The manufacturing methods may also be suitable for interpositional implants with tailored frictional properties and morphology to prevent dislocation. Each of these themes will be pursued within the fellowship.

The aim of this place based impact acceleration account (PBIAA) is to support the translation of University research in medical technologies into new clinical products and services. There is a vibrant Medical Technology (MedTech) business cluster in the Yorkshire region, with over 200 companies employing more than 16,000 people, mostly in high value technical roles. The Universities of Leeds and Sheffield have strong track records in engineering and physical sciences research related to MedTech, particularly in areas that mirror the local business strengths (e.g. orthopaedics, dental, implantable devices and surgical technologies). While there is clear synergy between University research strengths and the business prominence in the region, there is currently a gap in the innovation funding pathway that is preventing technology innovations developed at the region's universities from being adopted by local companies. The aim of this PBIAA is to provide support to bridge this gap and build the connections between the academic, industrial and clinical assets in the region that will help grow the regional economy. It is particularly timely because the MedTech sector is transforming and there is increasing integration of new technologies into products and services. There are growing numbers of high-growth, high-innovation MedTech companies in the region with an absorptive capacity to benefit from this PBIAA, but we will also proactively engage with established companies that need to adopt new innovations to address the changing markets. We have worked with civic partners including the West Yorkshire Combined Authority and South Yorkshire Mayoral Combined Authority, NHS Trusts through the Leeds and Sheffield Biomedical Research Centres, local industry, investors and innovation support organisations to develop this proposal and shape the activities to most effectively enable impact to be realised from the region's engineering and physical sciences research base. Commercialisation of innovations in the MedTech sector is challenging due to the regulatory barriers for products intended for use in humans, with evidence from extensive pre-clinical testing required to demonstrate the safety and efficacy. The PBIAA will fund Impact Projects that aim to generate evidence to derisk a technology, both to prove the technical concept is effective and to demonstrate that it is a commercially attractive proposition. A stage-gated approach will be used to encourage higher risk in the early stages and fast failure. These projects will act as exemplars to encourage further business engagement and outcomes will form a portfolio of evidence to inform future activities. The PBIAA will also support activities to build the regional innovation environment. These include a suite of training activities and events that raise understanding of technical advances and translational processes in the MedTech sector, and act to bring together academic, clinical and industrial partners to help build a lasting innovation community. The PBIAA will support events to identify clinical needs, two-way secondments, as well as public and patient engagement activities that aim to improve understanding of needs across the diverse regional population. A dedicated collaboration fund will be used to support impact activities at universities across the region, nurturing the wider regional strengths in this sector, and draw on wider collaborations that utilise the full strengths of the UK research base. The PBIAA will provide regional industry with a vital connection to state-of-the-art research, enabling a sustainable regional research-derived product development pipeline. It will help drive regional economic growth, with new innovations being adopted by regional industry, creating high value jobs and unlocking private sector investment in R&D, supporting a £3bn/year industry beyond 2035.

Our vision is that patients with knee pain receive the right treatment at the right time. In the UK, one third of people aged over 45 have sought treatment for osteoarthritis, and the disease costs the NHS over £5 billion per year. The knee is the most common site for osteoarthritis, with over four million sufferers in England alone. The aging population with expectations of more active lifestyles, coupled with the increasing demand for treatment of younger and more active patients, are challenging the current therapies for knee joint degeneration. There is a major need for effective earlier stage interventions that delay or prevent the requirement for total knee replacement surgery. There are large variations in patients' knees and the way that they function, and it is important that this variation is taken into account when treatments are developed, so that the right treatment can be matched to the right patient. Through this ambitious programme of research we will develop novel testing methods that combine laboratory-based simulation and computer modelling to predict the mechanical performance of new therapies for the knee and enable their design and usage to be optimised. Importantly these tests will take into account the variation in patients' anatomy and knee biomechanics, as well as variations in device design and surgical technique. This will enable different therapies, or different variants of a device, to be matched to different patient groups. The tools will be applied to existing treatments using clinical data to help validate that our model predictions are correct. The outcomes will better define which patients will benefit from a particular intervention and help optimise their usage. We will then apply the methods to new and emerging treatments, including regenerative devices, so that they can be tested and optimised before costly clinical trials take place. We will use these examples as case studies to demonstrate how the new testing methods can optimise the products before they reach the patient, and we will work with industry, standards agencies and regulators to promote the adoption of these methods across the sector. This programme will benefit patients, the NHS and the growing UK industry and science base that are developing new therapies for the knee.

The Centre for Doctoral Training in Tissue Engineering and Regenerative Medicine will provide postgraduate research and training for 75 students, who will be able to research, develop and deliver regenerative therapies and devices, which can repair or replace diseased tissues and restore normal tissue function. By using novel scaffolds in conjunction with the patient`s own (autologous) cells, effective acellular regenerative therapies for tissue repair can be developed at a lower cost, reduced time and reduced risk, compared to alternative and more complex cell therapy approaches. Acellular therapies have the additional advantage as being regulated as a class three medical device, which reduces the cost and time of development and clinical evaluation. Acellular technologies, whether they be synthetic or biological, are of considerable interest to industry as commercial medical products and for NHS Blood and Transplant as enhanced bioprocesses for human transplant tissues. There are an increasing number of small to medium size companies in this emerging sector and in addition larger medical technology companies see opportunities for enhancing their medical product range and address unmet clinical needs through the development of regenerative devices. The UK Life Sciences Industry Strategy and the UK Strategy for Regenerative Medicine have identified this an opportunity to support wealth and health, and the government has recently identified Regenerative Medicine as one of UK`s Great Technologies. In one recent example, we have already demonstrated that this emergent technology be translated successfully into regenerative interventions, through acellular human tissue scaffolds for heart valve repair and chronic wound treatment, and be commercialised as demonstrated by our University spin out Tissue Regenix who have developed acellular scaffold from animal tissue, which has been commercialised as a dCEL scaffold for blood vessel repair. The concept can potentially be applied to the repair of all functional tissues in the body. The government has recognised that innovation and translation of technology across "the innovation valley of death" (Commons Science and Technology Select Committee March 2013), is challenging and needs additional investment in innovation. In addition, we have identified with our partners in industry and Health Service, a gap in high level skills and capability of postgraduates in this area, who have appropriate multidisciplinary training to address the challenges in applied research, innovation, evaluation, manufacturing, and translation of regenerative therapies and devices. This emerging sector needs a new type of multidisciplinary engineer with research and training in applied physical sciences and life sciences, advanced engineering methods and techniques, supported by training in innovation, regulation, health economics and business, and with research experience in the field of regenerative therapies and devices. CDT TERM will create an enhanced multidisciplinary research training environment, by bringing together academics, industry and healthcare professionals in a unique research and innovation eco system, to train and develop the medical and biological engineers for the future, in the emerging field of regenerative therapies and devices. The CDT TERM will be supported by our existing multidisciplinary research and innovation activities and assets, which includes over 150 multidisciplinary postgraduate and postdoctoral researchers, external research funding in excess of £60M and new facilities and laboratories. With our partners in industry and the health service we will train and develop the next generation of medical and biological engineers, who will be at the frontier in the UK in innovation and translation of regenerative therapies and devices, driving economic growth and delivering benefits to health and patients