This cross-sectional study aimed to investigate the in vivo ankle kinetic alterations in patients with concomitant chronic ankle instability (CAI) and osteochondral lesion of the talus (OLT), which may offer opportunities for clinician intervention in treatment and rehabilitation. A total of 16 subjects with CAI (eight without OLT and eight with OLT) and eight healthy subjects underwent gait analysis in a stair descent setting. Inverse dynamic analysis was applied to ground reaction forces and marker trajectories using the AnyBody Modeling System. One-dimensional statistical parametric mapping was performed to compare ankle joint reaction force and joint moment curve among groups.Aims
Methods
A recent study used the RAND Corporation at University of California, Los Angeles (RAND/UCLA) method to develop anatomical total shoulder arthroplasty (aTSA) appropriateness criteria. The purpose of our study was to determine how patient-reported outcome measures (PROMs) vary based on appropriateness. Clinical data from a multicentre database identified patients who underwent primary aTSA from November 2004 to January 2023. A total of 390 patients (mean follow-up 48.1 months (SD 42.0)) were included: 97 (24.9%) were classified as appropriate, 218 (55.9%) inconclusive, and 75 (19.2%) inappropriate. Patients were classified as “appropriate”, “inconclusive”, or “inappropriate”, using a modified version of an appropriateness algorithm, which accounted for age, rotator cuff status, mobility, symptomatology, and Walch classification. Multiple pre- and postoperative scores were analyzed using Pearson’s chi-squared test and one-way analysis of variance (ANOVA). Postoperative complications were also analyzed.Aims
Methods
The first metatarsal pronation deformity of hallux valgus feet is widely recognized. However, its assessment relies mostly on 3D standing CT scans. Two radiological signs, the first metatarsal round head (RH) and inferior tuberosity position (ITP), have been described, but are seldom used to aid in diagnosis. This study was undertaken to determine the reliability and validity of these two signs for a more convenient and affordable preoperative assessment and postoperative comparison. A total of 200 feet were randomly selected from the radiograph archives of a foot and ankle clinic. An anteroposterior view of both feet was taken while standing on the same x-ray platform. The intermetatarsal angle (IMA), metatarsophalangeal angle (MPA), medial sesamoid position, RH, and ITP signs were assessed for statistical analysis.Aims
Methods
We sought to compare functional outcomes and survival between non-smokers, former smokers, and current smokers who underwent anatomical total shoulder arthroplasty (aTSA) in a large cohort of patients. A retrospective review of a prospectively collected shoulder arthroplasty database was performed between August 1991 and September 2020 to identify patients who underwent primary aTSA. Patients were excluded for preoperative diagnoses of fracture, infection, or oncological disease. Three cohorts were created based on smoking status: non-smokers, former smokers, and current smokers. Outcome scores (American Shoulder and Elbow Surgeons (ASES), Constant-Murley score, Shoulder Pain and Disability Index (SPADI), Simple Shoulder Test (SST), University of California, Los Angeles activity scale (UCLA)), range of motion (external rotation (ER), forward elevation (FE), internal rotation, abduction), and shoulder strength (ER, FE) evaluated at two- to four-year follow-up were compared between cohorts. Evaluation of revision-free survival was performed using the Kaplan-Meier method to final follow-up.Aims
Methods
This study aims to describe a new method that may be used as a supplement to evaluate humeral rotational alignment during intramedullary nail (IMN) insertion using the profile of the perpendicular peak of the greater tuberosity and its relation to the transepicondylar axis. We called this angle the greater tuberosity version angle (GTVA). This study analyzed 506 cadaveric humeri of adult patients. All humeri were CT scanned using 0.625 × 0.625 × 0.625 mm cubic voxels. The images acquired were used to generate 3D surface models of the humerus. Next, 3D landmarks were automatically calculated on each 3D bone using custom-written C++ software. The anatomical landmarks analyzed were the transepicondylar axis, the humerus anatomical axis, and the peak of the perpendicular axis of the greater tuberosity. Lastly, the angle between the transepicondylar axis and the greater tuberosity axis was calculated and defined as the GTVA.Aims
Methods
The aims were to assess whether joint-specific outcome after total knee arthroplasty (TKA) was influenced by implant design over a 12-year follow-up period, and whether patient-related factors were associated with loss to follow-up and mortality risk. Long-term follow-up of a randomized controlled trial was undertaken. A total of 212 patients were allocated a Triathlon or a Kinemax TKA. Patients were assessed preoperatively, and one, three, eight, and 12 years postoperatively using the Oxford Knee Score (OKS). Reasons for patient lost to follow-up, mortality, and revision were recorded.Aims
Methods
This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated. Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA).Aims
Methods
This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels. A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process.Aims
Methods
This study aimed to analyze kinematics and kinetics of the tibiofemoral joint in healthy subjects with valgus, neutral, and varus limb alignment throughout multiple gait activities using dynamic videofluoroscopy. Five subjects with valgus, 12 with neutral, and ten with varus limb alignment were assessed during multiple complete cycles of level walking, downhill walking, and stair descent using a combination of dynamic videofluoroscopy, ground reaction force plates, and optical motion capture. Following 2D/3D registration, tibiofemoral kinematics and kinetics were compared between the three limb alignment groups.Aims
Methods
Favourable short-term outcomes have been reported following latissimus dorsi tendon transfer for patients with an irreparable subscapularis (SSC) tendon tear. The aim of this study was to investigate the long-term outcomes of this transfer in these patients. This was a retrospective study involving 30 patients with an irreparable SSC tear and those with a SSC tear combined with a reparable supraspinatus tear, who underwent a latissimus dorsi tendon transfer. Clinical scores and active range of motion (aROM), SSC-specific physical examination and the rate of return to work were assessed. Radiological assessment included recording the acromiohumeral distance (AHD), the Hamada grade of cuff tear arthropathy and the integrity of the transferred tendon. Statistical analysis compared preoperative, short-term (two years), and final follow-up at a mean of 8.7 years (7 to 10).Aims
Methods
This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation. In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.Aims
Methods
Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers. We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI.Aims
Methods
Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI). A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR.Aims
Methods
The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice. Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.Aims
Methods
Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.Aims
Methods
This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients. A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry.Aims
Methods
The aim was to assess whether robotic-assisted total knee arthroplasty (rTKA) had greater knee-specific outcomes, improved fulfilment of expectations, health-related quality of life (HRQoL), and patient satisfaction when compared with manual TKA (mTKA). A randomized controlled trial was undertaken (May 2019 to December 2021), and patients were allocated to either mTKA or rTKA. A total of 100 patients were randomized, 50 to each group, of whom 43 rTKA and 38 mTKA patients were available for review at 12 months following surgery. There were no statistically significant preoperative differences between the groups. The minimal clinically important difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score was defined as 7.5 points.Aims
Methods
Refobacin Bone Cement R and Palacos Overall, 75 patients were included in the study and 71 were available at two years postoperatively. Prior to surgery, they were randomized to one of the three combinations studied: Palacos cement with use of the Optivac mixing system, Refobacin with use of the Optivac system, and Refobacin with use of the Optipac system. Cemented MS30 stems and cemented Exceed acetabular components were used in all hips. Postoperative radiographs were used to assess the quality of the cement mantle according to Barrack et al, and the position and migration of the femoral stem. Harris Hip Score, Oxford Hip Score, Forgotten Joint Score, and University of California, Los Angeles Activity Scale were collected.Aims
Methods
Osteosarcoma is the most common primary bone malignancy among children and adolescents. We investigated whether benzamil, an amiloride analogue and sodium-calcium exchange blocker, may exhibit therapeutic potential for osteosarcoma in vitro. MG63 and U2OS cells were treated with benzamil for 24 hours. Cell viability was evaluated with the MTS/PMS assay, colony formation assay, and flow cytometry (forward/side scatter). Chromosome condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay, cleavage of poly-ADP ribose polymerase (PARP) and caspase-7, and FITC annexin V/PI double staining were monitored as indicators of apoptosis. Intracellular calcium was detected by flow cytometry with Fluo-4 AM. The phosphorylation and activation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) were measured by western blot. The expression levels of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xL), SOD1, and SOD2 were also assessed by western blot. Mitochondrial status was assessed with tetramethylrhodamine, ethyl ester (TMRE), and intracellular adenosine triphosphate (ATP) was measured with BioTracker ATP-Red Live Cell Dye. Total cellular integrin levels were evaluated by western blot, and the expression of cell surface integrins was assessed using fluorescent-labelled antibodies and flow cytometry.Aims
Methods
The aim of this study was to characterize the influence of social deprivation on the rate of complications, readmissions, and revisions following primary total shoulder arthroplasty (TSA), using the Social Deprivation Index (SDI). The SDI is a composite measurement, in percentages, of seven demographic characteristics: living in poverty, with < 12 years of education, single-parent households, living in rented or overcrowded housing, households without a car, and unemployed adults aged < 65 years. Patients aged ≥ 40 years, who underwent primary TSA between 2011 and 2017, were identified using International Classification of Diseases (ICD)-9 Clinical Modification and ICD-10 procedure codes for TSA in the New York Statewide Planning and Research Cooperative System database. Readmission, reoperation, and other complications were analyzed using multivariable Cox proportional hazards regression controlling for SDI, age, ethnicity, insurance status, and Charlson Comorbidity Index.Aims
Methods
To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism. In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.Aims
Methods
cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect. CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA).Aims
Methods
Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown. We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators.Aims
Methods
The surgical helmet system (SHS) was developed to reduce the risk of periprosthetic joint infection (PJI), but the evidence is contradictory, with some studies suggesting an increased risk of PJI due to potential leakage through the glove-gown interface (GGI) caused by its positive pressure. We assumed that SHS and glove exchange had an impact on the leakage via GGI. There were 404 arthroplasty simulations with fluorescent gel, in which SHS was used (H+) or not (H-), and GGI was sealed (S+) or not (S-), divided into four groups: H+S+, H+S-, H-S+, and H-S-, varying by exposure duration (15 to 60 minutes) and frequency of glove exchanges (0 to 6 times). The intensity of fluorescent leakage through GGI was quantified automatically with an image analysis software. The effect of the above factors on fluorescent leakage via GGI were compared and analyzed.Aims
Methods
Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Blood and femoral bone marrow suspension Aims
Methods
This prospective study reports longitudinal, within-patient, patient-reported outcome measures (PROMs) over a 15-year period following cemented single radius total knee arthroplasty (TKA). Secondary aims included reporting PROMs trajectory, 15-year implant survival, and patient attrition from follow-up. From 2006 to 2007, 462 consecutive cemented cruciate-retaining Triathlon TKAs were implanted in 426 patients (mean age 69 years (21 to 89); 290 (62.7%) female). PROMs (12-item Short Form Survey (SF-12), Oxford Knee Score (OKS), and satisfaction) were assessed preoperatively and at one, five, ten, and 15 years. Kaplan-Meier survival and univariate analysis were performed.Aims
Methods
The risk factors for abnormal spinopelvic mobility (SPM), defined as an anterior rotation of the spinopelvic tilt (∆SPT) ≥ 20° in a flexed-seated position, have been described. The implication of pelvic incidence (PI) is unclear, and the concept of lumbar lordosis (LL) based on anatomical limits may be erroneous. The distribution of LL, including a unusual shape in patients with a high lordosis, a low pelvic incidence, and an anteverted pelvis seems more relevant. The clinical data of 311 consecutive patients who underwent total hip arthroplasty was retrospectively analyzed. We analyzed the different types of lumbar shapes that can present in patients to identify their potential associations with abnormal pelvic mobility, and we analyzed the potential risk factors associated with a ∆SPT ≥ 20° in the overall population.Aims
Methods
This study aimed to establish the optimal fixation methods for calcaneal tuberosity avulsion fractures with different fragment thicknesses in a porcine model. A total of 36 porcine calcanea were sawed to create simple avulsion fractures with three different fragment thicknesses (5, 10, and 15 mm). They were randomly fixed with either two suture anchors or one headless screw. Load-to-failure and cyclic loading tension tests were performed for the biomechanical analysis.Aims
Methods
The aim of this study was to analyze how proximal radial neck resorption (PRNR) starts and progresses radiologically in two types of press-fit radial head arthroplasties (RHAs), and to investigate its clinical relevance. A total of 97 patients with RHA were analyzed: 56 received a bipolar RHA (Group 1) while 41 received an anatomical implant (Group 2). Radiographs were performed postoperatively and after three, six, nine, and 12 weeks, six, nine, 12, 18, and 24 months, and annually thereafter. PRNR was measured in all radiographs in the four radial neck quadrants. The Mayo Elbow Performance Score (MEPS), the abbreviated version of the Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH), and the patient-assessed American Shoulder and Elbow Surgeons score - Elbow (pASES-E) were used for the clinical assessment. Radiological signs of implant loosening were investigated.Aims
Methods
Rotator cuff muscle atrophy and fatty infiltration affect the clinical outcomes of rotator cuff tear patients. However, there is no effective treatment for fatty infiltration at this time. High-intensity interval training (HIIT) helps to activate beige adipose tissue. The goal of this study was to test the role of HIIT in improving muscle quality in a rotator cuff tear model via the β3 adrenergic receptor (β3AR). Three-month-old C57BL/6 J mice underwent a unilateral rotator cuff injury procedure. Mice were forced to run on a treadmill with the HIIT programme during the first to sixth weeks or seventh to 12th weeks after tendon tear surgery. To study the role of β3AR, SR59230A, a selective β3AR antagonist, was administered to mice ten minutes before each exercise through intraperitoneal injection. Supraspinatus muscle, interscapular brown fat, and inguinal subcutaneous white fat were harvested at the end of the 12th week after tendon tear and analyzed biomechanically, histologically, and biochemically.Aims
Methods
Glenoid bone loss is a significant problem in the management of shoulder instability. The threshold at which the bone loss is considered “critical” requiring bony reconstruction has steadily dropped and is now approximately 15%. This necessitates accurate measurement in order that the correct operation is performed. CT scanning is the most commonly used modality and there are a number of techniques described to measure the bone loss however few have been validated. The aim of this study was to assess the accuracy of the most commonly used techniques for measuring glenoid bone loss on CT. Anatomically accurate models with known glenoid diameter and degree of bone loss were used to determine the mathematical and statistical accuracy of six of the most commonly described techniques (relative diameter, linear ipsilateral circle of best fit (COBF), linear contralateral COBF, Pico, Sugaya, and circle line methods). The models were prepared at 13.8%, 17.6%, and 22.9% bone loss. Sequential CT scans were taken and randomized. Blinded reviewers made repeated measurements using the different techniques with a threshold for theoretical bone grafting set at 15%.Aims
Methods
To assess the incidence of radiological lateral osteoarthritis (OA) at 15 years after medial unicompartmental knee arthroplasty (UKA) and assess the relationship of lateral OA with symptoms and patient characteristics. Cemented Phase 3 medial Oxford UKA implanted by two surgeons since 1998 for the recommended indications were prospectively followed. A 15-year cumulative revision rate for lateral OA of 5% for this series was previously reported. A total of 163 unrevised knees with 15-year (SD 1) anterior-posterior knee radiographs were studied. Lateral joint space width (JSWL) was measured and severity of lateral OA was classified as: nil/mild, moderate, and severe. Preoperative and 15-year Oxford Knee Scores (OKS) and American Knee Society Scores were determined. The effect of age, sex, BMI, and intraoperative findings was analyzed. Statistical analysis included one-way analysis of variance and Kruskal-Wallis H test, with significance set at 5%.Aims
Methods
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
Glucose-insulin-potassium (GIK) is protective following cardiac myocyte ischaemia-reperfusion (IR) injury, however the role of GIK in protecting skeletal muscle from IR injury has not been evaluated. Given the similar mechanisms by which cardiac and skeletal muscle sustain an IR injury, we hypothesized that GIK would similarly protect skeletal muscle viability. A total of 20 C57BL/6 male mice (10 control, 10 GIK) sustained a hindlimb IR injury using a 2.5-hour rubber band tourniquet. Immediately prior to tourniquet placement, a subcutaneous osmotic pump was placed which infused control mice with saline (0.9% sodium chloride) and treated mice with GIK (40% glucose, 50 U/l insulin, 80 mEq/L KCl, pH 4.5) at a rate of 16 µl/hr for 26.5 hours. At 24 hours following tourniquet removal, bilateral (tourniqueted and non-tourniqueted) gastrocnemius muscles were triphenyltetrazolium chloride (TTC)-stained to quantify percentage muscle viability. Bilateral peroneal muscles were used for gene expression analysis, serum creatinine and creatine kinase activity were measured, and a validated murine ethogram was used to quantify pain before euthanasia.Aims
Methods
The aim of the study was to investigate whether the primary stability of press-fit acetabular components can be improved by altering the impaction procedure. Three impaction procedures were used to implant acetabular components into human cadaveric acetabula using a powered impaction device. An impaction frequency of 1 Hz until complete component seating served as reference. Overimpaction was simulated by adding ten strokes after complete component seating. High-frequency implantation was performed at 6 Hz. The lever-out moment of the acetabular components was used as measure for primary stability. Permanent bone deformation was assessed by comparison of double micro-CT (µCT) measurements before and after impaction. Acetabular component deformation and impaction forces were recorded, and the extent of bone-implant contact was determined from 3D laser scans.Aims
Methods
Prior to the availability of vaccines, mortality for hip fracture patients with concomitant COVID-19 infection was three times higher than pre-pandemic rates. The primary aim of this study was to determine the 30-day mortality rate of hip fracture patients in the post-vaccine era. A multicentre observational study was carried out at 19 NHS Trusts in England. The study period for the data collection was 1 February 2021 until 28 February 2022, with mortality tracing until 28 March 2022. Data collection included demographic details, data points to calculate the Nottingham Hip Fracture Score, COVID-19 status, 30-day mortality, and vaccination status.Aims
Methods
Myokine developmental endothelial locus-1 (DEL-1) has been documented to alleviate inflammation and endoplasmic reticulum (ER) stress in various cell types. However, the effects of DEL-1 on inflammation, ER stress, and apoptosis in tenocytes remain unclear. Human primary tenocytes were cultured in palmitate (400 μM) and palmitate plus DEL-1 (0 to 2 μg/ml) conditions for 24 hours. The expression levels of ER stress markers and cleaved caspase 3, as well as phosphorylated 5' adenosine monophosphate-activated protein kinase (AMPK) and autophagy markers, were assessed by Western blotting. Autophagosome formation was measured by staining with monodansylcadaverine, and apoptosis was determined by cell viability assay and caspase 3 activity assay.Aims
Methods
There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN). The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Aims
Methods
The involvement of cyclin D1 in the proliferation of microglia, and the generation and maintenance of bone cancer pain (BCP), have not yet been clarified. We investigated the expression of microglia and cyclin D1, and the influences of cyclin D1 on pain threshold. Female Sprague Dawley (SD) rats were used to establish a rat model of BCP, and the messenger RNA (mRNA) and protein expression of ionized calcium binding adaptor molecule 1 (IBA1) and cyclin D1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blot, respectively. The proliferation of spinal microglia was detected by immunohistochemistry. The pain behaviour test was assessed by quantification of spontaneous flinches, limb use, and guarding during forced ambulation, mechanical paw withdrawal threshold, and thermal paw withdrawal latency.Aims
Methods
Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages. Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot.Aims
Methods
Adult male C57Bl/6 mice (n = 75) were randomized into three groups to receive 1.0 to 1.4 × 107 colony-forming units (CFUs)/ml of 8325-4, DU1090, or saline into the right stifle joint. Chondrocyte death was assessed by confocal microscopy. Histological changes to inoculated joints were graded for inflammatory responses along with gait, weight changes, and limb swelling.Aims
Methods
Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA. Firstly, OA mouse models and interleukin (IL)-1β-induced mouse chondrocytes were established. Expression patterns of IL-38 were determined in the synovial fluid and cartilage tissues from OA patients. Furthermore, the targeting relationship between lncRNA H19, tumour protein p53 (TP53), and IL-38 was determined by means of dual-luciferase reporter gene, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Subsequent to gain- and loss-of-function assays, the levels of cartilage damage and proinflammatory factors were further detected using safranin O-fast green staining and enzyme-linked immunosorbent assay (ELISA) in vivo, respectively, while chondrocyte apoptosis was measured using Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) in vitro.Aims
Methods
Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). Growth differentiation factor 11 (GDF11) is crucial in inhibiting the differentiation of bone marrow mesenchymal stem cells into adipocytes. However, whether GDF11 participates in the abnormal adipogenesis of chondrocytes in OA cartilage is still unclear. Six-week-old female mice were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical staining (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. Primary condylar chondrocytes of rats were stimulated with fluid flow shear stress (FFSS) and collected for oil red staining, immunofluorescence staining, qRT-PCR, and immunoprecipitation analysis.Aims
Methods
Insufficient treatment response in rheumatoid arthritis (RA) patients requires novel treatment strategies to halt disease progression. The potential benefit of combination of cytokine-inhibitors in RA is still unclear and needs further investigation. To explore the impact of combined deficiency of two major cytokines, namely interleukin (IL)-1 and IL-6, in this study double deficient mice for IL-1αβ and IL-6 were investigated in different tumour necrosis factor (TNF)-driven inflammatory bone disorders, namely peripheral arthritis and sacroiliitis, as well as systemic bone loss. Disease course, histopathological features of arthritis, and micro-CT (µCT) bone analysis of local and systemic bone loss were assessed in 15-week-old Aims
Methods
The frequency of severe femoral retroversion is unclear in patients with femoroacetabular impingement (FAI). This study aimed to investigate mean femoral version (FV), the frequency of absolute femoral retroversion, and the combination of decreased FV and acetabular retroversion (AR) in symptomatic patients with FAI subtypes. A retrospective institutional review board-approved observational study was performed with 333 symptomatic patients (384 hips) with hip pain due to FAI evaluated for hip preservation surgery. Overall, 142 patients (165 hips) had cam-type FAI, while 118 patients (137 hips) had mixed-type FAI. The allocation to each subgroup was based on reference values calculated on anteroposterior radiographs. CT/MRI-based measurement of FV (Murphy method) and AV were retrospectively compared among five FAI subgroups. Frequency of decreased FV < 10°, severely decreased FV < 5°, and absolute femoral retroversion (FV < 0°) was analyzed.Aims
Methods
The aim of this study was to explore the relationship between reason for revision total hip arthroplasty (rTHA) and outcomes in terms of patient-reported outcome measures (PROMs). We reviewed a prospective cohort of 647 patients undergoing full or partial rTHA at a single high-volume centre with a minimum of two years’ follow-up. The reasons for revision were classified as: infection; aseptic loosening; dislocation; structural failure; and painful THA for other reasons. PROMs (modified Oxford Hip Score (mOHS), EuroQol five-dimension three-level health questionnaire (EQ-5D-3L) score, and visual analogue scales for pain during rest and activity), complication rates, and failure rates were compared among the groups.Aims
Methods
Osteoarthritis (OA) is a common degenerative joint disease. The osteocyte transcriptome is highly relevant to osteocyte biology. This study aimed to explore the osteocyte transcriptome in subchondral bone affected by OA. Gene expression profiles of OA subchondral bone were used to identify disease-relevant genes and signalling pathways. RNA-sequencing data of a bone loading model were used to identify the loading-responsive gene set. Weighted gene co-expression network analysis (WGCNA) was employed to develop the osteocyte mechanics-responsive gene signature.Aims
Methods
Post-traumatic osteoarthritis (PTOA) is a subset of osteoarthritis (OA). The gut microbiome is shown to be involved in OA. However, the effect of exercise on gut microbiome in PTOA remains elusive. A total of 18 eight-week Sprague-Dawley rats were assigned into three groups: Sham/sedentary (Sham/Sed), PTOA/sedentary (PTOA/Sed), and PTOA/treadmill-walking (PTOA/TW). PTOA model was induced by transection of the anterior cruciate ligament (ACLT) and the destabilization of the medial meniscus (DMM). Treadmill-walking (15 m/min, 30 min/d, five days/week for eight weeks) was employed in the PTOA/TW group. The response of cartilage, subchondral bone, serology, and gut microbiome and their correlations were assessed.Aims
Methods
Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 ( We examined vulnerability of Aims
Methods
The aim of this study was to report the incidence of implant-related complications, further operations, and their influence on the outcome in a series of patients who underwent primary reverse total shoulder arthroplasty (RTSA). The prospectively collected clinical and radiological data of 797 patients who underwent 854 primary RTSAs between January 2005 and August 2018 were analyzed. The hypothesis was that the presence of complications would adversely affect the outcome. Further procedures were defined as all necessary operations, including reoperations without change of components, and partial or total revisions. The clinical outcome was evaluated using the absolute and relative Constant Scores (aCS, rCS), the Subjective Shoulder Value (SSV) scores, range of motion, and pain.Aims
Methods
The aim of this study was to determine whether total hip arthroplasty (THA) for chronic hip pain due to unilateral primary osteoarthritis (OA) has a beneficial effect on cognitive performance. A prospective cohort study was conducted with 101 patients with end-stage hip OA scheduled for THA (mean age 67.4 years (SD 9.5), 51.5% female (n = 52)). Patients were assessed at baseline as well as after three and months. Primary outcome was cognitive performance measured by d2 Test of Attention at six months, Trail Making Test (TMT), FAS-test, Rivermead Behavioural Memory Test (RBMT; story recall subtest), and Rey-Osterrieth Complex Figure Test (ROCF). The improvement of cognitive performance was analyzed using repeated measures analysis of variance.Aims
Methods
The aim of this study was to compare the characteristics and outcomes of L-shaped and reverse L-shaped rotator cuff tears. A total of 82 shoulders (81 patients) after arthroscopic rotator cuff repair were retrospectively enrolled. The mean age of the patients was 62 years (SD 6), 33 shoulders (40.2%) were in male patients, and 57 shoulders (69.5%) were the right shoulder. Of these, 36 shoulders had an L-shaped tear (group L) and 46 had a reverse L-shaped tear (group RL). Both groups were compared regarding characteristics, pre- and postoperative pain, and functional outcomes. Muscle status was assessed by preoperative MRI, and re-tear rates by postoperative ultrasonography or MRI.Aims
Methods
Slipped upper femoral epiphysis (SUFE) has well documented biochemical and mechanical risk factors. Femoral and acetabular morphologies seem to be equally important. Acetabular retroversion has a low prevalence in asymptomatic adults. Hips with dysplasia, osteoarthritis, and Perthes’ disease, however, have higher rates, ranging from 18% to 48%. The aim of our study was to assess the prevalence of acetabular retroversion in patients presenting with SUFE using both validated radiological signs and tomographical measurements. A retrospective review of all SUFE surgical cases presenting to the Royal Children’s Hospital, Melbourne, Australia, from 2012 to 2019 were evaluated. Preoperative plain radiographs were assessed for slip angle, validated radiological signs of retroversion, and standardized postoperative CT scans were used to assess cranial and mid-acetabular version.Aims
Methods
With the ageing population, fragility fractures have become one of the most common conditions. The objective of this study was to investigate whether microbiological outcomes and fracture-healing in osteoporotic bone is worse than normal bone with fracture-related infection (FRI). A total of 120 six-month-old Sprague-Dawley (SD) rats were randomized to six groups: Sham, sham + infection (Sham-Inf), sham with infection + antibiotics (Sham-Inf-A), ovariectomized (OVX), OVX + infection (OVX-Inf), and OVX + infection + antibiotics (OVX-Inf-A). Open femoral diaphysis fractures with Kirschner wire fixation were performed. Aims
Methods
To determine the value of scoliosis surgery, it is necessary to evaluate outcomes in domains that matter to patients. Since randomized trials on adolescent idiopathic scoliosis (AIS) are scarce, prospective cohort studies with comparable outcome measures are important. To enhance comparison, a core set of patient-related outcome measures is available. The aim of this study was to evaluate the outcomes of AIS fusion surgery at two-year follow-up using the core outcomes set. AIS patients were systematically enrolled in an institutional registry. In all, 144 AIS patients aged ≤ 25 years undergoing primary surgery (median age 15 years (interquartile range 14 to 17) were included. Patient-reported (condition-specific and health-related quality of life (QoL); functional status; back and leg pain intensity) and clinician-reported outcomes (complications, revision surgery) were recorded. Changes in patient-reported outcome measures (PROMs) were analyzed using Friedman’s analysis of variance. Clinical relevancy was determined using minimally important changes (Scoliosis Research Society (SRS)-22r), cut-off values for relevant effect on functioning (pain scores) and a patient-acceptable symptom state (PASS; Oswestry Disability Index).Aims
Methods
Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation. The effects of a HSR PEMF signal with three daily treatment durations (0.5, one, and three hours/day) were investigated in an established rat DO model with comparison of an FDA-approved classic signal (three hrs/day). PEMF treatments were applied to the rats daily for 35 days, starting from the distraction phase until termination. Radiography, micro-CT (μCT), biomechanical tests, and histological examinations were employed to evaluate the quality of bone formation.Aims
Methods
Single-shot adductor canal block (ACB) after total knee arthroplasty (TKA) for postoperative analgesia is a common modality. Patients can experience breakthrough pain when the effect of ACB wears off. Local anaesthetic infusion through an intra-articular catheter (IAC) can help manage breakthrough pain after TKA. We hypothesized that combined ACB with ropivacaine infusion through IAC is associated with better pain relief compared to ACB used alone. This study was a prospective double-blinded placebo-controlled randomized controlled trial to compare the efficacy of combined ACB+ IAC-ropivacaine infusion (study group, n = 68) versus single-shot ACB+ intra-articular normal saline placebo (control group, n = 66) after primary TKA. The primary outcome was assessment of pain, using the visual analogue scale (VAS) recorded at 6, 12, 24, and 48 hours after surgery. Secondary outcomes included active knee ROM 48 hours after surgery and additional requirement of analgesia for breakthrough pain.Aims
Methods
Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) have been reported to be a promising cellular therapeutic approach for various human diseases. The current study aimed to investigate the mechanism of BMSC-derived exosomes carrying microRNA (miR)-136-5p in fracture healing. A mouse fracture model was initially established by surgical means. Exosomes were isolated from BMSCs from mice. The endocytosis of the mouse osteoblast MC3T3-E1 cell line was analyzed. CCK-8 and disodium phenyl phosphate microplate methods were employed to detect cell proliferation and alkaline phosphatase (ALP) activity, respectively. The binding of miR-136-5p to low-density lipoprotein receptor related protein 4 (LRP4) was analyzed by dual luciferase reporter gene assay. HE staining, tartrate-resistant acid phosphatase (TRAP) staining, and immunohistochemistry were performed to evaluate the healing of the bone tissue ends, the positive number of osteoclasts, and the positive expression of β-catenin protein, respectively.Aims
Methods
The aim of this study was to identify the minimal clinically important difference (MCID), minimal important change (MIC), minimal detectable change (MDC), and patient-acceptable symptom state (PASS) in the Forgotten Joint Score (FJS) according to patient satisfaction six months following total hip arthroplasty (THA) in a UK population. During a one-year period, 461 patients underwent a primary THA and completed preoperative and six-month FJS, with a mean age of 67.2 years (22 to 93). At six months, patient satisfaction was recorded as very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied. The difference between patients recording neutral (n = 31) and satisfied (n = 101) was used to define the MCID. MIC for a cohort was defined as the change in the FJS for those patients declaring their outcome as satisfied, whereas receiver operating characteristic curve analysis was used to determine the MIC for an individual and the PASS. Distribution-based methodology was used to calculate the MDC.Aims
Methods
This study investigates head-neck taper corrosion with varying head size in a novel hip simulator instrumented to measure corrosion related electrical activity under torsional loads. In all, six 28 mm and six 36 mm titanium stem-cobalt chrome head pairs with polyethylene sockets were tested in a novel instrumented hip simulator. Samples were tested using simulated gait data with incremental increasing loads to determine corrosion onset load and electrochemical activity. Half of each head size group were then cycled with simulated gait and the other half with gait compression only. Damage was measured by area and maximum linear wear depth.Aims
Methods
Cam and pincer morphologies are potential precursors to hip osteoarthritis and important contributors to non-arthritic hip pain. However, only some hips with these pathomorphologies develop symptoms and joint degeneration, and it is not clear why. Anterior impingement between the femoral head-neck contour and acetabular rim in positions of hip flexion combined with rotation is a proposed pathomechanism in these hips, but this has not been studied in active postures. Our aim was to assess the anterior impingement pathomechanism in both active and passive postures with high hip flexion that are thought to provoke impingement. We recruited nine participants with cam and/or pincer morphologies and with pain, 13 participants with cam and/or pincer morphologies and without pain, and 11 controls from a population-based cohort. We scanned hips in active squatting and passive sitting flexion, adduction, and internal rotation using open MRI and quantified anterior femoroacetabular clearance using the β angle.Aims
Methods
Pelvic incidence (PI) is considered an important anatomical parameter for determining the sagittal balance of the spine. The contribution of an abnormal PI to hip osteoarthritis (OA) remains controversial. In this study, we aimed to investigate the relationship between PI and hip OA, and the difference in PI between hip OA without anatomical abnormalities (primary OA) and hip OA with developmental dysplasia of the hip (DDH-OA). In this study, 100 patients each of primary OA, DDH-OA, and control subjects with no history of hip disease were included. CT images were used to measure PI, sagittal femoral head coverage, α angle, and acetabular anteversion. PI was also subdivided into three categories: high PI (larger than 64.0°), medium PI (42.0° to 64.0°), and low PI (less than 42.0°). The anterior centre edge angles, posterior centre edge angles, and total sagittal femoral head coverage were measured. The correlations between PI and sagittal femoral head coverage, α angle, and acetabular anteversion were examined.Aims
Methods
Pelvic tilt (PT) can significantly change the functional orientation of the acetabular component and may differ markedly between patients undergoing total hip arthroplasty (THA). Patients with stiff spines who have little change in PT are considered at high risk for instability following THA. Femoral component position also contributes to the limits of impingement-free range of motion (ROM), but has been less studied. Little is known about the impact of combined anteversion on risk of impingement with changing pelvic position. We used a virtual hip ROM (vROM) tool to investigate whether there is an ideal functional combined anteversion for reduced risk of hip impingement. We collected PT information from functional lateral radiographs (standing and sitting) and a supine CT scan, which was then input into the vROM tool. We developed a novel vROM scoring system, considering both seated flexion and standing extension manoeuvres, to quantify whether hips had limited ROM and then correlated the vROM score to component position.Aims
Methods
The effect of pelvic tilt (PT) and sagittal balance in hips with pincer-type femoroacetabular impingement (FAI) with acetabular retroversion (AR) is controversial. It is unclear if patients with AR have a rotational abnormality of the iliac wing. Therefore, we asked: are parameters for sagittal balance, and is rotation of the iliac wing, different in patients with AR compared to a control group?; and is there a correlation between iliac rotation and acetabular version? A retrospective, review board-approved, controlled study was performed including 120 hips in 86 consecutive patients with symptomatic FAI or hip dysplasia. Pelvic CT scans were reviewed to calculate parameters for sagittal balance (pelvic incidence (PI), PT, and sacral slope), anterior pelvic plane angle, pelvic inclination, and external rotation of the iliac wing and were compared to a control group (48 hips). The 120 hips were allocated to the following groups: AR (41 hips), hip dysplasia (47 hips) and cam FAI with normal acetabular morphology (32 hips). Subgroups of total AR (15 hips) and high acetabular anteversion (20 hips) were analyzed. Statistical analysis was performed using analysis of variance with Bonferroni correction.Aims
Methods
The aim of this study was to compare the clinical outcomes of robotic arm-assisted bi-unicompartmental knee arthroplasty (bi-UKA) with conventional mechanically aligned total knee arthroplasty (TKA) during the first six weeks and at one year postoperatively. A per protocol analysis of 76 patients, 43 of whom underwent TKA and 34 of whom underwent bi-UKA, was performed from a prospective, single-centre, randomized controlled trial. Diaries kept by the patients recorded pain, function, and the use of analgesics daily throughout the first week and weekly between the second and sixth weeks. Patient-reported outcome measures (PROMs) were compared preoperatively, and at three months and one year postoperatively. Data were also compared longitudinally and a subgroup analysis was conducted, stratified by preoperative PROM status.Aims
Methods
In total knee arthroplasty (TKA), blood loss continues internally after surgery is complete. Typically, the total loss over 48 postoperative hours can be around 1,300 ml, with most occurring within the first 24 hours. We hypothesize that the full potential of tranexamic acid (TXA) to decrease TKA blood loss has not yet been harnessed because it is rarely used beyond the intraoperative period, and is usually withheld from ‘high-risk’ patients with a history of thromboembolic, cardiovascular, or cerebrovascular disease, a patient group who would benefit greatly from a reduced blood loss. TRAC-24 was a prospective, phase IV, single-centre, open label, parallel group, randomized controlled trial on patients undergoing TKA, including those labelled as high-risk. The primary outcome was indirect calculated blood loss (IBL) at 48 hours. Group 1 received 1 g intravenous (IV) TXA at the time of surgery and an additional 24-hour postoperative oral regime of four 1 g doses, while Group 2 only received the intraoperative dose and Group 3 did not receive any TXA.Aims
Methods
To evaluate the effect of ultrasound-targeted simvastatin-loaded microbubble destruction (UTMD In vitro, OA chondrocytes were treated with ultrasound (US), US-targeted microbubble destruction (UTMD), simvastatin (SV), and UTMDAims
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
This study assesses patient barriers to successful telemedicine care in orthopaedic practices in a large academic practice in the COVID-19 era. In all, 381 patients scheduled for telemedicine visits with three orthopaedic surgeons in a large academic practice from 1 April 2020 to 12 June 2020 were asked to participate in a telephone survey using a standardized Institutional Review Board-approved script. An unsuccessful telemedicine visit was defined as patient-reported difficulty of use or reported dissatisfaction with teleconferencing. Patient barriers were defined as explicitly reported barriers of unsatisfactory visit using a process-based satisfaction metric. Statistical analyses were conducted using analysis of variances (ANOVAs), ranked ANOVAs, post-hoc pairwise testing, and chi-squared independent analysis with 95% confidence interval.Aims
Methods
Orthopaedic infection is a potentially serious complication of elective and emergency trauma and orthopaedic procedures, with a high associated burden of morbidity and cost. Optimization of vitamin D levels has been postulated to be beneficial in the prevention of orthopaedic infection. This study explores the role of vitamin D in orthopaedic infection through a systematic review of available evidence. A comprehensive search was conducted on databases including Medline and Embase, as well as grey literature such as Google Scholar and The World Health Organization Database. Pooled analysis with weighted means was undertaken.Aims
Methods
This study aimed to describe preoperative waiting times for surgery in hip fracture patients in Norway, and analyze factors affecting waiting time and potential negative consequences of prolonged waiting time. Overall, 37,708 hip fractures in the Norwegian Hip Fracture Register from January 2014 to December 2018 were linked with data in the Norwegian Patient Registry. Hospitals treating hip fractures were characterized according to their hip fracture care. Waiting time (hours from admission to start of surgery), surgery within regular working hours, and surgery on the day of or on the day after admission, i.e. ‘expedited surgery’ were estimated.Aims
Methods
MicroRNA-183 ( Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (Aims
Methods
Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model. Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 μl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (μCT) and histological studies.Aims
Methods
MRI has been suggested as an objective method of assessing anterior crucate ligament (ACL) graft “ligamentization” after reconstruction. It has been proposed that the MRI appearances could be used as an indicator of graft maturity and used as part of a return-to-sport assessment. The aim of this study was to evaluate the correlation between MRI graft signal and postoperative functional scores, anterior knee laxity, and patient age at operation. A consecutive cohort of 149 patients who had undergone semitendinosus autograft ACL reconstruction, using femoral and tibial adjustable loop fixations, were evaluated retrospectively postoperatively at two years. All underwent MRI analysis of the ACL graft, performed using signal-to-noise quotient (SNQ) and the Howell score. Functional outcome scores (Lysholm, Tegner, International Knee Documentation Committee (IKDC) subjective, and IKDC objective) were obtained and all patients underwent instrumented side-to-side anterior laxity differential laxity testing.Aims
Methods
The aim of this study was to describe a quantitative 3D CT method to measure rotator cuff muscle volume, atrophy, and balance in healthy controls and in three pathological shoulder cohorts. In all, 102 CT scans were included in the analysis: 46 healthy, 21 cuff tear arthropathy (CTA), 18 irreparable rotator cuff tear (IRCT), and 17 primary osteoarthritis (OA). The four rotator cuff muscles were manually segmented and their volume, including intramuscular fat, was calculated. The normalized volume (NV) of each muscle was calculated by dividing muscle volume to the patient’s scapular bone volume. Muscle volume and percentage of muscle atrophy were compared between muscles and between cohorts.Aims
Methods
Osteoarthritis (OA) is characterized by persistent destruction of articular cartilage. It has been found that microRNAs (miRNAs) are closely related to the occurrence and development of OA. The purpose of the present study was to investigate the mechanism of miR-486 in the development and progression of OA. The expression levels of miR-486 in cartilage were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN), matrix metalloproteinase (MMP)-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4) in SW1353 cells at both messenger RNA (mRNA) and protein levels was determined by qRT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA). Double luciferase reporter gene assay, qRT-PCR, and western blot assay were used to determine whether silencing information regulator 6 (SIRT6) was involved in miR-486 induction of chondrocyte-like cells to a more catabolic phenotype.Aims
Methods
Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model. The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA).Aims
Methods
Hip arthroplasty does not always restore normal anatomy. This is due to inaccurate surgery or lack of stem sizes. We evaluated the aptitude of four total hip arthroplasty systems to restore an anatomical and medialized hip rotation centre. Using 3D templating software in 49 CT scans of non-deformed femora, we virtually implanted: 1) small uncemented calcar-guided stems with two offset options (Optimys, Mathys), 2) uncemented straight stems with two offset options (Summit, DePuy Synthes), 3) cemented undersized stems (Exeter philosophy) with three offset options (CPT, ZimmerBiomet), and 4) cemented line-to-line stems (Kerboul philosophy) with proportional offsets (Centris, Mathys). We measured the distance between the templated and the anatomical and 5 mm medialized hip rotation centre.Aims
Methods
A typical pattern of blood loss associated with total hip arthroplasty (THA) is 200 ml intraoperatively and 1.3 l in the first 48 postoperative hours. Tranexamic acid (TXA) is most commonly given as a single preoperative dose only and is often withheld from patients with a history of thromboembolic disease as they are perceived to be “high-risk” with respect to postoperative venous thromboembolism (VTE). The TRanexamic ACid for 24 hours trial (TRAC-24) aimed to identify if an additional 24-hour postoperative TXA regime could further reduce blood loss beyond a once-only dose at the time of surgery, without excluding these high-risk patients. TRAC-24 was a prospective, phase IV, single centre, open label, parallel group, randomized controlled trial (RCT) involving patients undergoing primary unilateral elective THA. The primary outcome measure was the indirect calculated blood loss (IBL) at 48 hours. The patients were randomized into three groups. Group 1 received 1 g intravenous (IV) TXA at the time of surgery and an additional oral regime for 24 hours postoperatively, group 2 only received the intraoperative dose, and group 3 did not receive any TXA.Aims
Methods
Open tibial fractures are limb-threatening injuries. While limb loss is rare in children, deep infection and nonunion rates of up to 15% and 8% are reported, respectively. We manage these injuries in a similar manner to those in adults, with a combined orthoplastic approach, often involving the use of vascularised free flaps. We report the orthopaedic and plastic surgical outcomes of a consecutive series of patients over a five-year period, which includes the largest cohort of free flaps for trauma in children to date. Data were extracted from medical records and databases for patients with an open tibial fracture aged < 16 years who presented between 1 May 2014 and 30 April 2019. Patients who were transferred from elsewhere were excluded, yielding 44 open fractures in 43 patients, with a minimum follow-up of one year. Management was reviewed from the time of injury to discharge. Primary outcome measures were the rate of deep infection, time to union, and the Modified Enneking score.Aims
Methods
The purpose of this study was to examine the efficacy and safety of carbazochrome sodium sulfonate (CSS) combined with tranexamic acid (TXA) on blood loss and inflammatory responses after primary total hip arthroplasty (THA), and to investigate the influence of different administration methods of CSS on perioperative blood loss during THA. This study is a randomized controlled trial involving 200 patients undergoing primary unilateral THA. A total of 200 patients treated with intravenous TXA were randomly assigned to group A (combined intravenous and topical CSS), group B (topical CSS), group C (intravenous CSS), or group D (placebo).Aims
Methods
The objective of this study is to assess the use of ultrasound (US) as a radiation-free imaging modality to reconstruct 3D anatomy of the knee for use in preoperative templating in knee arthroplasty. Using an US system, which is fitted with an electromagnetic (EM) tracker that is integrated into the US probe, allows 3D tracking of the probe, femur, and tibia. The raw US radiofrequency (RF) signals are acquired and, using real-time signal processing, bone boundaries are extracted. Bone boundaries and the tracking information are fused in a 3D point cloud for the femur and tibia. Using a statistical shaping model, the patient-specific surface is reconstructed by optimizing bone geometry to match the point clouds. An accuracy analysis was conducted for 17 cadavers by comparing the 3D US models with those created using CT. US scans from 15 users were compared in order to examine the effect of operator variability on the output.Aims
Methods
Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI. In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI.Aims
Methods
The morphology of medial malleolar fracture is highly variable and difficult to characterize without 3D reconstruction. There is also no universally accepeted classification system. Thus, we aimed to characterize fracture patterns of the medial malleolus and propose a classification scheme based on 3D CT reconstruction. We retrospectively reviewed 537 consecutive cases of ankle fractures involving the medial malleolus treated in our institution. 3D fracture maps were produced by superimposing all the fracture lines onto a standard template. We sliced fracture fragments and the standard template based on selected sagittal and coronal planes to create 2D fracture maps, where angles α and β were measured. Angles α and β were defined as the acute angles formed by the fracture line and the horizontal line on the selected planes.Aims
Methods
Periprosthetic joint infections (PJIs) are among the most devastating complications after joint arthroplasty. There is limited evidence on the efficacy of different antiseptic solutions on reducing biofilm burden. The purpose of the present study was to test the efficacy of different antiseptic solutions against clinically relevant microorganisms in biofilm. We conducted an in vitro study examining the efficacy of several antiseptic solutions against clinically relevant microorganisms. We tested antiseptic irrigants against nascent (four-hour) and mature (three-day) single-species biofilm created in vitro using a drip-flow reactor model.Aims
Methods
The aim of this study was to assess orthopaedic oncologic patient morbidity resulting from COVID-19 related institutional delays and surgical shutdowns during the first wave of the pandemic in New York, USA. A single-centre retrospective observational study was conducted of all orthopaedic oncologic patients undergoing surgical evaluation from March to June 2020. Patients were prioritized as level 0-IV, 0 being elective and IV being emergent. Only priority levels 0 to III were included. Delay duration was measured in days and resulting morbidities were categorized into seven groups: prolonged pain/disability; unplanned preoperative radiation and/or chemotherapy; local tumour progression; increased systemic disease; missed opportunity for surgery due to progression of disease/lost to follow up; delay in diagnosis; and no morbidity.Aims
Methods
The primary objective was to determine the incidence of COVID-19 infection and 30-day mortality in patients undergoing foot and ankle surgery during the global pandemic. Secondary objectives were to determine if there was a change in infection and complication profile with changes introduced in practice. This UK-based multicentre retrospective national audit studied foot and ankle patients who underwent surgery between 13 January and 31 July 2020, examining time periods pre-UK national lockdown, during lockdown (23 March to 11 May 2020), and post-lockdown. All adult patients undergoing foot and ankle surgery in an operating theatre during the study period were included. A total of 43 centres in England, Scotland, Wales, and Northern Ireland participated. Variables recorded included demographic data, surgical data, comorbidity data, COVID-19 and mortality rates, complications, and infection rates.Aims
Methods
The aims of the study were to analyze differences in surgical and oncological outcomes, as well as quality of life (QoL) and function in patients with ankle sarcomas undergoing three forms of surgical treatment, minor or major limb salvage surgery (LSS), or amputation. A total of 69 patients with ankle sarcomas, treated between 1981 and 2017 at two tumour centres, were retrospectively reviewed (mean age at surgery: 46.3 years (SD 22.0); 31 females (45%)). Among these 69 patients 25 were analyzed prospectively (mean age at latest follow-up: 61.2 years (SD 20.7); 11 females (44%)), and assessed for mobility using the Prosthetic Limb Users Survey of Mobility (PLUS-M; for amputees only), the Toronto Extremity Salvage Score (TESS), and the University of California, Los Angeles (UCLA) Activity Score. Individual QoL was evaluated in these 25 patients using the five-level EuroQol five-dimension (EQ-5D-5L) and Fragebogen zur Lebenszufriedenheit/Questions on Life Satisfaction (FLZ).Aims
Methods
Minimally invasive fixation of pelvic fragility fractures is recommended to reduce pain and allow early mobilization. The purpose of this study was to evaluate the outcome of two different stabilization techniques in bilateral fragility fractures of the sacrum (BFFS). A non-randomized, prospective study was carried out in a level 1 trauma centre. BFFS in 61 patients (mean age 80 years (SD 10); four male, 57 female) were treated surgically with bisegmental transsacral stablization (BTS; n = 41) versus spinopelvic fixation (SP; n = 20). Postoperative full weightbearing was allowed. The outcome was evaluated at two timepoints: discharge from inpatient treatment (TP1; Fitbit tracking, Zebris stance analysis), and ≥ six months (TP2; Fitbit tracking, Zebris analysis, based on modified Oswestry Disability Index (ODI), Majeed Score (MS), and the 12-Item Short Form Survey 12 (SF-12). Fracture healing was assessed by CT. The primary outcome parameter of functional recovery was the per-day step count; the secondary parameter was the subjective outcome assessed by questionnaires.Aims
Methods
In orthopaedic and trauma surgery, implant-associated infections are increasingly treated with local application of antibiotics, which allows a high local drug concentration to be reached without eliciting systematic adverse effects. While ceftriaxone is a widely used antibiotic agent that has been shown to be effective against musculoskeletal infections, high local concentrations may harm the surrounding tissue. This study investigates the acute and subacute cytotoxicity of increasing ceftriaxone concentrations as well as their influence on the osteogenic differentiation of human bone progenitor cells. Human preosteoblasts were cultured in presence of different concentrations of ceftriaxone for up to 28 days and potential cytotoxic effects, cell death, metabolic activity, cell proliferation, and osteogenic differentiation were studied.Aims
Methods
Hip reconstruction after resection of a periacetabular chondrosarcoma is complex and associated with a high rate of complications. Previous reports have compared no reconstruction with historical techniques that are no longer used. The aim of this study was to compare the results of tantalum acetabular reconstruction to both historical techniques and no reconstruction. We reviewed 66 patients (45 males and 21 females) with a mean age of 53 years (24 to 81) who had undergone acetabular resection for chondrosarcoma. A total of 36 patients (54%) underwent acetabular reconstruction, most commonly with a saddle prosthesis (n = 13; 36%) or a tantalum total hip arthroplasty (THA) (n = 10; 28%). Mean follow-up was nine years (SD 4).Aims
Methods
For many designs of total knee arthroplasty (TKA) it remains unclear whether cemented or uncemented fixation provides optimal long-term survival. The main limitation in most studies is a retrospective or non-comparative study design. The same is true for comparative trials looking only at the survival rate as extensive sample sizes are needed to detect true differences in fixation and durability. Studies using radiostereometric analysis (RSA) techniques have shown to be highly predictive in detecting late occurring aseptic loosening at an early stage. To investigate the difference in predicted long-term survival between cemented, uncemented, and hybrid fixation of TKA, we performed a randomized controlled trial using RSA. A total of 105 patients were randomized into three groups (cemented, uncemented, and hybrid fixation of the ACS Mobile Bearing (ACS MB) knee system, implantcast). RSA examinations were performed on the first day after surgery and at scheduled follow-up visits at three months, six months, one year, and two years postoperatively. Patient-reported outcome measures (PROMs) were obtained preoperatively and after two years follow-up. Patients and follow-up investigators were blinded for the result of randomization.Aims
Methods
Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI). Blood and synovial fluid samples were collected prospectively from 195 patients undergoing primary or revision hip and knee arthroplasty. Patients were divided into five groups: 1) primary total hip and knee arthroplasty performed due to idiopathic osteoarthritis (OA; n = 60); 2) revision hip and knee arthroplasty performed due to aseptic failure of the implant (AR-TJR; n = 40); 3) patients with a confirmed diagnosis of chronic PJI awaiting surgery (n = 45); 4) patients who have finished the first stage of the PJI treatment with the use of cemented spacer and were qualified for replantation procedure (SR-TJR; n = 25), and 5) patients with rheumatoid arthritis undergoing primary total hip and knee arthroplasty (RA; n = 25). CLP concentrations were measured quantitatively in the blood and synovial fluid using an immunoturbidimetric assay. Additionally, blood and synovial CRP, blood interleukin-6 (IL-6), and ESR were measured, and a leucocyte esterase (LE) strip test was performed.Aims
Methods
Biofilm formation is one of the primary reasons for the difficulty in treating implant-related infections (IRIs). Focused high-energy extracorporeal shockwave therapy (fhESWT), which is a treatment modality for fracture nonunions, has been shown to have a direct antibacterial effect on planktonic bacteria. The goal of the present study was to investigate the effect of fhESWT on
Aims
Methods
The prevalence of combined abnormalities of femoral torsion (FT) and tibial torsion (TT) is unknown in patients with femoroacetabular impingement (FAI) and hip dysplasia. This study aimed to determine the prevalence of combined abnormalities of FT and TT, and which subgroups are associated with combined abnormalities of FT and TT. We retrospectively evaluated symptomatic patients with FAI or hip dysplasia with CT scans performed between September 2011 and September 2016. A total of 261 hips (174 patients) had a measurement of FT and TT. Their mean age was 31 years (SD 9), and 63% were female (165 hips). Patients were compared to an asymptomatic control group (48 hips, 27 patients) who had CT scans including femur and tibia available for analysis, which had been acquired for nonorthopaedic reasons. Comparisons were conducted using analysis of variance with Bonferroni correction.Aims
Methods
Gender bias and sexual discrimination (GBSD) have been widely recognized across a range of fields and are now part of the wider social consciousness. Such conduct can occur in the medical workplace, with detrimental effects on recipients. The aim of this review was to identify the prevalence and impact of GBSD in orthopaedic surgery, and to investigate interventions countering such behaviours. A systematic review was conducted by searching Medline, EMCARE, CINAHL, PsycINFO, and the Cochrane Library Database in April 2020, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to which we adhered. Original research papers pertaining to the prevalence and impact of GBSD, or mitigating strategies, within orthopaedics were included for review.Aims
Methods
Osteoarthritis (OA) is a disabling joint disorder and mechanical loading is an important pathogenesis. This study aims to investigate the benefits of less mechanical loading created by intermittent tail suspension for knee OA. A post-traumatic OA model was established in 20 rats (12 weeks old, male). Ten rats were treated with less mechanical loading through intermittent tail suspension, while another ten rats were treated with normal mechanical loading. Cartilage damage was determined by gross appearance, Safranin O/Fast Green staining, and immunohistochemistry examinations. Subchondral bone changes were analyzed by micro-CT and tartrate-resistant acid phosphatase (TRAP) staining, and serum inflammatory cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA).Aims
Methods
To determine whether half-threaded screw holes in a new titanium locking plate design can substantially decrease the notch effects of the threads and increase the plate fatigue life. Three types (I to III) of titanium locking plates were fabricated to simulate plates used in the femur, tibia, and forearm. Two copies of each were fabricated using full- and half-threaded screw holes (called A and B, respectively). The mechanical strengths of the plates were evaluated according to the American Society for Testing and Materials (ASTM) F382-14, and the screw stability was assessed by measuring the screw removal torque and bending strength.Aims
Methods
The aim of this study is to test the hypothesis that three grades of sagittal compensation for standing posture (normal, compensated, and decompensated) correlate with health-related quality of life measurements (HRQOL). A total of 50 healthy volunteers (normal), 100 patients with single-level lumbar degenerative spondylolisthesis (LDS), and 70 patients with adult to elderly spinal deformity (deformity) were enrolled. Following collection of demographic data and HRQOL measured by the Scoliosis Research Society-22r (SRS-22r), radiological measurement by the biplanar slot-scanning full body stereoradiography (EOS) system was performed simultaneously with force-plate measurements to obtain whole body sagittal alignment parameters. These parameters included the offset between the centre of the acoustic meatus and the gravity line (CAM-GL), saggital vertical axis (SVA), T1 pelvic angle (TPA), McGregor slope, C2-7 lordosis, thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), PI-LL, sacral slope (SS), pelvic tilt (PT), and knee flexion. Whole spine MRI examination was also performed. Cluster analysis of the SRS-22r scores in the pooled data was performed to classify the subjects into three groups according to the HRQOL, and alignment parameters were then compared among the three cluster groups.Aims
Methods
Platelet concentrates, like platelet-rich plasma (PRP) and platelet lysate (PL), are widely used in regenerative medicine, especially in bone regeneration. However, the lack of standard procedures and controls leads to high variability in the obtained results, limiting their regular clinical use. Here, we propose the use of platelet-derived extracellular vesicles (EVs) as an off-the-shelf alternative for PRP and PL for bone regeneration. In this article, we evaluate the effect of PL-derived EVs on the biocompatibility and differentiation of mesenchymal stromal cells (MSCs). EVs were obtained first by ultracentrifugation (UC) and then by size exclusion chromatography (SEC) from non-activated PL. EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and the expression of CD9 and CD63 markers by western blot. The effect of the obtained EVs on osteoinduction was evaluated in vitro on human umbilical cord MSCs by messenger RNA (mRNA) expression analysis of bone markers, alkaline phosphatase activity (ALP), and calcium (Ca2+) content.Aims
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