In the past decade, over 2.5 million people in the UK had a metal device implanted to replace a skeletal joint in their body. With our chances of living to 100 years old predicted to double in the next 50 years, these bone implants will need to last substantially longer. Alarmingly, current data demonstrates that failure rates rapidly increase each subsequent year after implantation. The metals we currently make bone implants from were not specifically developed for use within the body. Instead, these materials were originally designed for aerospace applications. In addition to being much stiffer than bone, these metal alloys may also contain toxic elements that cause adverse biological reactions. The aim of this fellowship is to design a new generation of bioinspired alloys that promote advantageous cellular responses while exhibiting mechanical properties that are aligned with the body. In order to design the ideal biomedical alloy, there are a number of properties that need to be balanced, for example biocompatibility (i.e. non-toxic), mechanical performance, and wear resistance. Optimising lots of parameters simultaneously via current trial-and-error approaches may take years or even decades. To significantly speed up this process, a computational modelling approach, called Alloys-By-Design (ABD), will be used to discover a range of titanium compositions that match the mechanical properties of bone. For the first time, by searching for alloys with specific microstructures, ABD will be employed to identify compositions with promising biological functionality, such as infection prevention. Since ABD is a theory-based approach, it will be important to validate the model predictions. This will be done by using a unique laser-based system to melt together all the alloying elements. To maintain rapid progress towards using these new metals clinically, a novel high throughput test will be developed as a screening tool to identify compositions that provoke promising mammalian and bacterial cell responses. From these results, non-toxic and antimicrobial compositions will be selected. High resolution microscopy will subsequently be used to understand the relationships between alloying elements, microstructure and biological behaviour. Before bone implants made of these new alloys may be implanted into patients, it will be critical to deepen our understanding of how the body may respond. Importantly, the behaviour of various cell types involved in bone regeneration will be considered, including bone forming osteoblasts and stem cells found in bone marrow. The rate at which these cells grow and their ability to form new bone on the surface of the novel alloys will be benchmarked against currently used metals. Since it is known that ions may leach from alloys within the body and cause damage to surrounding tissue, this will also be carefully studied. The patient and economic benefits gained from personalised devices that anatomically fit perfectly is rapidly growing in bone implants. As such, the possibility to 3D print bespoke implants made from the most promising bioinspired alloy will be explored. For the first time, the ability to locally tailor alloy composition in-situ using a metal laser-based 3D printer will be investigated. By systematically changing the laser processing parameters and characterising the resultant composition, a universal protocol to optimise in-situ alloy formation will be developed. This will open up an entirely new dimension of bone implant customisation, making it possible to tailor mechanical performance or biological functionality in selected areas of a single implant. Underpinning this fellowship is an experienced clinical and industrial advisory board that will support translation of these novel bioinspired alloys. This will ensure that the research may be transformed into approved medical devices that improve patient lives, reduce healthcare costs, and grow the UK economy.

The fundamental goal of this proposal is to Re-Imagine Design Engineering so that new ideas and concepts are generated rapidly, and where both the product and its associated manufacturing system (including its supply chain and people) are designed concurrently and fully tailored to each other. By doing this the >70% of lifecycle and supply chain costs that are "locked in" at the concept design stage can be understood, minimised and verified. This programme will target the transformation of Design Engineering via Interoperable Cyber-Physical-Social (CPS) Services in which: (i) engineering competences and multiscale physics are integrated by innovative digital capabilities, (ii) advanced analytics support capture of knowledge, enhance resilience and predict compliance by interoperable 'smart testing' and fully simulated lifecycle analyses to validate model-centric designs, (iii) novel business/supply chain models provide a transparent value stream from digital design through to manufacturing and pathways to ensure the UK develops the next generation of digital engineering talent. Our vision of the future where manufacturing systems are self-organising, self-aware and distributed, brings a radically different manufacturing industry than exists today. This leads naturally to identifying four major research challenges to this programme: 1. Interoperability - CPS Design Theory: How can we generate ideas and concepts rapidly such that artefacts are designed concurrently with manufacturing systems to create resilient extended enterprises with open communication throughout the whole system? 2. The Cyber World - CPS Modelling Design & Manufacture: How can we represent concepts virtually such that key design characteristics driving intended behaviour are understood, coded and realised via robust, intelligently manufactured product variants? 3. The Physical World - CPS Concept to Reality: What verification and validation concepts are needed to find the shortest and most beneficial pathway to physical realisation aided by a cyber-physical-socio manufacturing ecosystem? 4. The Socio World - CPS The Extended Manufacturing Enterprise: How can we translate and exploit concepts in new organisational structures within a cyber-physical-socio ecosystem to accelerate evolution of design solutions across extended enterprises? The four technical challenges are integrated and pose interdependent challenges. They form the four threads which are to be woven together in this programme. A range of approaches for modelling, evaluation and prediction are needed for the whole programme, and dealing with such diverse system entities from simulation models to individual human and business organisations necessitates a diversity of technical approaches. The concept of 'cyber-genes' and 'cyber-seeds' that can be used in an evolutionary approach form the core thread to provide a new CPS design theory but requires significant interlinkage with the other aspects. For example, CAD models in the cyber world are sufficient for some products, but in general systems are multi-functional and multi-disciplinary and will require a range of modelling methods to provide the necessary design evaluation data, such as with whole life costing. Similarly, although possible to communicate with manufacturing (e.g. CNC machines), feedback of intelligent data directly into a live design is not yet done, and new methods are needed in both design systems and the organisation to allow this capability. Overlaying evolutionary algorithms to these will necessarily require all elements to be adapted and changed, as both the system and underlying methods evolve. Therefore, these nature analogous processes and a range of alternative approaches (e.g. fractals, agent-based systems, response surface methodologies etc.) will be explored.