Replicating a human organ is a highly complex challenge both structurally and functionally. At the core of this grand challenge lies the critical need for vascularisation and more broadly the need for cellularisation. Cellular systems in our bodies are naturally programmed in a bottom-up fashion where structure is an evolutionary consequence of function. For instance, the need for optimal exchange and transport drives morphogenesis, manifesting itself via dynamic signalling and secretion patterns during vascularisation, alveolarization and the formation of all self-organised tissue compartments. Tissue engineers have attempted the inverse hoping function will also follow form, with a laser focus on the structure problem: the ability to produce acellular architectures such as perfusable networks for transport and microporous scaffolds for cellular aggregation. These top-down engineered matrices are intricate yet static and non-responsive, leaving us with rudimental means of bulk seeding, cellularisation and stimulation, and limiting cell-mediated bottom-up growth and remodelling. Organotypic growth patterns are a dynamic response to physiological needs, driven by the spatiotemporally controlled release of biochemical factors and stimuli, and require extremely soft and degradable cell encapsulated extracellular microenvironments capable of bottom-up remodelling, both of which are currently only afforded at small microfluidic footprints. The 3D SPARK project offers a game-changing solution to large-scale volumetric tissue production via computed axial lithography (CAL) and computed axial stimulation (CAS) - the optical inverses of computed axial tomography (CAT). Volumetric processing challenges conventional wisdom in tissue engineering showing that complex and delicate 3D cellular architectures can be produced all-at-once without relying on slow, sequential processing of biological matter, and that large volumes of manufactured tissue can be accessible at a single cell level without a need for physical manipulation or slow optical scanning. At its core, this revolutionary CAT-inspired method utilises a superposition of 2D angular light projections to construct a 3D spatial distribution of exposure dose, and volumetrically trigger photopolymerization (bioprinting), photorelease (biomodulation) and photoexcitation (imaging) to regulate and monitor key cellular events during tissue development in a photoactive cell-encapsulated hydrogel matrix. With light-mediated volumetric processing and the ability to pattern light intensity in 3D at multiple wavelengths, we introduce a scalable solution to: (1) trigger photopolymerization and manufacture intact vascular structures in such soft (<10 kPa) cell-encapsulated photoactive gels; (2) control the light-induced depletion of chemical species such as oxygen (via radical quenching), and secretion of biochemical factors such as growth factors (via uncaging) directing tissue development across the entire volume; and (3) rapidly image the entire volume to monitor 3D cellularisation concurrent with photomodulation and tissue growth. In our tissue models, larger features such as macrovascular networks are designed and volumetrically printed in a top-down fashion and are internally coated with endothelial cells (ECs). Finer features such as microvascular capillaries are then stimulated with light to emerge and develop from sparsely encapsulated ECs within the printed gel to bridge the macrovascular gaps in a bottom-up fashion. This all-in-one platform goes beyond patterning the physical and chemical properties of the matrix, to enable dynamic manipulation of cellular processes allowing us to accommodate for top-down engineering and bottom-up development simultaneously. Hence, the proposed technology will be the dream tool of tissue engineers giving them spatiotemporal access to large volumes of printed tissue at a single cell level with light in a way never achievable before.

The world's manufacturing economy has been transformed by the phenomenon of globalisation, with benefits for economies of scale, operational flexibility, risk sharing and access to new markets. It has been at the cost of a loss of manufacturing and other jobs in western economies, loss of core capabilities and increased risks of disruption in the highly interconnected and interdependent global systems. The resource demands and environmental impacts of globalisation have also led to a loss of sustainability. New highly adaptable manufacturing processes and techniques capable of operating at small scales may allow a rebalancing of the manufacturing economy. They offer the possibility of a new understanding of where and how design, manufacture and services should be carried out to achieve the most appropriate mix of capability and employment possibilities in our economies but also to minimise environmental costs, to improve product specialisation to markets and to ensure resilience of provision under natural and socio-political disruption. This proposal brings together an interdisciplinary academic team to work with industry and local communities to explore the impact of this re-distribution of manufacturing (RDM) at the scale of the city and its hinterland, using Bristol as an example in its European Green Capital year, and concentrating on the issues of resilience and sustainability. The aim of this exploration will be to develop a vision, roadmap and research agenda for the implications of RDM for the city, and at the same time develop a methodology for networked collaboration between the many stakeholders that will allow deep understanding of the issues to be achieved and new approaches to their resolution explored. The network will study the issues from a number of disciplinary perspectives, bringing together experts in manufacturing, design, logistics, operations management, infrastructure, resilience, sustainability, engineering systems, geographical sciences, mathematical modelling and beyond. They will consider how RDM may contribute to the resilience and sustainability of a city in a number of ways: firstly, how can we characterise the economic, social and environmental challenges that we face in the city for which RDM may contribute to a solution? Secondly, what are the technical developments, for example in manufacturing equipment and digital technologies, that are enablers for RDM, and what are their implications for a range of manufacturing applications and for the design of products and systems? Thirdly, what are the social and political developments, for example in public policy, in regulation, in the rise of social enterprise or environmentalism that impact on RDM and what are their implications? Fourthly, what are the business implications, on supply networks and logistics arrangements, of the re-distribution? Finally, what are the implications for the physical and digital infrastructure of the city? In addition, the network will, through the way in which it carries out embedded focused studies, explore mechanisms by which interdisciplinary teams may come together to address societal grand challenges and develop research agendas for their solution. These will be based on working together using a combination of a Collaboratory - a centre without walls - and a Living Lab - a gathering of public-private partnerships in which businesses, researchers, authorities, and citizens work together for the creation of new services, business ideas, markets, and technologies.

The Innovative Manufacturing and Construction Research Centre (IMCRC) will undertake a wide variety of work in the Manufacturing, Construction and product design areas. The work will be contained within 5 programmes:1. Transforming Organisations / Providing individuals, organisations, sectors and regions with the dynamic and innovative capability to thrive in a complex and uncertain future2. High Value Assets / Delivering tools, techniques and designs to maximise the through-life value of high capital cost, long life physical assets3. Healthy & Secure Future / Meeting the growing need for products & environments that promote health, safety and security4. Next Generation Technologies / The future materials, processes, production and information systems to deliver products to the customer5. Customised Products / The design and optimisation techniques to deliver customer specific products.Academics within the Loughborough IMCRC have an internationally leading track record in these areas and a history of strong collaborations to gear IMCRC capabilities with the complementary strengths of external groups.Innovative activities are increasingly distributed across the value chain. The impressive scope of the IMCRC helps us mirror this industrial reality, and enhances knowledge transfer. This advantage of the size and diversity of activities within the IMCRC compared with other smaller UK centres gives the Loughborough IMCRC a leading role in this technology and value chain integration area. Loughborough IMCRC as by far the biggest IMRC (in terms of number of academics, researchers and in funding) can take a more holistic approach and has the skills to generate, identify and integrate expertise from elsewhere as required. Therefore, a large proportion of the Centre funding (approximately 50%) will be allocated to Integration projects or Grand Challenges that cover a spectrum of expertise.The Centre covers a wide range of activities from Concept to Creation.The activities of the Centre will take place in collaboration with the world's best researchers in the UK and abroad. The academics within the Centre will be organised into 3 Research Units so that they can be co-ordinated effectively and can cooperate on Programmes.