In 2018 there were over 4.5 million people with diabetes in the UK, with this number expected to rise to 5 million by 2025. One of the most serious complications of diabetes is ulceration of the feet - a Diabetic Foot Ulcer (DFU). This is caused by a poor blood supply and nerve damage, meaning that patients cannot feel when they are starting to damage their feet by, for example, having poorly fitting shoes. Around 34% of patients with diabetes are likely to develop a DFU. Once a DFU is established it can rapidly become infected (50% likelihood); once infected it is difficult to treat, taking months or even years to heal. Soft tissue infection can lead to bone infection, which is really only treatable by amputation. By the time a patient's DFUs get to the stage of requiring amputation the prognosis for the patient is grim: 70% of patients with DFU-associated amputations are dead within 5 years. Infected DFUs are treated by antibiotics and surgical wound debridement: cutting away infected tissue. However antibiotics are becoming less effective, and with the rise of "superbugs" (known as antimicrobial resistance, AMR) infection will present a serious threat to anyone with an open wound. Consequently, there is an urgent need for non-antibiotic approaches for treating infected DFUs, to augment antibiotic treatment and to extend the "lifetime" of existing antibiotics (whilst new ones are developed). The clinical need is to treat infected DFUs at an earlier stage before bone infection takes hold. And in a manner that doesn't just kill the surface bacteria (and fungi), but reaches microorganisms buried deep within the dense slimy colonies (biofilms) in which the organisms live. Our novel technology is based upon utilising electrically-excited gases (known as cold atmospheric plasma, CAP) to create and deliver potent antimicrobial agents deep into infected wounds via interaction of the CAP with a wound dressing and the wound itself. Antimicrobial agents are released from wound dressings applied over the DFU. In this research project, we will develop this technology and demonstrate its potential in robust laboratory-based models of real-world biofilms that are found in DFUs. To ensure that this project realises the potential to deliver patient benefit (as soon as possible) we will map out how to assess the health economic benefits and the parameters needed for a robust clinical trial. We will engage with healthcare providers and patients early, and will achieve this through a range of outreach activities. This project is an important step in realising a novel technology treatment package that is cheap and easy to use, and which has the potential to greatly improve the care of patients with DFUs and decrease the need for amputation. This would improve patient quality of life, improve survival rates and save the NHS money.

Both "Advanced and Functional Materials" and "Biotechnology" have been identified as pervasive technologies for future manufacturing activities in the UK. This Fellowship will join these two areas by developing chemical and biological technologies to create advanced functionalized biomaterials, taking advantage of the Fellow's cross-disciplinary expertise at the chemistry/biology interface. Working with manufacturers of biomaterials for healthcare and personal care, hybrid biomaterials will be produced that are able to heal and diagnose. An aging population needs cheaper biomedical materials with improved performance, but robust chemical and biotechnological processes for biomaterial functionalization are needed to create these materials. High-throughput modular methodologies are proposed for the modification of nanostructured biomaterials that will allow manufacturers to create tailored high-quality products for different markets, methodology that is able to respond quickly to the needs of customers (e.g. patients). These methodologies will draw on the UK's strengths in biotechnology to achieve a step change in cost reduction and an increase in performance; even a small reduction in costs to the NHS would bring significant benefits to the UK. The Fellowship will address this problem through work in three key theme areas: (1) developing simple, cheap and easy-to-access methodologies for adding reactive nanoparticles to biomaterials; (2) using synthetic biology and biotechnology to functionalise biomaterials; (3) using synthetic chemistry to produce value-added biomaterials. Each theme area has been identified as an exciting and highly interdisciplinary field that is ripe for exploitation, but where poor communication between experts in different fields is hampering progress. For example, there is insufficient involvement of industrial biotechnologists, synthetic chemists and supramolecular chemists in biomaterials manufacture despite clear synergies in expertise and the importance of this area to UK manufacturing. This Fellowship will build networks between biomaterials academics and biomaterials manufacturers, with partnerships backed up through meetings, researcher exchanges and follow-on funding. The Fellow will stimulate new innovative approaches to collaborative research by interacting with leading international researchers in Europe, the US and Australia/New Zealand who have complementary expertise to that of the applicant. The applicant will engage with leading UK manufacturers and international academic researchers, both through personal meetings and by helping to organise industry-academia meetings and developing new funded collaborations. At the end of this Fellowship, new easy-to-use chemical and biochemical methodologies will have been developed that will have applicability across academic and non-academic biomaterials research, producing new opportunities for UK manufacturing.

IMMPETUS (Institute for Microstructural and Mechanical Process Engineering: The University of Sheffield) was founded in 1997 to undertake truly integrated interdisciplinary research across the disciplines of systems, mechanical and metallurgical engineering, addressing key issues in the metals processing industry. Over the last ten years the unique inter-disciplinary research produced by IMMPETUS has secured national and international acclaim for its systems driven approach to process and property optimisation of a wide range of metals process routes. Using systems engineering we target and optimise experiments to develop basic physical metallurgy in specific areas where knowledge is incomplete, to inform model elicitation, testing and validation. For the complex industrial processes we investigate, there is insufficient basic knowledge to construct true through-process physically based models. In order to cover the intractable factors not adequately described by the existing physically based models, we use hybrid models that merge discrete data, knowledge-based and physically-based models in a unique manner to give unprecedented precision in predictive model capability. All the modelling is verified through the use of a world class array of experimental techniques. The proposal comprises 12 projects which have been constructed in conjunction with our industrial collaborators in order to answer the following questions: 1. How do we formulate a 'generic' framework for 'through-process' modelling to achieve 'right first-time' production of metals?2. Which of the metallurgical and thermomechanical variables affect the microstructure and therefore the final properties of metals, but are not yet fully described by existing models?3. How do causalities (deterministic behaviours) as well as uncertainties (heterogeneities, random behaviours) influence the processing and affect the final properties of metals?4. What are the specific modelling strategies 'best' suited for answering 1, 2, and 3 above?5. Using the elicited models in 4, can we identify the achievable properties for a given process route, and what to do if a particular property is not achievable?6. Using 5, how do we optimise the process route?The programme of work is presented as four themes, all of which are inter-dependent and interwoven. PHYSICAL SYSTEMS will be aimed at developing basic physical metallurgical understanding where knowledge is inadequate, in areas including microstructural heterogeneities, and process conditions that are dynamic and non-linear. In MODELLING SYSTEMS, the physical metallurgy, mechanical engineering and systems engineering will be fully integrated, both through the development of new modelling approaches, and the coupling of existing state-of-the-art modelling that in itself produces new methodologies. PROCESS SIMULATION will involve the upscaling of focused laboratory experiments to accurately and completely simulate the relevant industrial process routes and validate them through appropriate mill trials. SYSTEMS OPTIMISATION will act as a powerful vehicle for integrating these themes and via a careful tuning of model structures/parameters will be core to our technology transfer to our will target specific industrial sponsors and to the wider academic community.

The urgent need for EV technology is clear. Consequently, this project is concerned with two key issues, namely the cost and power density of the electrical drive system, both of which are key barriers to bringing EVs to the mass market. To address these issues a great deal of underpinning basic research needs to be carried out. Here, we have analysed and divided the problem into 6 key themes and propose to build a number of demonstrators to showcase the advances made in the underlying science and engineering. We envisage that over the coming decades EVs in one or more variant forms will achieve substantial penetration into European and global automotive markets, particularly for cars and vans. The most significant barrier impeding the commercialisation EVs is currently the cost. Not until cost parity with internal combustion engine (ICE) vehicles is achieved will it become a seriously viable choice for most consumers. The high cost of EVs is often attributed to the cost of the battery, when in fact the cost of the electrical power train is much higher than that of the ICE vehicle. It is reasonable to assume that that battery technology will improve enormously in response to this massive market opportunity and as a result will cease to be the bottleneck to development as is currently perceived in some quarters. We believe that integration of the electrical systems on an EV will deliver substantial cost reductions to the fledgling EV market Our focus will therefore be on the two major areas of the electrical drive train that is generic to all types of EVs, the electrical motor and the power electronics. Our drivers will be to reduce cost and increase power density, whilst never losing sight of issues concerning manufacturability for a mass market.

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.