This network will focus on developing the next generation of advanced technologies for rehabilitation, targeting musculoskeletal, cardiorespiratory, neurological and mental health conditions. It will be connected to the new £70 million National Rehabilitation Centre (NRC), a major national investment in patient care, innovation and technology, due to open to patients in 2024. The NRC is being co-located with the specialist £300m+ Defence Medical Rehabilitation Centre on the Stamford Hall Rehabilitation Estate so that the two centres can benefit from the sharing of a wealth of knowledge, expertise and facilities. This EPSRC networkplus is therefore an exceptionally timely opportunity to capitalise on this significant investment, actively involving the UK Engineering & Physical Science community in this initiative and embedding technology innovation at the earliest stage. Advances in medicine have resulted in a significant increase in survival rates from trauma and injury, disorders and disease (acute and chronic). However, survival is often just the start, and the higher rates have led to an increase in rehabilitation needs, involving many patients with complex conditions. Technology has an increasingly important part to play in rehabilitation, to support a limited number of skilled healthcare professionals, reduce hospital stays, improve engagement with rehabilitation programmes, increase independence and improve outcomes. Speeding up recovery and helping patients get back to work and life has considerable personal, social and economic impact. This network will bring together researchers, healthcare providers, patient & user groups, industrial partners and supporting organisations (e.g. policy makers, charities) to develop a world-class research community and infrastructure for advanced rehabilitation technologies. By connecting new innovative technologies and advanced materials with our growing understanding of mental and physical health, this network will support the provision of novel, transformative, affordable solutions that will address current issues, allowing patients to lead more independent and fulfilling lives and reducing the burden on limited NHS resources. Supported by a core membership of experts from the rehabilitation field, this network aims to introduce researchers who are not typically involved in rehabilitation technology research into a network of rehabilitation experts. Central to the grant will be a series of Grand Challenge Blended Workshops and supported conversations designed to identify critical areas for research, with funding for feasibility projects to build those collaborations and drive forward innovation. The network will explore multimodal approaches that target both physical and mental rehabilitation. Technology innovation will focus around three key areas: 1) advanced functional materials, 2) patient-specific devices & therapy, and 3) closed loop measurement and rehabilitation.

One in three people in the UK population will develop cancer during their life time. The incidence of cancer continues to increase world-wide and healthcare providers are facing increasing challenges in the management of this expanding group of patients. However, new imaging technologies allow detection of tumours at earlier stages and now more cancer patients than ever can be successfully treated by surgery. Tissue conserving surgery is an advanced surgical procedure that tries to only remove cancerous tissue and leave healthy tissue in place. In skin conserving surgery (also known as Mohs micrographic surgery), one layer after another of tissue is cut away and examined under the microscope to make sure that all the cancer is out. This process is stopped when only healthy tissue is left. Successful removal of all cancer cells is the key to achieving lower rates of the cancer returning. There is always a balance to be struck between making sure that all the cancer is removed and preserving as much healthy tissue as possible in order to reduce scarring and disfigurement. The real challenge however is to know where the cancer starts and ends when looking at it during an operation so that the surgeon knows when to stop cutting. Although Mohs surgery provides the highest cure rates for basal cell carcinoma, the most common type of cancer in humans with ~60,000 new patients each year in the UK, it takes around 1-2 hours per layer to prepare and diagnose under the microscope. The high costs and the need for highly specialized surgeons, has limited the availability of Mohs surgery in the UK and led to "post-code" treatment variability. Compared to Mohs surgery, breast conserving surgery (more than 10,000 procedures per year) is considerably more complex and for practical reasons, the traditional methods of diagnosis by preparing thin tissue specimens cannot be performed during surgery. As a consequence, in England more than 2,000 patients per year require a second operation, usually complete removal of the breast. Recently, my research group has developed a new method to diagnose cancer cells in tissue layers removed during surgery. The main advantage of this technique is that the time consuming steps of tissue fixation, staining, and sectioning are eliminated. This new diagnosis method uses a combination of two techniques called auto-fluorescence imaging and Raman scattering, that can measure the molecular composition of tissue and provide objective diagnosis of cancer. However, this breakthrough is just the beginning and further work is required to take these successes forward and improve patient care. In the short and medium term, I will focus on reducing the diagnosis time for skin cancers to only a few minutes by developing a method to measure Raman spectra from eighteen regions of the tissue simultaneously. In collaboration with cancer surgeons, we will expand this new technology to diagnosis of other cancers, such as breast and lung. This will be achieved by optimizing the auto-fluorescence imaging and Raman scattering to take into consideration the chemical make up of these tissues. In the longer term, I plan to develop novel hand-held medical devices based on multimodal spectral imaging that could be used by the surgeons to diagnose the tissues directly on the body and remove tissue only if cancerous cells are detected. These methods for tumour diagnosis can revolutionise the surgical treatment of cancers, by providing a fast and objective way for surgeons to make sure that all cancer cells have been removed whilst at the same time preserving as much healthy tissue as possible. To achieve these ambitious objectives I will work in close partnership with other scientists, engineers, doctors, surgeons and industry. Such collaborations will ensure that cutting-edge science and engineering is exploited to develop leading healthcare technologies for the benefit of patients.

Information about the external and internal world is conveyed to the brain by an extensive system of sensory nerves. The skin contains multiple types of sensory receptors/nerves which inform the brain about events occurring on the body surface. There are many very basic questions about the neuroscience underlying human tactile processing that remain unanswered. We aim to use recent advances in the neuroimaging techniques of ultra-high field functional magnetic resonance imaging (UHF-fMRI) and magnetoencephalography (MEG), coupled in conjunction with nerve recording (microneurography) and stimulating techniques (intraneural microstimulation (INMS)), to provide novel insight into the brain mechanisms involved in operating the sense of touch in humans. Using fMRI, we can measure changes in the local blood flow that occur with increased neural activity. These changes cause an increase in the signal intensity in the MR image in the part of brain that is active. This means that we can measure, for example, which parts of the brain are more active while subjects feel an object touch their finger. One of the problems we face when studying the mechanism underlying our sense of touch is that the changes in signal intensity that occur are relatively small. We have overcome this problem by using a very high field magnetic resonance scanner which allows us to measure robust neural responses to touch, non-invasively, with much higher spatial resolution than has previously been possible, and we can now obtain robust activation maps of individual participants brains. This makes UHF- fMRI a very attractive tool for clinical applications. MEG is another non-invasive neuroimaging technique that offers a way to probe the temporal aspects of somatosensory processing. The technique of microneurography allows unprecedented access to the earliest stages of information transfer to the brain, it involves inserting a very fine needle through the skin into an underlying nerve, so you can hear and see (the nerve recording) sending messages to the brain. A step further is to electrically stimulate a single nerve fibre with a very small current, using the technique of INMS, so that a person can feel touch when there is no actual skin stimulus. Combining INMS with neuroimaging UHF-fMRI and MEG, will allow us to reveal the representation of single sensory nerves in the brain. In this project, we will use these cutting-edge techniques and take a multidisciplinary approach, combining expertise in MRI, neuroscience, neurophysiology and neurology, to improve our understanding of sensory pathways. Specifically, we will use UHF-fMRI to map carefully the detailed anatomy and function of the somatosensory cortex, and will use MEG to characterize the temporal dynamics of brain responses to tactile stimulation of the skin. We will develop a new MR- and MEG-compatible device to perform INMS in the UHF-fMRIscanner and MEG scanner. The use of fMRI during INMS will allow us to map the brain's response to single sensory afferents (in contrast to vibration, which stimulates multiple sensory receptors of various types). We will also apply these methods to measure alterations in the somatosensory pathways in patient groups with neuropathologies. Specifically we will study Focal Hand Dystonia and Carpal Tunnel Syndrome, and assess how somatosensory processing is altered by therapeutic interventions. Overall, this research will considerably advance our understanding of human somatosensation and perception and will be relevant to a wide range of clinical disorders related to neurotraumatic injury, neurology, neurodevelopment, neurodegeneration, neuropathology, pharmaceutical interventions and pain.

3D Printing elicits tremendous excitement from a broad variety of industry - it offers flexible, personalised and on demand scalable manufacture, affording the opportunity to create new products with geometrical / compositional freedoms and advanced functions that are not possible with traditional manufacturing practices. 3D Printing progresses rapidly: for polymerics, we have seen significant advances in our ability to be able to manufacture highly functional structures with high resolution projection through developments in projection micro stereolithography, multimaterial ink jet printing and two photon polymerisation. There have also been exciting advances in volumetric 3DP with the emergence of Computational Axial Lithography and more recent work such as 'xolo'. Alongside these advances there has also been developments in materials, e.g., in the emergence of '4D printing' using responsive polymers and machine learning / AI on 3DP is beginning to be incorporated into our understanding. The impact of these advances is significant, but 3D printing technology is reaching a tipping point where the multiple streams of effort (materials, design, process, product) must be brought together to overcome the barriers that prevent mass take up by industry, i.e., materials produced can often have poor performance and it is challenging to match them to specific processes, with few options available to change this. Industry in general have not found it easy to adopt this promising technology or exploit advanced functionality of materials or design, and this is particularly true in the biotech industries who we target in this programme grant - there is the will and the aspiration to adopt 3D printing but the challenges in going from concept to realisation are currently too steep. A key challenge stymying the adoption of 3D printing is the ability to go from product idea to product realisation: each step of the workflow (e.g., materials, design, process, product) has significant inter-dependent challenges that means only an integrated approach can ultimately be successful. Industry tells us that they need to go significantly beyond current understanding and that manufacturing products embedded with advanced functionality needs the capability to quickly, predictably, and reliably 'dial up' performance, to meet sector specific needs and specific advanced functionalities. In essence, we need to take a bottom-up, scientific approach to integrate materials, design and process to enable us to produce advanced functional products. It is therefore critical we overcome the challenges associated with identifying, selecting, and processing materials with 3DP in order to facilitate wider adoption of this pivotal manufacturing approach, particularly within the key UK sectors of the economy: regenerative medicine, pharmaceutical and biocatalysis. Our project will consider four Research Challenges (RCs): PRODUCT: How can we exploit 3D printing and advanced polymers to create smart 21st Century products ready for use across multiple sectors? MATERIALS: How can we create the materials that can enable control over advanced functionality / release, that are 3D Printable? DESIGN: How can we use computational / algorithmic approaches to support materials identification / product design? PROCESS: How can we integrate synthesis, screening and manufacturing processes to shorten the development and translation pipeline so that we can 'dial up' materials / properties? By integrating these challenges, and taking a holistic, overarching view on how to realise advanced, highly functional bespoke 3D printed products that have the potential to transform UK high value biotechnology fields and beyond.

Background: In the UK, four babies are born deaf each day. Children with hearing loss not only have delayed speech and language development, but also have lower educational achievements compared with children who have normal hearing. A cochlear implant is a device that can restore a sensation of hearing to children who are born or become deaf. All newborns are now tested for a hearing loss. Subsequently, children who are suitable for a cochlear implant can be identified in the first few days or months of life. Overall, speech understanding in children improves after cochlear implantation. However, some children's speech and language abilities are much worse than we would otherwise expect and we don't fully understand why this happens. The current tests for assessing levels of hearing and speech understanding are unreliable in very young children. Since children that are born deaf often receive their cochlear implants within the first year or two of life, years can often pass before parents and healthcare professionals become aware of poor speech and language skills. Currently, it is extremely difficult to distinguish between very young children with cochlear implants who are performing well and those who are performing not so well. We want to understand why some children can hear well with a cochlear implant and others cannot. We would also like to predict and identify at the earliest possible stage those children with a cochlear implant who have poor speech understanding. Aims of this research: At the Nottingham Hearing Biomedical Research Centre, we propose to use a non-invasive brain scanning method called functional near-infrared spectroscopy, or fNIRS for short, to measure brain activity in deaf children before and immediately after they receive a cochlear implant. We want to know if this brain scanning technique can be used to test how well a child can hear and understand speech instead of having to rely on existing hearing tests that are only suitable for older children. Although we have considered other methods for measuring brain activity, they are either not safe for use in patients with a cochlear implant or are associated with potential harmful effects. fNIRS is completely safe for children both before and after cochlear implantation and does not have any side effects or risks to health. Expected benefits of this research: If we are able to assess how well a child can hear using fNIRS, clinical professionals could measure speech abilities in much younger children than is presently possible. Subsequently, we will be able to identify and treat children who are not hearing so well at the earliest age. In so doing, we will identify those children with a cochlear implant who struggle with their hearing and need extra speech and language support. At present, without any idea of the abilities of our very young children with cochlear implants, valuable NHS resources for speech and language support are provided to every single child, so that some children may receive more support than they require, whilst others receive too little. fNIRS may help us to tailor and more appropriately direct speech and language support to those children who need it the most. We would also be able to give parents a more accurate explanation of how likely their child is to improve with their cochlear implant. Cochlear implants also need to be 'fine tuned' or programmed regularly so that they provide the best possible level of hearing to meet the needs of an individual. fNIRS has the potential to guide and improve this programming process. This is because it may be able to inform us on how well speech and sound is understood by the brain, years before a child is old enough to tell us, and enable us to make the appropriate adjustments to their cochlear implant. We believe that fNIRS has the potential to allow every child with a cochlear implant to have the best possible treatment that is tailored to their individual needs.