Rapid Design of Bioinspired Alloys - From Modelling to Manufacture

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.

Millions of bone implants made from metal alloys developed for aerospace applications have been inserted worldwide. We know that using these materials, which may contain toxic elements, leads to disastrous cell responses and device failure. An entirely new generation of biomedical alloys that are fit for purpose will be pioneered in this fellowship. Modelling will be used to rapidly design compositions from non-toxic elements that are mechanically matched to bone and antimicrobial in order to prevent infection. Following identification of promising formulations, the possibility to manufacture them into patient specific implants will be explored. Working closely with world-leading industrial partners, regulation and commercialisation experts, and surgeons will ensure this research delivers widespread impact.

Patients: this research will ultimately be of most benefit to the millions of people who receive metal implants to replace damaged or diseased bones. The proposed multidisciplinary approach is distinctive in its potential to rapidly discover alloys that are mechanically and biologically aligned to the body. Simultaneously mapping a regulatory path for these new metals will accelerate translation thereby enabling the societal benefits of using these materials to be realised sooner. Notably, these devices represent an opportunity to speed up recovery, prolong implant lifespan, and prevent revision. This will be beneficial to the patient's quality of life and welfare, and represents a significant cost saving for the NHS.

Industrial sectors: demonstrating the value that may be achieved in the biomedical sector by adopting new alloys may create a widespread desire for new titanium products, which impacts metal manufacturers. By raising the profile of additive manufacturing, this research may also result in increased demand for all the technologies and materials involved within the metal 3D printing supply chain. In the long-term, this research will also enhance the reputations of medical device manufacturers through reduced revision rates achieved by improved osseointegration and infection prevention. Establishing an ISO accredited medical additive manufacturing innovation facility would be a national first and provide an answer to the government's healthy ageing strategy by sustainably supporting UK innovation, thus enhancing economic competitiveness. Notably, significant support has been secured to engage with companies whom will benefit from the research, this is in addition to the committed industrial partners.

Clinical: given that failed devices may diminish surgical reputation, the potential of these bioinspired alloy to inherently reduce the risk of device failure is particularly attractive. This multidisciplinary fellowship is the ideal opportunity to enhance clinical understanding of various academic disciplines, which may drive innovation across orthopaedics, craniomaxillofacial, spine, trauma, and dental applications. By regularly engaging with key clinical opinion leaders, it is anticipated that other collaboration opportunities will arise and lead to further impact for associated research communities and industrial supply chains. Furthermore, a significant focus of this fellowship is to translate this research, which would lead to cost-saving benefits for the NHS.

Educational beneficiaries: involvement in this multidisciplinary fellowship is a great training opportunity for the research team. By proactively engaging with world-leading academic groups around the globe, the new knowledge generated in this fellowship will be widely disseminated and used to inspire future generations into STEM subjects. Through sharing of best practise with the diverse range of industrial partners, academic standards and commercialisation potential will be enhanced. By regularly engaging with the public through workshops and events, we will understand perceptions on the research and implement this feedback moving forward.