Biomechanics and Orthopaedic Interventions
Head of Research: Dr. Jan Herman Kuiper
Collaborators: Prof. James Richardson, Mr Mike Carmont, Dr Tim Knight, Dr Llewellyn Thomas, Mrs Kelly Campbell, Dr Shailesh Naire
Surgical repair of Achilles tendon ruptures
Achilles tendon rupture is one of the commonest sports injuries, with an incidence rate that has been rising over the last decade. These days most Achilles tendon ruptures are treated conservatively using bracing, but surgical treatment can be necessary, especially in cases of chronic rupture. In addition, surgical treatment will allow earlier functional mobilization. Surgery involves suturing to keep the ruptured ends together. Less-invasive surgery, which leaves a very small skin wound, reduces the incidence of healing complications. However, if using less-invasive suturing techniques it is not clear which material, a resorbable monofilament or a non-resorbable braided, gives the strongest repair and will allow the fastest rehabilitation.
We performed an experiment to find out which material makes the strongest sutures. For this we used Achilles tendons from cows, which we cut through and then repaired using either of the materials. We then placed them in our materials testing machine where we first loaded them cyclically to mimic typical rehabilitation activities (Fig. 1). If they had not failed by this stage, we pulled them slowly to find their rupture strength.
Figure 1. Cut and repqire Achilles tendons after 100 cycles of 190N loading; a repaired using a braided non-resorbable suture, b repaired using a monofilament resorbable suture
We found that the repairs using braided material were better at resisting cyclic loading, resulting in smaller gaps between the tendon ends. The mean strength of the repairs was well above the expected forces on the Achilles tendon. We therefore concluded that braided suture materials will provide a more secure fixation.
An undescribed structure in the foot
It is hard to believe in 2017 that there are still anatomical structures in the human that no-one has described, but in the past year we have found and described just such a structure in the foot. As one can imagine, the structure is miniscule (Fig. 2); it sits in the synovial capsule under the big toe. We have tested its mechanical properties using our materials testing machine (Fig. 2) and found that its properties are similar to those of tendons and ligaments in the foot. It is not attached to muscles, which together with its properties suggests it might act more like a ligament, perhaps restricting upward movement of the big toe.
Figure 2. Newly discovered and described ligamentous structure under the big toe.
Cell therapy for cartilage repair
Our hospital is at the forefront of the clinical use of cell therapy in orthopaedics. We are heading a number of clinical trials in this area, and have collected a large amount of clinical data. Cartilage defect patients are treated using Autologous Chondrocyte Implantation, whereby cartilage cells (chondrocytes) are isolated from a small biopsy and expanded in our OsCell cell manufacturing facility, eventually yielding between 1 and 20 million cells. These cells are implanted into the defect, after which they grow new cartilage. At the moment, we are conducting a clinical trial (ASCOT) to find out if it is best to use cultured chondrocytes, cultured mesenchymal stromal cells or a combination of the two.
The combination of stromal cells and chondrocytes seems attractive because the two cell types are thought to influence each other beneficially. Stromal cells are thought to make the chondrocytes grow (proliferate) faster, amongst others by producing a growth factor known as FGF-1. This would increase the number of chondrocytes in the defect, potentially speeding up healing. On the other hand, chondrocytes are thought to enhance the differentiation of stromal cells into chondrocytes, mainly by producing a growth factor known as BMP-2. This will also increase the number of chondrocytes in the defect. However, having more chondrocytes does not necessarily improve the clinical outcome, something we have found in our clinical data and our earlier mathematical models (, summarised in the 2011 Annual Report).
To find out if any of these interactions between stromal cells and chondrocytes influence cartilage healing, we adapted our mathematical model of a healing cartilage defect following implantation of chondrocytes . This model took into account such phenomena as cell proliferation, cell migration, production of cartilage and diffusion of nutrients, all expressed as mathematical equations. We added equations representing the mutual influences between stromal cells on chondrocyte proliferation. We found that, after implanting a 50/50 mixture of chondrocytes and stromal cells, the largest effect of any interaction on cartilage production occurs three months after implantation (Fig. 3a,b), when cartilage production has clearly advanced towards the surface of the defect. Further in time, the differences are much smaller (Fig. 3a). The increased cartilage production is a consequence of the stimulating effect of chondrocytes on stromal cell differentiation (BMP-2), which increases the number of chondrocytes close to the surface (Fig. 3c). We think the diminishing effect beyond 3 months can be explained by a lack of nutrients. The extra chondrocytes give extra cells at early time points, producing more cartilage matrix, but those extra cells need more nutrients, the transport of which is hindered by the denser cartilage. This will cancel any benefit from the extra cells.
Statistical advice and analysis
Collaborators: Prof. James Richardson, Dr Richa Kulshrestha, Mr Naveen Kumar, Mr Shaughn O’Brien, Dr Bushra Naheed, Prof. Sally Roberts, Mr Eric Robinson, Mr Mike Williams.
This year saw our department again put much effort into statistical advice and analysis. This helped in the design and successful funding or ethical applications of several new clinical studies or trials, and in the analysis and publication of several completed studies. One example is the largest study on the onset of scoliosis in children admitted with spinal injuries. We found evidence that lower age at admission increases the risk of trauma, with children under 14.3 years old especially at risk. Another example is a Cochrane systematic review and meta-analysis of trials on the effectiveness of oestrogen with progestogen to treat the symptoms of premenstrual syndrome (PMS). We found that the current evidence is very weak, but does suggest that oestrogen with progestogen could help to reduce these symptoms. Finally, we analysed the long-term health economic benefits of Autologous Chondrocyte Implantation (ACI) to treat cartilage defect. This study won the poster prize at the Annual Research Day and found that the benefits of ACI are sustained up to 15 years after ACI.
Figure 3 Predicted cartilage matrix and chondrocyte distribution through the thickness of a healing cartilage defect (0=bottom, 1=surface) after implanting a 50/50 mixture of chondrocytes and stromal cells. a Cartilage matrix density at 3, 6 and 9 months after cell implantation; a density of 1 represents fully matured (“normal”) articular cartilage. b Cartilage matrix density 3 months after implantation. c Chondrocyte density 3 months after cell implantation; a density of 1 represents maximum physically possible density.
A change in practice following the Fused Ankle Shoe (FAST) Study
Mr Patrick Laing (Chief Investigator), Dr Caroline Stewart, Victoria Kidgell, Neil Postans, Jan-Herman Kuiper, Antonia Isaacson, Dr Sarah Turner, Dr Kirsty Davies, Megan Hyne, Julia Kennedy & Jenny Hunt
Funded by the Orthopaedic Institute
Ankle fusion can be necessary following trauma or osteoarthritis and can be used to treat pain, deformity and instability. However, it results in a loss of some movement within the ankle.
One can compensate for the loss of the ankle rocker by modifying the patient's footwear to incorporate a 'rocker sole', historically done by NHS orthotic departments either by modifying the patient’s shoe or by creating bespoke shoes, costing up to £200 a pair. A wide range of commercial shoes are now available, with a boat shaped sole claiming to provide a similar rocker effect. These can often be bought for under £100.
In the FAST study, 14 patients performed a series of standardised walks across the ORLAU gait laboratory barefoot and in standard (no rocker) shoes, modified (rocker sole) shoes, MBTs and Sketchers shape ups. Each patient's gait was analysed.
Typical commercially available "rocker" shoes, Skechers Shape-ups (left) and MBTs (right)
The data gathered in this study shows that the commercially available shoes significantly improve the gait and walking speed of people with ankle arthrodesis, compared to standard or NHS modified shoes.
Following this study, the orthotics department at the RJAH Orthopaedic Hospital have changed their practice regarding ankle fusion patients as well as those referred for rocker shoes to help with other diagnoses. Instead of providing the NHS adapted shoes, patients will be advised by the orthotics department on the type of commercial rocker sole shoe that would benefit them and given an information leaflet to help them shop for rocker sole footwear. They will then be followed up by phone to see how they got on with the new shoes.
This change in practice, a direct result of this study, will not only save money but will directly benefit both existing and new ankle fusion patients.
Feasibility of Other Orthosis for Talipes (FOOT) trial
Mr Nigel Kiely (Chief Investigator), Claire Sproston, Dr Sarah Turner, Hilary Shepley, Jan Morris and Sarah McCartney.
Funded by the Orthopaedic Institute Ltd
Clubfoot (or congenital talipes equinovarus – CTEV) is the most common limb deformity affecting newborn children in the UK. The current most widely used treatment is the Ponseti method, involving serial plaster casts followed by maintenance in an orthosis, typically a ‘boots and bar’ device (Figure 1), where two boots are held in a dorsiflexed and externally rotated position by a connecting bar. This is worn for 23 hours a day for 3 months, followed by night time use until the age of 4 or 5 years and is used for children with CTEV of one or both feet. In order to get a good result from the treatment, compliance with the boots and bar needs to be maintained. This is difficult, particularly as the children get older and more mobile.
There are two arms to this study, a clinical arm and a survey arm. The clinical arm intended to assess a new orthosis (Abduction Dorsiflexion Mechanism – ADM) (Figure 2), a singular boot which does not require the use of a bar to achieve the same maintenance as the traditional boots and bar. The survey arm asks questions regarding current orthotic use and opinions of the new device from consultant paediatric orthopaedic surgeons across the UK, plus parents/guardians of children currently using the boots and bar device.
We have now completed the clinical arm of the study. 10 children currently compliant with their boots and bar wore the ADM boot at night for 12 weeks. Abduction and dorsiflexion measurements (Figure 3) as well as Pirani scores (a measure of deformity), and records of any skin problems, were taken at baseline and every 4 weeks during the trial period. The children’s parent/guardians also completed a diary, documenting their experiences with the boot. All children had an increase in degrees of abduction during the 12 week trial period, whilst dorsiflexion changed very little. Nine of the 10 participants had no change in Pirani score and one had a reduction from 0.5 to 0, suggesting that the device maintained the correction. All 10 families have opted to remain using the boot until the child reaches 5 years.
We have had 21 responses from consultants currently treating CTEV, including a lot of opinions and feedback on the ADM and possible trials, 20 of the responders stated that they would be interested in taking part in a future (larger) randomized study of the ADM device.
We have had 85 responses from parents/guardians of children (aged 5 weeks to 5 years) currently being treated for CTEV, across the country. Many responses indicated that the boots and bar frequently posed issues with comfort and practicality at night time for both the children and the parents/guardians. Parents/guardians typically expressed that the most important aspects of their child’s treatment were effectiveness and comfort. When comparing the ADM boot to their current orthosis, 69% of respondents thought it looked to be a good alternative and 58% expressed an interest in being involved in a future ADM trial.
The results of this study have now been submitted for publication. The survey responses, plus the data gathered from the clinical arm of the trial will now be used to help design a larger multi-centre trial of the ADM.
Tennis Elbow Platelet-rich plasma Injection Study
Platelet-rich plasma (PRP) versus autologous whole blood versus saline injection in the treatment of resistant tennis elbow – a pilot study.
Cormac Kelly, Johanna Wales, Jan Herman Kuiper, Megan Hyne, Leighann Sharp, Julie Lloyd Evans
Funders: Orthopaedic Institute Ltd and the British Elbow and Shoulder Society. Consumables and equipment are being provided free of charge by Lavender Medical.
Tennis elbow is a common condition that causes lateral elbow pain. It is associated with repetitive activity at work and play and is thought to be caused by micro-tears in the tendons of the elbow. Although many cases resolve over a period of 3 months, either with or without non-surgical treatments such as rest, exercises and bracing, other treatments may be necessary such as corticosteroid injections or surgery.
In an autologous blood injection, blood is taken from the patient and re-injected around the affected tendon. Autologous blood injection is thought to promote healing through the action of growth factors on the affected tendon.
The injection is given using a technique called needle barbotage that disrupts tendon fibres and is also thought to promote the healing process.
Either whole blood can be injected, or a fragment known as platelet-rich plasma (PRP) can be separated from the red blood cells and then injected. PRP may have a more effective tendon repair potential compared to whole blood however there is a lack of well-designed studies to support this.
Autologous blood injection has been identified by the National Institute of Clinical Excellence (NICE) as a technology that requires further research.
We chose to carry out a pilot study of 30 patients initially, in order to ensure a well-designed study that will reach its recruitment targets, help to inform the number of participants needed in future studies and investigate measures that are both clinically relevant and important to patients. All participants will be required to complete a standardised program of physiotherapy prior to enrolment in the study to ensure that their symptoms cannot be relieved by more conservative means. Participant will then be allocated to one of three treatment groups at random, (an injection of whole blood, PRP or saline). Assessments of pain and elbow function will be carried out at 6 weeks, 12 weeks, 6 months and 1 year. We will also collect information on any side effects experienced, use of pain medications, quality of life and satisfaction with treatment.
Recruitment has progressed more slowly than we anticipated and so we revised the study timelines and now aim to complete recruitment into the study in May 2018 (see chart below). Recruitment is currently on target, with 17 of the 30 patients enrolled.
Greater Trochanteric Pain Syndrome: Does extracorporeal shock wave help?
Mr Robin Banerjee (Chief Investigator), Mr Ben Burston, Mr Simon Lewthwaite (Principle Investigators), Catriona Heaver (Specialist Trainee), Andrea Bailey (Senior Physiotherapist), Rajesh Gilla, Tessa Rowlands, Jean Denton (Physiotherapists), Lisa Burgess (Trial Administrator) and Jan Herman Kuiper (Statistician).
Funded by the Orthopaedic Institute Ltd
Greater trochanteric pain syndrome (GTPS) is a common problem affecting 10-25% of the population and is characterised by pain and tenderness over the greater trochanter, which is the bony bump on the outside of your hip or by pain when lying on your hip. You are more likely to be affected if you are between the ages of 40 and 60 years and 4 times more likely to be affected if you are female.
Although uncommon, it can affect both side (bilateral) and if this is the case, mobility and thus quality of life can be severely reduced.
Any condition which causes altered biomechanics around the hip can result in the development of GTPS including, leg length discrepancy, osteoarthritis, total hip or knee replacement and obesity, but also as a result of participation is such sports as road running and step aerobics. Tears in the gluteal (buttocks) tendons and inflammation of the bursae (fluid filled sac) on the outside of the hip can also cause GTPS.
There is no gold standard treatment for GTPS; rest, non-steroidal anti- inflammatories, physiotherapy and corticosteroid injections have all been used with variable results. Extracorporeal shockwave therapy (ESWT) is used to treat other tendon injuries with good results, but there are few that have looked at GTPS. This study aims to provide evidence to support the use of ESWT for GTPS when compared to the standard treatment.
The study began recruiting on 28th July 2015 with a target of 140 patients. In April 2017, we completed recruitment at 104 patients, which was the new target following some early analysis of results. Of the 104 patients, 51 were randomised to steroid injections (standard treatment) and 53 to ESWT. Four (4) patients are yet to have their 3 month follow-up visit and 69 have completed the study. Full completion of the study is due April 2018 at which point analysis will begin.
We are grateful to the Orthopaedic Institute Ltd for the funding of this study as well as to Impact Medical and ED Shockwave Ltd for the loan of the ESWT machine, but also to the patients who came forward and volunteered to be part of this study.
A quote from one of our patients:
“It’s all totally voluntary and an incredibly worthwhile experience - especially as it really helped with my hip pain.”
Arm cycling in Facioscapulohumeral Dystrophy (FSHD) study
Dr Tracey Willis (Chief Investigator), Dr Richa Kulshrestha, Nick Emery, Jean Denton, Sarah Turner, Charlotte Perkins, Barbara Linklater-Jones and Marco Arkesteijn (Sports and Exercise Research Scientist, Aberystwyth University).
Funded by the Orthopaedic Institute Ltd
Facioscapulohumeral Dystrophy (FSHD) is a muscular dystrophy that affects approximately 2400 people in the UK. FSHD patients live a long life with disability. Symptoms may develop in early childhood and weakness usually noticeable in the teenage years with 95% of affected individuals manifesting disease by age 20 years. The disorder impacts on the arm, shoulders and torso, resulting in reduced muscle mass, shoulder mobility and ability to undertake day to day tasks. At present there is no known cure. Surgery is used to stabilise the shoulder blades, but this does not have a significant effect on disease progression. Several studies have shown that exercise with moderate weights or resistance is not detrimental to patients with FSHD. More recently, a study showed that consistent aerobic training in patients with FSHD not only improves cardiovascular fitness but also improves strength. We believe that arm cycling has the potential to be effective in maintaining or improving shoulder muscle functioning. However, there is no evidence for its safety or effectiveness in the upper extremity.
The main objective of this pilot study is to determine whether FSHD sufferers are physically capable of performing arm cycling. The secondary objective of this stage of the study is to determine what duration, resistance and cadence (speed) of arm cycling each participant can achieve. We plan to use this information to design a larger trial incorporating an at-home arm cycling exercise programme.
We plan to recruit 20 patients to attend a one-off arm cycling session. Prior to exercise participants will complete The Oxford Shoulder Score (OSS) a questionnaire assessing shoulder pain and disability. We will also assess the strength and movement of the shoulder and elbow joints. Participants will then perform arm cycling using a table-top arm cycler supervised by the neuromuscular specialist physiotherapist, for a maximum of 20 minutes. Cadence and resistance of the exercise will be determined as per each individual's tolerance. We will also capture video footage of the arm cycling for further analysis.
At the time of writing, we have recruited 11 participants into this study, from all over the country.
Kinematic Alignment compaRed to Mechanical Alignment technique for total knee replacement surgery (KARMA)
Mr JP Whittaker (Chief Investigator), Sara Owen, Jean Denton, Tess Rowland, Raj Gilla
This study is funded by the Orthopaedic Institute Ltd
Total knee replacement (TKR) is a common operation that involves the removal of the damaged bone and cartilage in the knee and its replacement with an implant. During a total knee replacement the damaged portion of the femur, tibia and patella are removed and replaced with metal and/or plastic components that will reproduce the knee’s natural movement and function.
Recently, substantial healthcare resources have been devoted to the development and use of computer navigation and patient-specific instrumentation systems that achieve neutral mechanical alignment. However the conventional assumption that mechanically aligned TKR leads to the best implant survival has been brought into doubt. Although mechanically aligned TKR improves function, 20 % of patients remain dissatisfied according to reports from Canada, England and Wales.
In an attempt to improve patient satisfaction recent developments have included the individualisation of component alignment with the goal of achieving pre- arthritic alignment through restoration of the axes of rotation, a technique called kinematic alignment (KA). The outcomes of kinematic alignment have been assessed in case series but so far only one randomised controlled trial (RCT) [DOI: 10.1302/0301-620X.96B7.32812 Published 1 July 2014] undertaken in the USA has compared the clinical results of kinematic alignment using patient-specific instruments with the traditional technique of mechanical alignment, demonstrating a substantial benefit in postoperative patient pain relief and function.
Therefore, for direct comparison between kinematic aligned and mechanically aligned surgical techniques for total knee replacement, a pilot study funded by the Orthopaedic Institute is being undertaken prior to a larger RCT with longer term follow up to recruit a cohort of 15 patients undergoing kinematical aligned TKR. The same device will be used as in a previous mechanically aligned study undertaken at RJAH (REC ref: 12/NE/0293 Attune, DePuy, Warsaw IN, in 35 patients based on the same eligibility criteria who will act as controls), which will allow the opportunity to estimate the standard deviation in the control arm in preparation for the larger RCT.
Recruitment to the pilot study commenced at the beginning of 2017 and to date there are 18 control arm participants and 2 study arm participants.