Muscles help us move, enable us to interact with objects and the environment, and regulate critical internal functions. Unfortunately, they are susceptible to damage due to disease, ageing and trauma and are a central factor in diverse serious healthcare conditions including sarcopenia (age-related loss of muscle mass and function, where decline in muscle mass between 40 and 80 years ranges from 30% to 50%), stroke, muscular dystrophy, multiple sclerosis, soft-tissue cancers, venous ulceration, diabetes, degenerative myopathy and incontinence (between 3 and 6 million people in the UK, and 24% of older people, suffer from urinary incontinence). The emPower Transformative Healthcare Technologies 2050 programme will overcome the limitations of current wearable assistive technologies and regenerative medicine by deploying engineered robotic artificial muscular assistance inside the body, exactly where it is needed, to: 1. restore strength and control in mobility and manipulation in older people who have lost muscle strength and precision; and 2. restore controllable muscular capabilities for sufferers of trauma, stroke, incontinence and degenerative diseases. This will have significant knock-on effects on whole-body and mind health through increased confidence, independence and quality of life, massively reducing the healthcare burden and facilitating the return of sufferers to productive and fulfilling lives. The emPOWER artificial muscles will be engineered to bridge the gap between the nanoscale of fundamental energy transduction phenomena and the centimetre scale of bulk muscle action, and will be implantable using minimally invasive (including robot-assisted) surgery and advanced imaging to replace or supplement ailing muscles, providing short-term rehabilitation, long-term assistance or complete functional restoration as needed. To achieve our vision, we have brought together leading experts in soft robotics, regenerative medicine, bio-interfacing, smart structures, synthetic biology, polymer chemistry, self-assembly, bio-printing and tissue analysis, and clinical partners in neuro-rehabilitation, cardiovascular disease, head and neck surgery, urology, geriatrics and musculoskeletal medicine. Together, and with key industrial and social care partners, we will deliver the foundational technologies and first-stage proof-of-concept of the emPOWER artificial muscles within the five years of this transformative project, leading to major healthcare, economic and social impact to 2050 and beyond.

Kidney function is essential for life and treatment for kidney failure costs the NHS £2 billion each year. Most scientists investigating kidney development and failure in disease use animal in vivo and ex-vivo models particularly mice. However, mouse kidneys are not the same as human kidneys, either in gross organisation or in the precise molecular composition during development. This may explain why mice with particular gene defects often do not show the same symptoms as a human with these changes. The aim of this proposal is to use very early stem cells (human pluripotent stem cells: hPSCs) to establish a human 3D model of the developing kidney at very small scale (micro-organoids). At the moment the standard kidney organoids we and others make, require a large number of cells/organoid (about 100,000+) and lack certain cell types including critically, cells of the immune system called macrophages. These macrophages play roles in development of the fetal kidney, roles that are different from their role in inflammation after birth. They promote blood vessel development and that of the outflow regions of the kidney, both of which develop poorly in the current hPSC-kidney models. We hypothesise that kidney organoids can be made dramatically better kidney models by introducing macrophages and improving nutrient/waste diffusion. We will generate macrophages from our hPSCs according to published methods, aided by our experienced collaborators, and test the effect of different proportions of these in improving our stem cell-kidney organoids, first in the conventional 'macro'-organoids, then in micro-organoids with 1/10th the number of cells or fewer. We will use this platform to ask whether immune macrophages can enhance kidney organoid developmental. In our study, the organoids will be grown in a way that compensates for lack of blood flowing through, by generating flow around the tiny kidney micro-organoids through culturing them in specially designed purpose built chambers. This model will allow the time in culture to be increased so that the kidney tissue remains healthy and develops further. The micro-organoids will be more complex and more similar in composition to developing kidneys than current stem cell derived macro-organoids. This human system will be better for understanding human kidney development and diseases affecting development of the human kidney, particularly those caused by detrimental changes in genes. It will replace the need to introduce similar gene changes into mice and look at their kidney development-which may anyway be affected differently. We can adapt the model for other tissues like liver gut or lung hPSC- or tissue-organoid models. Thus, this platform will be suitable for use in better understanding of human development and disease and by generating many micro organoids (scale up), for use in testing drug, which may alleviate kidney disease, or testing if they are harmful to the kidney. In the long term, it could provide a route for generating supplementary kidney tissue to aid ailing kidneys.

The chemical and pharmaceutical industries are currently reliant on petrochemical derived intermediates for the synthesis of a wide range of valuable chemicals, materials and medicines. Decreasing petrochemical reserves, and concerns over increasing cost and greenhouse gas emissions, are now driving the search for renewable and environmentally friendly sources of these critically needed compounds. This project aims to establish a range of new manufacturing technologies for efficient conversion of biomass in agricultural waste streams into sustainable sources of these valuable chemical intermediates. The UK Committee on Climate Change (2018) has highlighted the importance of the efficient use of agricultural biomass in tackling climate change. The work undertaken in this project will contribute to this effort and help the UK government achieve its stated target of 'net-zero emissions' by 2050. The new approaches will be exemplified using UK-sourced Sugar Beet Pulp (SBP) a renewable resource in which the UK is self-sufficient. Over 8 million tonnes of sugar beet is grown annually in the UK on over 3500 farms concentrated in East Anglia and the East Midlands. After harvest, the beet is transported to a small number of advanced biorefineries to extract the main product; the sucrose we find in table sugar. SBP is the lignocellulosic material left after sucrose extraction. Currently it is dried (requiring energy input) and then sold as a low-value animal feed. SBP is primarily composed of two, naturally occurring, biological polymers; cellulose and pectin. Efficient utilisation of this biomass waste stream demands that applications are found for both of these. This work will establish the use of the cellulose nanofibres for making antimicrobial coatings and 3D-printed scaffolds (in which cells can be cultured for tissue engineering and regenerative medicine applications). The pectin will be broken down into its two main components: L-arabinose and D-galacturonic acid. The L-arabinose can be used directly as a low-calorie sweetener to combat the growing problem of obesity. The D-galacturonic acid will be modified in order to allow formation of biodegradable polymers which have a wide range of applications. This new ability to convert SBP into a range of useful food, chemical and healthcare products is expected to bring significant social, economic and environmental benefits. In conducting this research we will adopt a holistic approach to the design of integrated biorefineries in which these new technologies will be implemented. Computer-based modelling tools will be used to assess the efficiency of raw material, water and energy utilisation. Techno-Economic Analysis (TEA) and Life Cycle Analysis (LCA) approaches will be employed to identify the most cost-effective and environmentally benign product and process combinations for potential commercialisation. The results will be widely disseminated to facilitate public engagement with the research and ethical evaluation. In this way the work will support the UK in its transition to a low-carbon, bio-based circular economy.