Abstract

Abstract

Abstract

Abstract

Abstract

Abstract

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.