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.

Maintaining sustainable productivity of pharmaceutical research and development is one of the most significant challenges faced by this major UK industry. Pre-clinical models for testing drug safety and efficacy are poorly predictive of human response, making our ability to translate new scientific discovery to impactful therapy extremely costly and time consuming. Organ-chips are small, bioengineered devices which replicate important aspects of human health and disease, and thus provide the predictivity of human response required to transform therapeutic delivery. The organ-chip industry is one of the fastest growing worldwide, as the transformative potential of organ-chip technology is realised. For the UK to ensure ongoing growth and productivity of the pharmaceutical industry, it is imperative we deliver a workforce able to advance this technology and bring it into use, to drive successful healthcare innovation. COaCT sets a transformative vision to bring together the full stakeholder community in organ-chip technology, to collectively develop and deliver a training programme designed to equip graduates with the skills and knowledge required to be the next generation of leaders in organ-chip technology and advance the technology into regulatory use. We focus on three core areas: 1. delivering the technical skills required to design, manufacture and advance organ-chip models: Organ-chip models are microfluidic devices, in which the physics of managing organ growth and drug delivery are different to those in standard cell cultures. We provide training to ensure students understand how to work with a wide range of commercial organ-chip systems and build their own devices, appreciating the specific biosensing, nano-patterning, mechanobiology, microfluidics and microfabrication requirement of organ-chip systems, and the rationale and decision making associated with selecting different approaches, so they are fully prepared to work across the sector in future roles. 2. ensuring students are equipped with the broader understanding of the societal implications of the technology, and the regulatory and policy changes which will be necessary to ensure impactful delivery. There is clear potential for organ-chip approaches to revolutionise therapeutic discovery, but for the technology to achieve its potential, it is imperative that the field fully considers and responds to the societal and regulatory environment as it evolves and develops, thus our future leaders must be fully trained in this area. 3. providing a focus on transferable skills training, to help students develop into effective future leaders in this field: The rapid growth of organ-chip technology offers exciting future opportunities for researchers shaping the field. To be effective in driving the field, it is important graduates possess the transferable skills to lead teams and companies designing or implementing organ-chip technology, and are able to communicate effectively with the broad range of stakeholders involved. Our stakeholder community brings together the pharmaceutical and organ-chip industries, varied medicine-related regulatory bodies, policy groups, and charities, all with a strong commitment to deliver organ-chip technology. The COaCT investigator team have been leading the efforts of this stakeholder community to coordinate and drive organ-chip research for the last 5 years, though leadership of the UK organ-on-a-chip technologies network. Indeed, the ideas for the CDT scope and training remit have been developed collectively through those discussion panels and workshops.

AIMS AND OBJECTIVES: We aim to reduce the cost, burden, and time to conduct randomised controlled trials (RCT) to improve the care of sick and preterm babies and develop medicines, diagnostics and devices that meet their needs. RCT are the most reliable and fair way to test treatments because every patient has an equal chance of receiving the best approach. Data collection is a major cost of RCT hence we will use data recorded as part of clinical care that is already available in a high-quality repository we established, the UK National Neonatal Research Database (NNRD). We will also use digital technologies and innovative study designs. The idea for NNRD-RCT is simple but the technical processes to flow data securely, develop and implement robust, transparent operational procedures, ensure trust in processes, and deliver solutions at scale, are complex, and our principal objectives. NEED: Neonatal care is an area of great national and global need. Newborn health sets trajectories for life; e.g. a baby born preterm, or over or underweight, is at up to 8 times greater risk of developing a chronic disease like diabetes or high blood pressure in adult life, that will decrease healthy life expectancy by as much as 15-20 years. Though improving their health has life-long benefits, newborn babies are disadvantaged in accessing biomedical innovations because of real or perceived difficulties in conducting RCT involving them. There has only ever been a single medicine specifically developed for a newborn condition, and over 90% of medicines used to treat babies have inadequate data on safety, dose, and efficacy because they have only been evaluated in older patients. This is dangerous because the way in which medicines work in babies is often very different from other age groups. Another difficulty is that reliably resolving healthcare uncertainties often requires the participation of large numbers of infants; e.g. to identify whether a treatment reduces severe retinopathy of prematurity, the major cause of childhood blindness, by 25%, would require a study involving about 14,000 infants which would be costly, difficult, and take a long time. Therefore many RCT, though needed, are never done or are too small or poor quality. The consequence is that there are many uncertainties in even routine aspects of care such as the best type of nutrition for preterm babies, and the best way to reduce the risk of infection. WHAT WE WILL DO: We will create standard operating processes to flow data from the NNRD to RCT master-files and electronic forms and digital tools e.g. for automated reminders and staff training. We will obtain stakeholder perspectives to build understanding and trust in NNRD-RCT and develop multi-media communications and transparent, well-governanced processes for commercial RCT. We will involve stakeholders in developing two exemplar NNRD-RCT (to resolve a long-standing, priority-ranked uncertainty in clinical care and to evaluate a neonatal medicine). We will also develop statistical and design solutions that maximise NNRD-RCT efficiency. Outputs will include resources to help clinical investigators, and guidance for industry researchers. WHY A PARTNERSHIP IS NEEDED: A partnership is needed to bring together expertise in scalable technical solutions that meet regulatory standards, develop NNRD-RCT design options, secure stakeholder involvement and engagement, and create impactful communications. Our partners are Bliss (national charity for sick and preterm babies), Health Data Research UK (national institute for health data science), Neonatal Society (clinical research society), Strategic Intelligence Alliance for Healthcare (SME supporting the NHS and industry), OpenClinica (provider of clinical trial cloud technologies) and UK Medicines and Healthcare products Regulatory Agency. The resources developed, know-how and knowledge, will be available to all clinical trials units and researchers around the world.

The lifETIME CDT will focus on the development of non-animal technologies (NATs) for use in drug development, toxicology and regenerative medicine. The industrial life sciences sector accounts for 22% of all business R&D spend and generates £64B turnover within the UK with growth expected at 10% pa over the next decade. Analysis from multiple sources [1,2] have highlighted the limitations imposed on the sector by skills shortages, particularly in the engineering and physical sciences area. Our success in attracting pay-in partners to invest in training of the skills to deliver next-generation drug development, toxicology and regenerative medicine (advanced therapeutic medicine product, ATMP) solutions in the form of NATs demonstrates UK need in this growth area. The CDT is timely as it is not just the science that needs to be developed, but the whole NAT ecosystem - science, manufacture, regulation, policy and communication. Thus, the CDT model of producing a connected community of skilled field leaders is required to facilitate UK economic growth in the sector. Our stakeholder partners and industry club have agreed to help us deliver the training needed to achieve our goals. Their willingness, again, demonstrates the need for our graduates in the sector. This CDT's training will address all aspects of priority area 7 - 'Engineering for the Bioeconomy'. Specifically, we will: (1) Deliver training that is developed in collaboration with and is relevant to industry. - We align to the needs of the sector by working with our industrial partners from the biomaterials, cell manufacture, contract research organisation and Pharma sectors. (2) Facilitate multidisciplinary engineering and physical sciences training to enable students to exploit the emerging opportunities. - We build in multidisciplinarity through our supervisor pool who have backgrounds ranging from bioengineering, cell engineering, on-chip technology, physics, electronic engineering, -omic technologies, life sciences, clinical sciences, regenerative medicine and manufacturing; the cohort community will share this multidisciplinarity. Each student will have a physical science, a biomedical science and a stakeholder supervisor, again reinforcing multidisciplinarity. (3) Address key challenges associated with medicines manufacturing. - We will address medicines manufacturing challenges through stakeholder involvement from Pharma and CROs active in drug screening including Astra Zeneca, Charles River Laboratories, Cyprotex, LGC, Nissan Chemical, Reprocell, Sygnature Discovery and Tianjin. (4) Embed creative approaches to product scale-up and process development. - We will embed these approaches through close working with partners including the Centre for Process Innovation, the Cell and Gene Therapy Catapult and industrial partners delivering NATs to the marketplace e.g. Cytochroma, InSphero and OxSyBio. (5) Ensure students develop an understanding of responsible research and innovation (RRI), data issues, health economics, regulatory issues, and user-engagement strategies. - To ensure students develop an understanding of RRI, data issues, economics, regulatory issues and user-engagement strategies we have developed our professional skills training with the Entrepreneur Business School to deliver economics and entrepreneurship, use of TERRAIN for RRI, links to NC3Rs, SNBTS and MHRA to help with regulation training and involvement of the stakeholder partners as a whole to help with user-engagement. The statistics produced by Pharma, UKRI and industry, along with our stakeholder willingness to engage with the CDT provides ample proof of need in the sector for highly skilled graduates. Our training has been tailored to deliver these graduates and build an inclusive, cohesive community with well-developed science, professional and RRI skills. [1] https://goo.gl/qNMTTD [2] https://goo.gl/J9u9eQ

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.