Treatment of prosthetic joint infection (PJI) by systemic administration of high doses of long-term antibiotics often proves ineffective, causing severe side effects. Thus, we presented the phage Sb-1, which coding extracellular polymeric substances (EPS) degradation depolymerases, conjugated with rifampicin-loaded liposomes (Lip-RIF@Phage) by bio-orthogonal functionalization strategy to target biofilm (Figure1). Methicillin-resistant Staphylococcus aureus (MRSA) biofilm was grown on porous glass beads for 24 h Aim
Method
This study seeks to outline the clinical, laboratory, and imaging features of patients with pyogenic spondylitis. It aims to define a novel imaging sign that could indicate the severity of suppurative spondylitis, aiding in its early diagnosis and treatment. This retrospective study included 137 patients from 2013 to 2023. Through the analysis and summary of imaging characteristics among all patients, we identified a distinct MRI sign known as ‘the Disc Penetration sign’ (DP). This sign is defined as an image finding on sagittal MRI depicting the anterior and posterior penetration of an abscess through the intervertebral disc space, affecting both the anterior margin of the vertebrae and the structures within the spinal canal. Observational parameters included WBC, ESR, CRP, hemoglobin, and albumin levels. Documentation of the study included location and segment of the lesion, presence or absence of spinal cord compression, and paravertebral abscesses.Aim
Method
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.
It has been established that mechanical stimulation benefits tendon-bone (T-B) healing, and macrophage phenotype can be regulated by mechanical cues; moreover, the interaction between macrophages and mesenchymal stem cells (MSCs) plays a fundamental role in tissue repair. This study aimed to investigate the role of macrophage-mediated MSC chondrogenesis in load-induced T-B healing in depth. C57BL/6 mice rotator cuff (RC) repair model was established to explore the effects of mechanical stimulation on macrophage polarization, transforming growth factor (TGF)-β1 generation, and MSC chondrogenesis within T-B enthesis by immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Macrophage depletion was performed by clodronate liposomes, and T-B healing quality was evaluated by histology and biomechanics. In vitro, bone marrow-derived macrophages (BMDMs) were stretched with CELLOAD-300 load system and macrophage polarization was identified by flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). MSC chondrogenic differentiation was measured by histochemical analysis and qRT-PCR. ELISA and qRT-PCR were performed to screen the candidate molecules that mediated the pro-chondrogenic function of mechanical stimulated BMDMs.Aims
Methods
Circular RNA (circRNA) S-phase cyclin A-associated protein in the endoplasmic reticulum (ER) (circSCAPER, ID: hsa_circ_0104595) has been found to be highly expressed in osteoarthritis (OA) patients and has been associated with the severity of OA. Hence, the role and mechanisms underlying circSCAPER in OA were investigated in this study. In vitro cultured human normal chondrocyte C28/I2 was exposed to interleukin (IL)-1β to mimic the microenvironment of OA. The expression of circSCAPER, microRNA (miR)-140-3p, and enhancer of zeste homolog 2 (EZH2) was detected using quantitative real-time polymerase chain reaction and Western blot assays. The extracellular matrix (ECM) degradation, proliferation, and apoptosis of chondrocytes were determined using Western blot, cell counting kit-8, and flow cytometry assays. Targeted relationships were predicted by bioinformatic analysis and verified using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The levels of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway-related protein were detected using Western blot assays.Aims
Methods
Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone. The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety.Aims
Methods
Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation.Aims
Methods
The importance of cup position on the performance of total hip replacements (THR) has been demonstrated in Pelvic movement data for walking for 39 unilateral THR patients was acquired (Leeds Biomedical Research Centre). Patient's elected walking speed was used to group patients into high- and low-functioning (mean speed, 1.36(SD 0.09)ms−1 and 0.85(SD 0.08)ms−1 respectively). A computational algorithm (Python3.7) was developed to calculate cup version during gait cycle. Inputs were pelvic angles and initial cup orientation (assumed to be 45° inclination and 7° version, anterior pelvic plane was parallel to radiological frontal plane). Outputs were cup version angles during a gait cycle (101 measurements/cycle). Minimum, maximum and average cup version during gait cycle were measured for each patient. Two-sample t-test (p=0.05) was used to compare groups.Abstract
Objectives
Methods
Rifampicin plays an important role in the treatment of staphylococcal prosthetic joint infection, as rifampicin-containing combinations have shown a high efficacy against Four rifampicin-resistant MRSA strains were used in this study. The MIC for all tested antibiotics was determined by Etest. Biofilms were formed on porous glass beads for 24h and exposed to Sb1 (107 PFU/mL) for 24h followed by exposure to antibiotic for 24h. Viability of bacteria after antimicrobial treatment was detected by beads sonication and plating of the sonication fluids. The minimum biofilm eradication concentration (MBEC) was defined as the lowest concentration of antibiotic required to kill all cells resulting in the appearance of no colony after plating of the sonication fluid (detection limit <20 CFU/mL). The synergistic effects were observed when Sb1 combined with antibiotics used at least 2 log-reduction lower concentrations.Aim
Method
Total Hip Arthroplasty (THA) devices are now increasingly subjected to a progressively greater range of kinematic and loading regimes from substantially younger and more active patients. In the interest of ensuring adequate THA solutions for all patient groups, THA polyethylene acetabular liner (PE Liner) wear representative of younger, heavier, and more active patients (referred to as HA in this study) warrants further understanding. Previous studies have investigated HA joint related morbidity [1]. Current or past rugby players are more likely to report osteoarthritis, osteoporosis, and joint replacement than a general population. This investigation aimed to provide a preliminary understanding of HA patient specific PE liner tribological performance during Standard Walking (SW) gait in comparison to IS0:14242-1:2014 standardized testing. Nine healthy male subjects volunteered for a gait lab-based study to collect kinematics and loading profiles. Owing to limitations in subject selection, five subjects wore a weighted jacket to increase Body Mass Index ≥30 (BMI). An induced increase in Bodyweight was capped (<30%BW) to avoid significantly effecting gait [3] (mean=11%BW). Six subjects identified as HA per BMI≥30, but with anthropometric ratios indicative of lower body fat as previously detailed by the author [2] (Waist-to-hip circumference ratio and waist circumference-to-height ratio). Three subjects identified as Normal (BMI<25). Instrumented force plate loading profiles were scaled (≈270%BW) in agreement with instrumented hip force data [4]. A previously verified THA (Pinnacle® Marathon® 36×56mm, DePuy Synthes) Finite Element Analysis wear model based on Archard's law and modified time hardening model [5] was used to predict geometrical changes due to wear and deformation, respectively (Figure 1). Subject dependent kinematic and loading conditions were sampled to generate, for both legs, 19 SW simulation runs using a central composite design of response surface method.Introduction
Materials and Methods
Persistent post-surgical pain affects 10%-80% of individuals after common operations, and is more common among patients with psychological factors such as depression, anxiety, or catastrophising. We conducted a systematic review and meta-analysis of randomised, controlled trials to evaluate the efficacy of perioperative psychotherapy for persistent postsurgical pain and physical impairment. We searched Medline, PsycINFO, CINAHL, and the Cochrane Central Registry of Controlled Trials to identify relevant RCTs, in any language, from inception of each database to September 1, 2016. Paired independent reviewers identified studies, extracted data, and assessed risk of bias. We pooled treatment effects of perioperative psychotherapy on similar outcomes across eligible trials, focusing on intention-to-treat analysis. We used random effects models to perform all meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluation system was used to assess the quality of evidence. Our search found 15 trials (2220 patients) that were eligible for review. For both persistent post-surgical pain and physical impairment, perioperative education was ineffective, while active psychotherapy suggested a benefit (test of interaction P=0.01 for both outcomes). Moderate quality evidence showed that active perioperative psychotherapy (cognitive-behaviour therapy, relaxation therapy, or both) significantly reduced persistent post-surgical pain [weighted mean difference (WMD) −1.06 cm on a 10 cm visual analogue scale for pain, 95% confidence interval (CI) −1.56 to −0.55 cm, risk difference (RD) for achieving no more than mild pain (3 cm or less) 14%, 95% CI 8–21%] and physical impairment [WMD −9.87% on the 0–100% Oswestry Disability Index, 95% CI −13.42 to −6.32%, RD for achieving no more than mild disability (20% or less) 21%, 95% CI 13–29%]. Perioperative cognitive behavioural therapy and relaxation therapy are effective for reducing persistent pain and physical impairment after surgery. High quality evidence shows no significant effects of perioperative education or psychological support on persistent post-surgical pain or physical impairment compared with usual care. Future studies should explore targeted psychotherapy for surgical patients at higher risk for poor outcome.
Tibial plateau fractures (TPFs) are complex injuries around the knee caused by high- or low-energy trauma. In the present study, we aimed to define the distribution and frequency of TPF lines using a 3D mapping technique and analyze the rationalization of divisions employed by frequently used classifications. In total, 759 adult patients with 766 affected knees were retrospectively reviewed. The TPF fragments on CT were multiplanar reconstructed, and virtually reduced to match a 3D model of the proximal tibia. 3D heat mapping was subsequently created by graphically superimposing all fracture lines onto a tibia template.Aims
Methods
Ciprofloxacin is recommended as anti-biofilm therapy for gram-negative periprosthetic joint infection. With ciprofloxacin monotherapy, resistance in gram-negative bacteria was observed. Therefore, we evaluated
Aim
Method
There is great potential for the use of computational tools within the design and test cycle for joint replacement devices. The increasing need for stratified treatments that are more relevant to specific patients, and implant testing under more realistic, less idealised, conditions, will progressively increase the pre-clinical experimental testing work load. If the outcomes of experimental tests can be predicted using low cost computational tools, then these tools can be embedded early in the design cycle, e.g. benchmarking various design concepts, optimising component geometrical features and virtually predicting factors affecting the implant performance. Rapid, predictive tools could also allow population-stratified scenario testing at an early design stage, resulting in devices which are better suited to a patient-specific approach to treatment. The aim of the current study was to demonstrate the ability of a rapid computational analysis tool to predict the behaviour of a total hip replacement (THR) device, specifically the risk of edge loading due to separation under experimental conditions. A series of models of a 36mm BIOLOX® Delta THR bearing (DePuy Synthes, Leeds, UK) were generated to match an experimental simulator study which included a mediolateral spring to cause lateral head separation due to a simulated mediolateral component misalignment of 4mm. A static, rigid, frictionless model was implemented in Python (PyEL, runtime: ∼1m), and results were compared against 1) a critically damped dynamic, rigid, FE model (runtime: ∼10h), 2) a critically damped dynamic, rigid, FE model with friction (µ = 0.05) (runtime: ∼10h), and 3) kinematic experimental test data from a hip simulator (ProSim EM13) under matching settings (runtime: ∼6h). Outputs recorded were the variation of mediolateral separation and force with time.INTRODUCTION
METHODS
Component positioning of an artificial hip joint plays a key role in durability of implant. Despite the fact that a number of numerical, experimental and clinical studies have been carried out to investigate the effects of cup inclination on polyethylene wear, steep inclination has been reported to be associated with both high and low volumetric wear. Moreover, how cup anteversion affects wear and its interaction with inclination are still unclear. To address these knowledge gaps, in this study wear and contact mechanics of a hip joint under various cup positioning has been investigated by using FEA (Finite Element Analysis). A Pinnacle® Marathon neutral liner 36×56mm was chosen to model the wear and creep over 3 million cycles (mc) based on the Archard's law and modified time hardening model in ANSYS, respectively. Central composite design of response surface method was used to generate 9 FEA runs, where the operative inclination angles varied from 35º, 45º to 55º and operative anteversion angles differed amongst 0º, 15º and 30º. The range of cup angles were chosen to be similar to the Lewinnek “golden” safe zone for dislocation. The gait cycle as specified in ISO 14242-1 was applied to the femoral head.INTRODUCTION
METHOD
Mismatch of bearing component centres and tension of soft tissues surrounding the hip joint can lead to component separation during gait cycle and cause the femoral head to contact the rim of an acetabular liner, which could increase wear and shorten lifespan of an implant. This study aims to investigate the contact and wear mechanics of a metal-on-polyethylene hip joint under dynamic separation by using Finite Element Analysis (FEA). A Pinnacle® cup with a Marathon neutral liner 36×56mm with a 45° inclination was constrained by a spring element in the medial-lateral axis. The spring was pre-compressed by 4mm to represent the corresponding translational mismatch of a simulator testing. Archard's law was used to predict wear over one ISO 14242-1 gait cycle. Contact pressure is proportional to the load input during the stance phase, associated with concentric contact condition; it increases threefold just before the swing phase (time C), reaching 46.2MPa, where edge loading occurs. Consequently, separation climbs to 3.54mm, which is comparable to the mathematical prediction (3.34mm) and dynamic FEA (3.2mm). The predicted volumetric wear after this gait cycle is 1.22 × 10–5 mm3. Dynamic separation between femoral head and acetabular liner can result in edge loading, consequently high contact pressure on the edge of a liner. In combination with cyclic loading, fatigue damage could take place and may be worth investigating in the future.
Cyclooxygenase-2 (COX-2) enzyme is one of the major mediators during inflammation reactions, and COX-2 gene polymorphisms of rs20417 and rs689466 have been reported to be associated with several inflammatory diseases. However, potential links between the two polymorphisms and risk of developing post-traumatic osteomyelitis remain unclear. The present study aimed to investigate associations between the rs20417 and rs689466 polymorphisms and susceptibility to post-traumatic osteomyelitis in Chinese population. A total of 189 patients with definite diagnosis of post-traumatic osteomyelitis and 220 healthy controls were genotyped for rs20417 and rs689466 using the genotyping method*. Chi-square test was used to compare differences of genotype distributions as well as outcomes of five different genetic models between the two groups.Aim
Methods
To evaluate the clinical and radiographic outcomes of total knee arthroplasty using Vega® Knee System (B Braun-Aesculap, Tuttlingen, Germany) [Fig. 1] designed to allow high flexion by shortening the length of posterior condylar flange of femoral component after at least 2 year and to assess the occurrence of periprosthetic osteolysis and loosening at final follow-up. Of the patients who underwent total knee arthroplasty using Vega® Knee System between April 2011 and May 2013, 40 patients (46 knees) were enrolled. The mean age of the patients at the time of surgery was 72.3 years and the mean follow-up period was 29.4 months. Clinical parameters, including Knee Society Knee score, Knee Society Function score, maximal flexion and range of motion were evaluated. Relationship between postoperative maximal flexion and radiographic factors including the posterior tibial slope, the femoral condylar offset and the change of the posterior flange length of femoral condyle was analyzed. Also, the occurrence of periprosthetic osteolysis and loosening was assessed.Objectives
Materials and Methods
Increased Dkk-1 signaling is associated with OA occurrence and joint microenvironment damage. Interruption of Dkk1 action is beneficial to improve OA knees. Osteoarthritis (OA) is a leading cause of disability and healthcare financial burden for total knee arthroplasty, rehabilitation, and disability. Inappropriate mechanical stress, immunological, or biochemical regulation reportedly disturbs homeostasis among cartilage, synovium and subchondral bone microstructure that contributes to OA pathogenesis. Control of joint-deleterious factor action is an emerging strategy to ameliorate OA-induced joint deterioration. Dickkopf-1 (Dkk-1) is a potent inhibitor for Wnt/β-catenin signaling regulation of tissue development and remodeling in physiological or pathological contexts. Dkk-1 also acts as a master deleterious factor that represses osteoblast differentiation capacity and bone repair. Associations among Dkk-1 expression, chondrocyte fate, synovial fibroblast behavior or OA incidence are merit of characterization.Summary Statement
Introduction
The purpose of this study was to compare the biomechanical effects of the trapezius transfer and the latissimus dorsi transfer in a cadaveric model of a massive posterosuperior rotator cuff tear. Eight cadaveric shoulders were tested at 0°, 30°, and 60° of abduction in the scapular plane with anatomically based muscle loading. Humeral rotational range of motion and the amount of humeral rotation due to muscle loading were measured. Glenohumeral kinematics and joint reaction forces were measured throughout the range of motion. After testing in the intact condition, the supraspinatus and infraspinatus were resected, simulating a massive rotator cuff tear. The lower trapezius transfer was then performed. Three muscle loading conditions for the trapezius (12N, 24N, 36N) were applied to simulate a lengthened graph as a result of excessive creep, a properly tensioned graph exerting a force proportional to the cross-sectional area of the inferior trapezius, and an over-constrained graph respectively. Next the latissimus dorsi transfer was performed and tested with one muscle loading condition 24N. A repeated-measures analysis of variance was used for statistical analysis.Background:
Methods:
