SummaryContinued improvement in the nation's health depends upon the efficient development of affordable replacement human tissue and related therapies; an acute shortage of willing organ donors and the shortcomings of conventional therapies leads to the preventable death of many patients each year. The next healthcare revolution will apply regenerative medicines, creating biological therapies or substitutes for the replacement or restoration of tissue function lost through failure or disease. However, whilst science has revealed the potential, and early products have shown the power of such therapies, there is now a need for the long term supply of people properly trained with the necessary skills to face the engineering and life science challenges before the predicted benefits in human healthcare can be realised. Because the products arising from this technology differ significantly from those made by mainstream pharmaceutical companies, training programmes currently available are poorly equipped to meet the demand for increasing numbers of appropriately trained personnel. We estimate that the number of engineers with the necessary skills to interact `on the same level' with cutting edge bioscientists and clinicians is very small, perhaps no more than 100 nationally; in such a small community 50 newly trained PhD's will have a very large impact. Here we propose a new UK based DTC in Regenerative Medicine integrated across three Universities with highly complementary expertise where students will be trained in the core skills needed to work at the life science/engineering interface and then engaged in strategic research programmes designed to address the major challenges in the field. This will ensure that the necessary people and enabling technologies are developed for the UK to lead in this rapidly growing worldwide marketplace.

Definition: A rapidly developing area at the interfaces of engineering/physical sciences, life sciences and medicine. Includes:- cell therapies (including stem cells), three dimensional cell/ matrix constructs, bioactive scaffolds, regenerative devices, in vitro tissue models for drug discovery and pre-clinical research.Social and economic needs include:Increased longevity of the ageing population with expectations of an active lifestyle and government requirements for a longer working life.Need to reduce healthcare costs, shorten hospital stays and achieve more rapid rehabilitationAn emergent disruptive industrial sector at the interface between pharmaceutical and medical devicesRequirement for relevant laboratory biological systems for screening and selection of drugs at theearly development stage, coupled with Reduction, Refinement, Replacement of in vivo testing. Translational barriers and industry needs: The tissue engineering/ regenerative medicine industry needs an increase in the number of trained multidisciplinary personnel to translate basic research, deliver new product developments, enhance manufacturing and processing capacity, to develop preclinical test methodologies and to develop standards and work within a dynamic regulatory environment. Evidence from N8 industry workshop on regenerative medicine.Academic needs: A rapidly emerging internationally competitive interdisciplinary area requiring new blood ---------------------

Regenerative medicine aims to develop biomaterial and cell-based therapies that restore function to damaged tissues and organs. It is a cornerstone of contemporary and future medicine that needs a multidisciplinary approach. There is a world-wide shortage in scientists with such skillsets, which was highlighted in 2012 by the Research Councils UK in their 'A Strategy for UK Regenerative Medicine" which promotes 'training programmes to build capacity and provide the skills-base needed for the field to flourish'. The major clinical need for regenerative medicine was highlighted by the Science and Technology Committee (House of Lords; July 2013), who identified that 'The UK has the chance to be a leader in [regenerative medicine] and this opportunity must not be missed', and that 'there is likely to be a £44-54bn NHS funding gap by 2022 and that management of chronic disease accounts for around 75% of all UK health costs'. Vascular diseases are the leading cause of death and disability worldwide, musculoskeletal diseases have a huge burden in pain and disability, diabetes may be the 7th leading cause of death by 2030, and peripheral nerve injuries impair mobility after traumatic injuries. There is a pressing need for commercial input into regenerative medicine. Whilst the next generation of therapies, such as stem cells and biomaterials, will be underpinned by cutting-edge biology and bioengineering, strong industrial-academic partnerships are essential for developing and commercialising these advances for clinical benefit. We have established strong industrial partnerships which will both enhance the CDT training experience and provide major added value to our industrial partners. Regenerative medicine is a top priority for the University of Manchester (UoM) which has excellence in interdisciplinary graduate training and a critical mass of internationally renowned researchers, including newly appointed world-leaders. Our regenerative medicine encompasses physical, chemical, biological and medical sciences; we focus on tissue regeneration and inflammation, engineering and fabrication of biomaterials, and in vivo imaging and clinical translation, all on our integrated biomedical campus. We propose a timely Centre for Doctoral Training in Regenerative Medicine in Manchester that draws on our exceptional multidisciplinary depth and breadth, and directly addresses the skills shortage in non-clinical and clinical RM scientists. Our expertise integrates tissue regeneration & repair, the design & engineering of biomaterials, and the clinical translation of both biological and synthetic constructs. Our centres of excellence and internationally-leading supervisors across this multidisciplinary spectrum (details in Case for Support and UoM Letter of Support) highlight the strength of our scientific training environment. Defining CDT features will be: integrated cohort-based multidisciplinary training; skills training in engineering, biomedical sciences and pre-clinical translation; imaging in national Large Facilities; medical problem-solving nature of clinically co-supervised PhD projects, including in vivo training; comprehensive instruction in transferable skills and commercialisation; outward-facing ethos with placements with UK Regenerative Medicine Platform hub partners (UoM is partner on all three funded hubs), industrial partners, and international exchanges with world-class similarly-orientated doctoral schools; presentations in seminars and conferences. In this way, we will deliver a cadre of multidisciplinary scientists to meet the needs of academia and industry, and ensure the UK's continuing international leadership in RM. Ultimately, through training this cadre of doctoral scientists in regenerative medicine, we will be able to improve wound healing, repair injured nerves, blood vessels, tendon and ligaments, treat joint disease and restore function to organs damaged by disease.

The digital games market is an enormous and fast-growing industry with extraordinary impact, particularly on young people and increasingly on other segments of the population. The importance of the UK games industry (3rd largest in the world) was underlined in the Chancellor's Autumn statement (5th December 2012), which confirmed substantial tax reliefs for the digital games industry, saying that "the Government will ensure that the reliefs are among the most generous in the world". Enthusiasm for digital games is underlined by a 2012 Forbes magazine article suggesting that, by the age of 21, the typical child has played 10,000 hours of digital games. How can we harness widespread enthusiasm for digital games to contribute to advances in society and science in addition to economic impacts? For example, we can test economic theories by analysing the artificial economies in online games, or we can improve the motor skills of recovering stroke patients by using games based on motion detection devices such as the Wii controller, Kinect or simply the mobile phone. In this proposal we will bring the UK digital games industry closer to scientists and healthcare workers to unlock the potential for scientific and social benefits in digital games. The numbers of games sold and the numbers of game hours played mean that we only need to persuade a small fraction of the games industry to consider the potential for social and scientific benefit to achieve a massive benefit for society, and potentially to start a movement that will lead to mainstream distribution of games aimed at scientific and social benefits. In order to do this we need to understand the current state of the digital games industry, by engaging directly with games companies and with industry network associations like the Creative Industries Knowledge Transfer Network. We have a group of 12 games companies and 9 network organisations, all of whom have pledged their support, to get us started. Then we need to build simulation models that will allow us to investigate what might happen in the future (e.g. if government policy were to encourage the development of games with scientific and social benefits). We need to conduct research into sustainable business models for digital games, and particularly for games with scientific and social goals. These will show us how businesses can start up and grow to develop a new generation of games with the potential to improve society. Every action in an online game, from an in-game purchase to a simple button push, generates a piece of network data. This is a truly immense source of information about player behaviours and preferences. We will explore what online data is available now and might become available in the future, investigate the issues around gathering such data, and develop new algorithms to "mine" that data to better understand game players as an avenue for making better games, societal impact and scientific research. It is an ambitious programme, but the potential benefits if we are even partially successful could have a huge impact on children, science and wider society.