Refine and Translate Bioinspired Alloys

There are millions of people walking around with metallic devices to repair or replace part of their skeleton. This includes joint replacements, dental implants, spinal devices or parts to reconstruct traumatic injuries. Titanium and titanium-based alloys are one of the most common materials used for these implants. However, these materials were originally designed for an entirely different sector, aerospace. As a result of this misalignment there are several biologically driven failure mechanisms for skeletal implants. For example, mechanical instability due to mismatched mechanical properties or infection due to a lack of protection. Failure of these devices costs the NHS £250 million per year in additional surgical and patient management costs. In reality these costs are higher when considering the impact on people's quality of life and the loss of working days to the economy. The vision for this fellowship is to transform biomedical alloy design to offer new materials that are specifically designed to function within the body. Our approach is to move away from the limited goalposts of mechanical performance and binary biocompatibility assessments, and to embed new beneficial biological properties into implant material design. For example antimicrobial or pro-regeneration. Ultimately the outputs from the project aim to revolutionise patient outcomes through increased device life-spans and reduced complications. This renewal award will focus on using the methods and data generated from the initial fellowship as a springboard to progress the most promising alloy compositions closer to clinical adoption. Specifically, we will focus on developing high-throughput computational and experimental methods to screen and validate new biomedical alloys. Alongside this we will regularly engage with clinical partners and patients to ensure that our solutions may be more readily translated. Through a series of objectives we will achieve the various components of the project's aim: O1 Refine standard operating protocol for engineered gradient alloy samples O2 Validate acellular mineralisation screening and high throughput antimicrobial tests O3 Demonstrate applicability of biological merit indices through in-vitro testing O4 Engage with stakeholders to establish translational pathway for a maximise of three alloy compositions, including identification of target device(s) O5 Secure onward funding to demonstrate superior performance of a selected antimicrobial alloy composition against Ti-6Al-4V in an in-vivo infection model Beneficiaries of the project are widespread, spanning from patients whom will ultimately benefit from improved device outcomes to surgeons who will have new solutions to the most challenging issues in skeletal implants. The multidisciplinary approach creates a significant opportunity to share knowledge across the disciplines of materials science, additive manufacturing and biomaterials. Alongside this given the significant engagement with a diversity of stakeholders throughout this award there is great potential for best practice in research translation to be shared across communities. In summary, this renewal award aims to leverage the initial fellowship findings and accelerate these towards real-world impact by driving forward new biomedical alloy compositions. The continued flexibility of the award will also continue to support Dr Cox's career trajectory, through mentoring, coaching, mobility to mature influential partnerships, and the opportunity for her to promote a positive research culture locally and nationally through a Plus Fund project.