NIHRDataInsights/HRCSData huggingface dataset:
Title: Evolving the design of unicondylar knee replacement to improve post operative function
Funder: Engineering and Physical Sciences Research Council

Abstract: The aim of this project is to evolve current unicondylar knee replacement (UKR) design paradigms based on contemporary knowledge of natural knee kinematics. The design concepts shall consider implants specific for knees with varus and valgus deformity, and an all polymer configuration that would remove metal from the replaced joint entirely. To achieve these aims, a large dataset of computed tomography scans of normal, varus and valgus knees will be generated. The geometry and morphology of these data will be analysed using principal component analysis and multivariate statistical methods such that key relationships are identified. These data shall be used to generate implant design concepts for normal, varus and valgus knees that can recreate the natural anterioposterior constraint of the medial tibiofemoral articulation during flexion. Design concepts shall be assessed for implant stress, bone strains and interface micromotion using an experimentally validated finite element (FE) protocol previously generated in our group. Once the FE gives acceptable values, rapid prototypes of the designs shall be manufactured and implanted in cadaver knees by an experienced surgeon. The kinematics during flexion shall be measured using established methods in our laboratory and compared to the natural knee to prove the concept of the prototype design. Successful delivery of the proposal will lead to the development of a UKR with significant advantages over existing devices including more natural kinematics and soft tissue tension, morphology to suit common deformities, and potentially lower cost materials and manufacturing methods. By supporting the final design concepts, the proposed research can be used to support clinical trials of the device or any subsequent regulatory submission. The proposed research is highly likely to succeed due to the close relationship our lab has with orthopaedic surgeons, our track record of commercialising concepts and the support of a well respected industry partner. The environment in which the proposed research will be conducted will therefore allow the project to thrive.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: MUSCULOSKELETAL
Title: Point-of-Care High Accuracy Fracture Risk Prediction
Funder: Engineering and Physical Sciences Research Council

Abstract: A significant and escalating worldwide health burden is the aging population and its demand for accurate medical diagnostics. Of particular concern are osteo diseases such as osteoporosis as these become significantly more apparent in elderly populations. Unfortunately, current diagnostic methods are poor predictors of pathology outcomes such as fracture risk. The challenge then is to identify and develop enhanced and new approaches to bone quality appraisal that can be employed for accurate prognosis, targeted therapies and therapy assessment. It has been well demonstrated that 'bone quality' (including characteristics such as collagen/mineral ratio, collagen integrity, mineral crystallite size, microstrain) has a marked affect on a bone's mechanical properties and is probably the 'missing' information required to produce diagnostically predictive models of fracture. Unfortunately there is no current technique for its in vivo determination. However, such information is embodied within conventional X-ray scatter signatures (e.g. X-ray diffraction) although these are weak and present significant measurement difficulties. We have identified a potential route to in vivo measurement of these clinically valuable but weak signals. The technology has only recently become available through independent innovations for (i) X-ray generation (flat panel/source-on-a-chip) and (ii) obtaining 'amplified' information from scattered X-rays (using 'focal construct technology', FCT). Critically, the multi-emitter flat panel X-ray source will enable us to engineer precisely the analytical X-ray beam required to provide scatter signatures enhanced by several orders of magnitude. The FCT beam topology also enables the simultaneous measurement of the absorbed X-rays (to estimate bone mineral density) and those coherently (and incoherently) scattered. The source-on-a-chip technology is manufactured as a flat-panel device capable of generating X-rays from very low-power sources. It has the additional advantage that it may be fabricated to produce an X-ray source of precisely the geoemetric form required for FCT. Ultimately we envisage these techniques being integrated within a single imaging/DEXA/scatter system to provide a comprehensive diagnostic tool. The nature of the techniques also enables design towards hand portable devices for point-of-patient care. Thus this proposal principally concerns the development of a new instrument that will be subsequently used to examine the possibilities of applying our novel technologies to a number of different areas and therefore it will enable a new and exciting research capability.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: A Biomimetic, Self Tuning, Fully Adaptable Smart Lower Limb Prosthetics with Energy Recovery
Funder: Engineering and Physical Sciences Research Council

Abstract: Every year, thousands of people lose a lower limb as a result of a range of factors such as circulatory problems, complications of diabetes or trauma. Current lower limb prostheses can be divided into three groups: i) Purely passive mechanical and requiring a significant voluntary control effort; ii) Actively controlled in which the limb performance is measured and parameters altered to improve performance; iii) Actively driven, or powered prostheses using actuators to directly input mechanical work into the limb. The latter devices do not take into consideration the dynamic interaction between the body elements and prostheses. As a result, they require large amounts of energy and have low efficiency. Therefore they are not in harmony and synergy with the human body. Hence, there is a need for a new generation of lower limb prostheses which can mimic the human muscle by combining active and passive modes. The new generation of prostheses should have a plug and play characteristic and the limb would self tune to the current walking situation (level, slopes and stairs) to optimise the system performance to the user. During the walking cycle, the artificial limb will switch between delivering energy to the walking motion to harvesting energy during the swing phase; prolonging battery power and reducing the burden on the batteries. The aim of this project is to design and develop a new smart lower limb prosthesis through a research programme structured around the following activities. 1) Use of body hub sensors to measure gait dynamics in real time; 2) Use of prosthesis integrated sensors interfaced with the human limb to measure reaction loads during prosthesis use; 3) Estimation of user intent and evaluation of the potential for haptic or other forms of feedback from the prosthesis to enhance its usability; 4) Optimisation of energy use through dynamic coupling and energy generation; and 5) Improvements in limb comfort associated with extended periods of wear. The outcome of the research will be a step change towards the use of technology in relation to the human body and mobility considering human-machine dynamic interaction. The research outcomes will address a number of healthcare challenges associated with the restoration of mobility in amputees, and paves the way for a new direction in the design and development of devices to support mobility in an aging population and applications such as the rehabilitation of stroke patients. The world's third largest manufacture of prosthetics is in the UK and this research will boost the advancement of the UK position worldwide by providing enhanced opportunities for commercialisation.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: MUSCULOSKELETAL
Title: Nanostructured gels for intervertebral disc load support and directed regeneration
Funder: Engineering and Physical Sciences Research Council

Abstract: Lower back pain is a major and growing healthcare problem in the UK. It causes morbidity and significantly reduces national productivity through employee absence. A major cause of lower back pain is degeneration of the intervertebral disc (DIVD). The most common treatment for DIVD is spinal fusion, which is a major surgical procedure with variable patient outcome. In principle, injectable gels that provide load support while allowing tissue regeneration can provide a non-surgical, cost-effective therapy for DIVD. We aim to establish an injectable synthetic copolymer gel that provides immediate load support (to alleviate pain) and then biodegrades to be replaced by regenerated tissue. A non-biodegradable injectable gel technology developed by the U. Manchester team has provided load support for degenerated IVDs. However, these gels fracture at high strain (low ductility) and do not recreate the nanometre-scale structural features of the natural extracellular matrix (ECM) within the intervertebral disc (IVD). Moreover, they were not able to support tissue regeneration. In the proposed work programme, we will design novel injectable biomimetic gels by combining new anisotropic block copolymer worm-like particles with new pH-responsive nanogel particles in order to produce the nanometre-scale features that are characteristic of the ECM within human IVDs. Such nanostructured gels should have improved ductility and provide both load support and the appropriate physical / biological cues to direct ECM synthesis and tissue growth. Furthermore, they will be designed to biodegrade and be gradually replaced by regenerated tissue. A successful outcome will establish a new family of injectable synthetic copolymer gels that should bring non-surgical therapies for DIVD closer to reality.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL
Title: Developing a Bespoke Incremental Sheet Forming Machine for Cranioplasty
Funder: Engineering and Physical Sciences Research Council

Abstract: Cranioplasty is a surgical procedure for the repair of deformity of a human skull due to brain tumour, stroke or traumatic injuries. Among all available materials, titanium continues to be a main stream material used in cranioplasty surgeries because of its excellent biocompatibility, resistance to infection, excellent material properties and lightweight. However, in spite of the popular use of titanium in cranial reconstruction, there is a wide variety of methods including casting, manual shaping and rubber press forming commonly used in cranial plate manufacture. Even with the assistance of advanced CAD/CAM (computer-aided design and manufacture) and computed tomographic (CT) and magnetic resonance imaging (MRI) technologies, currently the process for manufacturing customised cranial plates by conventional methods normally takes up to two weeks to completion mainly due to the time required for the manufacture of dies and tools. Recent advances in 3D printing or additive manufacturing based techniques make it possible to complete the 3D printing of a cranial or a maxillofacial prosthetic part within several hours. However, there are still a number of impediments including material property and cost issues to be overcome before its wide clinical applications. This project proposes a novel alternative solution for an even faster and more cost effective method for the manufacture of personalised cranial plates by using the incremental sheet forming (ISF) technique. Our recent work has shown that a typically large size cranial plate can be made satisfactorily by using the ISF process in 7~8 minutes rather than hours or days. This outcome has considerable implications in potential technological advances and economic benefits as well as improvement to quality of life. In this project we aim to develop the new ISF based cranioplasty manufacturing technique, to design and build a bespoke desktop ISF machine for cranial reconstruction with full CT/MRI and CAD/CAM software integration and ISF process automation. By using the developed bespoke ISF machine, we will conduct a series of ISF benchmark testing and cranial reconstruction pre-clinical trials of 3 demonstration case studies using the developed bespoke ISF machine. The project will demonstrate its technical viability, economic benefit and potential improvement of quality of life. By the end of the project we aim to achieve up to 95% manufacturing lead time reduction with associated cost benefits as compared to the conventional methods. We also plan to show that the bespoke ISF machine can be used as a new and viable medical device for cranial manufacturing and there is a niche market place for speedy commercial exploitation.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: MUSCULOSKELETAL
Title: Nano Materials and Structures for Superior Implants (Nanoplants)
Funder: Engineering and Physical Sciences Research Council

Abstract: Various RCUK funded projects at Loughborough University over the years have delivered significant foreground intellectual property and technology know-how related to the fabrication of nanostructured materials with outstanding properties, surpassing some of the commercial counterparts, relevant to the energy, electronic security and in particular healthcare sectors. Specifically it has been demonstrated that the hydrothermal ageing (HTA) resistance of zirconia based ceramics can be enhanced significantly by retaining a nano grain size below 180 nm even at low density components. This is highly relevant to the ~$5B hip replacement market where concerns about the toxicity / wear debris in metal and polymer components renders all-ceramic solutions increasingly attractive. HTA degradation (the unwanted conversion of tetragonal zirconia to a weaker monoclinic form in an aqueous environment) is the Achilles-heel for the use of zirconia ceramics in biomedical sector and was the reason behind the well-publicised failure of zirconia hip replacements around 2000. Thus, when HTA is countered, new opportunities open up. The proposed technology (involving novel nano-suspension control, granulation and then microwave assisted hybrid heating as well as flash sintering regimes; zirconia toughened alumina and zirconia ceramics will be considered) aims to deliver very small zirconia grain sizes that will both assist current compliance (e.g. ISO 13356, ISO 633-3) and open up novel all-ceramic hip replacements via multi-fold enhancement in HTA-resistance of porous and dense graded zirconia based structures. The methodology will be applicable to ceramic-metal graded implant structures also with suitable modifications. The retention of nano-size throughout all stages of ceramic component production is critical to delivering the target end properties that will assist the health and quality of life in a growing ageing population. This will be achieved via the development of implant structures (applicable for hip/knee prosthesis, finger joints and jaw & skull repairs) that deliver improved mobility over a longer time period thus reducing reliance on repeat surgery and in some cases confinement to use of wheelchair.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: MUSCULOSKELETAL
Title: A radiostereometry assessment of bone graft processed with novel sterilisation techniques (a study of patients undergoing acetabular impaction grafting hip revision surgery).
Funder: Chief Scientist Office (Scotland)

Abstract: the impaction of allograft bone into areas of bone loss during hip revision surgery has become a standard procedure in the NHS. Due to concerns about potential viral and prion transmission, a novel chemical sterilisation procedure has been developed jointly by the Scottish Blood Transfusion Service (SNBTS) and the NHSBT (NHS Blood and Transplant) which we believe will preserve the biological and mechanical properties of the bone. This will allow the continuation of a highly successful technique. A prospective study is proposed on 50 patients undergoing impaction revision of the acetabulum. Patients will be randomised to impaction using standard fresh frozen allograft or processed bone. Radiostereometry will be used to measure the movement of the cup in terms of migration and rotation over a two year follow up period. Increased migration will imply poorer incorporation of bone graft and hence a significant change in either biological or mechanical properties.


Research activity codes: 6.4 SURGERY
Health categories: MUSCULOSKELETAL
Title: The Water project:which aquatic excercises work best? Identifying muscle recruitment for aquatic excercises used in interventions for core strengthening and rehabilitation from musculoskeletal disorders
Funder: Chief Scientist Office (Scotland)

Abstract: People suffering from musculoskeletal disorders and populations susceptible to back pain, such as pregnant women, the obese and elderly, often use aquatic exercise for rehabilitation and strengthening purposes. Aquatic exercise reduces spine and joint loads, and is beneficial in reducing pain, disability, and absence from work, increasing muscle function and improving quality of life. However, information on the appropriateness of aquatic exercises targeting trunk supporting muscles is lacking. This project combines electromyography and three-dimensional videography to evaluate aquatic exercises used for strengthening and rehabilitation. The aim is to assess which exercises are most effective in activating trunk supporting muscles, and to quantify and compare the perceived exertion and physical effort demands of different exercises. The findings would provide an evidence base to inform clinical practice and improve quality, efficiency and effectiveness of aquatic interventions. This would positively affect patients’ health and wellbeing, and reduce the economic cost of health care.


Research activity codes: 6.7 PHYSICAL
Health categories: MUSCULOSKELETAL
Title: Lentivirally-mediated stem cells to treat Duchenne muscular dystrophy
Funder: Medical Research Council

Abstract: Genetic correction of autologous stem cells is a potential therapy for Duchenne muscular dystrophy (DMD). However, key questions need to be resolved before this approach could be realistically used in DMD. These include the determination of the best stem cell and a safe lentivirus containing a dystrophin gene that is small enough to fit into the vector, yet large enough to code for a functional protein. We aim to design a safe lentiviral vector, coding for an effective dystrophin gene (opti-dystrophin). In parallel, we will compare the ability of induced pluripotent stem cells (iPS) and adult stem cells (AC133+ cells), firstly of mouse origin and then of human origin, to efficiently regenerate skeletal muscle and functionally reconstitute the satellite cell (muscle stem cell) pool following intra-arterial injection in an immunodeficient mouse model of DMD. We will then combine the optimised lentivirus with the most favourable stem cell of DMD origin and test this in our in vivo model. Solving these preclinical questions will allow us to plan for future clinical trials for DMD.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL
Title: Autologous cell therapy of fracture nonunion - cell phenotype as a predictor of outcome
Funder: Medical Research Council

Abstract: Although most fractures heal well, the significant minority that progress to nonunion carry a heavy price, both in quality of life and NHS costs. Preclinical work suggests that culture-expanded autologous mesenchymal stem cells (MSC) could be helpful in stimulating the healing of human fracture nonunions. However, clinical experience has been that implanted cells are inconsistent in their ability to stimulate healing and this may be partly due to variation in their phenotype. We will conduct a randomised controlled trial comparing MSC (40 patients) with fresh bone marrow (20 patients). The clinical model will be the docking site in tibial bone transport and the primary outcome measure will be the increase in bone mineral content, measured by spiral CT, of a defined region of interest at this site in the first 12 weeks after implantation. We will characterise the phenotype of the implanted cells using proteomics, avoiding the potential pitfalls of assessing only the transcriptome. We will correlate the proteome of implanted cells with the extent to which they stimulate bone formation, aiming to lay the foundation for the development of more effective protocols for culture expansion. The proposal comes from a partnership of UCL Proteomics and two established Limb Reconstruction Services, both with strong academic leadership, at the Royal National Orthopaedic Hospital (UCL) and Bristol Royal Infirmary (University of Bristol). Between them, these provide a service to a population of several million and apply the (Ilizarov) technique of bone transport to substantial numbers of patients. A regenerative approach based on adult stem cells holds promise for many clinical situations of bone loss or failed fracture healing,however the extreme variability of such cases makes it difficult to conduct robust trials. The tibial docking site is chosen for this study because it is a relatively constant test-bed in which to establish efficacy. In UCL Proteomics, stable isotope labelling with amino acids in cell culture (SILAC) will be used to comprehensively characterise the proteomes of the implanted cell batches. Samples will be frozen and analysed once the clinical outcome has become clear. Samples from the six patients who produced the most bone regeneration in response to cells will be compared with those from the six who produced the least. We will focus on known bone-associated proteins but also screen for unexpected differences. The proteomic findings will be validated by quantitative Western blotting or ELISA, applied to all 40 MSC-treated cases.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL