The EPSRC Centre in Innovative Manufacturing in Medical Devices will research and develop advanced methods for functionally stratified design and near patient manufacturing, to enable cost effective matching of device function to the patient needs and surgical environment. This will deliver "the right product, by the right process to the right patient at the right time" to an enhanced standard of reliability and performance. The centre will research and develop: 1) Functionally stratified design systems, which will be initially applied to existing device manufacturing processes and subsequently to the manufacture of scaffolds, developing novel pre-clinical simulation methods, which match implant design to patient function, delivering a cost effective Stratified Approach for Enhanced Reliability (SAFER) 2) Innovative near patient manufacturing processes, enabled by stratified and individualised definitions of patient need, to provide a more cost effective approach to personalised devices. The two flagship challenges will be integrated with the key platform capabilities, across the centre to generate, for the first time, a closed loop design and manufacturing framework for medical devices to deliver enhanced performance and reliability. These innovative design and manufacturing advances will focus in the first instance on class 3 medical devices for musculoskeletal disease, where the cost of device failure and need for throughout life reliability are high. The National Centre will develop, lead and integrate an international network of industrialists, academics, clinicians and regulatory body representatives in order to support the musculoskeletal medical device manufacturing industry to deliver the innovative design and manufacturing challenges and implement the outcomes into manufacturing practice in a global highly regulated market. The Centre will create the research infrastructure, tools and methods, expertise and suitably qualified personnel to support continued innovation and growth of the medical device manufacturing sector in the UK. To do so, the Centre will work across the EPSRC priority research areas "Manufacturing the Future" and "Towards next generation healthcare," drawing upon capabilities and collaborating with existing centres of excellence. The Centre will provide a platform for fundamental innovative device manufacturing research and promote its rapid exploitation by industry through outreach and translation activities and a generic platform for diversification into other technologies. It will grow the UK's research capability in medical device manufacturing research to underpin the development of next generation medical devices and the development of high quality manufacturing processes to provide cost effective, reliable and effective devices. It will be applied to enhanced manufacturing of existing devices such as joint replacements and support manufacture of new products and biomaterial scaffolds. The Centre will operate across five leading academic centres of excellence in the field. The Centre will be led by Leeds University (Fisher, Williams, Ingham, Wilcox, Jennings and Redmond) and will be supported by collaboration from Newcastle (Dalgarno and McKaskie), Nottingham (Grant, Ahmed and Warrior), Sheffield (Hatton) and Bradford (Coates). The Centre will work closely with major manufacturers and users including surgeons who see at first hand the challenges of patient and surgical variation. The Centre will provide a platform for developing fundamental medical device manufacturing science and promote its rapid exploitation by industry.

The joints of the body are frequently involved in bone breaks, typically classified as intra-articular fractures. If a joint is to function properly again, that is to provide pain-free stability and movement, the broken pieces of the joint must be subjected to an anatomic reduction e.g. put back together as perfectly as possible. This project's aim is to set a research basis for creating a robotics device for precise anatomic reduction of complex, joints' fractures using the state of the art of 3D imaging, pattern recognition and robotics. The cost of trauma in hospitals is massive and a saving that robotics could potentially bring is promising. We believe that Bristol Robotics Laboratory's vibrant cross-disciplinary environment and its close association with Bristol Royal Infirmary places the investigators in an excellent position to exploit the opportunity of combining their robotics and clinical expertise with commercial 3D imaging software solutions developed by Simpleware.Trauma accounts for the highest proportion of healthcare expenditure. The BRI Limb unit has been at the forefront of injury research for the past three decades. BRL has, on the robotics side, been a fast developing robotics laboratory with a wide expertise in many areas of service and swarm robots. In order to promote the research in the area of orthopaedic robotics, we have formed a collaboration between the department of orthopedic surgery at the University of Bristol (Professor Roger Atkins), the Bristol Robotics Laboratory (Dr S Dogramadzi), the Centre for Fine Print Research at the University of the West of England (Dr P Walters and Dr D Huson) and a software company (Simpleware Ltd). This proposal is a first attempt to initiate the realization of an ambitious idea that can potentially bring benefits to a broad community of stakeholders. It is a feasibility study that aims to develop a novel robotic device capable of reducing complex joint fractures at the appropriate level of autonomy. An automated 3D jigsaw solving algorithm needs to be developed at this stage that would allow calculation of the optimum paths in overall alignment of the broken joint's segments. When the fracture is successfully reduced in simulation, the next step is to develop a robotic device to manipulate the fractured joint's parts using a fine wire circular frame applied across the joint. This will allow less exposure to CT scan for patients and staff, considerable resource saving, more rapid recovery and less scarring of the limb.Robot assisted surgery is an emerging interdisciplinary field that aims at improving the outcome of surgical procedures, reducing intra-operative time and radiation exposure to patients and staff as well as minimizing the invasiveness of a variety of surgical procedures. It seems very likely that Medical Robotics and Computer Assisted Surgery (MRCAS) will be a pervasive element of future society; there are many indications e.g. MRCAS report (http://www.piribo.com/publications/medical_devices/medical_robotics_computerassisted_surgery.html) that this will be a huge opportunity for life enhancement and commercial exploitation. The total worldwide market for MRCAS devices and equipment was around $1.3 billion in 2006 and is expected to reach $5.7 billion by 2011, an average annual grow rate of 34.7%. There is a natural synergy in this project; the PI has a track record in robotics and a strong background in mathematics and control, the Advisor is an experienced clinician with an academic portfolio of developments in orthopaedics surgery. The collaborating company Simpleware will provide their software licence for the duration of the project as well as the software support. BRL's rapid prototyping facilities will contribute to realisation of the project's hardware and the visualisation of the real fractures obtained from BRI's medical archives.

Regenerative devices (scaffolds, biomaterials and interventions) which can repair and regenerate tissues using the patients` own cells, can be translated into successful clinical products and deliver patient benefit at much lower cost and risk and in shorter timescales then other regenerative therapies such as culture expanded cell therapies or molecular (drug) therapies. It is estimated that the global market for regenerative devices will grow to £50bn by 2020 and this offers a real opportunity to grow a £1bn per year industry in the UK in this field. The UK has genuine research strengths in the areas of biomaterials and tissue engineering, musculoskeletal mechanics (prioritised by EPSRC) and regenerative medicine. Regenerative medicine is one of the eight great technologies prioritised across the Research Councils. Research discoveries, new knowledge, outputs and outcomes are often not ready for uptake by industry to take forward through product development to the market and patient benefit. New technologies need to be advanced and de-risked. The clinical needs, potential products and markets need to be defined in order to make them attractive for investment, product development and clinical trials by industry. In the Medical Technologies Innovation and Knowledge Centre (MTIKC) Phase 1, working with industry and clinical partners, we have developed a professional innovation team and a unique innovation and translation process, creating a multidisciplinary research and innovation ecosystem. We have successfully identified research outcomes and new knowledge and created, advanced and translated technology across the innovation valley of death, enabling successful investment (over £100m) by industry and the private sector in new product development. Some products have already progressed to clinical trials and commercialisation and are realising patient benefits. We have established a continuous innovation pipeline of over fifty proofs of concept technology projects. Over the next five years in MTIKC Phase 2, we will address unmet clinical needs and market opportunities in wound repair, cardiovascular repair, musculoskeletal tissue repair, maxillofacial reconstruction, dental reconstruction and general surgery and diversify our research supply chain to over ten other Universities. We will support 150 collaborative projects with industry and initiate forty new industry inspired and academically led proof of concept projects, which are predicted to lead to a further £100m investment by the private sector in subsequent product development. This will enable a sustainable research and product development pipeline to be established in the UK which will support a £1bn / year industry in regenerative devices beyond 2020.

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 cost and safety of the important elements of our life - energy, transport, manufacturing - depend on the engineering materials we use to fabricate components and structures. Engineers need to answer the question of how fit for purpose is a particular component or a system: a pressure vessel in a nuclear reactor; an airplane wing; a bridge; a gas turbine; at both the design stage and throughout their working life. The current cost of unexpected structural failures, 4% of GDP, illustrates that the answers given with the existing engineering methods are not always reliable. These methods are largely phenomenological, i.e. rely on laboratory length- and time-scale experiments to capture the overall material behaviour. Extrapolating such behaviour to real components in real service conditions carries uncertainties. The grand problem of current methods is that by treating materials as continua, i.e. of uniformly distributed mass, they cannot inherently describe the finite nature of the materials aging mechanisms leading to failure. If we learn how to overcome the constraint of the lab-based phenomenology, we will be able to make predictions for structural behaviour with higher confidence, reducing the cost of construction and maintenance of engineering assets and thus the cost of goods and services to all individuals and society. For example, by extending the life of one civil nuclear reactor the produced electricity each hour will cost £10k-15k less than from a new built nuclear reactor, or from a conventional power plant. This project is about the creation of a whole new technology for high-fidelity design and assessment of engineering structures. I will explore an original geometric theory of solids to overcome the phenomenological constraint, produce a pioneering software platform for structural analysis, validate the theory at several length scales, and demonstrate to the engineers how the new technology solves practical problems for which the present methods are inadequate. In contrast to the classical methods, the engineering materials will be seen as discrete collections of finite entities, or cells; importantly this is not a discretization of a continuum, such as those used in the current numerical methods, but a reflection of how materials organise at any length scale of observation - from atomic through to the polycrystalline aggregates forming engineering components. The cellular structure is characterised by distinct elements - cells, faces, edges and nodes - and the theory proposes an inventive way to describe how such a structure behaves by linking energy and entropy to the geometric properties of these elements - volumes, areas, lengths, positions. This theory will be implemented in a highly efficient software platform by adopting and modernising existing algorithms and developing new ones for massively parallel computations, which will enable engineers and scientists to exploit the impending acceleration in hardware power. With the expected leaps of computing power over the next five years (1018 operations per second by 2020) the new technology will allow for calculating the behaviour of engineering components and structures zooming in and out across length-scales from the atomic up to the structural. The verification and validation of the theory at multiple length-scales are now possible due to exceptionally powerful experimental techniques, such as lab- or synchrotron-based tomography, combined by image analysis techniques, such as digital volume correlation. Once verified, the technology will be applied to a series of engineering problems of direct industrial relevance, such as cleavage and ductile fracture and fatigue crack growth, providing convincing demonstrations to the engineering community. The product of the work will make a step change in the modelling and simulation of structures, suitable for the analysis of high value, high risk high reward engineering cases.