For chondral damage in younger patients, surgical best practice is microfracture, which involves drilling into the bone to liberate the bone marrow. This leads to a mechanically inferior fibrocartilage formed over the defect as opposed to the desired hyaline cartilage that properly withstands joint loading. While some devices have been developed to aid microfracture and enable its use in larger defects, fibrocartilage is still produced and there is no clear clinical improvement over microfracture alone in the long term. Our goal is to develop 3D printed devices, which surgeons can implant with a minimally invasive technique. The scaffolds should match the functional properties of cartilage and expose endogenous marrow cells to suitable mechanobiological stimuli in-situ, in order to promote healing of articular cartilage lesions before they progress to osteoarthritis, and rapidly restore joint health and mobility. Importantly, scaffolds should direct a physiological host reaction, instead of a foreign body reaction, associated with chronic inflammation and fibrous capsule formation, negatively influencing the regenerative outcome.

Our novel silica/polytetrahydrofuran/polycaprolactone hybrids were prepared by sol-gel synthesis and scaffolds were 3D printed by direct ink writing. 3D printed hybrid scaffolds with pore channels of ~250 µm mimic the compressive behaviour of cartilage. Our results show that these scaffolds support human bone marrow stem/stromal cell (hMSC) differentiation towards chondrogenesis in vitro under hypoxic conditions to produce markers integral to articular cartilage-like matrix evaluated by immunostaining and gene expression analysis. Macroscopic and microscopic evaluation of subcutaneously implanted scaffolds in mice showed that scaffolds caused a minimal resolving inflammatory response. Our findings show that 3D printed hybrid scaffolds have the potential to support cartilage regeneration.

Acknowledgements: Authors acknowledge funding provided by EPSRC grant EP/N025059/1.

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Autologous osteochondral grafting has demonstrated positive outcomes for treating articular cartilage defects by replacing the damaged region with a cylindrical graft consisting of bone with a layer of cartilage, taken from a non-loadbearing region of the knee. Despite positive clinical use, factors that cause graft subsidence or poor integration are relatively unknown. The aim of this study was to develop finite element (FE) models of osteochondral grafts within a tibiofemoral joint and to investigate parameters affecting osteochondral graft stability.

Initial experimental tests on cadaveric femurs were performed to calibrate the bone properties and graft-bone frictional forces for use in corresponding FE models, generated from µCT scan data. The effects of cartilage defects and osteochondral graft repair were measured by examining contact pressure changes using in vitro tests on a single cadaveric human tibiofemoral joint. Six defects were created in the femoral condyles which were subsequently treated with osteochondral autografts or metal pins. Matching µCT scan-based FE models were created, and the contact patches were compared. Sensitivity to graft bone properties was investigated.

The bone material properties and graft-bone frictional forces were successfully calibrated from the initial tests with good resulting levels of agreement (CCC=0.87). The tibiofemoral joint experiment provided a range of cases to model. These cases were well captured experimentally and represented accurately in the FE models. Graft properties relative to host bone had large effects on immediate graft stability despite limited changes to resultant cartilage contact pressure.

Model confidence was built through extensive validation and sensitivity testing, and demonstrated that specimen-specific properties were required to accurately represent graft behaviour. The results indicate that graft bone properties affect the immediate stability, which is important for the selection of allografts and design of future synthetic grafts.

Non-optimal clinical alignment of components in total hip replacements (THRs) may lead to edge loading of the acetabular cup liner. This has the potential to cause changes to the liner rim not accounted for in standard wear models. A greater understanding of the material behaviours could be beneficial to design and surgical guidance for THR devices. The aim of this research was to combine finite element (FE) modelling and experimental simulation with microstructural assessment to examine material behaviour changes during edge loading.

A dynamic deformable FE model, matching the experimental conditions, was created to simulate the stress strain environment within liners. Five liners were tested for 4Mc (million cycles) of standard loading (ISO14242:1) followed by 3Mc of edge loading with dynamic separation (ISO14242:4) in a hip simulator. Microstructural measurements by Raman spectroscopy were taken at unloaded and highly loaded rim locations informed by FE results. Gravimetric and geometric measurements were taken every 1Mc cycles.

Under edge loading, peak Mises stress and plastic deformation occur below the surface of the rim during heel strike. After 7Mc, microstructural analysis determined edge loaded regions had an increased crystalline mass fraction compared to unloaded regions (p<0.05). Gravimetric wear rates of 12.5mm³/Mc and 22.3mm³/Mc were measured for standard and edge loading respectively. A liner penetration of 0.37mm was measured after 7Mc.

Edge loading led to an increase in gravimetric wear rate indicating a different wear mechanism is occurring. FE and Raman results suggest that changes to material behaviour at the rim could be possible. These methods will now be used to assess more liners and over a larger number of cycles. They have potential to explore the impact of edge loading on different surgical and patient variables.

The aim of this work was to develop a novel, accessible and low-cost method, which is sufficient to measure changes in meniscal position in a whole-knee joint model performing dynamic motion in a knee simulator.

An optical tracking method using motion markers, MATLAB (MATLAB, The MathWorks Inc.) and a miniature camera system (Raspberry Pi, UK) was developed. Method feasibility was assessed on porcine whole joint knee samples (n = 4) dissected and cemented to be used in the simulator (1). Markers were placed on three regions (medial, posterior, anterior) of the medial meniscus with corresponding reference markers on the tibial plateau, so the relative meniscal position could be calculated. The Leeds high kinematics gait profile scaled to the parameters of a pig (1, 2) was driven in displacement control at 0.5 Hz. Videos were recorded at cycle-3 and cycle-50. Conditions tested were the capsule retained (intact), capsule removed and a medial posterior root tear. Mean relative displacement values were taken at time-points relating to the peaks of the axial force and flexion-extension gait inputs, as well as the range between the maximum and minimum values. A one-way ANOVA followed by Tukey post hoc analysis were used to assess differences (p = 0.05).

The method was able to measure relative meniscal displacement for all three meniscal regions. The medial region showed the greatest difference between the conditions. A significant increase (p < 0.05) for the root tear condition was found at 0.28s and 0.90s (axial load peaks) during cycle-3. Mean relative displacement for the root tear condition decreased by 0.29 mm between cycle-3 and cycle-50 at the 0.28s time-point. No statistically significant differences were found when ranges were compared at cycle-3 and cycle-50.

The method was sensitive to measure a substantial difference in medial-lateral relative displacement between an intact and a torn state. Meniscus extrusion was detected for the root tear condition throughout test duration. Further work will progress onto human specimens and apply an intervention condition.

Cam-type femoroacetabular impingement is caused by bone excess on the femoral neck abutting the acetabular rim. This can cause cartilage and labral damage due to increased contact pressure as the cam moves into the acetabulum. However, the damage mechanism and the influence of individual mechanical factors (such as sliding distance) are poorly understood. The aim of this study was to identify the cam sliding distance during impingement for different activities in the hip joint.

Motion data for 12 different motion activities from 18 subjects, were applied to a hip shape model (selected as most likely to cause damage, anteriorly positioned with a maximum alpha angle of 80°). The model comprised of a pointwise representation of the acetabular rim and points on the femoral head and neck where the shape deviated from a sphere (software:Matlab).

The movement of each femoral point was tracked in 3D while an activity motion was applied, and impingement recorded when overlap between a cam point and the acetabular rim occurred. Sliding distance was recorded during impingement for each relevant femoral point.

Angular sliding distances varied for different activities. The highest mean (±SD) sliding distance was for leg-crossing (42.62±17.96mm) and lowest the trailing hip in golf swing (2.17±1.11mm). The high standard deviation in the leg crossing sliding distances, indicates subjects may perform this activity in a different manner.

This study quantified sliding distance during cam impingement for different activities. This is an important parameter for determining how much the hip moves during activities that may cause damage and will provide information for future experimental studies.

Multiple biochemical biomarkers have been previously investigated for the diagnosis, prognosis and response to treatment of articular cartilage damage, including osteoarthritis (OA). Synovial fluid (SF) biomarker measurement is a potential method to predict treatment response and effectiveness. However, the significance of different biomarkers and their correlation to clinical outcomes remains unclear. This systematic review evaluated current SF biomarkers used in investigation of cartilage degeneration or regeneration in the knee joint and correlated these biomarkers with clinical outcomes following cartilage repair or regeneration interventions.

PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials, and Embase databases were searched. Studies evaluating SF biomarkers and clinical outcomes following cartilage repair intervention were included. Two researchers independently performed data extraction and QUADAS-2 analysis. Biomarker inclusion, change following intervention and correlation with clinical outcome was compared.

9 studies were included. Study heterogeneity precluded meta-analysis. There was significant variation in sampling and analysis. 33 biomarkers were evaluated in addition to microRNA and catabolic/anabolic ratios. Five studies reported on correlation of biomarkers with six biomarkers significantly correlated with clinical outcomes following intervention. However, correlation was only demonstrated in isolated studies.

This review demonstrates significant difficulties in drawing conclusions regarding the importance of SF biomarkers based on the available literature. Improved standardisation for collection and analysis of SF samples is required. Future publications should also focus on clinical outcome scores and seek to correlate biomarkers with progression to further understand the significance of identified markers in a clinical context.

Stimulation of the mechanosensitive ion channel, Piezo1 promotes bone anabolism and SNPs in the Piezo1 locus are associated with changes in fracture risk. Osteocytes function as critical regulators of bone homeostasis by sensing mechanical signals. The current study used a human, cell-based physiological, 3D in vitro model of bone to determine whether loading of osteocytes in vitro results in upregulation of the Piezo1 pathway.

Human Y201 MSCs, embedded in type I collagen gels and differentiated to osteocytes for 7-days, were subjected to pathophysiological load (5000 µstrain, 10Hz, 5 mins; n=6) with unloaded cells as controls (n=4). RNA was extracted 1-hr post load and assessed by RNAseq analysis. To mimic mechanical load and activate Piezo1, cells were differentiated to osteocytes for 13 days and treated ± Yoda1 (5µM, 2- and 24-hs, n=4); vehicle treated cells served as controls (n=4). RNA was subjected to RT-qPCR and data normalised to the housekeeping gene, YWHAZ. Media was analysed for IL6 release by ELISA.

Mechanical load upregulated Piezo1 gene expression (16.5-fold, p<0.001) and expression of the transcription factor NFATc1, and matricellular protein CYR61, known regulators of Piezo1 mechanotransduction (3-fold; p= 5.0E-5 and 6.8-fold; p= 6.0E-5, respectively). After 2-hrs, Yoda1 increased the expression of the early mechanical response gene, cFOS (11-fold; p=0.021), mean Piezo1 expression (2.3-fold) and IL-6 expression (103-fold, p<0.001). Yoda1 increased the release of IL6 protein after 24 hours (7.5-fold, p=0.001).

This study confirms Piezo1 as an important mechanosensor in osteocytes. Piezo1 activation mediated an increase in IL6, a cytokine that drives inflammation and bone resorption providing a direct link between mechanical activation of Piezo1, bone remodeling and inflammation, which may contribute to mechanically induced joint degeneration in diseases such as osteoarthritis. Mechanistically, we hypothesize this may occur through promoting Ca2+ influx and activation of the NFATc1 signaling pathway.

Osteoarthritis (OA) is a common cause of chronic pain. Subchondral bone is highly innervated, and bone structural changes directly correlate with pain in OA. Mechanisms underlying skeletal–neural interactions are under-investigated. Bone derived axon guidance molecules are known to regulate bone remodelling. Such signals in the nervous system regulate neural plasticity, branching and neural inflammation. Perturbation of these signals during OA disease progression may disrupt sensory afferents activity, affecting tissue integrity, nociception, and proprioception.

Osteocyte mechanical loading and IL-6 stimulation alters axon guidance signalling influencing innervation, proprioception, and nociception.

Human Y201 MSC cells, embedded in 3D type I collagen gels (0.05 × 106 cell/gel) in 48 well plastic or silicone (load) plates, were differentiated to osteocytes for 7 days before stimulation with IL-6 (5ng/ml) with soluble IL-6 receptor (sIL-6r (40ng/ml) or unstimulated (n=5/group), or mechanically loaded (5000 μstrain, 10Hz, 3000 cycles) or not loaded (n=5/group). RNA extracted 1hr and 24hrs post load was quantified by RNAseq whole transcriptome analysis (NovaSeq S1 flow cell 2 × 100bp PE reads and differentially expressed neurotransmitters identified (>2-fold change in DEseq2 analysis on normalised count data with FDR p<0.05). After 24 hours, extracted IL-6 stimulated RNA was quantified by RT-qPCR for neurotrophic factors using 2–∆∆Ct method (efficiency=94-106%) normalised to reference gene GAPDH (stability = 1.12 REfinder). Normally distributed data with homogenous variances was analysed by two-tailed t test.

All detected axonal guidance genes were regulated by mechanical load. Axonal guidance genes were both down-regulated (Netrin1 0.16-fold, p=0.001; Sema3A 0.4-fold, p<0.001; SEMA3C (0.4-fold, p<0.001), and up-regulated (SLIT2 2.3-fold, p<0.001; CXCL12 5-fold, p<0.001; SEMA3B 13-fold, p<0.001; SEMA4F 2-fold, p<0.001) by mechanical load. IL6 and IL6sR stimulation upregulated SEMA3A (7-fold, p=0.01), its receptor Plexin1 (3-fold, p=0.03). Neutrophins analysed in IL6 stimulated RNA did not show regulation.

Here we show osteocytes regulate multiple factors which may influence innervation, nociception, and proprioception upon inflammatory or mechanical insult. Future studies will establish how these factors may combine and affect nerve activity during OA disease progression.

Mechanical loading of joints with osteoarthritis (OA) results in pain-related functional impairment, altered joint mechanics and physiological nociceptor interactions leading to an experience of pain. However, the current tools to measure this are largely patient reported subjective impressions of a nociceptive impact. A direct measure of nociception may offer a more objective indicator. Specifically, movement-induced physiological responses to nociception may offer a useful way to monitor knee OA. In this study, we gathered preliminary data on healthy volunteers to analyse whether integrated biomechanical and physiological sensor datasets could display linked and quantifiable information to a nociceptive stimulus.

Following ethical approval, 15 healthy volunteers completed 5 movement and stationary activities in 2 conditions; a control setting and then repeated with an applied quantified thermal pain stimulus to their right knee. An inertial measurement unit (IMU) and an electromyography (EMG) lower body marker set were tested and integrated with ground reaction force (GRF) data collection. Galvanic skin response electrodes for skin temperature and conductivity and photoplethysmography (PPG) sensors were manually timestamped to the integrated system.

Pilot data showed EMG, GRF and IMU fluctuations within 0.5 seconds of each other in response to a thermal trigger. Preliminary analysis on the 15 participants tested has shown skin conductance, PPG, EMG, GRFs, joint angles and kinematics with varying increases and fluctuations during the thermal condition in comparison to the control condition.

Preliminary results suggest physiological and biomechanical data outputs can be linked and identified in response to a defined nociceptive stimulus. Study data is currently founded on healthy volunteers as a proof-of-concept. Further exploratory statistical and sensor readout pattern analysis, alongside early and late-stage OA patient data collection, can provide the information for potential development of wearable nociceptive sensors to measure disease progression and treatment effectiveness.

To determine the risk of total knee replacement (TKR) for primary osteoarthritis (OA) associated with overweight/obesity in the Australian population.

This population-based study analyzed 191,723 cases of TKR collected by the Australian Orthopaedic Association National Joint Registry and population data from the Australian Bureau of Statistics. The time-trend change in incidence of TKR relating to BMI was assessed between 2015-2018. The influence of obesity on the incidence of TKR in different age and gender groups was determined. The population attributable fraction (PAF) was then calculated to estimate the effect of obesity reduction on TKR incidence.

The greatest increase in incidence of TKR was seen in patients from obese class III. The incidence rate ratio for having a TKR for obesity class III was 28.683 at those aged 18-54 years but was 2.029 at those aged >75 years. Females in obesity class III were 1.7 times more likely to undergo TKR compared to similarly classified males. The PAFs of TKR associated with overweight or obesity was 35%, estimating 12,156 cases of TKR attributable to obesity in 2018. The proportion of TKRs could be reduced by 20% if overweight and obese population move down one category.

Obesity has resulted in a significant increase in the incidence of TKR in the youngest population in Australia. The impact of obesity is greatest in the young and the female population. Effective strategies to reduce the national obese population could potentially reduce 35% of the TKR, with over 10,000 cases being avoided.

Variations in component positioning of total hip replacements can lead to edge loading of the liner, and potentially affect device longevity. These effects are evaluated using ISO 14242:4 edge loading test results in a dynamic system. Mediolateral translation of one of the components during testing is caused by a compressed spring, and therefore the kinematics will depend on the spring stiffness and damping coefficient, and the mass of the translating component and fixture. This study aims to describe the sensitivity of the liner plastic strain to these variables, to better understand how tests using different simulator designs might produce different amounts of liner rim deformation.

A dynamic explicit deformable finite element model with 36mm Pinnacle metal-on-polyethylene bearing geometry (DePuy Synthes, Leeds, UK) was used with material properties for conventional UHMWPE. Setup was 65° clinical inclination, 4mm mismatch, 70N swing phase load, and 100N/mm spring. Fixture mass was varied from 0.5-5kg, spring damping coefficient was varied from 0-2Ns/mm. They were changed independently, and in combination.

Maximum separation values were relatively insensitive to changes in the mass, damping coefficient, or both. The sensitivity of peak plastic strain, to this range of inputs, was similar to changing the swing phase load from 70N to approximately 150N – 200N. Increasing the fixture mass and/or damping coefficient increased the peak plastic strain, with values from 0.15-0.19.

Liner plastic deformation was sensitive to the spring damping and fixture mass, which may explain some of the differences in fatigue and deformation results in UHMWPE liners tested on different machines or with modified fixtures. These values should be described when reporting the results of ISO14242:4 testing.

Acknowledgements

Funded by EPSRC grant EP/N02480X/1; CAD supplied by DePuy Synthes.

Knee pain is common, representing a significant socioeconomic burden. Caused by a variety of pathologies, its evaluation in primary-care is challenging. Subsequently, an over-reliance on magnetic resonance imaging (MRI) exists. Prior to orthopaedic surgeon referral, many patients receive no, or incorrect, imaging. Electronic-triage (e-triage) tools represent an innovative solution to address this problem. The primary aim of this study was to ascertain whether an e-triage tool is capable of outperforming existing clinical pathways to determine the correct pre-hospital imaging based on knee pain diagnosis.

Patients ≥18 years with a new presentation of knee pain were retrospectively identified. The timing and appropriateness of imaging was assessed. A symptom-based e-triage tool was developed, using the Amazon LEXbotplatform, and piloted to predict five common knee pathologies and suggest appropriate imaging.

1462 patients were identified. 17% of arthroplasty patients received an ‘unnecessary MRI’, whilst 28% of arthroscopy patients did not have a ‘necessary MRI’, thus requiring a follow-up appointment, with a mean delay of three months (SD 2.6, range 0.2-20.2). Using NHS tariffs, a wasted cost through unnecessary/necessary MRIs and subsequent follow-up appointments was estimated at £45,816. The e-triage pilot was trialled with 41 patients (mean age:58.4 years, 58.5% female). Preliminary diagnoses were available for 34 patients. Using the highest proportion of reported symptoms in the corresponding group, the e-triage tool correctly identified three of the four knee pathologies. The e-triage tool did not correctly identify anterior cruciate ligament injuries (n=3). 79.2% of participants would use the tool again.

A significant number of knee pathology patients received incorrect imaging prior to their initial hospital appointment, incurring delays and unnecessary costs. A symptom-based e-triage tool was developed, with promising pilot data and user feedback. With refinement, this tool has the potential to improve wait-times and referral quality, whilst reducing costs.

Abstract

Shoulder replacements have evolved and current 4th generation implants allow intraoperative flexibility to perform anatomic, reverse, trauma, and revision shoulder arthroplasty. Despite high success rates with shoulder arthroplasty, complication rates high as 10–15% have been reported and progressive glenoid loosening remains a concern.

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Decellularised extracellular matrix scaffolds show great promise for the regeneration of damaged musculoskeletal tissues (cartilage, ligament, meniscus), however, adequate fixation into the joint remains a challenge. Here, we assess the osseo-integration of decellularised porcine bone in a sheep model. This proof-of-concept study supports the overall objective to create composite decellularised tissue scaffolds with bony attachment sites to enable superior fixation and regeneration.

Porcine trabecular bone plugs (6mm diameter, 10mm long) were decellularised using a novel bioprocess incorporating low-concentration sodium dodecyl sulphate with protease inhibitors. Decellularised bone scaffolds (n=6) and ovine allograft controls (n=6) were implanted into the condyle of skeletally mature sheep for 4 and 12 weeks. New bone growth was visualised by oxytetracycline fluorescence and standard resin semi-quantitative histopathology.

Scaffolds were found to be fully decellularised and maintained the native microarchitecture. Following 4-week implantation in sheep, both scaffold and allograft appeared well integrated. The trabecular spaces of the scaffold were filled with a fibro-mesenchymal infiltrate, but some areas showed a marked focal lymphocytic response, associated with reduced bone deposition. A lesser lymphocytic response was observed in the allograft control. After 12-weeks the lymphocytic reaction was minimised in the scaffold and absent in allografts. The scaffold showed a higher density of new mineralized bone deposition compared to allograft. New marrow had formed in both the scaffold and allografts.

Following the demonstration of osteointegration this bioprocess can now be transferred to develop decellularised composite musculoskeletal tissue scaffolds and decellularised bone scaffolds for clinical regeneration of musculoskeletal tissues.

Acetabular tissue damage is implicated in osteoarthritis (OA) and investigation of in situ acetabular soft tissues behaviour will improve understanding of tissue properties and interconnections. The study aim was to visualise acetabular soft tissues under load and to quantify displacements using computed tomography (CT) scans (XtremeCT, Scano Medical).

A CT scan (resolution 82 μm) was performed on the disarticulated, unloaded porcine acetabulum. The femoral head was soaked in Sodium Iodide (NaI) solution and cling film wrapped to prevent transfer to the acetabular side. The joint was realigned, compressed using cable ties and re-scanned. The two images were down-sampled to 0.3 mm. Acetabular bone and soft tissues were segmented. Bony features were used to register the two background images, using Simpleware ScanIP 7.0 (Synopsys), to the same position and orientation (volume difference < 5%). Acetabular soft tissues displacements were measured by tracking the same points at the tissue edges on the two acetabular masks, along with difference in bone position as an additional error assessment.

The use of radiopaque solution provided a clear contrast allowing separation of the femoral and acetabular soft tissues in the loaded image. The image registration process resulted in a difference in bone position in the areas of interest equivalent to image resolution (0.3 mm, a mean of 3 repeats by same user). A labral tip displacement of 1.7 mm and a cartilage thickness change from 1.5 mm unloaded to 0.9 mm loaded, were recorded.

The combination of contrast enhancement, registration and focused local measurement was precise enough to reduce bone alignment error to that of image resolution and reveal local soft tissue displacements. These measurement methods can be used to develop models of soft tissues properties and behaviour, and therapy for hip tissue damage at early stage may be reviewed and optimised.

Whilst home-based exercise rehabilitation plays a key role in determining patient outcomes following orthopaedic intervention (e.g. total knee replacement), it is very challenging for clinicians to objectively monitor patient progress, attribute functional improvement (or lack of) to adherence/non-adherence and ultimately prescribe personalised interventions. This research aimed to identify whether 4 knee rehabilitation exercises could be objectively distinguished from each other using lower body inertial measurement units (IMUs) and principle components analysis (PCA) in the hope to facilitate objective home monitoring of exercise rehabilitation.

5 healthy participants performed 4 repetitions of 4 exercises (knee flexion in sitting, knee extension, single leg step down and sit to stand) whilst wearing lower body IMU sensors (Xsens, Holland; sampling at 60 Hz). Anthropometric measurements and a static calibration were combined to create the biomechanical model, with 3D hip, knee and ankle angles computed using the Euler sequence ZXY. PCA was performed on time normalised (101 points) 3D joint angle data which reduced all joint angle waveforms into new uncorrelated PCs via an orthogonal transformation. Scatterplots of PC1 versus PC2 were used to visually inspect for clustering between the PC values for the 4 exercises. A one-way ANOVA was performed on the first 3 PC values for the 9 variables under analysis. Games-Howell post hoc tests identified variables that were significantly different between exercises.

All exercises were clearly distinguishable using the PC scatterplot representing hip flexion-extension waveforms. ANOVA results revealed that PC1 for the knee flexion angle waveform was the only PC value statistically different across all exercises.

Findings demonstrate clear potential to objectively distinguish between different knee rehabilitation exercises using IMU sensors and PCA. Flexion-extension angles at the hip and knee appear most suited for accurate separation, which will be further investigated on patient data and additional exercises.

The current ‘gold’ standard surgical intervention for critical size bone defect repair involves autologous bone grafting, that risks inadequate graft containment and soft tissue invasion. Here, a new regenerative strategy was explored, that uses a barrier membrane to contain bone graft. The membrane is designed to prevent soft tissue ingrowth, whilst supporting periosteal regrowth, an important component to bone regeneration. This study shows the development of a collagen-based barrier membrane supportive of periosteal-derived mesenchymal stem cell (P-MSC) growth.

P-MSC-homing barrier membranes were successfully obtained with nonaligned fibres, via free-surface electrospinning using type I collagen and poly(E-caprolactone) in 1,1,1,3,3,3-Hexafluoro-2-propanol. Introduction of collagen in the electrospinning mixture was correlated with decreased mean fibre diameter (d: 319 nm) and pore size (p: 0.2–0.6 μm), with respect to collagen-free membrane controls (d: 372 nm; p: 1–2 μm). Consequently, as the average MSC diameter is 20 μm, this provides convincing evidence of the creation of a MSC containment membrane.

SEM-EDX confirmed Nitrogen and therefore collagen fibre localisation. Quantification of collagen content, using Picro Sirius Red dye, showed a 50% reduction after 24 hours (PBS, 37 °C), followed by a drop to 25% at week 3. The collagen-based membrane has a significantly higher elastic modulus compared to collagen-free control membranes. P-MSCs attached and proliferated when grown onto collagen-based membranes, imaged using confocal microscopy over 3 weeks. A modified transwell cell migration assay was developed, using MINUSHEET® tissue carriers to assess barrier functionality. In line with the matrix architecture, the collagen-based membrane proved to prevent cell migration (via confocal microscopy) in comparison to the migration facilitating positive control.

The aforementioned results obtained at molecular, cellular and macroscopic scales, highlight the applicability of this barrier membrane in a new ‘hybrid graft’ regenerative approach for the surgical treatment of critical size bone defects.

With increasing numbers of total joint arthroplasties being performed, peri-prosthetic fracture incidence is rising, and operative management remains the gold standard. Short-term survivorship up to 12 months has been well-documented but medium to long-term is almost unknown. We present survivorship review from a district general hospital, undertaking 800 primary hip and knee arthroplasties per year. Patients with peri-prosthetic fractures and background total knee replacements were identified using our computer database between 2006–2011. All patients were operated on our site; methods used include open reduction, internal fixation (ORIF) using Axsos (Stryker Newbury) locking plates (28), intra-medullary nailing (1) or complex revision (6) depending on fracture and patient factors and surgeon's preference. Mortality was assessed at 30 days, 12 months and 5 years. Thirty-four patients were identified with a 7:1 female to male ratio and mean age of 76. 75% of patients had their primary arthrodesis at our hospital. There was only 1 plate failure noted requiring revision plating. Mortality at 30 days, 12 months and 5 years were 3.2, 12.5% and 50% respectively. When compared to the literature our time interval from index surgery to fracture is considerably longer (115 vs 42 months). Further multi-centre reviews are required to further asses this unexpected finding. Overall mortality is better than our hip fracture cohort, suggesting that good results can be achieved in District Hospital. The longer-term results are encouraging and can act as a guide for patients with this injury. We recommend that patients are managed in consultant-led, multi-disciplinary teams.

Objectives

This study reports on a secondary exploratory analysis of the early clinical outcomes of a randomised clinical trial comparing robotic arm-assisted unicompartmental knee arthroplasty (UKA) for medial compartment osteoarthritis of the knee with manual UKA performed using traditional surgical jigs. This follows reporting of the primary outcomes of implant accuracy and gait analysis that showed significant advantages in the robotic arm-assisted group.

Introduction

The stability of the elbow joint following an acute elbow dislocation is dependent on associated injuries. The ability to identify these concomitant injuries correctly directs management and improves the chances of a successful outcome. Interpretation of plain radiographs in the presence of either a dislocation or post-reduction films with plaster in-situ is difficult. This study aimed to assess the ability of orthopaedic registrars to accurately identify associated bony injuries on initial plain radiographs using CT as the gold standard for comparison.

Background

Since 2011, the knee service at the Nuffield Orthopaedic Centre has been offering a neutralising medial opening wedge high tibial osteotomy (HTO) to a group of patients presenting with early medial osteoarthritis of the knee, varus alignment and symptoms for more than 2 years. During development of this practice an association was observed between this phenotype of osteoarthritis and the presence of CAM deformity at the hip.

Background

Frequency of primary total hip (THA) and total knee (TKA) arthroplasty procedures is increasing, with a subsequent rise in revision procedures. This study aims to describe timing and excess surgical mortality associated with revision THA and TKA compared to those on the waiting list.

Background

Many factors contribute to the occurrence of edge-loading conditions in hip replacement; soft tissue tension, surgical position, patient biomechanical variations and type of activities, hip design, etc. The aim of this study was to determine the effect of different levels of rotational and translational surgical positioning of hip replacement bearings on the occurrence and severity of edge-loading and the resultant wear rates.

Prosthetic joint infection (PJI) is an uncommon but serious complication of hip and knee replacement. We investigated the rates of revision surgery for the treatment of PJI following primary and revision hip and knee replacement, explored time trends, and estimated the overall surgical burden created by PJI.

We analysed the National Joint Registry for England and Wales for revision hip and knee replacements performed for a diagnosis of PJI and their index procedures from 2003–2014. The index hip replacements consisted of 623,253 primary and 63,222 aseptic revision hip replacements with 7,642 revisions subsequently performed for PJI; for knee replacements the figures were 679,010 primary and 33,920 aseptic revision knee replacements with 8,031 revisions subsequently performed for PJI. Cumulative incidence functions, prevalence rates and the burden of PJI in terms of total procedures performed as a result of PJI were calculated.

Revision rates for PJI equated to 43 out of every 10,000 primary hip replacements (2,705/623,253), i.e. 0.43%(95%CI 0.42–0.45), subsequently being revised due to PJI. Around 158 out of every 10,000 aseptic revision hip replacements performed were subsequently revised for PJI (997/63,222), i.e. 1.58%(1.48–1.67). For knees, the respective rates were 0.54%(0.52–0.56) for primary replacements, i.e. 54 out of every 10,000 primary replacements performed (3,659/679,010) and 2.11%(1.96–2.23) for aseptic revision replacements, i.e. 211 out of every 10,000 aseptic revision replacements performed (717/33,920). Between 2005 and 2013, the risk of revision for PJI in the 3 months following primary hip replacement rose by 2.29 fold (1.28–4.08) and after aseptic revision by 3.00 fold (1.06–8.51); for knees, it rose by 2.46 fold (1.15–5.25) after primary replacement and 7.47 fold (1.00–56.12) after aseptic revision. The rates of revision for PJI performed at any time beyond 3 months from the index surgery remained stable or decreased over time.

From a patient perspective, after accounting for the competing risk of revision for an aseptic indication and death, the 10-year cumulative incidence of revision hip replacement for PJI was 0.62%(95%CI 0.59–0.65) following primary and 2.25%(2.08–2.43) following aseptic revision; for knees, the figures were 0.75%(0.72–0.78) following primary replacement and 3.13%(2.81–3.49) following aseptic revision.

At a health service level, the absolute number of procedures performed as a consequence of hip PJI increased from 387 in 2005 to 1,013 in 2014, i.e. a relative increase of 2.6 fold. While 70% of those revisions were two-stage, the use of single stage revision increased from 17.6% in 2005 to 38.5% in 2014. For knees, the burden of PJI increased by 2.8 fold between 2005 and 2014. Overall, 74% of revisions were two-stage with an increase in use of single stage from 10.0% in 2005 to 29.0% in 2014.

Although the risk of revision due to PJI following hip or knee replacement is low, it is rising. Given the burden and costs associated with performing revision joint replacement for prosthetic joint infection and the predicted increased incidence of both primary and revision hip replacement, this has substantial implications for service delivery.

Adductor canal blocks offer an alternative to femoral nerve block for postoperative pain relief in knee arthroplasty. They may reduce the risk of quadriceps weakness, allowing earlier mobilisation of patients postoperatively. However, little is known about the effect of a tourniquet on the distribution of local anaesthetic in the limb.

Ultrasound-guided adductor canal blocks were performed on both thighs of five human cadavers. Left and right thighs of each cadaver were randomised to tourniquet or no tourniquet for one hour. Iohexol radio-opaque contrast (Omnipaque 350) was substituted for the local anaesthetic for X-Ray imaging. All limbs underwent periodic flexion and extension during this hour to simulate positioning during surgery. The cadavers were refrozen. Fiducial markers were inserted into the frozen tissue. X-rays were obtained in 4 planes (AP, lateral 45° oblique/medial oblique, lateral). University Research Ethics Approval was obtained and cadavers were all pre-consented for research, imaging and photography according to the Anatomy Act (1984).

Analysis of radiographs showed contrast distribution in all thighs to be predominantly on the medial aspect of the thighs. The contrast margins were entire and well circumscribed, strongly suggesting it was largely contained within the aponeurosis of the adductor canal. Tourniquets appeared to push the contrast into a narrower and more distal spread along the length of the thigh compared to a more diffuse spread for those without. Proximal spread towards the femoral triangle was reduced in limbs without tourniquets.

The results suggest that contrast material may remain within the adductor canal structures during adductor canal blocks. Tourniquets may cause greater distribution of contrast proximally and distally in the thigh, but this does not appear to be clinically significant. Further studies might include radio-stereo photometric analysis using the fiducial markers in the limbs and in vivo studies to show the effect of haemodynamics on distribution.

Introduction

The exact mechanisms leading to tendinopathies and tendon ruptures remain poorly understood while their occurrence is clearly associated with exercise. Overloading is thought to be a major factor contributing to the development of tendon pathologies. However, as animal studies have shown, heavy loading alone won't cause tendinopathies. It has been speculated, that malfunctioning adaptation or healing processes might be involved, triggering tendon tissue degeneration. By analysing the expression of the entirety of degrading enzymes (degradome) in pathological and non-pathological, strained and non-strained tendon tissue, the aim of this study was to identify common or opposite patterns in gene regulation. This approach may generate new targets for future studies.

Introduction

Achilles tendinopathy (AT) is a highly prevalent injury in athletes and non-athletes with an unknown aetiology. Genetic risk factors have been a recent focus of investigation. The aim of this systematic review was to determine which loci have been linked with mid-portion AT and could potentially be used as biomarkers in tendinopathy risk models or as preventative or therapeutic targets.

Introduction

Tendinopathies are debilitating and painful conditions. They are believed to result from repetitive overuse, which can create micro-damage that accumulates over time, and initiates a catabolic cell response. The aetiology of tendinopathy remains poorly understood, therefore the ideal treatment remains unclear. However, current data support the use of eccentric exercise as an effective treatment. In a previous study, we have shown that eccentric loading generates perturbations in the tendon at 10Hz, which is not present during other less effective loading regimes. Consequently, we hypothesis that 10Hz loading initiates an increased anabolic response in tenocytes, that can promote tendon repair.

Successful treatment of periprosthetic joint infection involves surgical intervention and identification of infecting organisms to enable targeted antibiotic therapy. Current guidelines recommend intra-operative culture sampling to include at least 4 tissue samples and for each sample to be taken with a separate instrument.

We aimed to review current revision arthroplasty practice for Greater Glasgow, specifically comparing intra-operative sampling technique for infected revision cases with these guidelines.

We reviewed the clinical notes of all patients undergoing lower limb revision arthroplasty procedures in Greater Glasgow Hospitals (WIG, GRI, SGH) from July 2013 to August 2014. Demographics of all cases were collected. For revision procedures performed for infection we recorded details of intraoperative samples taken (number, type and sampling technique) and time for samples to reach the laboratory. Results of microbiology cultures were reviewed.

Two hundred and fifty five revision arthroplasty procedures (152 hips, 103 knees) were performed in the 12 month study period. Of these 57 (22%) were infected cases (28 hips, 29 knees). These cases were treated by 14 arthroplasty surgeons with a median number of 3 infected cases managed per surgeon (range 1–11). 58% of cases had the recommended number of tissue samples taken. The median number of microbiology samples collected was 4 (range 1–14). Most procedures (91%) had no documentation of whether separate instruments were used for sampling. Number of tissue samples taken (≥4, p=0.01), time to lab (<24 hours, p=0.03) were significantly associated with positive culture results.

In Greater Glasgow, a large number of surgeons manage infected arthroplasty cases with variability in intra-operative sampling techniques. Sample collection adheres to guideline recommendations in 58% cases. Adhering to guideline standards increases the likelihood of positive tissue cultures. Implementation of a standardised approach to intra-operative sampling for infected cases may improve patient management.

Summary Statement

This study provides preliminary evidence that people with knee osteoarthritis have greater asymmetry in joint loading than healthy controls. Altered loading of the contralateral limb may signify increased risk of injury to other lower limb joints in knee osteoarthritis.

Summary

This study shows a significant reduction in knee adduction moment in patients with medial compartment osteoarthritis, in both the symptomatic and asymptomatic knees. Long-term follow-up studies are required to confirm the effect of treating the asymptomatic side on disease progression.

Summary

The dGEMRIC index correlates more strongly with the pattern of radiographic joint space narrowing in hip osteoarthritis at five year follow-up than morphological measurements of the proximal femur. It therefore offers potential to refine predictive models of hip osteoarthritis progression.

Summary

162 patient cohort with serial Metal Artefact Reduction Sequence MRI scans. Patients with normal initial scans can be followed up at 1 year. Those with abnormal scans should be followed up at a shorter interval of 6 months.

Summary Statement

We have shown that integrin mRNA expression is regulated by the application of mechanical load. This indicates that mechanical loading may modify cell sensitivity to perceive further load through increased interaction with the ECM.

The number of primary Total Knee Arthroplasty (TKA) and primary Total Hip Arthroplasty (THA) procedures carried out in England and Wales is increasing annually. The British Orthopaedic Association guidelines for follow up currently differ for patients with TKA and THA. In THA the BOA recommends that Orthopaedic Data Evaluation Panel (ODEP) 10A rated implants should be followed up in the first year, once at seven years and three yearly thereafter. The BOA guidelines for TKA minimum requirement is radiographs at 5 years and each five years thereafter. Few studies have investigated if early follow up affects patient management following total hip and knee arthroplasty

We carried out a retrospective review of all revision procedures carried out in our institution between April 2010 to April 2013. The medical notes and radiographs for each patient were examined to determine the operative indications and patients symptoms. 92 knee revisions and 143 hip revisions were identified. Additionally we retrospectively reviewed the outcome of 300 one year routine arthroplasty follow up appointments.

The mean time of hip revision was 8.5years (range 0 to 27years) and 5.6years (range 0 to 20years) for knee revisions. The commonest cause for revision was aseptic loosening associated with pain in 49 (53%) of knee revision patients and 89 (63%) of hip revisions. Infection accounted for 26 (28%) knee revisions and 16 (12%) hip revisions. Only 1% of hip and knee revisions was carried out in asymptomatic patients with aseptic loosening.

We did not identify any cases were a patients management was altered at the routine arthroplasty review clinic and none were referred on for further surgical treatment. The findings of our study suggest there is no evidence for a routine one year arthroplasty review and revisions were carried out in asymptomatic patients in 1% of patients.

Introduction:

When having to remove broken or embedded metal implants using high speed burrs, the consequence is often a significant amount of metal debris which becomes embedded in the soft tissues. This may then act as a source for a foreign body inflammatory reaction or as a third body wear in the situation of joint arthroplasty. We describe a simple, cheap and effective method of reducing this debris using only a sterile water-based lubricating gel.

Decreased oxygenation and delayed wound healing may negate the advantages of using a medial parapatellar incision in Total Knee Replacement. Tissue biochemical and blood flow data are not currently available in the literature.

20 patients were included in the study and randomised to midline or medial parapatellar skin incision groups, being supervised by one of 3 Consultant surgeons. Cutaneous blood flow was measured using a Speckle Contrast Blood Perfusion Imager at pre-operative and Days 1 & 3 post-operative intervals. Interstitial fluid measurements for lactate, pyruvate, lactate/pyruvate ratio and glucose were obtained from subcutaneous catheters with a dialysis membrane. Pre-operative samples were obtained from a catheter inserted into the prospective lateral wound edge. A catheter inserted after wound closure supplied dialysates at 0.5, 1, 2, 4, 6, 12 and 24-hour intervals. One catheter was corrupted on insertion; therefore the patients with biochemical data numbered 19.

Cutaneous blood flow improved over the 3 post-operative days in both types of incision and both sides, the medial retaining comparatively better flow. At Day 3, the parapatellar incision group displayed better flow on both sides of the wound. The concentration of lactate was highest in the parapatellar incision group of patients at all intervals. Pyruvate concentrations did not appear to differ across the incision types. Similarly, glucose concentrations did not appear to differ until after 4 hours, when higher concentrations were recorded in the midline group. Lactate/pyruvate ratio appeared to be notably greater in the parapatellar incision group. Plotting change in blood flow relative to change in lactate concentration demonstrated an increase in lactate as flow deteriorates.

The study findings suggest medial parapatellar incisions have increased anaerobic metabolites due to tissue hypoperfusion. Previous studies have demonstrated decreased oxygen tension in lateral based flaps and more recently the medial to lateral arterial anatomy has been demonstrated.