To investigate differences in the drop vertical jump height in female adolescents with an ACL injury and healthy controls and the contribution of each limb in this task. Forty female adolescents with an ACL injury (ACLi, 15.2 ± 1.4 yrs, 164.6 ± 6.0 cm, 63.1 ± 10.0 kg) and thirty-nine uninjured (CON, 13.2 ± 1.7 yrs, 161.7 ± 8.0 cm, 50.6 ± 11.0 kg) were included in this study. A 10-camera infrared motion analysis system (Vicon, Nexus, Oxford, UK) tracked pelvis, thigh, shank, and foot kinematics at 200Hz, while the participants performed 3 trials of double-legged drop vertical jumps (DVJ) on two force plates (Bertec Corp., Columbus, USA) sampled at 2000Hz.The maximum jump height normalised by dominant leg length was compared between groups using independent samples t-test. The maximum vertical ground reaction force (GRFz) and sagittal ankle, knee and hip velocities before take-off were compared between limbs in both groups, using paired samples t-test. The normalised jump height was 11% lower in the ACLi than in the CON (MD=0.04 cm, p=0.020). In the ACLi, the maximum GRFz (MD=46.17N) and the maximum velocities of ankle plantar flexion (MD=79.83°/s), knee extension (MD=85.80°/s), and hip extension (MD=36.08°/s) were greater in the non-injured limb, compared to the injured limb. No differences between limbs were found in the CON. ACL injured female adolescents jump lower than the healthy controls and have greater contribution of their non-injured limb, compared to their injured limb, in the DVJ task. Clinicians should investigate differences in the contribution between limbs during double-legged drop vertical jump when assessing patients with an ACL injury, as this could help identify asymmetries, and potentially improve treatment, criteria used to clear athletes to sport, and re-injury prevention

To investigate if the countermovement jump height differs between ACL injured and uninjured female adolescents and to explore kinematic differences between limbs. Additionally, the association between isometric knee extension strength and jump height was investigated. Thirty-one ACL injured female adolescents (ACLi, 15.3 ± 1.4yrs, 163.9 ± 6.6cm, 63.0 ± 9.3kg) and thirty-eight uninjured (CON, 13.2±1.7yrs, 161.7 ± 8.1cm, 50.6 ± 11.1kg) participated in this study. All participants performed a countermovement jump task, with 3D kinematics collected using a motion analysis system (Vicon, Nexus, Oxford, UK) at 200Hz, and a maximum isometric knee extension task on an isokinetic dynamometer (Biodex Medical Systems, New York, USA) for three trials. The peak torque was extracted from the isometric trials. Independent samples t-test compared the maximum jump height normalised by the dominant leg length between groups, paired samples t-test compared the maximum hip and knee extension and ankle plantar flexion velocities before take-off between limbs in both groups, and a Pearson's correlation test investigated the association between the isometric knee extension strength and jump height. The ACLi jumped 13% lower compared to the CON (p=0.022). In the ACLi, the maximum hip and knee extension and ankle plantar flexion velocities were greater in the non-injured limb, compared to the injured limb; however, no differences between limbs were found in the CON. The isometric knee extension strength of both limbs was positively correlated with jump height (limb 1: r=0.329; p=0.006, and limb 2: r=0.386; p=0.001; whereas limb 1 corresponds to the ACLi injured limb and CON non-dominant limb, and limb 2 to the ACLi non-injured limb and CON dominant limb). ACL injured female adolescents present lower jump height than controls and greater contribution of their non-injured limb, compared to their injured limb, during a countermovement jump task. Also, current results indicate that jump height is positively related to isometric knee extension strength measure

Rotator cuff repair has excellent clinical outcomes but continues to be a challenge when it comes to large and massive tears as well as revision procedures. Reported symptomatic retear rates are still too high to be acceptable. The purpose of the present study was to evaluate the effectiveness of a combination of augmentation techniques consisting of microfractures of the greater tuberosity, extracellular matrix (ECM) patch graft and subsequent platelet concentrate (PC) subacromial injections in revision rotator cuff repair. The study was designed as a retrospective comparative study on prospectively collected data from a consecutive cohort of patients. All patients who underwent arthroscopic revision rotator cuff repair for symptomatic failure of previous posterosuperior rotator cuff repair were considered eligible for the study. Symptomatic failure had been diagnosed according to clinical examination and confirmed by magnetic resonance imaging (MRI). Structural integrity had been assessed on MRI and classified according to Sugaya classification. Only patients affected by stage IV-V were considered eligible. Tear reparability was confirmed during arthroscopy. Only patients with a minimum 2 years follow-up were included. Patients were divided in two groups. In group 1 (control group) a standard arthroscopic revision and microfractures of the greater tuberosity were performed; in group 2 (experimental group), microfractures of the greater tuberosity and a ECM patch graft were used to enhance tendon repair, followed by postoperative PC injections. Minimum follow-up was 12 months. Primary outcome was the Constant-Murley score (CMS) normalized for age and gender. Subjective outcome was assessed with the Disabilities of the Arm, Shoulder and Hand (DASH) score in its short version (Quick-DASH). Tendon integrity was assessed with MRI at 6 months after surgery. Comparison between groups for all discrete variables at baseline and at follow-up was carried out with the Student's t-test for normally distributed data, otherwise Mann-Whitney U-test was used. Within-group differences (baseline vs follow-up) for discrete variables were analyzed by paired t-test, or by Wilcoxon signed-rank test in case of data with non-normal distribution. Differences for categorical variables were assessed by chi-squared test. Significance was considered for p values < 0.05. Forty patients were included in the study (20 patients for each group). The mean follow-up was 13 ± 1.6 months. No patients were lost at the follow up. Comparison between groups did not show significant differences for baseline characteristics. At follow-up, mean CMS was 80.7 ± 16.6 points in group 1 and 91.5 ± 11.5 points in group 2 (p= 0.022). Mean DASH score was 28.6 ± 21.6 points in group 1 and 20.1 ± 17.4 points in group 2 (p= 0.178). Post-operative MRI showed 6 healed shoulders in Group 1 and 16 healed shoulders in Group 2 (p<0.004). No postoperative complications were reported in both groups. The combination of microfractures of the greater tuberosity, ECM patch graft, and subsequent PC subacromial injections is an effective strategy in improving tendon healing rate

Osteoarthritis (OA) is the most common disorder of the Sternoclavicular Joint (SCJ). In our case-control study, we evaluated the relationship between clavicular length and OA at the SCJ. CT scans of adults presenting to the Emergency Department of our hospital were examined to look for OA, defined as the presence of osteophytes, subchondral cysts, or cortical sclerosis at the SCJ. Medial-most and lateral-most points of the clavicle were marked on the slices passing through the SC and AC joints respectively. Using x, y, and z-axis coordinates from the DICOM metadata, clavicular length was calculated as the distance between these two points with 3D geometry. Preliminary data of 334 SCJs from 167 patients (64% males, 36% females) with a mean age of 48.5 ± 20.5 years were analysed. Multivariate regression models revealed that age and clavicular length were independent risk factors for OA while gender did not reach statistical significance. A 1mm increase in length was associated with 9% and 7% reduction in the odds of developing OA on the left and the right respectively. Comparing the mean clavicular length using t-test showed a significantly shorter clavicle in the group with OA (145.8 vs 152.7, p=0.0001, left and 144.2 vs 150.3, p=0.0007, right). Our data suggest that the risk of developing OA at the SCJ is higher for shorter clavicles. This could be of clinical relevance in cases of clavicular fracture where clavicular shortening might lead to a higher risk of developing OA. Biomechanical studies are needed to find out the mechanism of this effect

With an aging population and increase in total knee arthroplasty, periprosthetic distal femur fractures (PDFFs) have increased. The differences between these fractures and native distal femur fractures (NDFF) have not been comprehensively investigated. The purpose of this study was to compare the demographic, fracture, and treatment details of PDFFs compared to NDFFs. A retrospective study of patients ≥ 18 years old who underwent surgical treatment for either a NDFF or a PDFF from 2010 to 2020 at a level 1 trauma center was performed. Demographics, AO/OTA fracture classification, quality of reduction, fixation constructs, and unplanned revision reoperation were compared between PDFF patients and NDFF patients using t-test and Fisher's exact test. 209 patients were identified with 70 patients having a PDFF and 139 patients having a NDFF. Of note, 48% of NDFF had a concomitant fracture of the ipsilateral knee (14%) or tibial plateau (15%). The most common AO/OTA classification for PDFFs was 33A3.3 (71%). NDFFs had two main AO/OTA classifications of 33C2.2 (28%) or 33A3.2. (25%). When controlling for patient age, bone quality, fracture classification, and fixation, the PDFF group had increased revision reoperation rate compared to NDFF (P < 0.05). PDFFs tend to occur in elderly patients with low bone quality, have complete metaphyseal comminution, and be isolated; whereas, NDFF tend to occur in younger patients, have less metaphyseal comminution, and be associated with other fractures. When controlling for variables, PDFF are at increased risk of unplanned revision reoperation. Surgeons should be aware of these increased risks in PDFFs and future research should focus on these unique fracture characteristics to improve outcomes

A number of techniques have been developed to improve the immediate mechanical anchorage of implants for enhancing implant longevity. This issue becomes even more relevant in patients with osteoporosis who have fragile bone. We have previously shown that a dynamic hip screw (DHS) can be augmented with a calcium sulphate/hydroxyapatite (CaS/HA) based injectable biomaterial to increase the immediate mechanical anchorage of the DHS system to saw bones with a 400% increase in peak extraction force compared to un-augmented DHS. The results were also at par with bone cement (PMMA). The aim of this study was to investigate the effect of CaS/HA augmentation on the integration of a different fracture fixation device (gamma nail lag-screw) with osteoporotic saw bones. Osteoporotic saw bones (bone volume fraction = 15%) were instrumented with a gamma nail without augmentation (n=8) or augmented (n=8) with a CaS/HA biomaterial (Cerament BVF, Bonesupport AB, Sweden) using a newly developed augmentation method described earlier. The lag-screws from both groups were then pulled out at a displacement rate of 0.5 mm/s until failure. Peak extraction force was recorded for each specimen along with photographs of the screws post-extraction. A non-parametric t-test was used to compare the two groups. CaS/HA augmentation of the lag-screw led to a 650% increase in the peak extraction force compared with the controls (p<0.01). Photographs of the augmented samples shows failure of the saw-bones further away from the implant-bone interface indicating a protective effect of the CaS/HA material. We present a novel method to enhance the immediate mechanical anchorage of a lag-screw to osteoporotic bone and it is also envisaged that CaS/HA augmentation combined with systemic bisphosphonate treatment can lead to new bone formation and aid in the reduction of implant failures and re-operations

To quantify bone-nail fit in response to varying nail placements by entry point translation in straight antegrade humeral nailing using three-dimensional (3D) computational analysis. CT scans of ten cadaveric humeri were processed in 3D Slicer to obtain 3D models of the cortical and cancellous bone. The bone was divided into individual slices each consisting of 2% humeral length (L) with the centroid of each slice determined. To represent straight antegrade humeral nail, a rod consisting of two cylinders with diameters of 9.5mm and 8.5mm and length of 0.22L mm and 0.44L mm respectively joined at one end was modelled. The humeral head apex (surgical entry point) was translated by 1mm in both anterior-posterior and medio-lateral directions to generate eight entry points. Total nail protrusion surface area, maximum nail protrusion distance into cortical shell and top, middle, bottom deviation between nail and intramedullary cavity centre were investigated. Statistical analysis between the apex and translated entry points was conducted using paired t-test. A posterior-lateral translation was considered as the optimal entry point with minimum protrusion in comparison to the anterior-medial translation experiencing twice the level of protrusion. Statistically significant differences in cortical protrusion were found in anterior-medial and posterior-lateral directions producing increased and decreased level of protrusion respectively compared to the apex. The bottom anterior-posterior deviation distance appeared to be a key predictor of cortical breach with the distal nail being more susceptible. Furthermore, nails with anterior translation generated higher anterior-posterior deviation (>4mm) compared to posterior translation (<3mm). Aside from slight posterolateral translation of the entry point from the apex, inclusion of a distal posterior-lateral bend into current straight nail design could improve nail fitting within the curved humeral bone, potentially improving distal working length within the flat and narrow medullary canal of the distal humeral shaft

Nuclear factor erythroid 2–related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is key in maintaining redox homeostasis and the pathogenesis of osteoarthritis (OA) involves oxidative distress. We thus investigated whether Nrf2/ARE signaling may control expression of key chondrogenic differentiation and hyaline cartilage maintenance factor SOX9. In human C-28/I2 chondrocytes SOX9 expression was measured by RT–qPCR after shRNA-mediated knockdown of Nrf2 or its antagonist the Kelch-like erythroid cell-derived protein with cap “n” collar homology-associated protein 1 (Keap1). Putative ARE-binding sites in the proximal SOX9 promoter region were inactivated, cloned into pGL3, and co-transfected with phRL–TK for dual-luciferase assays to verify whether Nrf2 transcriptionally regulates SOX9. SOX9 promoter activity without and with Nrf2-inducer methysticin were analyzed. Sox9 expression in articular chondrocytes was correlated to cartilage thickness and degeneration in wild-type (WT) and Nrf2-knockout mice. Data were analyzed by one-way ANOVA, a Student's t-test, or Wilcoxon rank-sum test, according to the normal distribution. Statistical significance was set to p < 0.05. While Keap1-specific RNAi increased SOX9 expression, Nrf2-specific RNAi significantly decreased it. Putative ARE sites (ARE. 1. , ARE. 2. ) were identified in the SOX9 promoter region. ARE. 2. mutagenesis significantly reduced SOX9 promoter activity, while truncation of ARE. 1. did not. A functional ARE. 2. site was thus essential for methysticin-mediated induction of SOX9 promoter activity. Knee cartilage of young Nrf2-knockout mice further revealed significantly fewer Sox9-positive chondrocytes as compared to old Nrf2-knockout animals, which further showed thinner cartilage and more severe cartilage erosion. Our data suggest that SOX9 expression in articular cartilage is directly Nrf2-dependent and that pharmacological Nrf2 activation may hold potential to diminish age-dependent osteoarthritic changes in knee cartilage through improving protective SOX9 expression

This study aimed to quantify self-reported outcomes and walking gait biomechanics in patients following primary and revision THA. The specific goals of this study were to investigate: (i) if primary and revision THA patients have comparable preoperative outcomes; and (2) if revision THA patients have worse postoperative outcomes than primary THA patients. Forty-three patients undergoing primary THA for osteoarthritis and 23 patients undergoing revision THA were recruited and followed longitudinally for their first 12 postoperative months. Reasons for revision were loosening (73%), dislocation (9%), and infection (18%). Patients completed the Hip dysfunction and Osteoarthritis Outcome Score (HOOS), and underwent gait analysis preoperatively, and at 3 and 12 months postoperatively. A 10 camera motion analysis system (V5 Vantage, Vicon, UK) recorded marker trajectories (100 Hz) during walking at self- selected speeds. A generic lower-body musculoskeletal model (Gait2392) was scaled using principal component analysis [1] and the inverse kinematics tool in Opensim 3.3 was used to compute joint angles for the lower limbs in the sagittal plane. Independent samples t-test were used to compare patient reported outcomes between the primary and revision groups at each timepoint. Statistical parametric mapping was used to compare gait patterns between the two groups at each timepoint. Preoperatively, patients undergoing primary THA reported significantly worse pain (p<0.001), symptoms (p<0.001), function (p<0.001), and quality of life (p=0.004). No differences were observed at 3 and 12 months postoperatively between patients who had received a primary or revision THA. The only observed difference in gait pattern was that patients with a revision THA had reduced hip extension at 3 months, but no differences were observed preoperatively and 12 months. Despite the suggestions in the literature that revision THA is bound to have worse outcomes compared to primary THA, we found no differences in in patient-reported outcomes and gait patterns at 12 months postoperatively. This suggests that it may be possible, in some circumstances, for patients following revision THA to achieve similar outcomes to their peers undergoing primary THA

Falls in adults are a major problem and can lead to injuries and death. In order to better understand falls and successful recoveries, identifying kinematics, kinetics, and muscle forces during recovery from loss of balance is crucial. To obtain reactive gait patterns, participants must be subjected to unexpected perturbations such as trips and slips. Previous researchers have reported kinetics recovery data following stumbling; however, the muscle force recovery patterns remain unknown. To better target exercises to reduce the risk of falls, we must first understand which muscles, their magnitude, and their coordination patterns, play a role in a successful recovery from a trip and a slip. Additionally, knowing the successful patterns of lower limb function can help with the diagnosis of faulty movements. A total of 20 healthy adults in their twenties with similar athletic backgrounds were perturbed on a split-belt treadmill using Computer-Assisted Rehabilitation Environment (Motkforce Link) at a preset speed of 1.1m/s. Two kinds of perturbations were administered: slip and trip. Slips were simulated by accelerating one belt, whereas trips were simulated by decelerating one belt. Both perturbations had similar intensity and only differed in the direction. Computational modeling was used to obtain lower-limb function during the compensatory step. SPM paired t-test was used to compare differences in recovery strategies between slip and trip through magnitude and patterns of joints. There were no significant differences in joint angles post tripping vs post-slipping. Results of net joint moments showed that compensating for the loss of balance due to tripping required a higher ankle plantarflexion moment than slipping (at 22-52%; 1.2± 0.3vs0.4±0.2, p<0.001). Additionally, larger gluteus maximus (at 40-50%;8.7±3.8vs2.7±1.1N/kg, p=0.001), gluteus medius (at23~33%; 22.6±5.7vs6.8±3.6N/kg, p<0.001) were generated than post-slipping, respectively. These findings suggested that greater GMAX and GMED forces are required post-trip recovery than slip. Future analysis of trip recovery showed the importance of ankle joint in recovering from forward and backward fall. These results can be used as references in remote diagnosis of joint and muscle weakness and assessment of the risk of falls with the use of accelerometers

Recent studies on animal models focused on the effect of preserving tendon remnant of rotator cuff on tendon healing. A positive effect by combining tendon remnant preservation and small bone vents on the greater tuberosity in comparison with standard tendon-to-bone repair has been shown. The purpose of the present clinical study was to evaluate the efficacy of biologic augmentation of arthroscopic rotator cuff repair by maintaining tendon remnant on rotator cuff footprint combined with small bone vents of the greater tuberosity. A retrospective study was conducted. All patients who underwent arthroscopic rotator cuff repair associated with small bone vents (nanofractures) and tendon footprint preservation were considered eligible for the study. Inclusion criteria were: diagnosis of full-thickness rotator cuff tear as diagnosed at preoperative magnetic resonance imaging (MRI) and confirmed at the time of surgery; minimum 24-month of follow-up and availability of post-operative MRI performed not earlier than 6 months after surgery. Exclusion criteria were: partial thickness tears, irreparable tears, capsulo-labral pathologies, calcific tendonitis, gleno-humeral osteoarthritis and/or previous surgery. Primary outcome was the ASES score. Secondary outcomes were: Quick-DASH and WORC scores, and structural integrity of repaired tendons by magnetic resonance imaging (MRI) performed six months after surgery. A paired t-test was used to compare pre- and postoperative clinical outcomes. Subgroup analysis was performed according to tear size. Significance was set at p < 0.05. The study included 29 patients (M:F = 15:14). Mean age (+ SD) of patients was 61.7 + 8.9 years. Mean follow-up was 27.4 ± 2.3 months. Comparison between pre- and postoperative functional scores showed significant clinical improvement (p < 0.001). Subgroup analysis for tear size showed significant differences in the QuickDASH score (0.04). Particularly, a significant difference in the QuickDASH score could be detected between medium and large tears (p=0.008) as well as medium and massive lesions (p=0.04). No differences could be detected between large and massive tears (p= 0.35). Postoperative imaging showed healed tendons in 21 out of 29 (72%) cases. Preservation of tendon remnant combined with small bone vents in the repair of medium-to-massive full-thickness rotator cuff tears provided significant improvement in clinical outcome compared to baseline conditions with complete structural integrity in 72% of the cases

For clinical movement analysis, optical marker-based motion capture is the gold standard. With the advancement of AI-driven computer vision, markerless motion capture (MMC) has emerged. Validity against the marker-based standard has only been examined for lightly-dressed subjects as required for marker placement. This pilot study investigates how different clothing affects the measurement of typical gait metrics. Gait tests at self-selected speed (4 km/h) were performed on a treadmill (Motek Grail), captured by 9 cameras (Qualisys Miqus, 720p, f=100Hz) and analyzed by a leading MMC application (Theia, Canada). A healthy subject (female, h=164cm, m=54kg) donned clothes between trials starting from lightly dressed (LD: bicycle tight, short-sleeved shirt), adding a short skirt (SS: hip occlusion) or a midi-skirt (MS: partial knee occlusion) or street wear (SW: jeans covering ankle, long-sleeved blouse), the lattern combined with a short jacket (SWJ) or a long coat (SWC). Gait parameters (mean±SD, t=10s) calculated (left leg, mid-stance) were ankle pronation (AP-M), knee flexion (KF-M), pelvic obliquity (PO-M) and trunk lateral lean (TL-M) representing clinically common metrics, different joints and anatomic planes. Four repetitions of the base style (LD) were compared to states of increased garment coverage using the t-test (Bonferroni correction). For most gait metrics, differences between the light dress (LD) and various clothing styles were absent (p>0.0175), small (< 2SD) or below the minimal clinically important differences (MCID). For instance, KF-M was for LD=10.5°±1.7 versus MD=12.0°±0.5 (p=0.07) despite partial knee cover. AP-M measured for LD=5.2°±0.6 versus SW=4.1°±0.7 (p<0.01) despite ankle cover-up. The difference for KF-M between LD=10.5°±1.7 versus SWL=6.0°±0.9, SW and SWJ (7.6°±1.5, p<0.01) indicates more intra-subject gait variability than clothing effect. This study suggests that typical clothings styles only have a small clinically possibly negligible effect on common gait parameters measured with MMC. Thus, patients may not need to change clothes or be instructed to wear specific garments. In addition to avoiding marker placement, this further increases speed, ease and economy of clinical gait analysis with MMC facilitating high volume or routine application

Abstract. OBJECTIVE. Flattening of the talar dome is observed clinically in haemarthropathy as structural and functional changes advance but has not been quantified yet. In order to confirm clinical observation, and assess the degree of change, morphological measurements were derived from MR images. METHODS. Four measurements were taken, using ImageJ (1.52v), from sagittal MRI projections at three locations – medial, lateral and central: Trochlear Tali Arc Length (TaAL), Talar Height (TaH), Trochlear Tali Length (TaL), and Trochlear Tali Radius (TaR). These measurements were used to generate three ratios of interest: TaR:TaAL, TaAL:TaL, and TaL:TaH. With the hypothesis of a flattening of the talar dome with haemarthropathy, it was expected that TaR:TaAL and TaL:TaH should be greater for haemophilic ankles, and TaAL:TaL should be smaller. A total of 126 MR images (ethics: MEEC 18–022) were included to assess the difference in those ratios between non-diseased ankles (33 images from 11 volunteers) and haemophilic ankles (93 images from 8 patients’ ankles). Non-diseased control measurements were compared to literature to assess the capacity of doing measurements on MRI instead of radiographs or CT. RESULTS. Reasonable agreement was found between measurements on non-diseased ankles and those from literature, with greatest variance in TaAL. The medial talus demonstrated decreases in all dimensions with haemophilia (TaR=2.4%, TaL=14.7%, TaAL=19.5% and TaH=27.8%; t-test at p<0.05), as did the lateral talus (TaR=6.2%, TaL=6.8%, TaAL=12.0% and TaH=22.4%; t-test at p<0.05). The effect on the central talus was not significant. TaAL:TaL showed talar flattening in the medial and lateral haemophilic talus (healthy medial=1.21, lateral=1.20; haemophilic medial=lateral=1.14). CONCLUSION. The results demonstrate non-uniform increased influence of haemarthropathy at the medial and lateral talar extremes, with relatively healthy measurements seen in the centre. The degree of morphological change is however progressive, differing with each haemophilic ankle. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Introduction and Objective. Intervertebral disc (IVD) degeneration is one of the major contributors to low back pain, the leading cause of disability worldwide. This multifactorial pathological process involves the degradation of the extracellular matrix, inflammation, and cell loss due to apoptosis and senescence. While the deterioration of the extracellular matrix and cell loss lead to structural collapse of the IVD, increased levels of inflammation result in innervation and the development of pain. Amongst the known regulators of inflammation, toll-like receptors (TLRs) and more specifically TLR-2 have been shown to be specifically relevant in IVD degeneration. As strong post-transcriptional regulators, microRNAs (miRNAs) and their dysregulation has been connected to multiple pathologies, including degenerative diseases such as osteoarthritis and IVD degeneration. However, the role of miRNAs in TLR signalling in the IVD is still poorly understood and was hence investigated in this study. Materials and Methods. Human Nucleus pulposus (hNP) and Annulus fibrosus (hAF) cells (n=5) were treated with the TLR-2/6 specific agonist PAM2CSK4 (100 ng/mL for 6 hours) in order to activate the TLR2 signalling pathway. After the activation both miRNA and mRNA were isolated, followed by next-generation sequencing and qPCR analysis of proinflammatory cytokines respectively. Furthermore, cell supernatants were used to analyze the secretion of proinflammatory cytokines with enzyme-linked immunosorbent assay. TLR-2 knockdown (siRNA) cells were used as a control. Statistical analysis was conducted by performing Kolmogorov-Smirnov test and a two-tailed Student's t-test using GraphPad Prism version 9.0.2 for Windows (GraphPad Software, La Jolla California USA). Results. TLR-2 activation resulted in the induction of an inflammatory cell response, with a significant increase in gene expression of interleukin (IL)-6 (525 ± 180 fold change, p < 0.05) and IL-8 (7513 ± 1907 fold change, p < 0.05) and protein secretion of IL-6 (30.5 ± 8.1 pg/mL) and IL-8 (28.9 ± 5.4 pg/mL). TLR-2 activation was furthermore associated with changes in the miRNA profile of hNP and hAF cells. Specifically, we identified 10 differentially expressed miRNAs in response to TLR-2 activation, amongst which were miR-335–3p (1.45 log2 FC, p < 0.05), miR-125b-1–3p (0.55 log2 FC, p < 0.05), and miR-181a-3p (−1.05 log2 FC, p < 0.05). Conclusions. The identified miRNAs are known to be associated with osteoarthritis (miR-335-3p), inflammation and IVD degeneration (mir-125-1-3p and miR-181a-3p), but the link to TLR signalling has not been previously reported. Experiments to validate the identified miRNAs and elucidate their functional role are undergoing. The identification of these miRNAs provides an opportunity to further investigate miRNAs in the context of TLR activation and inflammation and to enhance our understanding of underlying molecular mechanisms behind disc degeneration, inflammation, and TLR dysregulation

More than 250,000 people are suffering from Anterior Cruciate Ligament (ACL) related injuries each year in the US, with a cost of $17–25K/patient. There is an unmet clinical demand for improving grafts/scaffolds to provide biological integration in addition to mechanical support. Currently, no data is available for the utilization of fibrous scaffolds with bimodal distribution for ACL regeneration. The novelty in this study is that it proposes for the first time to investigate the collagen fibril diameter distribution in healthy and injured bovine ACL tissue, and utilization of such structure for scaffold design. Objectives are 1) developing a bovine ACL tear model and measuring the collagen fibril diameter distribution of both healthy and injured ACL tissues, and 2) fabricating scaffolds to mimic the structural properties of healthy and injured ACL tissue. Bovine ACL tissues (1–3 years old) were harvested and characterized for their fibril diameter distribution using Transmission Electron Microscopy (TEM) and biomechanical properties under tension. The electrospun polycaprolactone (PCL) scaffolds were characterized using SEM and mechanical testing. Healthy and injured ACL fibril diameter, and that of PCL scaffolds representing healthy and injured ACL are compared using unpaired student t-test. The proposed fibrous scaffold design represents a significant departure from the conventional unimodal approach, and is expected to have significant contribution to ACL regeneration. These discoveries will serve as the foundation for the development of biomimetic tissue engineering substrates aimed at promoting biological graft fixation

Targeted delivery of drugs is a major challenge in diseases such as infections and tumors. The aim of this study was to demonstrate that hydroxyapatite (HA) particles can act as a recruiting moiety for various bioactive molecules and as a proof-of-concept demonstrate that the affinity of drugs to hydroxyapatite can exert a biological effect. A bisphosphonate, zoledronic acid (ZA), was used as a model drug. Experiment 1 (ZA seeks HA): Calcium sulphate (CaS)/hydroxyapatite (HA) biomaterial pellets (diameter¸=5 mm, height=2 mm) were implanted in the abdominal muscle pouch of rats. After 2-weeks of implantation, a sub-cutaneous injection of 14C-ZA (0.1 mg/kg) was given. 24 h later, the animals were sacrificed and the uptake of ZA determined in the pellets using scintillation counting. Experiment 2 (Systemically administered ZA seeks HA and exerts a biological effect): A fenestrated implant was filled with the CaS/HA biomaterial and inserted in the proximal tibia of rats. 2-weeks post-op, a subcutaneous injection of ZA (0.1 mg/kg) was given. Animals were sacrificed at 6-weeks post-op. Empty implant was used as a control. Peri-implant bone formation was evaluated using different techniques such as micro-CT, mechanical testing and histology. Welch's t-test was used for mechanical testing and Mann-Whitney U test for micro-CT data analysis. Experiment 1: Uptake of radioactive ZA in the CaS/HA biomaterial was confirmed. Almost no ZA was present in the surrounding muscle. These results show high specific binding between systemically administered ZA and synthetic particulate HA. Experiment 2: Significantly higher peri-implant bone was measured using micro-CT in the group wherein the implant contained the CaS/HA biomaterial and ZA was administered systemically (This study presents a method for biomodulating HA in situ by different bioactive molecules. The approach of implanting a biomaterial capable of recruiting systemically given drugs and thereby activate the material is novel and may present a possibility to treat bone infections or tumors

Abstract. Objectives. The role of MSCs in enhancing healing has been examined with allogeneic and xenogeneic cells in transplantation models. However, certain factors might limit the use of allogeneic cells in clinical practice, (e.g. disease transmission, ethical issues and patient acceptance). Adipose tissue represents an abundant source for autologous cells. The aim of this study was to evaluate adipose-derived autologous cells for preventing non-union. Methods. Adults male Wistar rats (n=5) underwent a previously published surgical procedure known to result in non-union if no treatment is given. This consisted of a mid-shaft tibial osteotomy with peri/endosteal stripping stabilized by intramedullary nail fixation with a 1mm gap maintained by a spacer shown to have minimal effect on fracture healing. During the same operation, ipsilateral inguinal subcutaneous fat was harvested and processed for cell isolation. After three weeks in culture, the cell number reached 5 million and were injected into the fracture site. Results. At the end of the experiment, all tibias (injected with autologous fat-MSCs) developed union, 5/5. These were compared with a control group injected with PBS (n=4) and with allogenic (n=5) and xenogeneic (n=6) cell transplantation groups. The amount of callus was noticeably large in the autologous cell group and the distal-callus index was significantly greater than that of the other groups, P-value < 0.05, unpaired t-test, corrected by Benjamini & Hochberg. Conclusion. We report a novel method for autologous MSCs implantation to stimulate fracture healing. Local injection of autologous fat-MSCs into the fracture site resulted in a solid union in all the tibias with statistically significantly greater amounts of callus. Xenogeneic Bone Marrow and Fat derived MSCs have previously been shown to have similar effects (Tawonsawatruk et al. 2014), we show here that autologous MSCs were significantly better than the xenogenic MSCs at producing union. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Abstract. OBJECTIVES. Valgus high tibial osteotomy (HTO) represents an effective treatment for patients with medial compartment osteoarthritis (OA) in a varus knee. However, the mechanisms which cause this clinical improvement are unclear. Previous studies suggest a wider stance gait can reduce medial compartment loading via reduction in the external knee adduction moment (KAM); a measure implicated in progression of medial compartment OA. This study aimed to measure whether valgus HTO is associated with a postoperative increase in static stance width. METHODS. 32 patients, recruited in the Biomechanics and Bioengineering Centre Versus Arthritis HTO study, underwent valgus (medial opening wedge) HTO. Weightbearing pre- and post- operative radiographs were taken showing both lower limbs. The horizontal distance, measured from a fixed point on the right talus to the corresponding point on the left, was divided by the talus width to give a standardised “stance width” for each radiograph. The difference between pre- and post- operative stance width was compared for each patient using a paired sample t-test. RESULTS. Preoperatively, mean stance was 4.00 talar-widths but postoperatively this increased to 5.41. This mean increase of 1.42 talar-widths was statistically significant (p=0.001) and represents a mean proportional increase in stance width of 35.5% following HTO. Of the 32 patients, 23 showed increased stance width and 9 decreased (range −4.64 to 6.00 talar-widths). CONCLUSIONS. These findings indicate an association of frontal plane surgical realignment at the proximal tibia via a medial opening wedge HTO with an increased stance width on postoperative radiographs. Considering both wider stance gait and HTO have been shown to affect the progression of medial compartment OA, these results may explain one mechanism contributing to the efficacy of HTO surgery. However, the range of changes in stance width suggests significant variability in how patients adapt at a whole-limb and whole-body level following HTO. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Limited information is published regarding the activity level after gracilis autograft reconstruction, and usually a knee-injury based score is used rather than a specific ankle PROM. The purpose of this study was to investigate the activity level and functional results after lateral ankle gracilis autograft reconstruction in patients with severe lateral ankle instability. The hypothesis was that patients would regain their pre-injury Tegner activity level or one level below and secondary to compare a specific ankle activity score, instability and function score. Finally, donor site and graft complications, clinical stability and range of motion were measured. All 69 patients (50 women, 19 men) recorded at the hospital with severe instability who underwent reconstruction of the anterior talofibular and the calcaneofibular ligament with a gracilis autograft and were minimum 6 months post-operative, were invited to participate in the study. Outcomes measures included the Tegner Activity level (1–10), Ankle Activity Score (0–10) recorded as pre-injury and at follow up. The Karlsson Petterson Ankle Function Score (0–100) and Visual Analog Score (VAS)(0–10) recorded pre-operatively and at follow up. All pre-injury and pre-operative data were recalled retrospectively from memory. Identification of functional ankle instability (IDFAI)(0–37) was recorded at follow up. The clinical tests, Anterior drawer test (0–4), Talar tilt test (0–4) and Range of motion (ROM)(degrees) were compared to the unaffected side at follow up. A difference of 1 in the activity scores was chosen as a clinical relevant difference. Data was tested for normal distribution and for statistical significant difference with a students t-test. study design: Cross sectional clinical study with a retrospective questionnaire. A total of 33 patients (27 women, 6 men), with a mean age on 45 years (range 19–68), were included in this study. Mean follow up was 3.7 years. Mean pre-operative Tegner score was 5.8 vs 5.6 at follow up (p. On average, the patients returned to their pre-injury activity level, with similar specific ankle activity scores to the Tegner. The majority had good functional results and few residual symptoms of functional instability. The response rate was low with few men responding; hence a prospective study is called for to establish the true effect of the surgical technique

Abstract. Objectives. Over 1% of the global population suffers with ankle osteoarthritis (OA), yet there is limited knowledge on the changes to subchondral bone with OA. In other joints, it has been shown that bone becomes osteosclerotic, with fewer, thicker trabeculae that become hypomineralised, causing an increased apparent bone volume fraction (BV/TV). Microstructural alterations reduce overall joint strength, which may impact the success of late-stage surgical interventions, such as total ankle arthroplasty (TAA). Previous ankle studies have evaluated changes to cartilage, bone plate and bone morphology with OA, hence this study aimed to characterise changes to trabecular architecture. Methods. Three ankle joints were isolated from non-diseased cadaveric feet (three males: 43, 50 and 57 years, MEEC 18-027). Cylindrical subchondral bone specimens (N=6, 6.5 mm Ø) were extracted from the tibial plafond. Osteoarthritic bone samples (N=6, distal tibia) were sourced from local patients (three males: 65, 58 and 68 years, NREC 07/Q1205/27) undergoing TAA surgery. Specimens were imaged using µCT at a 16 µm isotropic resolution (µCT-100 ScanCo Medical). Virtual cores of bone (6.5 mm Ø) were extracted from the image data of the osteoarthritic specimens and trimmed to a height of 4 mm. BoneJ was used to evaluate key morphological indices: BV/TV; anisotropy (DA); trabecular thickness (Tb.Th); trabecular density (Conn.D) and ellipsoid factor (EF) which characterises rod/plate geometry. Differences between the two groups of specimens were evaluated using a t-test with Bonferroni correction. Results. Significant increases in BV/TV and Tb.Th (p<0.01) were observed with OA compared to non-diseased. Differences in EF showed a shift to more rod-dominated structure with OA, but this was not significant. No significant differences to DA and Conn.D were observed. Conclusions. The results of this study agree with trends observed in other OA joints, but would benefit from a larger sample size. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project