Over forty percent of the population suffer from degenerative osteoarthritis of hip and knee and in ten percent this can result in the need for joint replacement. Articular cartilage has unique intrinsic biphasic lubrication properties. We have recently developed a novel joint simulation system for the medial compartment of the natural knee, and have shown the importance of the biphasic surface amorphous layer in articular cartilage on the reduction of friction and wear. We have shown a reduction in friction with simple geometry cartilage specimens using patented self assembling peptide (SAP) gels. In parallel, and in collaboration with an industrial partner, we have also shown the frictional advantage of a biphasic synthetic hydrogel in comparison with single phase polymer biomaterials.In this follow on fund application we intend to converge these three pieces of basic research and use our unique natural knee simulation system to evaluate the longer term performance of patented SAPs as potential injectable therapeutic lubricants for low grade cartilage degeneration. Additionally we will combine the SAPs with the synthetic biphasic hydrogels and evaluate the enhanced tribological performance in comparison with existing cartilage substitution biomaterials. Market potential and business opportunities will be evaluated and developed by the University technology transfer partners IP2IPO, BITECIC and industrial collaborator.

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.

Definition: A rapidly developing area at the interfaces of engineering/physical sciences, life sciences and medicine. Includes:- cell therapies (including stem cells), three dimensional cell/ matrix constructs, bioactive scaffolds, regenerative devices, in vitro tissue models for drug discovery and pre-clinical research.Social and economic needs include:Increased longevity of the ageing population with expectations of an active lifestyle and government requirements for a longer working life.Need to reduce healthcare costs, shorten hospital stays and achieve more rapid rehabilitationAn emergent disruptive industrial sector at the interface between pharmaceutical and medical devicesRequirement for relevant laboratory biological systems for screening and selection of drugs at theearly development stage, coupled with Reduction, Refinement, Replacement of in vivo testing. Translational barriers and industry needs: The tissue engineering/ regenerative medicine industry needs an increase in the number of trained multidisciplinary personnel to translate basic research, deliver new product developments, enhance manufacturing and processing capacity, to develop preclinical test methodologies and to develop standards and work within a dynamic regulatory environment. Evidence from N8 industry workshop on regenerative medicine.Academic needs: A rapidly emerging internationally competitive interdisciplinary area requiring new blood ---------------------

To maintain continuity with MATCH Phase 1, it has been requested that MATCH Phase 2 follows the current programme breakdown in terms of Projects A-F from 2008-2013 / a vision that is described below. We note that MATCH changed dramatically in creating the projects A-F and that further changes in the themes are inevitable. An overview of these themes is given below.Projects A, B and C address economic evaluation and its impact in decision-making by companies, governments and procurement agencies. We have identified a major demand for such research, but note that there is some convergence between these themes (for instance, A and C may well coalesce under the Bayesian banner). In particular, a 'methodologies' theme is likely to emerge in this. Under the former theme, a truly integrated Bayesian framework for medical devices would represent a strategically important achievement.On the other hand, the business of delivering these developments to industry, and the organisations or franchises that might ultimately provide the best vehicle for doing so, still requires further exploration and negotiation, and at this point there is considerable uncertainty about how this will best be done. However the critical element has been established, namely that MATCH can provide useful tools for, and attract significant levels of funding from industry. To this extent, the applied side of Project A-F and Project 5 might well evolve into a series of programmes designed to spin out tools, training and best practice into industry. Project 5 remains for the present because we have set it up with a framework within which company IP can be protected, and within which we can expedite projects to company goals and time scales.A similar pattern is likely to emerge from the single User project (D), where there is considerable scope for capability, and methodological development / and the size of this team needs to increase. The aim is to develop a suite of methods, guidelines and examples, describing when a given method is useful and when user needs assessment must be cost-effective. We will gain and share experience on what approach works best where. Our taxonomy will recognise circumstances where the novelty of a proposed device may undermine the validity of user needs assessment conducted before the 'technological push' has had a fair opportunity to impact on the human imagination.Moreover, new research is needed to 'glue' some of these themes together. Some of this is already included (for instance, in Projects C and D below) to link the user-facing social science with the economics, or the pathway-changing experiences (F) with formal economic evaluation, will require new, cross-disciplinary research. This type of research is essential to developing the shared view of value, which MATCH is pursuing. Similarly, integrating supply-chain decision-making and procurement elements of theme (E) with economic evaluation would represent an important element of unification.To achieve this, we will need to bring in some news skills. For instance, we are already freeing up some funding to bring in an economics researcher at Ulster; more statistical mathematical support may be needed to further develop the Bayesian theme; and we need to bolster the sociological element within the team.Finally, this vision cannot be funded entirely within a research framework, and we expect critical elements to be achieved under other funding (for instance, Theme E by the NHS, in due course).

When a person undergoes hip replacement surgery, there are many factors that can affect how long it will last, many of which are not immediately apparent to the patient. Within each patient, the properties of bone can vary considerably; this difference in bone quality may be even more apparent between patients, particularly if one patient is more active than another, is heavier, or even if their diets are different. Other factors to consider are the geometries of the bone and implant, the quality of the surrounding tissues, the trauma associated with surgery and how well aligned the implant is, the last two of which are related to the surgical technique. Traditionally, experimental investigations into the performance of hip replacements have been limited to analysing one situation per experiment (e.g. one alignment and one bone). The results of these investigations can really only provide a good qualitative indicator as the biological environment can not be adequately simulated in the laboratory. Add to this, the huge number of experiments that would be required to simulate all possible scenarios (combinations of alignment, geometries, bone quality etc.) and experimental investigations soon become unfeasible. In order to address this shortcoming, computational methods have been developed that are capable of simulating an experimental test in a much shorter time. However, to date, most of these investigations again describe only one situation and many computational models are required to fully describe the effect of variations in only a single parameter. The proposed research program therefore, will deliver new computational tools that can account for variations in parameters such as the properties of bone, the loading conditions and the surgical technique simultaneously and efficiently, in a single analysis. It is anticipated that the immediate benefits of this research will include the development of models capable of determining which current implant designs are more forgiving of variations in misalignment and bone geometry, and are therefore likely to perform well regardless of the patient. In the medium term, these analyses should enable the surgeon to make an informed decision when selecting the most appropriate implant for his/her patient. In the longer term, it is believed that the research will help prosthesis manufacturers to arrive at new designs with improved performance and longevity, to the benefit of the manufacturer, the health provider, and of course, the patient.