Peripheral arterial disease refers to partial or total block of limb arteries due to the accumulation of fatty deposits on the vessel wall. The disease imposes a progressive damage to patients' health and wellbeing due to the restriction of blood supply to leg muscles. Typical symptoms include pain when walking and dying of leg tissue. The disease can be effectively treated by vascular stents which are essentially meshes of synthetic materials used to reopen the blocked blood vessels. However, stenting in peripheral arteries has proved problematic, given the complexity of the disease and constant exposure to severe biomechanical forces. Consequently, it requires customised design in order to improve patency times and reduce complications in interventional therapy. In addition, current stent manufacturing (such as laser cutting and photo etching) is a material wasteful and time consuming process. Additive manufacturing (AM) via Selective Laser Melting (SLM) offers the most promising approach to generate stents with customized designs and extensive saving of raw materials. This research aims to develop smart stents for treatment of complex periphery artery stenosis in the lower limbs. Superelastic shape memory alloy, Nitinol, will be used in this study, as the material is extremely flexible and can automatically recover its original shape even after very large deformation (smart nature). Stents made of Nitinol demonstrate high conformability to the complex vessel geometry in diseased regions. To achieve the aim, the Mechanics of Advanced Materials group at LU, the Advanced Materials & Processing Lab at UoB and the Bioengineering group at MMU are brought together to collaboratively work on the project. UoB will focus on adapting SLM for manufacturing structures (samples and prototypes), with smaller feature sizes (less than 200 microns), out of Nitinol powders. In particular, UoB will apply micro-doping of platinum group metals to improve the biocompatibility and radiopacity of SLMed Nitinol, as well as develop techniques to prevent Ni evaporation which occurs during SLM and can result in significant loss of superelastic behaviour. Mechanical behaviour of the samples and stents, delivered by UoB, will be tested at LU using a stent crimper and a microtester fitted with an environmental bath. Samples and stents, both as-received and tested, will undergo SEM/TEM/EBSD characterisation to gain further insights of the SLMed Nitinol behaviour. An in-vitro setup at MMU will be used to study the in-vitro performance, including haemodynamics, of stent prototypes subjected to optional biomechanical forces such as bending and radial compression. These experimental studies will provide further guidance to UoB for optimisation of key SLM parameters. In addition, a mesoscale computer model will be developed at UoB to simulate the AM process, including micro-doping and Ni evaporation, to support the adaption and optimisation of the micro-SLM process. Finite element simulations of stent deformation will be carried out jointly by LU (solid mechanics) and MMU (fluid mechanics), including in-vitro and in-silico modelling of local deformation and haemodynamics of the stent-artery system. Simulation results will be compared with experimental results. The researchers at LU will also deliver the design of lesion-specific stents to UoB for AM of customised stents. Particular considerations will be given to designs which best suits the SLM process. The design will be based on 3D lesion imaging of actual patients provided by MMU and iterative finite element analyses at LU, with in-vitro performance assessment at MMU. The outcome will serve as a driving force to boost the development of personalised therapies, especially for complex and critical diseases in vulnerable patients such as ageing populations.

This proposal is tightly focussed on addressing major unmet clinical needs in the repair and rehabilitation of non-union fractures, in particular for long-bone and cranio-facial trauma. A non-union is a broken bone that fails to heal. These result from both civilian and military injuries including the consequences of cancer and lead to pain, suffering and loss of dignity. Our aim is to create a co-ordinated self-sustaining network linking the Trauma HTC and other major UK clinical research centres, both civilian and military, in order to pull solutions from the science and technology research community and assist their translation to the clinic. The network will link with centres of expertise and research excellence in healthcare technologies supported by EPSRC and others, and to industry and other key stakeholders including patients. This network will ensure, by a programme of activities with both proven and novel components, that these disparate communities are empowered to explore together those areas where new scientific and technological opportunities have the promise to resolve important clinical problems.

The development of implantable prosthetics has revolutionised medicine. Where joint injury or destruction would once have once significantly reduced quality of life, to the detriment of a patient's fitness and health, we can now almost fully restore function. The manufacturing methods used for the production of prosthetics are quite crude and often require the casting of metal into a mould before finishing by hand. As a consequence they are usually made to only a few different sizes and the resulting structures must be made to fit by the surgeon. This is acceptable for the majority of patients who require joint replacement, but there are some medical conditions that require very irregularly shaped (customised) structures to enable an adequate repair. For example, bone cancers often require extensive cutting away of the bone and this can leave a very large and irregular defect. Similarly the bone structure of the face and skull is very specific to an individual and when bone must be removed, again due to cancer or following physical damage. To restore physical appearance, it would be best if a clinician were able to generate a plate that could allow them to replace like for like. In this project, we will refine an Additive Layer Manufacturing (ALM) technology called selective laser meeting (SLM) to allow us to produce implants that are individual to a patient. These technologies use lasers to fuse powder and create a three dimensional object in a layer by layer fashion. By taking three dimensional images (MRI and CT) from a patient, operators can design structures that will be able to directly replace tissue with the optimum shaped implant. In this project, we will work with doctors from the Royal Orthopaedic Hospital, Queen Elizabeth Hospital and the Royal Centre for Defence Medicine to develop a process that we hope will eventually allow these clinicians to produce implants in their own hospitals or even on the front-line of a conflict and enable better treatment for their patients. As well as allowing the production of complex-shaped parts, ALM has another significant advantage over casting in that it allows the production of very complex porous structures within a material. This means that we can modify the physical properties of the material by incorporating holes or structured porosity into the structure. These holes can be sealed from the surface of the prosthesis, or can be linked to the surface using a network of even narrower holes. We would like to explore the use of this added manufacturing capability to make prosthetics with a very closely defined internal structure that is completely interconnected. A second, cement like, material can then be injected into the pore structure and will harden in place. This second phase can be used to modify mechanical properties or could be used as a carrier for drugs that may stop infection or help the tissue to heal. It is hoped that this modification could help us eliminate implant-based infections, which is the leading cause of failure following prosthetic implantation.

PREMIERE will integrate challenges identified by the EPSRC Prosperity Outcomes and the Industrial Strategy Challenge Fund (ISCF) in healthcare (Healthy Nation), energy (Resilient Nation), manufacturing and digital technologies (Resilient Nation, Productive Nation) as areas to drive economic growth. The programme will bring together a multi-disciplinary team of researchers to create unprecedented impact in these sectors through the creation of a next-generation predictive framework for complex multiphase systems. Importantly, the framework methodology will span purely physics-driven, CFD-mediated solutions at one extreme, and data-centric solutions at the other where the complexity of the phenomena masks the underlying physics. The framework will advance the current state-of-the-art in uncertainty quantification, adjoint sensitivity, data-assimilation, ensemble methods, CFD, and design of experiments to 'blend' the two extremes in order to create ultra-fast multi-fidelity, predictive models, supported by cutting-edge experimental investigations. This transformative technology will be sufficiently generic so as to address a wide spectrum of challenges across the ISCF areas, and will empower the user with optimal compromises between off-line (modelling) and on-line (simulation) efforts so as to meet an a priori 'error bar' on the model outputs. The investigators' synergy, and their long-standing industrial collaborations, will ensure that PREMIERE will result in a paradigm-shift in multiphase flow research worldwide. We will demonstrate our capabilities using exemplar challenges, of central importance to their respective sectors in close collaboration with our industrial and healthcare partners. Our PREMIERE framework will provide novel and more efficient manufacturing processes, reliable design tools for the oil-and-gas industry, which remove conservatism in design, improve safety management, and reduce emissions and carbon footprint. This framework will also provide enabling technology for the design, operation, and optimisation of the next-generation nuclear reactors, and associated reprocessing, as well as patient-specific therapies for diseases such as acute compartment syndrome.

Topology is a particular study of the spatial structure of objects, based on counting discrete properties, such as the number of holes and bridges in a sponge. Whichever way the sponge is stretched or squeezed, these numbers stay the same. In fact, the elastic properties of the sponge depend on this structure. It turns out that topological properties like this play a role in the physical properties of certain materials, such as the way they conduct electricity or how light propagates through them. This has led to an explosion of research and development into new kinds of materials with unprecedented properties, designed using fundamental physical and mathematical principles which can be fabricated and, in the future, manufactured on a large scale. We will train the first cohort of doctoral topological scientists, who will have a broad expertise in topological science and design, focused towards the development of new topological materials that address the needs of industry. Drawn from mathematically-informed backgrounds including physics, engineering and materials science, they will develop a broad technical appreciation of topological design within all of these disciplines, and gain research experience in mini-projects in theoretical and experimental groups. Their main PhD research project can be with supervisors drawn from all academic Schools in the College of Engineering and Physical Sciences at the University of Birmingham, in partnership with our wide range of partners from industry. This technical education will be entwined with a programme of transferable skills developing the critical skills of innovation, entrepreneurship and responsible innovation. The academic leadership of this CDT has co-created the training programme in collaboration with a range of industrial partners who will contribute to the directions of the research projects, provide internships and help the students and academic supervisors focus on the needs of end users in their research. These partners will not only be drawn from relevant industries, such as communications, manufacturing and defence sectors, but more widely from knowledge industries including software developers and commercialisation lawyers. The resulting CDT will be a beacon for cross-disciplinary research across the physical sciences and spearheading academic-industrial partnership over the coming decades as topological design becomes a crucial principle for the development of future technologies, underpinning the future prosperity of the UK.