The natural human knee is a complex and heavily loaded joint. Therefore, for functional reasons, freedom of movement and stability are important for artificial knee joints. Due to this demand, high stresses are placed on the articulation of the artificial knee joints. Polyethylene (with very high molecular weight, termed as UHMWPE) has been the material of choice for the load-bearing articulating surface in artificial knee joints. As a result, excessive wear and fatigue of the tibial polyethylene bearing are common and result in artificial knee joint failure. Polyethylene-related total knee failures have limited the lifetime of total knee joint replacements.However, there is an increasing demand for total knee replacement operations which now account for nearly half of all joint replacements in the UK. In fact, approximately one million UHMWPE components are implanted worldwide on a yearly basis. Also the number of operations carried out in those aged 55-64 has been rising significantly. The application of joint replacement to younger (aged < 64 years) and more active people plus the general increase in life expectancy make it an urgent need for longer lasting polyethylene with better wear and fatigue resistance. The Project is focused on reducing the incidence of material failure. The hypothesis to be examined is that the cause of material failure of UHMWPE knee-joint components lies in the precise time-temperature history employed during manufacture of the UHMWPE components from the virgin UHMWPE powder. Recent work has shown that toughness at macroscopic UHMWPE welded interface increases with welding time and temperature. This suggests that the toughness of UHMWPE powder particle interfaces may vary similarly with compression moulding time and temperature. Hence there is a need to optimise processing conditions to provide interfaces with adequate toughness at locations in tibial components where stress intensities are high. Radiation crosslinking of UHMWPE for artificial knee joints is still controversial and there is a debate over whether radiation crosslinking is beneficial. While crosslinking reduces UHMWPE wear, the method of post irradiation processing of the material to eliminate residual free radicals can affect the long-term performance of the material in the body. Radiation crosslinking will be incorporated and assessed in the Project in order to resolve the scientific controversy regarding its effects on wear and fatigue.The proposed project seeks to answer two important questions. 1) Does improved interface bonding improve the endurance of UHMWPE tibial components and to what extent? 2) Can an appropriate additional radiation crosslinking treatment be beneficial? The Project uses two novel approaches. One is to improve material integrity using computer-aided methodology for generating a range of actual customised tibial component with varying degrees of interface bonding. The other is to combine improved material integrity with state-of-art post irradiation treatment in order to reduce wear rate and improve fatigue resistance. A side-by-side comparison of a range of non-crosslinked and radiation cross-linked components, based upon evaluation of wear behaviour, wear particles and fatigue strength will be made. Identification of optimised manufacturing conditions will reduce the currently high rate of revision operations.

In England and Wales in 2017, 15,091 surgeries were performed due to failed hip and knee replacements. Although loosening of the implant is the main cause of failure, infection still remains a major problem, accounting for 2,865 of these procedures and over £73 million in annual costs for the NHS. This number is expected to rise with an ageing population and the number of joint replacement surgeries increasing annually. Infected joint replacements are more complicated and costly to treat, requiring longer surgical and hospital inpatient times, and are often at a higher risk of repeated failure. This significantly affects patient quality-of-life through increased morbidity and in severe cases it can also result in amputation or death. Few commercial technologies exist to prevent this problem. Often oral or intravenous antibiotics are used; however only low concentrations reach the implant site. Coatings attempt to achieve a prolonged local release of antibiotics; however long-term exposure to antibiotics can cause toxicity issues or even encourage antibiotic resistance. Other technologies such as implant surface treatments or topographies, only slow down bacterial attachment and do not eliminate the problem entirely. There is clearly a need for smarter, more effective technologies to prevent infections in orthopaedics. This project aims to achieve this by developing a novel smart implant coating that only releases an antimicrobial in the presence of bacteria. The concept exploits the fact that Staphylococcus aureus, a bacterium that causes joint replacement infections, releases a pore-shaped protein known as alpha-haemolysin. This protein inserts itself in cell membranes causing leakage and cell death. The implant coating consists of the same molecules as cell membranes however it contains a reservoir of antimicrobial within it. When the bacteria release alpha-haemolysin, this creates pores within the implant coating, releasing the antimicrobial and eradicating the infection locally. Three key objectives have been identified to achieve the aim of this project: Objective 1: Optimise and characterise the coating to maximise triggered antimicrobial release. Objective 2: Scale up the coating process and evaluate the antimicrobial activity and toxicity of the coating. Objective 3: Evaluate the performance of the coating in a more relevant bone infection model. Unlike existing coatings, which attempt to stimulate a response, this coating will react to the environment when bacteria are present. Using this approach, the amount of antimicrobial released will be proportional to the number of bacteria and the amount of alpha-haemolysin produced. This triggered delivery system therefore has the potential to overcome numerous issues with existing technologies. Outside of orthopaedics, this technology would have numerous applications, for example in dental and maxillofacial implants and ophthalmic and cardiovascular medical devices, where infections also pose major problems. This project also has the potential to lead to a completely new area of research, where cell and bacterial characteristics are exploited to develop smarter, more effective implant coatings and targeted drug delivery systems.

Traditional methods of treatment for conditions such as arthritis of the knee involve physiotherapy and medication. However, when the condition becomes excessively painful for the patient, surgical intervention is undertaken. Movement of the natural knee joint involves the base of the femur bone articulating against the top of the tibia bone. The surfaces of these bones are covered by articular cartilage which allows smooth, pain free movement at the joint. The base of the femur and the top of the tibia have two surfaces or 'condyles'; in severe cases, the cartilage is worn away from both condyles, and they have to be replaced by a total knee arthroplasty (TKA). In some cases only one of the condyles is affected by arthritis, and yet both condyles are replaced in a TKA procedure. Unicondylar Knee Arthroplasty (UKA), which resurfaces only the affected side, is an alternative to TKA which is becoming an increasingly popular because of its improved functional outcome, favourable long term clinical results and the benefits of minimally invasive surgical techniques. In particular, UKA offers a more effective solution than TKA for more active patients with single compartment knee disease, because the mechanics of the knee are better preserved, and more functional anatomy is maintained. UKA also has advantage of rapid rehabilitation, short hospital stay, quicker operation and quicker recovery. Evidence suggests that revision of a UKA to a TKA results in performance similar to a primary TKA and has been reported to be an easier procedure than the typical revision TKA. However, despite this, UKA is still under-exploited as an alternative to TKA. This is partly related to perception issues, and partly to historically higher failure rates due to improper technique. Therefore, it is desirable to improve the understanding of how surgical technique impacts UKA performance and failure risks, to inform clinical decision-making for UKA with best-practice surgical technique. Most attempts to assess the performance of a joint replacement computationally have involved a 'deterministic' approach, that is, a single implant is modelled in a single bone and a single load is applied. This represents only one possible situation, when potentially many thousands could exist. Recently, there has been a move to replace deterministic approaches with statistical approaches, which attempt to take into account all sources of variability in the system. For example, the performance of an implant in a series of bones under varying loads can be analysed. In this project, statistical approaches will be applied to analyse the performance of UKA. The research will utilise a 'statistical knee joint' based on a large library of bone CT scans. This statistical knee joint represents a wide population of patients into which the unicondylar implant will be implanted. Variations in surgical technique will be accounted for by altering the nature of the surgical cuts and positions of the surrounding soft tissue structures. In this way, a knowledge of how the surgical technique can affect implant performance, in how quickly it wears and how likely it is to loosen, can be ascertained. This knowledge will be used to develop a tool that can be used to guide surgeons on what aspects of their surgical technique need careful consideration when planning their surgery in order to achieve improved patient outcomes. Industry can also benefit from the tool as part of the implant design process. The performance of new and existing implants can be robustly evaluated rapidly at the design stage, and the number of physical tests required can be reduced dramatically. In addition, designs that are predicted to perform poorly can be eliminated at an early stage, leading to substantial cost and time benefits for the design process. The commensurate benefit of this tool will be more robust implants with a longer lifespan, benefiting both the patient and the healthcare provider.

Untreatable infections are one of the biggest modern-day dangers to society, which the current SARS-CoV-2 pandemic has highlighted. The development of antibiotics has been one of the major medical successes of the last 100 years. However, the capacity of pathogens to evolve and acquire resistance to new antibiotics makes their effectiveness necessarily precarious. Meanwhile, studies on the spread of drug-resistant pathogens such as MRSA, respiratory syncytial virus, norovirus and CoVID-19 suggest that surfaces are a major point of transmission with CoVID-19 remaining infectious on plastic and stainless steel surfaces for up to 6 days. Surfaces with an antimicrobial function that avoid or minimise the use of antibiotics whilst maintaining good efficacy after prolonged use are critically needed in hospitals, living spaces, and on biomedical implants, to reduce healthcare-acquired and public space-acquired infections, reduce healthcare costs, and promote healthier lives. However standard antimicrobial surfaces are not sufficiently robust to withstand the wear and tear encountered in a biomedical implant environment and in public spaces. Sheffield Hallam University and Imperial College London aim to develop superhard nanostructured surfaces with plasmonically-enhanced photocatalysis which will enable microbial inactivation in both illuminated and dark environments whilst retaining their robustness and effectiveness in the long term and which, as a result, will lead to orthopaedic implants and anti-microbial surfaces that are more functional than those produced with the current technologies. The innovative antimicrobial surfaces will be robust due to the use of superhard nanoscale multilayer coatings with wear rates up to 1000 times better than conventional metal alloys. At the same time the robust antimicrobial surfaces will have a dual functionality - (1) active, they will be able to kill microorganisms by photocatalysing the production of highly reactive singlet oxygen - one of the most effective killers of pathogens. The photocatalysis will be activated by visible light from the environment. The light will interact with a carefully prepared coating material to induce plasmonic resonance on its surface and generate high energy electrons which are needed to boost the photocatalytic reaction. (2) passive, mimicking naturally occurring surfaces such as the cicada wing, the surfaces will contain a number of appropriately dimensioned nanopillars which will stretch and mechanically rupture the walls of microorganisms. This functionality is potent in wet, dry, illuminated or dark environments. We have developed a new plasmonic nanoscale multilayer material which activates photocatalysis under standard (visible) light and have developed technology based on high power impulse magnetron sputtering which can produce these materials at room temperature on polymers. We will study the plasma processes needed to produce the materials and nanopillars, their response to light activation and the effect they have on microbials. This will help us to develop a cost-effective manufacturing technology to enable large scale production by upgrading systems which are already available in industry for coating deposition and nanopatterning with a digitalised system control which is driven by artificial intelligence algorithms. Together with the local NHS hospital trust we will trial the material on metal plates for door furniture and polymer sheets to cover surfaces in hospitals (beds, seating areas). When successful we will have some of the most exciting new developments in robust antimicrobial materials and their manufacturing and take a step closer to a world with fully effective infection control.

Muscles help us move, enable us to interact with objects and the environment, and regulate critical internal functions. Unfortunately, they are susceptible to damage due to disease, ageing and trauma and are a central factor in diverse serious healthcare conditions including sarcopenia (age-related loss of muscle mass and function, where decline in muscle mass between 40 and 80 years ranges from 30% to 50%), stroke, muscular dystrophy, multiple sclerosis, soft-tissue cancers, venous ulceration, diabetes, degenerative myopathy and incontinence (between 3 and 6 million people in the UK, and 24% of older people, suffer from urinary incontinence). The emPower Transformative Healthcare Technologies 2050 programme will overcome the limitations of current wearable assistive technologies and regenerative medicine by deploying engineered robotic artificial muscular assistance inside the body, exactly where it is needed, to: 1. restore strength and control in mobility and manipulation in older people who have lost muscle strength and precision; and 2. restore controllable muscular capabilities for sufferers of trauma, stroke, incontinence and degenerative diseases. This will have significant knock-on effects on whole-body and mind health through increased confidence, independence and quality of life, massively reducing the healthcare burden and facilitating the return of sufferers to productive and fulfilling lives. The emPOWER artificial muscles will be engineered to bridge the gap between the nanoscale of fundamental energy transduction phenomena and the centimetre scale of bulk muscle action, and will be implantable using minimally invasive (including robot-assisted) surgery and advanced imaging to replace or supplement ailing muscles, providing short-term rehabilitation, long-term assistance or complete functional restoration as needed. To achieve our vision, we have brought together leading experts in soft robotics, regenerative medicine, bio-interfacing, smart structures, synthetic biology, polymer chemistry, self-assembly, bio-printing and tissue analysis, and clinical partners in neuro-rehabilitation, cardiovascular disease, head and neck surgery, urology, geriatrics and musculoskeletal medicine. Together, and with key industrial and social care partners, we will deliver the foundational technologies and first-stage proof-of-concept of the emPOWER artificial muscles within the five years of this transformative project, leading to major healthcare, economic and social impact to 2050 and beyond.