The objectives of this study are to evaluate the impact of the CoVID-19 pandemic on the development of relevant emerging digital healthcare
Malalignment is often postulated as the main reason for the high failure rate of total ankle replacements (TARs). Only a few studies have been performed to correlate radiographic TAR malalignment to the clinical outcome, but no consistent
Our aim was to ascertain if K-wire configuration had any influence on the infection and complication rate for base of 4th and 5th metacarpal fractures. We hypothesised that in individuals whose wires crossed the 4th and 5th carpometacarpal joint (CMCJ), the rate of complications and infection would be higher. Data was retrospectively analysed from a single centre. 106 consecutive patients with a base of 5th (with or without an associated 4th metacarpal fracture) were analysed between October 2016 and May 2021. Patients were split into two groups for comparison; those who did not have K-wires crossing the CMCJ's and those in whose fixation had wires crossing the joints. Confounding factors were accounted for and Statistical analysis was performed using SPSS version 20 software. Of 106 patients, 60 (56.6%) patients did have K-wires crossing the CMCJ. Wire size ranged from 1.2-2.0 with 65 individuals (65.7%) having size 1.6 wires inserted. The majority of patients, 66 (62.9%) underwent fixation with two wires (range 1-4). The majority of infected cases (88.9%) were in patients who had k-wires crossing the CMCJ, this
There has been extensive research into neck of femur fractures in the elderly. Fragility non-hip femoral fractures share many of the same challenges [1]. Surgical management is complex, patients are frail and mortality rates have been reported as high as 38% [2]. Despite this, relatively little data is available evaluating the level of MDT care provided to non-hip femoral fractures. This audit aimed to evaluate the standard of MDT care provided for patients with non-hip femoral fractures according to the NHFD key performance indicators. The following fractures were included in the dataset: distal femoral, femoral shaft and peri-prosthetic femoral. Patients under 65 were excluded. Data was retrospectively collected using post-operative and medical documentation. Performance was assessed according to five key performance indicators:. Did orthogeriatrics review the patient within 72-hours?. Was surgery performed within 36-hours?. Was the patient weight bearing post-operatively?. Was a confusion assessment completed?. Was the patient discharged home?. 38 patients met the inclusion criteria. 84% of patients were seen by orthogeriatrics within 72 hours of admission. 32% of patients were operated on within 36-hours of admission, with time to theatre exceeding 36-hours in 92% of peri-prosthetic fractures. 37% of patients were not advised to full weight bear post operatively. 84% of patients received a confusion assessment whilst 61% of patients were discharged to their prior place of living. Our results suggest that non-hip femoral fractures do not receive the same standard of MDT care as neck of femur fractures. Greater prioritisation of resources should be given to this patient subset so that care is equivalent to hip-fracture patients. Time to surgery is a particular area for improvement, particularly in peri-prosthetic fractures, a
There are no efficient treatment options for osteoarthritis (OA) that delay further progression. Besides osteoinduction, there is growing evidence of also anti-inflammatory, angiogenetic and neuroprotective effects of biodegradable magnesium-based biomaterials. Their use for the treatment of cartilage lesions in contrast is not well-evaluated yet. Mg-cylinders were analysed in an in vitro and in vivo OA model. In vitro, SCP-1 stem cell line was analysed under inflammatory conditions and Mg-impact. In vivo, small Mg- and WE43 alloy-cylinders (1mm × 0,5mm) were implanted into the subchondral bone of the knee joint of 24 NZW rabbits after establishment of OA. As control, another 12 rabbits received only drill-holes. µCT-scan were performed and assessed for changes in bone volume and density. After euthanasia, cartilage was evaluated macroscopically and histologically after Safranin-O-staining. Furthermore, staining with CD271 directed antibody was performed to assess neuro-reactivity. In vitro, an increased gene expression of extracellular matrix proteins as collagen II or aggrecan even under inflammatory conditions was observed under Mg-impact. In vivo, µCT evaluation revealed twice-elevated values for bone volume in femoral condyles with Mg-cylinders compared to controls while density remained unchanged. Cartilage showed no significant differences between the groups. Mg- and WE-samples showed significantly lower levels of CD271+ cells in the cartilage and bone of the operated joints than in non-operated joints, which was not the case in the Drilling-group. Furthermore, bone in operated knees of Drilling-group showed a strong
In absence of available quantitative measures, the assessment of fracture healing based on clinical examination and X-rays remains a subjective matter. Lacking reliable information on the state of healing, rehabilitation is hardly individualized and mostly follows non evidence-based protocols building on common guidelines and personal experience. Measurement of fracture stiffness has been demonstrated as a valid outcome measure for the maturity of the repair tissue but so far has not found its way to clinical application outside the research space. However, with the recent technological advancements and
Mesenchymal stem cells (MSC) have potent immunomodulatory and regenerative effects via soluble factors. One approach to improve stem cell-based therapies is encapsulation of MSC in hydrogels based on natural proteins such as collagen and fibrin, which play critical roles in bone healing. In this work, we comparatively studied the influence of collagen and fibrin hydrogels of varying stiffness on the paracrine interactions established by MSC with macrophages and osteoblasts. Type I collagen and fibrin hydrogels in a similar stiffness range loaded with MSC from donants were prepared by modifying the protein concentration. Viability and morphology of MSC in hydrogels as well as cell migration rate from the matrices were determined. Paracrine actions of MSC in hydrogels were evaluated in co-cultures with human macrophages from healthy blood donors or with osteoblasts from bone explants of patients with osteonecrosis of the femoral head. Lower matrix stiffness resulted in higher MSC viability and migration. Cell migration rate from collagen hydrogels was higher than from fibrin matrices. The secretion of the immunomodulatory factors interleukin-6 (IL-6) and prostaglandin E. 2. (PGE. 2. ) by MSC in both collagen and fibrin hydrogels increased with increasing matrix stiffness. Tumor necrosis factor-α (TNF-α) secretion by macrophages cultured on collagen hydrogels was lower than on fibrin matrices. Interestingly, higher collagen matrix stiffness resulted in lower secreted TNF-α while the
Intervertebral disc (IVD) degeneration occurs with aging, leading to low back pain (LBP), which is one of the leading conditions of disability worldwide. With the lack of effective treatment, decellularized extracellular matrix (dECM) – based biomaterials have been proposed for IVD regeneration. However, the impact of donor ages on tissue repair had never been explored before in the disc field. Therefore, we aimed to address this question. For that, a decellularization protocol for bovine nucleus pulposus (NP) of different aged donors (fetus, young and old) was optimized by testing several detergents (SDS and Triton). The process efficiency was evaluated in terms of DNA and cell removal, as well as ECM preservation. Afterwards, dECMs were repopulated with bovine NP cells and cultured ex vivo. At day 7, cell behavior, ECM de novo synthesis and remodeling were evaluated [1]. Moreover, dECMs’ inflammatory response was assessed after in vivo CAM assay. Finally, inflammatory and angiogenic cytokines were analyzed in the conditioned media-derived from dECMs by using a cytokine array. As results, an optimal decellularization protocol (SDS 0.1%, 1h), efficient at removing cells and DNA from bovine NPs, while preserving ECM cues of native tissues, was developed. After repopulation, aggrecan increased in younger NPs, while collagen 2 decreased which may be indicative of matrix remodeling [1]. After in vivo CAM assay, fetal dECMs showed the highest inflammatory response. Finally, no statistically significant changes of cytokines were detected in the matrices, despite for a
Mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) have great promise in the field of orthopaedic nanomedicine due to their regenerative, as well as immunomodulatory and anti-inflammatory properties. Researchers are interested in harnessing these biologically sourced nanovesicles as powerful therapeutic tools with intrinsic bioactivity to help treat various orthopaedic diseases and defects. Recently, a new class of EV mimetics has emerged known as nanoghosts (NGs). These vesicles are derived from the plasma membrane of ghost cells, thus inheriting the surface functionalities and characteristics of the parent cell while at the same time allowing for a more standardized and reproducible production and significantly greater yield when compared to EVs. This study aims to investigate and compare the osteoinductive potential of MSC-EVs and MSC-NGs in vitro as novel tools in the field of bone tissue engineering and nanomedicine. To carry out this investigation, MSC-EVs were isolated from serum-free MSC conditioned media through differential ultracentrifugation. The remaining cells were treated with hypotonic buffer to produce MSC-ghosts that were then homogenized and serially extruded through 400 and 200 nm polycarbonate membranes to form the MSC-NGs. The concentration, size distribution, zeta potential, and protein content of the isolated nanoparticles were assessed. Afterwards, MSCs were treated with either MSC-EVs or MSC-NGs under osteogenic conditions, and their differentiation was assessed through secreted ALP assay, qPCR, and Alizarin Red mineralization staining. Isolation of MSC-EVs and MSC-NGs was successful, with relatively similar mean diameter size and colloidal stability. No effect on MSC viability and metabolic activity was observed with either treatment. Both MSC-EV and MSC-NG groups had enhanced osteogenic outcomes compared to the control; however, a
Patients with bone and muscle weakness from disuse have higher risk of fracture and worse post-injury mortality rates. The goal of this current study was to better inform post-fracture rehabilitation strategies by investigating if physical remobilization following disuse by hindlimb unloading improves osteochondral callus formation compared to continued disuse by hindlimb suspension (HLS). We hypothesized that continued HLS would impair callus bone and cartilage formation and that physical rehabilitation after HLS would increase callus properties. All animal procedures were approved by the VCU IACUC. Skeletally mature, male and female C57BL/6J mice (18 weeks) underwent HLS for 3 weeks. Mice then had their right femur fractured by open surgical dissection (stabilized with 24-gauge pin). Mice were then either randomly assigned to continued HLS or allow normal physical weight-bearing remobilization (HLS + R). Mice allowed normal cage activity throughout the experiment served as controls (GC). All mice were sacrificed 14-days following fracture with 4-8 mice (male and female) per treatment. Data analyzed by respective ANOVA with Tukey post-hoc (*p< 0.05; # p < 0.10). Male and female mice showed conserved and significant decreases in hindlimb callus bone formation from continued HLS versus HLS + R. Combining treatment groups regardless of mouse sex, histological analyses using staining on these same calluses demonstrated that HLS resulted in
Previous research has shown catabolic cell signalling induced by TNF-α and IL-1β within intervertebral (IVD) cells. However, these studies have investigated this in 2D monolayer cultures, and under hyper-physiological doses. Thus, we aim to revisit the catabolic responses of bovine IVD cells in vitro in 3D culture under increasing doses of TNF-α or IL-1β stimulation at three different timepoints. Primary bovine nucleus pulposus (NP) and annulus fibrosus (AF) cells were isolated and expanded for two weeks. Subsequently, NP and AF cells were encapsulated in 1.2% alginate beads (4 × 106 cells/ml) and cultured for two weeks for phenotype recovery. Re-differentiated cells were stimulated with 0.1, 1 and 10 ng/ml TNF-α or with 0.01, 0.1 and 10 ng/ml IL-1β for one week. Beads were collected on the stimulation day (Day 0) and on Day 1 and 7 after stimulation. A dose-dependent upregulation of catabolic markers was observed in both cell types after one day of TNF-α or IL-1β stimulation. 10 ng/ml TNF-α stimulation induced a significant upregulation (p<0.05) of ADAMTS4, MMP3 and MMP13 in AF cells after one day of stimulation. Similarly, MMP3 upregulation showed a strong
Reduction of length of stay (LOS) without compromising quality of care is a
Introduction. The concept of same-day discharge has garnered increasing significance within orthopedic surgery, particularly in hip and knee procedures. Despite initial concerns surrounding the absence of prolonged hospital care, a burgeoning body of evidence highlights numerous advantages associated with same-day discharge, ranging from mitigating in-hospital infections to offering substantial financial and psychosocial benefits for both patients and healthcare providers. In this study, we aim to scrutinize the
Abstract. Objectives. Spinal stiffness and flexibility terms are typically evaluated from linear regression of experimental data and are then assembled into 36-element matrices. Summarising in vitro test results in this manner is quick, computationally cheap and has the distinct advantage of outputting simple characteristic values which make it easy to compare results. However, this method disregards many important experimental features such as stiffening effects, neutral and elastic zones magnitudes, extent of asymmetry and energy dissipation (hysteresis). Alternatives to the linear least squares method include polynomials, separation of the load-displacement behaviour into the neutral and elastic zones using various deterministic methods and variations on the double sigmoid and Boltzmann curve fits. While all these methods have their advantages, none provide a comprehensive and complete characterisation of the load-displacement behaviour of spine specimens. In 1991, Panjabi demonstrated that the flexion-extension and mediolateral bending behaviour of functional spinal units could be approximated using the viscoelastic model consisting of a nonlinear spring in series with a linear Kelvin element. Nowadays viscoelastic models are mainly used to describe creep and stress relaxation, rather than for cyclic loading. The aim of this study was to conclusively prove the viscoelastic nature of spinal behaviour subject to cyclic loading. Being able to describe the behaviour of spine specimens using springs and dampers would yield characterising coefficients with recognisable physical meaning, thus providing an advantage over existing techniques. Methods. Six porcine isolated spinal disc specimens (ISDs) were tested under position and load control. Visual inspection of the load-displacement graphs from which the principal terms of the stiffness and flexibility matrices are derived suggest that the load-displacement behaviour could be idealised by a nonlinear spring system with damping. It was hypothesised that the contributions arising from non-linear spring-like behaviour and damping could be separated for each of the principal load-displacement graphs. Results. The principal elements from position and load control tests were plotted with load on the vertical axis and displacement on the horizontal axis, and a polynomial representing spring force was fitted to the data. This polynomial was subtracted from the experimental data. The remainder - representing damping force - was plotted against displacement and velocity and compared to idealised plots for different types of damping behaviour. Applying this reasoning to the six principal load-displacement plots obtained from stiffness and flexibility tests revealed that four of six exhibit behaviour which is a combination of a nonlinear hardening spring and viscous damper. However, for flexion-extension and mediolateral bending, the damping behaviour is more akin to coulomb damping with viscous influences, characterised by a steep central linear region and near horizontal regions at the extremes. These
Abstract. OBJECTIVES. Application of deep learning approaches to marker trajectories and ground reaction forces (mocap data), is often hampered by small datasets. Enlarging dataset size is possible using some simple numerical approaches, although these may not be suited to preserving the physiological relevance of mocap data. We propose augmenting mocap data using a deep learning architecture called “generative adversarial networks” (GANs). We demonstrate appropriate use of GANs can capture variations of walking patterns due to subject- and task-specific conditions (mass, leg length, age, gender and walking speed), which significantly affect walking kinematics and kinetics, resulting in augmented datasets amenable to deep learning analysis approaches. METHODS. A publicly available (. https://www.nature.com/articles/s41597-019-0124-4. ) gait dataset (733 trials, 21 women and 25 men, 37.2 ± 13.0 years, 1.74 ± 0.09 m, 72.0 ± 11.4 kg, walking speeds ranging from 0.18 m/s to 2.04 m/s) was used as the experimental dataset. The GAN comprised three neural networks: an encoder, a decoder, and a discriminator. The encoder compressed experimental data into a fixed-length vector, while the decoder transformed the encoder's output vector and a condition vector (containing information about the subject and trial) into mocap data. The discriminator distinguished between the encoded experimental data from randomly sampled vectors of the same size. By training these networks jointly using the experimental dataset, the generator (decoder) could generate synthetic data respecting specified conditions from randomly sampled vectors. Synthetic mocap data and lower limb joint angles were generated and compared to the experimental data, by identifying the statistically significant differences across the gait cycle for a randomly selected subset of the experimental data from 5 female subjects (73 trials, aged 26–40, weighing 57–74 kg, with leg lengths between 868–931 mm, and walking speeds ranging from 0.81–1.68 m/s). By conducting these comparisons for this subset, we aimed to assess the synthetic data generated using multiple conditions. RESULTS. We visually inspected the synthetic trials to ensure that they appeared realistic. The statistical comparison revealed that, on average, only 2.5% of the gait cycle showed significantly differences in the joint angles of the two data groups. Additionally, the synthetic ground reaction forces deviated from the experimental data distribution for an average of 2.9% of the gait cycle. CONCLUSIONS. We introduced a novel approach for generating synthetic mocap data of human walking based on the conditions that influence walking patterns. The synthetic data closely followed the
In a healthy joint, mechanical loading increases matrix synthesis and maintains cell phenotype, while reducing catabolic activities. It activates several pathways, most of them yet largely unknown, with integrins, TGF-β, canonical (Erk 1/2) and stress-activated (JNK) MAPK playing a key role. Degenerative joint diseases are characterized by Wnt upregulation and by the presence of proteolytic fibronectin fragments (FB-fs). Despite they are known to impair some of the aforementioned pathways, little is known on their modulatory effect on cartilage mechanoresponsiveness. This study aims at investigating the effect of mechanical loading in healthy and in vitro diseased cartilage models using pro-hypertrophic Wnt agonist CHIR99021 and the pro-catabolic FB-fs 30 kDa. Human primary chondrocytes from OA patients have been grown in alginate hydrogels for one week, prior to be incubated for 4 days with 3μM CHIR99021 or 1 μM FB-fs. Human cartilage explants isolated from OA patients have incubated 4 days with 3 μM CHIR99021 or 1 μM FB-fs. Both groups have then been mechanically stimulated (unconfined compression, 10% displacement, 1.5 hours, 1 Hz), using a BioDynamic bioreactor 5270 from TA Instruments. Expression of collagen type I, II and X, aggrecan, ALK-1, ALK-5, αV, α5 and β1 integrins, TGF-β1 have been assessed by Real Time-PCR and normalized with the expression of S29. Percentage of phosphorylated Smad2, Smad1 and JNK were determined through western blot. TGF-β1 content was quantified by sandwich ELISA; MMP-13 and GAG by western blot and DMMB assay, respectively. At least three biological replicates were used. ANOVA test was used for parametric analysis; Kruskal-Wallis and Mann-Whitney post hoc test for non-parametric. Preliminary data show that compression increased collagen II expression in control, but not in CHIR99021 and FB-fs pre-treated group (Fig. 1A-B). This was associated with downregulation of β1-integrin expression, which is the main collagen receptor and further regulates collagen II expression, suggesting inhibition of Erk1/2 pathway. A
Focal knee resurfacing implants (FKRIs) are typically intended to treat focal cartilage defects in middle-aged patients. All currently available FKRIs are (partly) composed of metal, which potentially leads to degeneration of the opposing articulating cartilage and hampers follow-up using magnetic resonance imaging (MRI). The purpose of this study was to investigate the in vivo osseointegration process of a novel non-degradable thermoplastic polycarbonate-urethane (TPU) osteochondral implant. Bi-layered implants measuring 6 mm in diameter, with a double-curvature to match the approximate curvature of the goat medial femoral condyle were fabricated. TPU implants were composed of an articulating Bionate® II 80A top layer, and a Bionate® 75D bottom layer (DSM Biomedical, Geleen, the Netherlands) which is intended to osseointegrate. A biphasic calcium phosphate coating formulation, optimized during a prior in vitro study, was applied to half of the TPU implants, while the other half was left uncoated. Bi-layered metal implants (articulating cobalt-chromium top layer and titanium bottom layer) were used as positive control implants. Eight implants per group were implanted bilaterally in the medial femoral condyle of the stifle joints in 12 Dutch milk goats. 18F-sodium fluoride (18F-NaF) positron emission tomography-computed tomography (PET-CT) scanning was performed at 3 and 12 weeks postoperatively, and the corrected maximum standard uptake values (cSUVmax) was calculated to assess the peri-implant bone metabolism. After sacrifice 12 weeks postoperatively, bone histomorphometric analysis was performed to assess the bone-to-implant contact area (BIC). Student's T-test was used in case of normal distribution and the Mann-Whitney-U-test was used in case of abnormal distribution for comparison of BIC and cSUVmax. The BIC value of 10.27 ± 4.50% (mean ± SD) for the BCP-coated TPU implants was significantly (P=0.03) higher than the 4.50 ± 2.61% for the uncoated TPU implants. The uncoated TPU implants scored significantly (P=0.04) lower than the BIC of 12.81 ± 7.55% for the metal implants, whereas there was no significant difference between BCP-coated TPU implants and the metal implants (P=0.68). There was a strong correlation between the cSUVmax values and the BIC values at 12 weeks (Pearson's R=0.74, P=0.001). The cSUVmax values significantly decreased between 3 and 12 weeks for the metal implants (p=0.04). BCP-coated TPU implants followed a similar
Abstract. Introduction. Bipolar hemiarthroplasty(BPHA) for displaced intracapsular neck of femur fractures(DICNOF) is a controversial topic as conflicting evidence exists. The most common reason for revision to total hip arthroplasty(THA) from BPHA is acetabular erosion. In our study, we sought to quantify the direction of migration of the bipolar head within the first 3 years post-operatively. Methods. A proportional index in the horizontal and vertical planes of the pelvis were used to quantify migration. This method removed the need to account for magnification and rotation of the radiographs. Results. There were a total of 35 patients (8males, 27females) included, with an average followup of 2.3years (816days). 7 did not migrate, these were all female. For the remainder, per year of insertion, the average horizontal migration was 0.005769439 and the average vertical migration was 0.004543352, suggesting superomedial movement. Discussion. BPHA has been shown to provide results similar to those of THA in patients with DICNOF. The main cause of revision to THA is migration thought to be from loss of cartilage volume from mechanical wear, that causes pain. We have quantified this migration as minimal. None of our patients required revision to THA and none sustained dislocation or loosening in this followup period. This would fit with the meta-analyses looking at BPHA, which shows bipolar articulations reduce the amount of wear. We also identified a
Fragility fractures are skeletal complications associated with type 2 diabetes (T2D) causing disability, hospitalization, impaired quality of life, and increased mortality. Increased circulating sclerostin and accumulation of advanced glycation end-products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk. We have recently shown that T2D affects the expression of genes controlling bone formation (SOST and RUNX2) and that accumulation of AGEs is associated with impaired bone formation in T2D. We hypothesized that Wnt/B- catenin target genes are down-regulated in bone of T2D subjects as a consequence of decreased SOST and AGEs accumulation. To this end, we studied gene expression in extracts of bone samples obtained from femoral heads of 14 subjects with relatively well-controlled T2D (HbA1c 6.5±1.7%) and 21 control, non-diabetic postmenopausal women (age >65 years) undergoing hip replacement. There were no differences in age (73.2± .8 vs. 75.2±8.5 years) or BMI (27.7±5.6 vs. 29.9±5.4 kg/m2) between control and T2D groups, respectively. Expression of LEF1 mRNA was significantly lower in T2D compared to non-diabetic subjects (p=0.002), while DKK1 was not different between groups (p=0.108). Correlation analysis showed that DKK1 (r2=0.038; p=0.043) and HbA1c (r2=0.503; p=0.048) increased with age in T2D. COL1A1 mRNA
Introduction and Objective. Malunion after trauma can lead to coronal plane malalignment in the lower limb. The mechanical hypothesis suggests that this alters the load distribution in the knee joint and that that this increased load may predispose to compartmental arthritis. This is generally accepted in the orthopaedic community and serves as the basis guiding deformity correction after malunion as well as congenital or insidious onset malalignment. Much of the literature surrounding the contribution of lower limb alignment to arthritis comes from cohort studies of incident osteoarthritis. There has been a causation dilemma perpetuated in a number of studies - suggesting malalignment does not contribute to, but is instead a consequence of, compartmental arthritis. In this investigation the relationship between compartmental (medial or lateral) arthritis and coronal plane malalignment (varus or valgus) in patients with post traumatic unilateral limb deformity was examined. This represents a specific niche cohort of patients in which worsened compartmental knee arthritis after extra-articular injury must rationally be attributed to malalignment. Materials and Methods. The picture archiving system was searched to identify all 1160 long leg x ray films available at a major metropolitan trauma center over a 12-year period. Images were screened for inclusion and exclusion criteria, namely patients >10 years after traumatic long bone fracture without contralateral injury or arthroplasty to give 39 cases. Alignment was measured according to established surgical standards on long leg films by 3 independent reviewers, and arthritis scores Osteoarthritis Research Society International (OARSI) and Kellegren-Lawrence (KL) were recorded independently for each compartment of both knees. Malalignment was defined conservatively as mechanical axis deviation outside of 0–20 mm medial from centre of the knee, to give 27 patients. Comparison of mean compartmental arthritis score was performed for patients with varus and valgus malalignment, using Analysis of Variance and linear regression. Results. In knees with varus malalignment there was a greater mean arthritis score in the medial compartment compared to the contralateral knee, with OARSI scores 5.69 vs 3.86 (0.32, 3.35 95% CI; p<0.05) and KL 2.92 vs 1.92 (0.38, 1.62; p<0.005). There was a similar
