RNOH-UCL partnership: Biomedical research

A biological approach to treating Achilles tendinopathy using culture expanded autologous mesenchymal stem cells – A First in Man Study

  • Andy Goldberg (Senior Clinical Lecturer; Honorary Consultant Orthopaedic Surgeon), Roger Smith (Professor of Equine Orthopaedics), Caroline Doré (Head of Statistics)
  • UCL Institute of Orthopaedic & Musculoskeletal Science; Foot & Ankle, Royal National Orthopaedic Hospital; Royal Veterinary College; UCL Comprehensive Clinuical Trials Unit
  • More information: andy.goldberg@ucl.ac.uk

Tendon disorders compromise pain-free activity and often progress to chronic pain with a major impact on quality of life. More than 85,000 patients each year see their GP with Achilles Tendinopathy. The main current treatment is physiotherapy, although surgery is eventually considered in 25-45% of patients, an intervention that has unpredictable outcomes. Current treatment options that have relied on an inflammation-repair sequence have not proven to be of benefit and tendon healing following injury results in deposition of fibrous scar tissue that is functionally inferior to the original structure. There is a need for improved non-surgical treatments, which can promote regenerative processes to restore tendon structure and function. Treatment of naturally-occurring tendon over-strain injuries with culture-expanded autologous bone-marrow derived mesenchymal stem cells (MSCs) is already well established in a highly relevant equine model which has ageing and loading (exercise) similarities. Preclinical data from more than 1,800 racehorses suggest that MSCs can lead to improvement in pain-free function. We are translating the technology to humans and conducting a UK Stem Cell Foundation-funded ‘First-in-man’ study using to establish the safety of autologous culture expanded MSCs implanted in diseased human tendon and to correlate an objective outcome measure of tendon regeneration, Ultrasound Tissue Characterisation, with clinical outcome scores can be achieved. The outcome from this study will be used to design a larger randomised controlled clinical trial to demonstrate the efficacy and cost-effectiveness of the treatment.

Outcomes of Ankle Replacement Surgery

  • Alexander MacGregore (Professor or Genetic Epidemiology), Andy Goldberg (Senior Clinical Lecturer & Honorary Consultant Orthopaedic Surgeon)
  • University of East Anglia; UCL Institute of Orthopaedic & Musculoskeletal Science; Foot & Ankle, Royal National Orthopaedic Hospital
  • More information: andy.goldberg@ucl.ac.uk

Ankle osteoarthritis (OA) that affects more than 29,000 patients annually in the UK, accounts for most end-stage ankle disease and has a similar impact on quality of life as end stage heart failure or hip arthritis. Ankle fracture incidence is increasing especially in young athletes and elderly females. Associated ankle OA is likely to be an increasingly important health problem in the future.

As with other forms of joint replacement, UK surgical practice varies greatly and evidence supporting optimal choice of specific implants and surgical procedures to maximize patient gain, together with knowledge of the cost effectiveness is incomplete. Surgeons choosing between total ankle replacement (TAR) and ankle fusion rely on findings from small observational samples and limited clinical trial data likely to be unrepresentative of current UK practice. This Arthritis Research UK funded study assesses major clinical, disease, surgical and implant related factors that predict patient reported outcome in the first 12 months following TAR and undertakes a health economic analysis of the impact of TAR. This project is the first pragmatic study of the clinical efficacy of TAR and the data will provide information that guide practice, clinical decision making and patient choice.

Cell Augmented Prostheses

  • Gordon Blunn (Professor of Biomedical Engineering), Melanie Coathup (Reader of Orthopaedic Implant Fixation and Bone Regeneration)
  • UCL Institute of Orthopaedic & Musculoskeletal Science
  • More information: g.blunn@ucl.ac.uk

Segmental implants combined with a prosthetic joint are used after failure of a number of previous revisions or for treating patients with bone cancer to replace part of the diaphysis of the bone. For bone cancer patients, fixation is important as these patients are generally young and implants have to last. The aim of this project is to enhance the fixation of implants using a cell augmented prostheses. The team has shown improved bone regeneration in femoral defects when mesenchymal stem cells in fibrin glue were used (Lee, et al 2005). Radiographic and histological analysis demonstrated that spraying autologous mesenchymal stem cells in fibrin glue onto grooved HA-coated collars of segmental bone implants resulted in twice the level of bone adjacent to the collars and greater osteointegration in the treated group (Kalia, et al 2006, Coathup, et al 2013). A more recent study has shown that osteointegration of HA-coated collars reduced the formation of radiolucent lines and loosening around cemented intramedullary stems (Coathup, et al 2015). These studies demonstrated that a tissue-engineering approach to enhance bone integration of prostheses might be beneficial. We now aim to apply this technology to patients being treated at the RNOH. At the present time there is a requirement in patients with segmental revision implants to improve fixation but due to the risk of neoplastic autologous stem cells used for bone cancer patients we are restricting this project to treating patients requiring revision segmental prostheses.

“Building Better Bone”– Enhancing Fracture Healing with Mesenchymal Stem Cells and Parathyroid Hormone

  • Liza Osagie (PhD student), Timothy Briggs (Professor of Orthopaedic Surgery; Consultant Orthopaedic Surgeon), Gordon Blunn (Professor of Biomedical Engineering)
  • UCL Institute of Orthopaedic & Musculoskeletal Science; Bone Tumour Unit, Royal National Orthopaedic Hospital
  • More information: liza.osagie@doctors.org.uk

Exponential population ageing, increasing joint replacement surgery and rising osteoporosis all underpin the growing “musculoskeletal burden”. Concurrently, more patients are suffering osteoporotic fractures around implants (“periprosthetic fractures”), the surgical treatment of which leads to increased morbidity, mortality and socio-economic cost. Thus, at the Institute of Orthopaedics and Musculoskeletal Sciences, we are investigating how to improve periprosthetic fracture healing in the elderly via minimally invasive treatment. By 2021, 23% of the population will be over 65. Consequently, the 80,000 hip replacements performed annually-are forecast to increase by 200%, and the 70,000 annual hip fractures-to increase by over 300%¹'².Within this age group 1 in 3 women and 1 in 4 men will experience a fracture due to reduced bone quality (osteoporosis/osteopenia).

Patients with hip implants have up to an 11% lifetime peri-prosthetic fracture risk. The surgical management of these injuries is often complex and is associated with a 45% complication rate, 10% 30-day mortality and costs an up to estimated £24,000 per patient. Our aim is to develop a minimally invasive technique that accelerates and enhances bone formation that may translate to significantly impact fracture management; reducing hospital length of stay and returning patients to pre-morbid functionality quicker than current treatment options.

The team have previously demonstrated the efficacy of healing a fracture by filling the gap with bone marrow derived stem cells; this Rosetrees Trust and Gwen Fish Trust funded work goes one step further, aiming to heal fractures by percutaneously injecting stem cells into the fracture gap and combining this with systemic injections of parathyroid hormone. Ultimately, we aim to create a translatable technique that uses parathyroid hormone to increase the functionality of senile cells and subsequently enhance bone formation in both normal and osteoporotic animal models.

A Study to Investigate Patient Related Outcome Measures of Muscle Renervation

  • Tom Quick (Consultant Orthopaedic Surgeon), Ashok Singh (Specialist Registrar), Michael Fox (Consultant Orthopaedic Surgeon), Marco Sinisi (Consultant Orthopaedic Surgeon), Anthony Macquicllan (Consultant Orthopaedic Surgeon)
  • Peripheral Nerve Injury Unit, Royal National Orthopaedic Hospital
  • More information: t.quick@ucl.ac.uk

Brachial Plexus injuries are rare but severely debilitating as the plexus supplies motor and sensory functions to the upper limb. This not only results in physical disability and psychological distress but also has socioeconomic implications, as a significant proportion of patients are not able to make a return to their previous level of activity. Surgical intervention such as nerve repair and/or nerve transfer gives the best chance for regaining maximum functional use of the affected limb after brachial plexus injuries. Nerve transfer surgery to restore elbow flexion (that is one of the aims of any surgical planning in this group of patients) has been adopted across the world and the results have been very encouraging.

We have reported the distribution of the power restored to elbow flexion using continuous variable (publication submitted to BJJ). We have shown that 80% of patients undergoing nerve transfer, irrespective of their level of injury, gained an elbow flexion strength of MRC grade 4, which when compared quantitatively to the elbow flexion strength on contralateral side would range between one-eighth to two-thirds of normal power, and an average of one-third of normal. Also, when these values were plotted on a graph, we got a normal distribution and were able to obtain a Gaussian curve. We can thus confirm a predictable pattern for power distribution in this subgroup. Our study presents an example of how in a practical manner a continuous quantitative measurement for regained elbow strength can be carried out in clinics. Also the values obtained during our assessment are similar to those obtained under biomechanical laboratory conditions, supporting the feasibility of use of dynamometer as a measurement tool in clinics.

Our study empowers the clinician with a quantitative measurement of their surgical intervention, and holds the potential for playing a key role in future research for nerve injury recovery.

Development of a Novel, Safe Method for the Non-invasive Assessment of Human Bone Quality, In Vivo, using spatially offset Raman spectroscopy

  • John Churchwell (Research Associate), Professor Allen Goodship (Professor of Orthopaedic Science), Richard Keen (Consultant Rheumatologist)
  • UCL Institute of Orthopaedic & Musculoskeletal Science; Rheumatology, Royal National Orthopaedic Hospital
  • More information: j.churchwell@ucl.ac.uk

Understanding and quantifying bone quality is of high importance in Britain’s aging society. Every year in the UK 300,000 patients receive treatment for fragility fractures as a result of osteoporosis and many patients are diagnosed with osteoarthritis. In addition, it is easy to confuse factures resulting from osteogenesis imperfecta in children with those from infant abuse.

Currently there is no definitive test for rapid non-invasive early stage diagnostic or screening for osteoarthritis or osteogenesis imperfecta. Also a key problem with DXA the current gold standard for osteoporosis diagnosis is the use of X-rays. Whilst radiography can be powerful for imaging some bone diseases and fractures, overexposure becomes dangerous and they do not provide any information on the organic part of bone, the collagen fibre matrix. The molecular level structure of collagen has a large effect on bone quality and strength. In fact only around 60-70% of bone strength can be related to bone mineral density – the parameter measured using DXA. It is therefore important that we take advantage of new methods that allow us to acquire information on the collagen component of bone in addition to bone mineral.

AT UCL IOMS in partnership with STFC and RNOH we are carrying out research using Raman spectroscopy. We have been developing Raman spectroscopy to understand bone quality in more detail. Spatially offset Raman spectroscopy (SORS) allows us to see through the skin and soft tissue and acquire spectral information back from the bone, a fingerprint of the bone chemistry for the individual patient. Recently our group have published journal articles that show differences can be detected with this technology between healthy bone and diseased, for osteoarthritis (Kerns, et al 2014), osteoporosis (Buckley, et al 2015) and osteogenesis imperfects. Most importantly our results have shown that is possible to discriminate between diseased and healthy bones non-invasively in vivo for a number of diseases. These results are very promising.

Our research also has the potential to yield new methods of diagnosis and early detection of bone disease. Offering the potential of saving those with undiagnosed osteoporosis from dangerous fragility fractures through cheap and reliable screening and patients with osteoarthritis from debilitating joint degradation by spotting the condition early ahead of irreversible debilitating joint destruction.

Ankle Raman Spectroscopy

  • Oliver Chan (MD research student), Andy Goldberg (Senior Clinical Lecturer; Honorary Consultant Orthopaedic Surgeon), John Churchwell (Research Associate), Professor Allen Goodship (Professor of Orthopaedic Science)
  • UCL Institute of Orthopaedic & Musculoskeletal Science; Foot & Ankle, Royal National Orthopaedic Hospital
  • More information: oliver.chan@doctors.org.uk

Osteoarthritis (OA) of the ankle is a debilitating condition that results in pain and dysfunction due to the degeneration of cartilage, bone and soft tissues. More than 29,000 patients a year present to specialists with symptomatic ankle OA in the UK, a condition which causes pain, disability and affects quality of life as much as end stage heart failure.

Little is known about the interaction between cartilage and bone as an osteochondral unit and their role in the OA pathogenesis. Alteration in bone matrix chemistry is central to one theory. Raman spectroscopy is a non-invasive technique used to characterise and differentiate alterations in bone matrix chemistry (in simple terms the technique measures the anelastic energy changes in light scattered from materials including both mineral and organics phases). This contrasts to conventional imaging systems utilising ionising radiation that interrogate only the mineral phase of the matrix.

The use of Raman Spectroscopy in orthopaedics has been pioneered by researchers at UCL IOMS and RNOH, in particular to assess abnormal molecular changes observed in the matrix of Osteoarthritic knees (Kerns et al, 2014). Expanding on this experience and using funding from BOFAS, we will explore whether alterations in bone matrix chemistry are associated with an increased propensity to develop ankle osteoarthritis and whether the chemical differences are associated with altered material properties in subchondral bone.

HipLink: Registry – Retrieval linkage to help understand failure mechanisms of Metal on Metal hip replacements

  • Alister Hart (Professor of Orthopaedic Surgery; Consultant Orthopaedic Surgeon), Shiraz Sabah (Specialist Registra), Johan Henckel (Specialist Registra), John Skinner (Consultant Orthopaedic Surgeon)
  • UCL Institute of Orthopaedic & Musculoskeletal Science; Joint Reconstruction Unit, Royal National Orthopaedic Hospital
  • More information: a.hart@ucl.ac.uk

There is now a wealth of information available to patients on joint replacements. One of the biggest sources is the National Joint Registry (NJR) for England, Wales and Northern Ireland, who have collected data on more than 1.8 million operations making it the world’s largest joint registry. Data on failure rate of hip implants from the UK NJR was used to recall some types of metal on metal hips in 2010, 2011 and 2012. An earlier recall would have prevented patient suffering but it is unclear when such action should be taken in the future for other implants. We aim to improve this process of post-marketing surveillance.

In this Dunhill Medical Trust and Gwen Fish Trust funded project, we have linked the NJR database to a database of 1400 failed hip implants collected by The London Implant Retrieval Centre. The failed implants collected by the LIRC can provide indisputable data on component characteristics (e.g. manufacturer, size, reference number) and cause of failure.

Using the linked record, we were able to assess the quality of the NJR data. Although the NJR database contains the majority of the hip implants that should have been recorded, we have so far found two major issues: i) a sizable number of procedures, 17%, had the wrong outcome recorded (either as death, or unrevised) (Sabah, et al 2015); ii) missing data has meant that revisions could not be linked to their primary data entry in 60% of failures: this linkage is essential to enable the survival curves of implants to be accurately drawn in the NJR annual report (Sabah, et al accepted for publication).

Despite our findings, the NJR remains the best source of data we currently have to analyse how joint replacements perform. Across the NJR as a whole, missing data probably ‘averages itself out’ to give a good idea of how an implant is performing. However, for individual surgeons (or even hospitals), where the number of cases is much smaller, this missing data could affect how we interpret their performance.

We are currently analysing the linked record to investigate implant failure mechanisms by implant type. We plan to develop methodology for local centres to validate cause of failure on the NJR that will be piloted at RNOH and LIRC.

SmartSpacer: sacrificial silver for implants

  • Alister Hart (Professor of Orthopaedic Surgery; Consultant Orthopaedic Surgeon), Jonathan Miles (Consultant Orthopaedic Surgeon), Damien Mack (Consultant Microbiologist), Joseph Zustin (Consultant Histopathologist), Laura Richards (Senior Researcher), Jonathan Housden (Head of R&D)
  • UCL Institute of Orthopaedic & Musculoskeletal Science; Joint Reconstruction Unit, Royal National Orthopaedic Hospital; Infection, Royal National Orthopaedic Hospital; Histopathology, Royal National orthopaedic Hospital; MatOrtho Ltd; Wallwork Cambridge
  • More information: a.hart@ucl.ac.uk

Infection accounts for 3% of the UK's annual 18,000 surgical operations for the revision of hip and knee replacements and is the 2nd most common cause of failure of knee replacements. Revision for infection is complex, traumatic, and costly with an estimated burden to the NHS of £300million per annum and is unsuccessful in 20% of cases.

We aim to increase the infection eradication by releasing antibacterial silver at the site where there are either well-established bacterial colonies, or where these colonies may arise. Our new SmartSpacer will have a CrNAg coating with a sacrificial silver rich top layer to provide an initial post-operative burst of antimicrobial nanoparticulate silver, and a lower silver content CrNAg layer below to provide a longer term wear resistant, ion-leach barrier with a controlled antimicrobial silver ion release over time. This coating technology was developed by the team (de Villiers et al, 2015; Lu et al, 2012), through 2 different projects funded by EPSRC and TSB. In this InnovateUK funded, first-in-man study, SmartSpacer will be used in patients undergoing 2-stage knee revision surgery due to infection to assess the safety and bacterial biofilm formation after 6 weeks of use in patients. Innovation in this project lies in the 'sacrificial' silver-rich surface coating which provides a post-operative 'burst' of antimicrobial activity World-leading SmartSpacer will deliver exceptional biocompatibility and antimicrobial properties directly fighting infection with the ultimate goal of preventing infection through ‘Smart-Primary-Implants’, reducing the burden of revision, benefiting the patient and economy worldwide.

Cardiac Assessment of Patients with Hip Implants

  • Alister Hart (Professor of Orthopaedic Surgery; Consultant Orthopaedic Surgeon), Reshid Berber (Clinical Research Fellow), John Skinner (Consultant Orthopaedic Surgeon)
  • UCL Institute of Orthopaedic & Musculoskeletal Science; Joint Reconstruction Unit, Royal National Orthopaedic Hospital
  • More information: a.hart@ucl.ac.uk

1.5 million patients worldwide have Metal-on-metal (MoM) hip implants (approx. 50,000 in the UK). These implants are made of metal that wears and corrodes to release cobalt and chromium metal ions into the bloodstream. In 2013 the Food and Drug Administration (FDA, USA) highlighted toxicity of many organs due to these metal ions and recommended that patients with certain symptoms are assessed in more detail.

A number of cases of suspected metal toxicity have been reported. The most profound case involves a patient who died from heart failure as a result of cobalt, released from the hip replacement in such high doses that it was deposited within the heart tissue. In addition a recent cross-sectional health screen suggested that raised metal ion levels have the potential to cause heart problems. These reports have raised public anxiety and therefore the need for a properly conducted study.

Cardiac MRI (CMR) is currently considered the ideal method for early detection of cardiac iron deposition in patients with iron overload disorder (haemochromatosis) and also is the reference-standard for quantification of cardiac volumes and function. Cobalt is similar to iron; it is paramagnetic and therefore should be detected by MRI in a similar way to iron. No study has attempted to use CMR for detection of metal ions deposited in cardiac tissues in patients with metal hip implants.

In this Gwen Fish Trust funded study, we aim to assess whether metal hip implants that release cobalt metal ions have any clinical impact on the heart function by studying 3 groups of patients (matched for age, sex and time since surgery): i) Patients with a MoM hip implant and raised metal ion level; ii) Patients with a MoM hip implant and normal metal ion level. iii) Patients with a non-metal bearing hip implant. We will detect cobalt deposition in the cardiac tissue of patients with metal hip implants with markedly raised cobalt blood ion level. These clinical data will be analysed and compared to assess if a significant difference exists between the 3 groups. We will also analyse the cardiac function in these 3 groups of patients to ascertain whether the metal from the hip implants has a clinical impact on the heart.

Measure the efficacy of a functionally biomimetic osteochondral scaffold for large osteochondral defect repair

  • Chaozong Liu (Non-Clinical Senior Lecturer), Gordon Blunn (Professor of Biomedical Engineering), Andy Goldberg (Senior Clinical Lecturer; Honorary Consultant Orthopaedic Surgeon)
  • UCL Institute of Orthopaedic & Musculoskeletal Science; Foot & Ankel, Royal National Orthopaedic Hospital
  • More information: c.liu@ucl.ac.uk

Implants that can help osteoarthritis patients to repair damaged or diseased cartilage have had limited success to date and are only available to repair small areas of cartilage damage. Researchers at UCL Institute of Orthopaedic & Musculoskeletal Science and the Royal National Orthopaedic Hospital, in collaborate with Collagen Solutions Plc and Oxford MEStar Ltd, are developing a novel biomimetic 3D scaffold that can be used for repair of larger areas of cartilage, where cartilage is either damaged or diseased.

The scaffold is implanted in the knee and hip, providing a structure onto which a patient’s own cells can grow to create new cartilage tissue. The team has developed an innovative design that replicates the properties of natural cartilage and can be shaped to fit the joint more effectively, preventing fluid leaking out from the joint and encouraging the formation of new cartilage.

In this project, we will refine the design of this biomimetic osteochondral scaffold, measure the in vivo efficacy of the scaffold in achieving mechanical stable and improved biological fixation in a sheep osteochondral defect model. Successful delivery of this program will lead to tangible and clinically relevant innovation that can be used in a one-step surgical procedure for treatment of large osteochondral defects. The funding from Arthritis Research UK and he Medical Technologies Innovation and Knowledge Centre enable the team to refining the design through work in animal models and ensuring that the design can be reliably manufactured and reproduced, and further to prepare for clinical trials. It is anticipated that this will create new treatments for early osteoarthritis. As a result, the quality of life of OCD suffers will be improved allowing a pain free, more active lifestyle.

Why sugar in ageing is not so sweet

  • Helen Birch (Professor of Skeletal Tissue Dynamics), Maria Notou (Research Associate), Andrea Lopez Clavijo (Research Associate), Nora DeLeuuw (Professor of Computational Materials Science), Anthony Nash (Research Associate), Thomas Collier (PhD student), Laurent Bozec (Senior Lecturer), Tarek Ahmed (PhD student)
  • UCL Institute of Orthopaedic & Musculoskeletal Science; UCL Chemistry Department; UCL Eastman Dental Institute
  • More information: h.birch@ucl.ac.uk

Have you ever wondered why, as we age, the function of our skeletal system declines displaying both reduced range and ease of movement? Furthermore, despite a lower level of performance we are far more likely to damage soft tissue structures such as tendons and ligaments in middle and old age.

In a BBSRC funded project, the Skeletal Tissue Dynamics group, lead by Professor Helen Birch, take a multidisciplinary approach to investigate one of the most intractable research problems that has been recognized as an important mechanism of ageing. A chemical process commonly known as ‘browning’ and more familiar in the food industry is likely to play a major role in changing the properties of tendons, the structures that connect muscle to bones. The first step in this adventitious process is the addition of sugars (glycation), such as the common sugar glucose, to the protein collagen in tendon tissue. A series of spontaneous chemical re-arrangements then occurs and further reactions with neighbouring peptides results in advanced glycation end-product (AGE) crosslinks; the most common of which is glucosepane. Collagen forms the majority of tendon (80% dry weight) providing high mechanical strength; as a result changes to the properties of collagen have a big impact on the ability of tendon to function effectively.

In our recent work published in Matrix Biology (Collier et al, 2015) we have identified 6 sites within the collagen molecule where glucosepane is likely to form. These sites coincide with regions of the molecule important in biological activity through interactions with other matrix proteins and tendons cells. Furthermore our work has shown that glucosepane formation at each of these sites would change mechanical properties by stiffening the collagen molecule.

Through a better understanding of AGE crosslinking we aim to provide novel therapeutic strategies to prevent AGE crosslinks from forming or to break crosslinks once formed thereby providing a pathway to improving tendon function and mobility into old age.

Bone Graft Substitute Development

  • Melanie Coathup (Reader of Orthopaedic Implant Fixation and Bone Regeneration), Professor of Biomedical Engineering)
  • UCL Institute of Orthopaedic & Musculoskeletal Science
  • More information: m.coathup@ucl.ac.uk

Bone graft substitutes are widely used in the field of orthopaedics, accounting account for over 2 million surgeries per year worldwide. Bone graft is used to fill in defects associated with revision total joint replacements, fill in bone cysts and for limb reconstruction as well as to provide structural support or augments healing in significant bone defects such as osteoporotic bone and non-union fracture. Spine fusion using bone grafts is the most common procedure in spine surgery treating numerous morbidities such as trauma, deformity and degeneration where allograft and autograft are currently the most commonly used bone grafts. However, use of allograft and autograft pose limitations and can present complications to the patient such as donor site morbidity. Numerous alternative bone graft substitutes are on the market or have been developed and are used clinically. The goal for the development of a bone graft substitute material is to replace autograft with enhanced osteogenic and osteoinductive properties. Bone graft substitutes are based on naturally occurring materials such as demineralized allograft bone matrix, bovine collagen mineral composites, ceramic hydroxyapatite (HA), non-ceramic hydroxyapatite, ceramic-coralline hydroxyapatite (cHA) and synthetic materials such as calcium sulphate pellets and non-ceramic calcium phosphate.

In our collaborative studies with Imperial College, University of Nottingham and University of Southampton that were funded by Baxter and Apatech and Orthogem, we have shown that bone formation adjacent to graft materials is augmented in bone defect models (Coathup et al. 2015, Tayton et al. 2014, McLaren et al. 2014, Coathup et al. 2013, Schindler et al. 2008, Schindler et al. 2007) and that the osteoinductive potential of bone graft substitute materials is increased when they are used with stem cells (Salmasi et al. 2015, De Godoy et al. 2015, Garcia-Gareta et al. 2014, Garcia-Gareta et al. 2014b, Korda et al. 2010, Korda et al. 2008). Stem cells mixed with allograft have been shown to improve fixation of implants and bone formation in impaction grafting, which is used to enhance bone formation around revision implants. We have also used HA for impaction grafting and have shown an equal performance of this material compared with allograft bone (Coathup et al. 2008) and that when the HA contains small pores osteoinduction is further promoted (Chan et al. 2012, Coathup et al. 2012). This is important as adopting a synthetic bone graft substitute would ensue reliability and a ready supply of material not reliant on the patients’ own bone or on donor graft material. Furthermore, we have shown that the chemistry of the bone graft is important and that substitution with a small amount of silicon into the HA crystal lattice induces greater osteoinduction (Coathup et al. 2011). Our research has led to develop a bone graft substitute materials with osteoinductive properties, which is now sold by Baxter under the name of InductigraftTM.

Working with Imperial College we have shown that when strontium is incorporated in porous granules of calcium phosphate bone formation is considerably increased. We are planning to translate this material into clinical use.

Shared Control for Wheelchair Interfaces

  • Chinemelu Ezeh (PhD Student), Catherine Holloway (Lecturer) and Tom Carlson (Lecturer)
  • UCL Aspire Centre for Rehabilitation Engineering and Assistive Technology; UCL Biomedical Instrumentation Group @ PAMELA
  • More information: t.carlson@ucl.ac.uk

The ability to move around independently is important for everyone’s self-esteem and wellbeing. People with severe mobility impairments (including many RNOH patients) need powered wheelchairs to get around. Unfortunately, some people are excluded from access to mobility because they cannot use commercially available interfaces reliably. However, they may be able to benefit from novel interfaces for a smart wheelchair: a powered wheelchair that combines inputs from the user with sensory data about the environment to drive safely and efficiently (Carlson & Demiris, 2012; Carlson & Millán, 2013). This technique is called Shared Control, where both the user and the wheelchair itself both contribute to the decision of exactly which path to follow, or how to perform a specific manoeuvre.

In this Aspire-UCL SLMS Grand Challenges funded research, we propose a new Shared Control method for out-of-laboratory use that adapts to a user’s changing level of expertise. It works by learning the user’s driving behaviour and conservatively assists the user towards his/her best driving performance, giving the user the freedom to control the learning process, whilst keeping him/her safe, comfortable and frustration-free. We have already begun to assess the driving styles of wheelchair users who drive with various interfaces (joystick, sip-and-puff, head-array etc.), by making use of standardized “wheelchair skills tests” and computer-vision based tracking systems (Ezeh et al., 2015). In the future stages of this research, we will be recruiting RNOH patients to test out our prototype smart wheelchairs and give us feedback, which will be incorporated into the successive designs.

Carlson T and Millán JDR. Brain-Controlled Wheelchairs: A Robotic Architecture. IEEE Robotics and Automation Magazine, 2013. 20:65-73
Ezeh C, Carlson T, Holloway C. MoRe-T2: An easy-to-use, low cost tracking system for mobility research. Proceedings of The 14th International Conference on Mobility and Transport for Elderly and Disabled Persons, p. in press, TRANSED, 2015

ITAP conduit for transmitting “physiological" signals (clinical application of technology developed from the Capitel project)

  • Gordon Blunn (Professor of Biomedical Engineering), Catherine Pendegrass (Senior Lecturer), Tim Briggs (Professor of Orthopaedic Surgery; Consultant Orthopaedic Surgeon)
  • UCL Institute of Orthopaedic & Musculoskeletal Science; Bone Tumour Unit, Royal National Orthopaedic Hospital
  • More information: g.blunn@ucl.ac.uk

The Intraosseous Transcutaneous Amputation Prostheses (ITAP) developed by the team have been used in patients at the RNOH and although some patients have a sealed interface (Kang et al, 2010) others still have a discharge. This concept has also been used to attach maxillofacial prosthetic devices (Kang et al, 2013) and to treat animals with amputations (Fitzpatrick et al, 2011). For amputees the secure attachment of the prosthesis to the amputation stump and control of the device are the two key issues. Current upper limb prostheses are controlled using muscle signals from skin-surface electrodes that have many disadvantages, such as difficulties with placing the electrodes in a repeatable location, poor signal generation, variable impedance, and crosstalk due to interference from deep or adjacent muscles.

One solution to the problems associated with skin-surface electrodes is the placement of the electrodes directly on or in the muscle. This also allows targeting of individual muscles responsible for specific actions, increasing selectivity and reducing crosstalk. In a Royal College of Surgeon and RAFT funded study, we have had a success in transmitting “physiological" signals with low signal-to-noise ratios through an ITAP device using animal models (Al-Ajam et al, 2013). Reliable transmission of multiple muscle signals across the skin barrier is essential for providing intuitive, biomimetic upper limb prostheses. This technology has the potential to provide a better functional and reliable solution for upper limb amputee rehabilitation, attachment and control. Ultimately electrodes placed into the residual nerve would allow the most intuitive control but reliable technology is some way off.

In a future clinical trial the use of enhanced skin integration technology for ITAP will be tested, which is produced by selective laser sintering combined with an antibacterial coating, such as well-studied AglunaTM. In upper limb amputees these technologies for ITAP will be combined with the use of epimyseal electrodes where signals are transmitted via the ITAP device.

Towards wearable neuromodulation devices for treating bladder, bowel and lower limb spasticity in Spinal Cord Injury

  • Sean Doherty (PhD stundet), Sarah Knight (Honorary Senior Lecturer; Healthcare Scientist), Anne Vanhoestenberghe (Aspire lecturer)
  • UCL Aspire Centre for Rehabilitation Engineering and Assistive Technology; London Spinal Cord Injury, Royal National Orthopaedic Hospital
  • More information: sean.doherty.15@ucl.ac.uk

In a INSPIRE Foundation funded project, the London Spinal Cord Injury Centre (LSCIC) at the Royal National Orthopaedic Hospital and UCL Aspire Centre for Rehabilitation Engineering and Assistive Technology are investigating the role of electrical stimulation in managing incontinence for people with spinal cord injuries (SCI).

The impact of injuring the spinal cord extends beyond the more obvious catastrophic effects to sensory and motor function – affecting the complex mechanisms that enable voluntary control over the bladder and bowel, leading to urinary and faecal incontinence. This lack of control over such vital functions can be detrimental to a patient’s quality of life. Unsurprisingly, addressing the effect of SCI on the bladder and bowel is consistently cited by patients as a key research objective.

Current management techniques are limited, and involve pharmaceutical or surgical intervention. However, these methods are not always satisfactory, with cases where side effects are intolerable or the treatments ineffective. Implantable stimulating devices have also been used, proving very therapeutic in many cases, but their invasive nature has led to limited uptake amongst patients.

Research conducted at the LSCIC and elsewhere has proven the efficacy of transcutaneous electrical neuromodulation for suppressing bladder over-activity (McGee et al, 2015). However, clinical adoption has been limited by the unavailability of suitable stimulators and effective methods of delivery outside of the acute environment.

In this study, we will identify the most efficient neuromodulation methods and prototype a device for patients to test at home. Our aim is to develop a portable, non-invasive, neuromodulation device to help reduce incontinence and unwanted spasticity.

Connected orthopaedic rehabilitation devices for remote patient monitoring during post-surgery care

  • Anju Jaggi (Consultant Physiotherapist), Susan Alexander (Consultant Orthopaedic Surgeon), Douglas Higgins (Managing Director), Robbie Hughes (CEO), John Ainsworth (Senior Research Fellow in Health Informatics)
  • Therapies, Royal National Orthopaedic Hospital; Shoulder Unit, Royal National Orthopaedic Hospital; MuJo Mechanics Ltd; Qinec Ltd; University of Manchester
  • More information: anju.jaggi@rnoh.nhs.uk

Shoulder pain is the 3rd most common reason for musculoskeletal consultations in general practice and the annual cost of treating shoulder injuries is estimated around £100 million. Shoulder pain and injuries cause severe pain and distress to patients and result in severe socio-economic cost in high performance athletes as well as the general population.
Various shoulder morbidities may lead to surgery or rehabilitation, or rehabilitation alone. Post-surgery rehabilitation and rehabilitation in general is usually provided by specialised physiotherapists who provide patients with written instructions to follow specific regime. Instructions are usually with drawn images of specific exercises. Conducting such exercises incorrectly can exacerbate the injury and further delay the patients recovery. Compliance can also be an issue. Developing novel methods, which allow patients to interact with specific equipment and conduct required exercises in a more controlled environment, where compliance and objective measures can also add to recovery, is essential.

The MuJo™ Internal and External Shoulder Machines load the shoulder joint independently in abduction and internal/external rotation to combine the benefits of four traditional shoulder exercises into one smooth, efficient and evenly loaded multi-joint exercise. The equipment is connected to an interface, which allows patients to monitor their own progress, and enables clinical teams to access data on patient’s progress and compliance.

In this InnovateUK funded multi-disciplinary study, the team aims to assess the usability and patient and clinician acceptability of the MuJo™ Shoulder system for shoulder rehabilitation purposes, and provide pilot data for a larger study to further determine the potential of MuJo™ Shoulder solution in an everyday rehabilitation.

Research into Phantom Limb Pain: A pilot Study on a Virtual reality Robot-mediated Technique to Decrease phantom limb pain

  • Rui Loureiro (Aspire Senior Lecturer; Visiting Associate Professor; Honorary Clinical Scientist), Peter Snow (Research Assitant; PhD student), Richard Comley (Professor of Computer Communications), Imad Sedki (Consultant in Rehabilitation Medicine), Marco Sinisi (Consultant Orthopaedic Surgeon)
  • Aspire CREATe, UCL Institute of Orthipaedics & Musculoskeletal Science; Middlesex University; Prosthetic Rehabilitation Unit, Royal National Orthopaedic Hospital; Peripheral Nerve Injury Unit, Royal National Orthopaedic Hospital
  • More information: r.loureiro@ucl.ac.uk

UCL in partnership with Middlesex University and RNOH, are conducting cutting edge research using robots and computer graphics that allowed the design the next generation of medical and rehabilitation devices. The research funded by the UK Ministry of Defence through a contract with Dstl, is using state of the art virtual reality (VR) glasses in conjunction with a robotic training system to create a realistic illusion for the wearer. In September 2015, we have started an NIHR adopted clinical trial evaluating our new sensorimotor training therapy for chronic pain. Our initial study at the RNOH aims to recruit 20 transradial amputees suffering from Phantom Lim Pain over 12 months.

The primary aim is to measure the effectiveness of an immersive Haptic system that combines a visual surrogate for the missing limb with haptic feedback (VR + Haptics) on reducing phantom limb pain, as compared with the same therapy without the haptic feedback (VR only).
Three technological elements summarise the innovation:

  1. Direct physical contact to the haptic device
  2. Mapping of the information from the device to the virtual representation of the physical limb
  3. An application that maintains challenge and interest to the individual

Based on these elements, the Haptic system is developed to acquire EMG commands and residual limb kinematics and display the combined residual limb and virtual prosthesis movements in a virtual reality environment that includes force-based interactions with virtual objects.

The proposed study will establish a more solid scientific framework for advancing the knowledge of haptic interaction in the treatment of Phantom Limb Pain and its outcome will be used to inform a future phase II trial to quantify the new approach in terms of cost benefit and therapeutic practice. The knowledge gained and the prototype developed will have applications in general robotics and rehabilitation. In the long term it could offer the potential to increase the possibility of retaining trained military personnel following trauma by providing the basic tools leading to the development of the next generation of sensorimotor control strategies, aiding in the design of more efficient prosthesis, as well as the integration with portable and cheaper therapy systems, thus opening up possibilities for training in remote and unsupervised environments.

The proposed innovation is intended for future use in military regional rehabilitation facilities, but clearly has more general application in NHS regional rehabilitation centres for the treatment of non-use of salvaged and amputated limbs and is likely to be effective for research on the treatment of Phantom Limb Pain. The research will benefit service men and women, and clinical providers of their rehabilitation treatments. The proposed research innovation may also have potential to reduce costs of rehabilitation but a more detailed research is needed to address this question.

DAISY study: Development of a screening instrument for dysphagia following acute cervical spinal cord injury: identification of current practice and validation of a tool

Data on the incidence of spinal cord injury in UK is limited, however the Spinal Injury Association (SIA) commissioned a report in order to establish a national model of care (2009). The findings estimate around 580 people are admitted to Spinal Injury Units in the UK per year and approximately half of these sustain an injury to the cervical spine. No data is available for patients who are not admitted to specialist spinal units.

The cause of dysphagia in patients with cervical spinal cord injury is not well understood. Significant complications arise from sub-optimal management of dysphagia in patients with cervical spinal injury, namely pneumonia, delayed rehabilitation and subsequent discharge from hospital. Dysphagia affects mood and quality of life (QoL) in many patient groups although has not been studied in this group.

In this NIHR funded study we aim to address the patient-centred and clinical importance of accurate and prompt identification of dysphagia. When this is achieved, it will help improve short and long-term quality of life of patients through improved health and social participation by being able to eat and drink more normally. We are conducting a survey with staff in ICUs to identify current practices in the management of CSCI patients in terms of clinical areas relating to swallowing safety, such as tracheostomy management, ventilator weaning, decisions around enteral feeding, mouthcare and screening for dysphagia. The results of these surveys will provide insight into common and differing clinical practices. We are also interviewing patients to gather information on their own experiences with the aim of informing better future practice. A swallow screening tool is developed for acute CSCI through consensus of an expert panel using a Delphi technique and validated against an existing swallow screen to test reliability and validity.

So far, the survey to staff working with acute cervical spinal cord injury patients across the UK generated over 200 replies from 87 different hospitals. There were differences in clinical practice between professional types and hospital types, with spinal units making long-term considerations and major trauma centres focusing on immediate risk rather than rehabilitation. Doctors and nurses often allowed patients to eat and drink without assessment whereas physiotherapists and speech therapists took a more risk-free approach.

Following on from this, eight patients with cervical spinal cord injury and dysphagia were interviewed about their own acute experiences. Many have had to be in hospital over a year, with report delays until transfer to a specialist spinal unit, transferring to up-to 3 intensive care units previously while they wait. Not being able to eat or drink was often upsetting with poor explanation for some. The lack of speech was also a frustration and made engagement with the team difficult.

The next stage is an international expert consensus aiming to achieve agreement on how dysphagia should be identified and managed in this patient group to improve their outcomes. These results will be developed into a screening tool and piloted with staff for usability before a larger pilot study.

The SenseWheel project: optimising over ground wheelchair propulsion biomechanics

  • Andrew Symonds (PhD student), Catherine Holloway (Senior Lecturer), Angela Gall (Rehabilitation Consultant), Peter Smitham (Orthopaedic Surgeon), Stephen Taylor (Reader in Implantable Instrumentation and Telemetry)
  • UCL Institute of Orthopaedics and Musculoskeletal Science; UCL Department of Civil, Environmental & Geomatic Engineering; London Spinal Cord Injury, Royal National Orthopaedic Hospital
  • More information: Andrew.Symonds@rnoh.nhs.uk

Self propelling a manual wheelchair during daily life is a demanding activity, and over time can lead to shoulder pain and injury. The team has developed a lightweight instrumented wheelchair (‘SenseWheel’) wheel capable of measuring forces applied by the wheelchair user to the wheelchair push rim. It has the potential for both tracking the activity of the user in the field, and also optimising pushing technique to minimise risk of injury.

The SenseWheel project is jointly funded by the EPSRC and the ASPIRE charity, and combines expertise from UCL Engineers and clinicians from the RNOH. In our recent work, the SenseWheel has been used to quantify upper limb demand during a variety of accessibility tasks, including pushing on cross slopes and climbing ramps (Holloway et al, 2015). When climbing a ramp set to the length and gradient of a London bus access ramp, the results demonstrated that loads of up to three times body weight are experienced at the shoulder joint. A further study has identified certain pushing parameters, measured using the SenseWheel, that when maximised can lead to more effective pushing. When applying similar force to the push rim over a greater push arc at a greater angular velocity, wheelchair users are able to complete functional tasks more quickly with fewer pushes.

The next phase of the study will apply the knowledge gained from these studies to educate novice wheelchair users on effective propulsion technique. This study will examine the impact of ‘real time’ verbal feedback on propulsion technique during over ground tasks. Movement metrics, a spinout company supported by ucl business, will develop the technology further for commercial use following the proof of ceoncept.

Holloway C, Symonds S, Suzuki T, Gall A, Smitham P. Taylor S. (2015) Linking wheelchair kinetics to Glenohumeral joint demand during everyday accessibility tasks. 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

Prevalence of gastrocnemius contracture in persons with and without foot and ankle pathology

  • Dishan Singh (Consultant Orthopaedic Surgeon), Simon Chambers (physiotherapist)
  • Foot & Ankle, Royal National Orthopaedic Hospital
  • More information: simon.chambers@rnoh.nhs.uk

The aim of this BOFAS funded study is to assess the prevalence of calf tightness in persons with and without foot and ankle pathology. Patients are often referred to health professionals for stretching of the calf as part of a conservative treatment programme. Patients are also offered surgery if conservative measures fail. However, there is still no gold standard test to measure calf tightness. We are currently carrying out a pilot study to assesse the best reliable test to measure calf tightness. We will compare different methods of assessing calf tightness in healthy volunteers recruited from the staff of the RNOH. Inter and intra observer reliability of the different tests are being assessed. Using the chosen test the main study will recruit patients and healthy volunteers with and without foot and ankle pathology. Each participant will have their ankle dorsiflexion range of movement measured with 2 tests during a period of approximately 30 minutes. These tests are non-invasive and simple to carry out for both the patient and tester.

Re-thinking exercise regimes to improve function following knee replacement surgery

  • Helen Birch (Professor of Skeletal Tissue Dynamics), Yelena Walters (PhD student), Ian McCarthy (Professorial Research Associate), Jonathan Miles (Consultant Orthopaedic Surgeon)
  • UCL Institute of Orthopaedic & Musculoskeletal Science; UCL Dept of Civil, Environmental &Geomatic Engineering; Joint Reconstruction Unit, Royal National Orthopaedic Hospital
  • More information: h.birch@ucl.ac.uk

Although joint replacement surgery is one of the most successful and cost effective interventions in medicine today, some patients do less well than expected. The most common joint replacements are those of the hip and knee and most often as a result of painful and debilitating end-stage osteoarthritis. Knee replacement usually results in relief from knee pain, however patient satisfaction one year after surgery is less than that following total hip replacement and some patients are disappointed with their mobility even though surgically the operation has been successful.

The Skeletal Tissue Dynamics group lead by Professor Helen Birch has an interest in using novel task-orientated physical therapy to improve outcome. Yelena Walters (PhD student) is combining her expertise as an Osteopath with that of Consultant Orthopaedic Surgeon, Jonathon Miles (RNOH) and Clinical Scientist Ian McCarthy (UCL) to develop more effective post-surgery rehabilitation programmes to help knee replacement patients at the RNOH to regain mobility, function and satisfaction. The importance of active rehabilitation immediately following knee replacement surgery is well recognised. Little consensus, however, exists regarding appropriate rehabilitation programmes for the longer term, and hence none is prescribed. We believe that task-orientated rehabilitation is the key to increasing overall performance and our research study will target patients 12 months post-operation who are not satisfied with their progress.

In task-orientated rehabilitation patients are instructed to carry our specific activities that form part of every day life rather than the current typically prescribed rehabilitation exercises which have an internal focus on, for example, a specific muscle or joint. Movement is a complex process driven by coordinated interaction between different muscles and the peripheral and central nervous systems and we believe that working on all aspects of this complex pathway will have a greater impact on patient mobility and satisfaction than traditional rehabilitation programmes.

Sound feedback and body image in Complex Regional Pain Syndrome

  • Ana Tajadura-Jimenez (Research Associate), Helen Cohen (Consultant Rheumatologist)
  • UCL Interaction Centre; Rheumatology, Royal National Orthopaedic Hospital
  • More Information: Helen.cohen@rnoh.nhs.uk

Complex Regional Pain Syndrome (CRPS) usually affects a single limb and may occur following major nerve damage (Type 2), minor trauma or even spontaneously (Type 1) with an incidence of 1:1000-1:5000. CRPS is a deeply distressing condition that has a significant impact on the sufferer's quality of life and over half of patients develop long-term disability and handicap. The cause of this condition is unknown and there is currently no cure. Published best practice primarily focuses therapies to the affected limb and these include early mobilisation, visualisation of the affected part and subjecting the limb, to a range of textures and other stimuli such as thermal challenges (known as sensory discrimination training or desensitisation therapy). The Royal National Hospital for Rheumatic Diseases provides a tertiary referral service for these patients that includes a two-week inpatient stay, where such therapies are delivered as part of routine care.

The ESRC funded project, the team aims to assess the feasibility and potential value of auditory simulation for enhancing the perception of one’s body and its related emotional state in those with complex regional pain syndrome. The outcome from this project will inform a future intervention study that will assess the impact of an auditory stimulation system to be used in CRPS Type 1 therapy.

Wearable Assistive Materials (WAM)

  • Debbie Hill (Physiotherapist), Peter Smitham (Lecturer in Trauma and Orthopaedic Surgery), Nick Tyler (Professor of Civil Engineering), Quentin Pankhurst (Professor of Physics), Mark Miodownik (Professor of Materials & Society), Ivan Paul Parkin (Professor of Chemistry)
  • Therapies, Royal National Orthopaedic Hospital; UCL Institute of Orthopaedic & Musculoskeletal Science; UCL Dept of Civil, Environmental &Geomatic Engineering; Institute of Biomedical Engineering; UCL Dept of Mechanical Engineering; UCL Department of Chemistry
  • More information: Debbie.Hill@rnoh.nhs.uk

Exoskeletons are electromechanical devices that are worn by a human operator and designed to increase the physical performance of the wearer.Exoskeleton technology has developed significantly over the past decade as a result of improvements in robotics technology and mechatronics technology. However the existing generation of exoskeletons have significant limitations with respect to their affordability, size, weight, speed and efficiency. These limitations may reduce the functional usefulness of the devices for individuals with neurological impairment, a population who are most likely to benefit from the technology.

The team is developing an exoskeleton that can be worn and that can also act as a muscle so that it can support the whole walking cycle, providing support and control to the user and enabling them to walk otherwise unaided. This EPSRC funded project will not deliver the full working prototype of a walking support system, but it will develop, test and show what can be done in terms of the material and its control system and the extent to which this approach to actuation of locomotory support could be achieved.

There is evidence in the literature that it is of value to involve end-users in the design of assistive technology to ensure their often complex needs are met. However, to date there have been no studies that consider the user’s perspective of exoskeleton technology.

Therefore, in addition to developing wearable assistive material, the WAM project group aims to understand the needs of potential users of this technology in order to ensure that devices developed meet the needs of the population they are being designed to assist. Researcher at RNOH aims to determine patient and healthcare practitioners’ expectations, aspirations and hard limits in terms of exoskeleton requirements, in order to develop a new exoskeleton material that would be acceptable, simple to use, reliable and functional. This information will be used to inform future studies that focus on developing new materials for exoskeleton systems. The preliminary findings from the work at the RNOH on user perspectives of exoskeleton technology in SCI has been reported in a ‘Ask me before you design it’

How helpful did you find this page?
Not helpful
Very helpful *
Required fields *

*We use this information to make improvements to our website and appreciate any feedback you can offer. Comments are emailed to the Communications Team at RNOH. The personal information collected is only used for email replies (Name and Email) and is stored encrypted in our database for 30 days and then permanently deleted.

Research & Innovation