Out of joint

Joint replacements become intrinsic to the maintenance and restoration of a good quality of life for hundreds of thousands of people each year. Used to treat a wide range of musculoskeletal problems, they are among the most common surgical procedures. In 2019 alone, more than 200,000 hip and knee replacements were performed in England, Wales and Northern Ireland. In the EU, 189 hip replacements and 130 knee replacements are performed per 100,000 people each year. As high as it already was, demand has since been exacerbated by delays caused by the pandemic, as lockdown measures led to the cancellation of millions of elective surgeries, while precious medical resources were diverted to tackling Covid-19.

The UK’s National Joint Registry reported a significant deficit in the provision of joint replacements in 2020 compared with 2019, with 48.8% fewer procedures performed across England, Wales and Northern Ireland. That included 45,116 fewer hip replacements and 57,115 fewer knee replacements. The registry estimated that even with a 5% increase in provision from the 2019 baseline, it would still take until 2031 to clear the UK’s backlog; a 10% expansion would see demand outstrip supply until at least 2026. Moreover, demand will only increase as the global population ages, with the number of people living with conditions like osteoarthritis expected to soar.

Hip and knee interventions are not only in demand – they are also relatively successful.

The rapid development of materials and techniques over the past 20 years has resulted in more than half of all hip and knee replacements now lasting more than 25 years. But there’s still room for improvement as well as expertise, as projects like BioTrib – a multinational collaboration designed to lay the foundations for the creation of a new generation of joint interventions – have set out to prove.

Project coordinator Professor Richard Hall explains that BioTrib aims to further enhance the life of joint interventions using advanced tribology – the science of interacting surfaces in relative motion, and how they cause friction, wear and lubrication. The project is designed to provide a platform from which scientists and researchers can pioneer the next wave of orthopaedic technology.

“BioTrib is about capacity building and providing a comprehensive training programme to early stage researchers through a balanced set of PhD activities,” he says. “The shortage of STEM-based researchers within the EU is significant, especially when the demand will rise over the next decade.”

Interdisciplinary skills

The BioTrib consortium brings together five universities, as well as representatives from across the supply chain, including materials and implant manufacturers, testing companies and clinical units.

“They all possess the international, intersectoral, and interdisciplinary skills and experience needed to develop a successful medical engineer,” explains Hall, adding that the five universities – the University of Leeds, Uppsala University, ETH Zurich, Imperial College London and Lulea Technical University – act as the “core” of the project. As world-leaders in medical engineering and biotribology, they’re responsible for enrolling researchers on to PhD programmes that align with the overall BioTrib ambitions.

Current focus areas include everything from the use of additive manufacturing for novel bearings with new lubrication properties to the development of next-generation soft-bearings through novel electrospun matrices or unique nanocomposite polymers.

One of the project’s hallmarks is its international nature, says Hall’s colleague and co-coordinator Dr Michael Bryant. “The engineering science base that supports the innovation and research process needs to reflect the global nature of the medical device business. This includes developing skills and a research culture that provides a recognition of the stakeholder needs not only nationally, but internationally and within different countries.” This objective is achieved through the recruitment of international students and a broad spectrum of global industry partners.

Curiously, the project is an EU-funded initiative spearheaded in the post-Brexit world by Hall and Bryant, both based at the University of Leeds in the north of England. The programme has been funded by the Marie Skłodowska-Curie Actions programme, which provides backing for doctoral and post-doctoral researchers under the European Commission’s Horizon 2020 research and innovation framework.

Bryant says UK researchers have had to rebuild some bridges and navigate additional bureaucracy in the wake of Brexit in order to ensure collaborations of this nature can continue seamlessly.

“In terms of Brexit, researchers in the EU often question whether UK institutions or industry can be bona fide partners in an EU-sponsored Horizon project,” he says. “They require continued reassurance – not having to do this would make life easier and allow us to focus on the research for the benefit of all stakeholders. Then there are the practical aspects, for instance, issues around visa requirements for different countries within the EU and the transfer of materials.”

Implant failure

Bryant points out that biotribology is not only a European concern, but a global one. Device failure remains an issue despite improvements in materials and designs over the past two decades. While total joint replacements have been a remarkable success in providing patients with pain-free lives and improved mobility, there are still a considerable number of revision procedures that take place annually due to the sheer volume of surgeries undertaken, defective implants and a rise in the number of younger patients needing primary operations. That’s all in addition to increased demand driven by an ageing population.

“Given the changing patient demographic, implants need to survive longer and be more robust against the variability encountered in vivo,” says Bryant.

The recorded failure rate is about 5% at ten years, according to Bryant. But there are significant differences in performance as a function of, for example, prosthesis type and surgeon skill. “Issues relating to early failure in metal-on-metal total hip and resurfacing replacements have been defined as a significant public health issue,” he says, adding that there is ongoing debate within the scientific and clinical communities that focuses on alternative materials and designs for replacement systems and orthopaedic implants. Hall points out that device failures also put the regulatory spotlight on authorities, which need to determine how to effectively test new devices preclinically. “[There is] significant potential in finding solutions through the rise of computational techniques, such as the use of digital twin and in silico clinical trials, which will augment clinical trials data, if not completely replace it,” he explains. “These and similar technologies will revolutionise regulatory science and affairs over the next 20 years, but there are challenges in terms of, for instance, validating these models.”

BioTrib believes improved testing should be a major focus, either computationally, experimentally, or both. “However, these methods are currently limited in both capacity and capability,” says Hall. “Failure to implement adequate preclinical testing leads to poor outcomes, including the loss of quality of life and continued disability for the patient. These high-profile failures also diminish trust in the healthcare system.”

With this in mind, Bryant says the BioTrib project will build on research done in the sector in the past five or ten years. “There have been significant developments in the materials used in joint replacement bearings, in particular the widespread use of XLPE (cross-linked polyethylene). This has reduced the wear in some devices considerably and, therefore, reduced the potential for osteolytic failure.” Other innovations, such as coatings for bearing surfaces, have not had the same success, he says, with significant evidence of delamination in real-world situations.

Looking ahead, regulatory science remains a worthwhile domain for research and innovation. Hall says interest in this area has been driven by multiple factors, including the pull of the industry trying to reduce costs while improving the effectiveness of implants and the fact that the public is now more vocal about their expectations. Researchers continue to push science forward, particularly in the computational domain. Hall says outstanding areas of investigation include how to maximise the synergy between traditional clinical trials and in silico versions. The relationship between computational tools and experiments, and the role of real-world data in the preclinical process will also help identify the possible design or implementation issues, and inform future assessment methods.

“This needs to be underpinned by improved capacity within the workforce through the deployment of the appropriate masters and PhD programmes,” he says. “The USA has a lead in this domain – driven by the industry and the FDA – and Europe needs to follow suit.”

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The challenge of testing longevity in artificial joints

The standard means of testing artificial hip and knee joints includes using devices to simulate the impact of walking. But neither Hall or Bryant believes this is adequate, and they’re attempting to improve testing procedures by putting the prosthetics through more rigorous assessments to reveal their weaknesses. One challenge in conducting these adverse loading tests is that the march of innovation in artificial joint technology can’t wait 15 or 20 years for the validation of new materials and designs in prosthetics. This is where the team at Leeds have to apply some mechanical engineering alchemy to speed up the process, but, in an interview with NS Medical Devices, Bryant says doing so with accuracy is still very much a work in progress for the entire orthopaedic research community.

“The simulators will run for a period of time that we think will replicate a wear rate typically expected in vivo, but the challenge is how we view that data,” he adds.

“Hip simulation can be viewed and used to interrogate mechanisms of wear, the tribology and more recently the corrosion. One of the challenges that comes with progressing the simulation techniques are that we want to have something that’s realistic and representative of patients’ activity, but to do this exactly would require 15 or 20 years in the simulator. We streamline that by accelerating it to a certain degree – but there are still quite a lot of questions around how to do that effectively and appropriately.”

Designing a testing protocol that effectively replicates human activity is one of the goals that BioTrib will attempt to meet in the four years it has runway from EU funding. But it’s a big task, and Hall is already looking for additional investment, as well as hoping to negotiate another grant from the EU. In the meantime, Bryant his colleagues hope to shift the priority of artificial joint testing so that assessment procedures involve a holistic view of an implanted joint, including wear, tribology and corrosion – rather than just a walking test based on wear.