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

We propose to build the EPSRC Centre for Doctoral Training in Sensor Technologies for a Healthy and Sustainable Future (Sensor CDT) on the foundations we have established with our current CDT (EPSRC CDT for Sensor Technologies and Applications, see http://cdt.sensors.cam.ac.uk). The bid falls squarely into EPSRC's strategic priority theme of New Science and Technology for Sensing, Imaging and Analysis. The sensor market already contributes an annual £6bn in exports to the UK economy, underpinning 73000 jobs and markets estimated at £120bn (source: KTN UK). Major growth is expected in this sector but at the same time there is a growing problem in recruiting suitably qualified candidates with the necessary breadth of skills and leadership qualities to address identified needs from UK industry and to drive sustainable innovation. We have created an integrated programme for high quality research students that treats sensing as an academic discipline in its own right and provides comprehensive training in sensor technologies all the way from the fundamental science of sensing, the networking and interpretation of sensory data, to end user application. In the new, evolved CDT, we will provide training for our CDT students on themes that are of direct relevance to a sustainable and healthy future society, whilst retaining a focus that delivers value to the UK economy and academia. The 4-year programme is strongly cross disciplinary and focuses on sustainable development goals and emphasises training in Responsible Innovation. One example of the latter is our objective to 'democratise sensor technologies': Our students will learn how to engage with the public during research, how to play a valuable part in public debate, and how to innovate technology that benefits society. Technical aspects will be taught in a bespoke training programme for the course, that includes lectures, practicals, lab rotations, industry secondments, and skills training on key underpinning technologies. To support this effort, we have created dedicated, state-of-the-art infrastructure for the CDT that includes laboratory, office, teaching, and social spaces, and we connect to the world leading infrastructure available in the participating departments and partner industries. The programme is designed to create strong identities both within and across CDT cohorts (horizontal and vertical integration) to maximise opportunities for peer-to-peer learning and leadership training through activities such as our unique sensor team challenges and the monthly Sensor Cafés, attended by representatives from academia, industry, government agencies, and the public. We will create a diverse and inclusive atmosphere where students feel confident and empowered to offer different opinions and experiences and which maximises creativity and innovation. We have attracted substantial interest and support (>£2.5M) from established industrial partners, but our new programme emphasises engagement also with UK start-ups and SMEs, who are particularly vulnerable in the current economic climate and who have expressed a need for researchers with the breadth and depth of skills the CDT provides (see letters of support). We recruit outstanding, prizewinning students from a diverse range of disciplines and the training programme connects more than 90 PIs across 15 departments and 40 industrial partners working together to address future societal needs with novel sensor technologies. Technology developers will benefit through connection with experts in middleware (e.g. sensor distribution and networking, data processing) and applications experts (e.g. life scientists, atmospheric scientists, etc.) and vice versa. This integrative character of the CDT will inspire innovations that transform capability in many disciplines of science and industries.

The study of human lung biology has a huge impact on our understanding of the disease process in a number of lung conditions such as asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD), disorders which have significant health and socioeconomic implications worldwide. At the moment, it is difficult to carry out such research on humans, because in many cases it is not safe or procedures are too invasive, and the use of animal models is not always appropriate. For instance, mice do not develop asthma naturally which suggest that the biology of their lungs is different to that of humans. These limitations in the availability of physiologically relevant human lung models are therefore set to continue having a negative knock-on effect on the search for novel targets and molecules for therapeutic interventions. For example, despite enhanced patient care, the morbidity and mortality of asthma has remained high with one asthma related death every 19 minutes and 20 million lost working days per annum in the UK alone. This is partly due to lack of efficient therapeutic strategies and the fact that a large proportion of patients do not respond to treatment. What we want to do in this project is to develop a model of the human lung in the laboratory using cells previously isolated from donated tissue or blood. We will grow these cells on materials that contain sensors that can pick up changes in, for example, oxygen, glucose and acidity. These sensors will allow us to observe how cells respond to stimulation in real time. By growing these cell types on these materials, we can arrange them into layers such that the cells are grown in the laboratory in the same position as in the lung. Such a model would give scientists and pharmaceutical companies a better tool for investigating some aspects of human lung biology, identifying new targets for treatment and testing new drug compounds.

Soft tissue related diseases (heart, cancer, eyes) are among the leading causes of death worldwide. Despite extensive biomedical research, a major challenge is a lack of mathematical models that predict soft tissue mechanics across subcellular to whole organ scales during disease progression. Given the tremendous scope, the unmet clinical needs, our limited manpower, and the existence of complementary expertise, we seek to forge NEW collaborations with two world-leading research centres: MIT and POLIMI, to embark on two challenging themes that will significantly stretch the initial SofTMech remit: A) Test-based microscale modelling and upscaling, and B) Beyond static hyperelastic material to include viscoelasticity, nonlinear poroelasticity, tissue damage and healing. Our research will lead to a better understanding of how our bodies work, and this knowledge will be applied to help medical researchers and clinicians in developing new therapies to minimise the damage caused by disease progression and implants, and to develop more effective treatments. The added value will be a major leap forward in the UK research. It will enable us to model soft tissue damage and healing in many clinical applications, to study the interaction between tissue and implants, and to ensure model reproducibility through in vitro validations. The two underlying themes will provide the key feedback between tissue and cells and the response of cells to dynamic local environments. For example, advanced continuum mechanics approaches will shed new light on the influence of cell adhesion, angiogenesis and stromal cell-tumour interactions in cancer growth and spread, and on wound healing implant insertion that can be tested with in vitro and in vivo systems. Our theoretical framework will provide insight for the design of new experiments. Our proposal is unique, timely and cost-effectively because advances in micro- and nanotechnology from MIT and POLIMI now enable measurements of sub-cellular, single cell, and cell-ECM dynamics, so that new theories of soft tissue mechanics at the nano- and micro-scales can be tested using in vitro prototypes purposely built for SofTMech. Bridging the gaps between models at different scales is beyond the ability of any single centre. SofTMech-MP will cluster the critical mass to develop novel multiscale models that can be experimentally tested by biological experts within the three world-leading Centres. SofTMech-MP will endeavour to unlock the chain of events leading from mechanical factors at subcellular nanoscales to cell and tissue level biological responses in healthy and pathological states by building a new mathematics capacity. Our novel multiscale modelling will lead to new mathematics including new numerical methods, that will be informed and validated by the design and implementation of experiments at the MIT and POLIMI centres. This will be of enormous benefit in attacking problems involving large deformation poroelasticity, nonlinear viscoelasticity, tissue dissection, stent-related tissue damage, and wound healing development. We will construct and analyse data-based models of cellular and sub-cellular mechanics and other responses to dynamic local anisotropic environments, test hypotheses in mechanistic models, and scale these up to tissue-level models (evolutionary equations) for growth and remodelling that will take into account the dynamic, inhomogeneous, and anisotropic movement of the tissue. Our models will be simulated in the various projects by making use of the scientific computing methodologies, including the new computer-intensive methods for learning the parameters of the differential equations directly from noisy measurements of the system, and new methods for assessing alternative structures of the differential equations, corresponding to alternative hypotheses about the underlying biological mechanisms.

Biomedical Materials have advanced dramatically over the last 50 years. Historically, they were considered as materials that formed the basis of a simple device, e.g. a hip joint or a wound dressing with a predominant tissue interface. However, biomedical materials have grown to now include the development of smart and responsive materials. Accordingly, such materials provide feedback regarding their changing physiological environment and are able to respond and adapt accordingly, for a range of healthcare applications. Two major areas underpinning this rapid development are advances in biomedical materials manufacture and their characterisation. Medical products arising from novel biomedical materials and the strategies to develop them are of great importance to the UK and Ireland. It is widely recognised that we have a rapidly growing and ageing population, with demand for more effective but also cost effective healthcare interventions, as identified in recent government White Paper and Foresight reports. This links directly to evidence of the world biomaterials market, estimated to be USD 70 billion (2016) and expected to grow to USD 149 billion by 2021 at a CAGR of 16%. To meet this demand an increase of 63% in biomedical materials engineering careers over the next decade is predicted. There is therefore a national need for a CDT to train an interdisciplinary cohort of students and provide them with a comprehensive set of skills so that they can compete in this rapidly growing field. In addition to the training of a highly skilled workforce, clinically and industrially led research will be performed that focuses on developing and translating smart and responsive biomaterials with a particular focus on higher throughput, greater reproducibility of manufacture and characterisation. We therefore propose a CDT in Advanced Biomedical Materials to address the need across The Universities of Manchester, Sheffield and The Centre for Research in Medical Devices (CÚRAM), Republic of Ireland (ROI). Our combined strength and track record in biomaterials innovation, translation and industrial engagement aligns the UK and ROI need with resource, skills, industrial collaboration and cohort training. This is underpinned strategically by the Biomedical Materials axis of the UK's £235 million investment of the Henry Royce Institute, led by Manchester and partner Sheffield. To identify key thematic areas of need the applicants led national Royce scoping workshops with 200 stakeholders through 2016 and 2017. Representation was from clinicians, industry and academia and a national landscape strategy was defined. From this we have defined priority research areas in bioelectronics, fibre technology, additive manufacturing and improved pre- clinical characterisation. In addition the need for improved manufacturing scale up and reproducibility was highlighted. Therefore, this CDT will have a focus on these specific areas, and training will provide a strongly linked multidisciplinary cohort of biomedical materials engineers to address these needs. All projects will have clinical, regulatory and industry engagement which will allow easy translation through our well established clinical trials units and positions the research well to interface with opportunities arising from 'Devolution Manchester', as Greater Manchester now controls long-term health and social care spending, ready for the full devolution of a budget of around £6 billion in 2016/17 which will continue through the CDT lifespan.