Autologous tendon cell injection (ATI) is a promising non-surgical treatment for tendinopathies and tendon tear that address its underlying pathology. The procedure involves harvesting autologous tendon tissue, the isolation of the tendon cells, expansion under quality assured GMP cell laboratory and the injection of the tendon cells via U/S into the degenerative tendon tissue. In clinical practice, the patella (PT) and palmaris longus (PL) tendons are common sites used for tendon tissue biopsy. The objective of this study is to compare the tendon cell quality, identity, purity, doubling time and yield of cells between PT and PL tendons for ATI.

Tendon tissue biopsies were harvested from PT via U/S using a 14-gauge needle or resected surgically from the PL tendon. The biopsies were transported to a GMP cell laboratory, where tendon cells were isolated, cultured and expanded for 4 to 6 weeks, and analysed for viability, cell doubling time, cellular characteristics including cell purity, potency and identity (PPI).

Tendon samples from 149 patients were analysed (63 PT). Average biopsy weight was 62mg for PT and 119mg for PI (p<0.001). Average cell doubling time (83.9 vs 82.7 hours), cellular yield (16.2 vs 15.2×106), viability (98.7 vs 99.0%) and passage number (3 vs 3) were not significantly different between tendons. Additionally, ddPCR analyses showed no differences of PPI including tendon cell markers of collagen type I, scleraxis and tenomodulin. No post-biopsy complications or contamination were reported for either group. Assessing tendon tissue from palmaris tendon is relatively easier.

Tendon tissue biopsy tissue for autologous tendon cell therapy can be obtained from either the PT or PL tendons. Tendon cells isolated from PT and PL were equal in growth characteristics and PPI. There are no differences in the quality of tendon cells isolated from the PT or PL.

A painful “dreaded black line” (DBL) has been associated with progression to complete fractures in atypical femur fractures (AFF). Adjacent sclerosis, an unrecognized radiological finding, has been observed in relation to the DBL. We document its incidence, associated features, demographics and clinical progression.

We reviewed plain radiographs of 109 incomplete AFFs between November 2006 and June 2021 for the presence of sclerosis adjacent to a DBL. Radiographs were reviewed for location of lesions, and presence of focal endosteal or periosteal thickening. We collected demographical data, type and duration of bisphosphonate therapy, and progression to fracture or need for prophylactic stabilization, with a 100% follow up of 72 months (8 – 184 months).

109 femurs in 86 patients were reviewed. Seventeen sclerotic DBLs were observed in 14 patients (3 bilateral), involving 15.6% of all femora and 29.8% of femora with DBLs. Location was mainly subtrochanteric (41.2%), proximal diaphyseal (35.3%) and mid-diaphyseal (23.5%), and were associated with endosteal or periosteal thickening. All patients were female, mostly Chinese (92.9%), with a mean age of 69 years. 12 patients (85.7%) had a history of alendronate therapy, and the remaining 2 patients had zoledronate and denosumab therapy respectively. Mean duration of bisphosphonate therapy was 62 months. 4 femora (23.5%) progressed to complete fractures that were surgically managed, whilst 6 femora (35.3%) required prophylactic fixation.

Peri-lesional sclerosis in DBL is a new radiological finding in AFFs, predominantly found in the proximal half of the femur, at times bilateral, and are always associated with endosteal or periosteal thickening. As a high proportion of patients required surgical intervention, these lesions could suggest non-union of AFFs, similar to the sclerotic margins commonly seen in fractures with non-union. The recognition of and further research into this new feature could shed more light on the pathophysiological progression of AFFs.

µCT images are commonly analysed to assess changes in bone density and architecture in preclinical murine models. Several platforms provide automated analysis of bone architecture parameters from volumetric regions of interest (ROI). However, segmentation of the regions of subchondral bone to create the volumetric ROIs remains a manual and time-consuming task. This study aimed to develop and evaluate automated pipelines for trabecular bone architecture analysis of mouse proximal tibia subchondral bone.

A segmented dataset involving 62 knees (healthy and arthritic) from 10-week male C57BL/6 mice were used to train a U-Net type architecture, with µCT scans (downsampled) input that output segmentation and bone volume density (BV/TV) of the subchondral trabecular bone. Segmentations were upsampled and used in tandem with the original scans (10µ) as input for architecture analysis along with the thresholded trabecular bone. The analysis considered the manually and U-Net segmented ROIs using two available pipelines: the ITKBoneMorphometry library and CTan (SKYSCAN). The analyses included: bone volume (BV), total volume (TV), BV/TV, trabecular number (TbN), trabecular thickness (TbTh), trabecular separation (TbSp), and bone surface density (BSBV).

There was good agreement for bone measures between the manual and U-Net pipelines utilizing ITK (R=0.88-0.98) and CTan (R=0.91-0.98). ITK and CTan showed good agreement for BV, TV, BV/TV, TbTh and BSBV (R=0.9-0.98). However, a limited agreement was seen between TbN (R=0.73) and TbSb (R=0.59) due to methodological differences in how spacing is evaluated.

This U-Net/ITK pipeline seamlessly automated both segmentation and quantification of the proximal tibia subchondral bone. This automated pipeline allows the analysis of large volumes of data, and its open-source nature may enable the standardization of stereologic analysis of trabecular bone across different research groups.

There is still no consensus on which concentration of mesenchymal stem cells (MSCs) to use for promoting fracture healing in a rat model of long bone fracture.

To assess the optimal concentration of MSCs for promoting fracture healing in a rat model.

Wistar rats were divided into four groups according to MSC concentrations: Normal saline (C), 2.5 × 106 (L), 5.0 × 106 (M), and 10.0 × 106 (H) groups. The MSCs were injected directly into the fracture site. The rats were sacrificed at 2 and 6 자 post-fracture. New bone formation [bone volume (BV) and percentage BV (PBV)] was evaluated using micro-computed tomography (CT). Histological analysis was performed to evaluate fracture healing score. The protein expression of factors related to MSC migration [stromal cell-derived factor 1 (SDF-1), transforming growth factor-beta 1 (TGF-β1)] and angiogenesis [vascular endothelial growth factor (VEGF)] was evaluated using western blot analysis. The expression of cytokines associated with osteogenesis [bone morphogenetic protein-2 (BMP-2), TGF-β1 and VEGF] was evaluated using real-time polymerase chain reaction.

Micro-CT showed that BV and PBV was significantly increased in groups M and H compared to that in group C at 6 wk post-fracture (P = 0.040, P = 0.009; P = 0.004, P = 0.001, respectively). Significantly more cartilaginous tissue and immature bone were formed in groups M and H than in group C at 2 and 6 wk post-fracture (P = 0.018, P = 0.010; P = 0.032, P = 0.050, respectively). At 2 wk post fracture, SDF-1, TGF-β1 and VEGF expression were significantly higher in groups M and H than in group L (P = 0.031, P = 0.014; P < 0.001, P < 0.001; P = 0.025, P < 0.001, respectively). BMP-2 and VEGF expression were significantly higher in groups M and H than in group C at 6 wk postfracture (P = 0.037, P = 0.038; P = 0.021, P = 0.010). Compared to group L, TGF-β1 expression was significantly higher in groups H (P = 0.016). There were no significant differences in expression levels of chemokines related to MSC migration, angiogenesis and cytokines associated with osteogenesis between M and H groups at 2 and 6 wk post-fracture.

The administration of at least 5.0 × 106 MSCs was optimal to promote fracture healing in a rat model of long bone fractures.

The objective of this study was to investigate how a new customizable light-curable osteosynthesis method (AdFix) compared to traditional metal hardware when loaded in torsion in an ovine phalanx model.

Twenty-one ovine proximal phalanges were given a 3mm transverse osteotomy and four 1.5mm cortex screws were inserted bicortically on either side of the gap. The light-curable polymer composite was then applied using the method developed by Hutchinson [1] to create osteosyntheses in two groups, having either a narrow (6mm, N=9) or a wide (10mm, N=9) fixation patch. A final group (N=3) was fixated with conventional metal plates. The constructs were loaded in torsion at a rate of 6°/second until failure or 45° of rotation was reached. Torque and angular displacement were measured, torsional stiffness was calculated as the slope of the Torque-Displacement curve, and maximum torque was queried for each specimen.

The torsional stiffnesses of the narrow, wide, and metal plate constructs were 39.1 ± 6.2, 54.4 ± 6.3, and 16.2 ± 3.0 Nmm/° respectively. All groups were statistically different from each other (p<0.001). The maximum torques of the narrow, wide, and metal plate constructs were 424 ± 72, 600 ± 120, and 579 ± 20 Nmm respectively. The narrow constructs were statistically different from the other two (p<0.05), while the wide and metal constructs were not statistically different from each other (p=0.76).

This work demonstrated that the torsional performance of the novel solution is comparable to metal fixators. As a measure of the functional range, the torsional stiffness in the AdhFix exceeded that of the metal plate. Furthermore, the wide patches were able to sustain a similar maximum toque as the metal plates. These results suggest AdhFix to be a viable, customizable alternative to metal implants for fracture fixation in the hand.

Due to their immunomodulatory and regenerative capacity, human bone marrow-derived mesenchymal stromal cells (hBMSCs) are promising in the treatment of polytrauma patients. However, few studies evaluated the effects of sera from polytraumatized patients on hBMSCs. The aim of this study was to explore changes in hBMSCs exposed to serum from polytrauma patients from different time points after trauma.

Sera from 84 patients on day 1 (D1), 5 (D5) and 10 (D10) after polytrauma (ISS ≥ 16) were pooled respectively to test the differential influence on hBMSC. As a control, sera from three healthy age- and gender-matched donors (HS) were collected. The pooled sera were analyzed by Multicytokine Array for pro-/anti-inflammatory cytokines. For the cell culture experiments, hBMSCs from four healthy donors were used. The influence of the different sera on hBMSC regarding cell proliferation, colony forming unit-fibroblast (CFU-F) assay, cell viability and toxicity, cell migration, as well as osteogenic and chondrogenic differentiation was analyzed. One-Way-ANOVA and LSD-test were used for the parametric, Kruskal-Wallis-test for non-parametric data. p≤0.05 was considered as statistically significant.

The results showed that D5 serum reduced hBMSCs cell proliferation capacity by 41.26% (p=0.000) compared with HS and increased the proportion of dead cells by 3.19% (p=0.008) and 2.25% (p=0.020) compared with D1 and D10. The frequency of CFU-F was reduced by 49.08% (p=0.041) in D5 and 53.99% (p=0.027) in D10 compared with HS, whereas the other parameters were not influenced.

The serological effect of polytrauma on hBMSCs was related to the time after trauma. It is disadvantageous to use BMSCs in polytraumatized patients five days after the incidence as obvious cytological changes could be found at that time point. However, it is promising to use hBMSCs to treat polytrauma after 10 days, combined with the concept of “Damage Control Orthopaedics” (DCO).

Following anterior cruciate ligament reconstruction (ACLR) using a semitendinosus (ST) autograft measures such as length, cross-sectional area, and volume may not fully describe the effects of tendon harvest on muscle morphology as these discrete measures cannot characterize three-dimensional muscle shape. This study aimed to determine between-limb ST shape similarity and regional morphology in individuals with a unilateral history of ACLR using a ST graft, and healthy controls.

A secondary analysis of magnetic resonance imaging was undertaken from 18 individuals with unilateral history of ST ACLR and 18 healthy controls. ST muscles were manually segmented, and shape similarity were assessed between limbs and groups using Jaccard index (0-1) and Hausdorff distance (mm). ST length (cm), peak cross-sectional area (CSA) (cm²), and volume (cm³) was compared between surgically reconstructed and uninjured contralateral limbs, and between the left and right limbs of control participants with no history of injury. Cohen's d was reported as a measure of effect size.

Compared to healthy controls, the ACLR group had significantly (p<0.001, d= −2.33) lower bilateral ST shape similarity. Furthermore, the deviation in muscle shape was significantly (p<0.001, d= 2.12) greater in the ACLR group. Within the ACLR group, maximum Hausdorff distance indicated ST from the ACLR limb deviated (23.1±8.68 mm) from the shape of the healthy contralateral ST, this was observed particularly within the distal region of the muscle. Compared to the uninjured contralateral limb and healthy controls, deficits in peak cross-sectional area and volume in ACLR group were largest in proximal (p<0.001, d= −2.52 to −1.28) and middle (p<0.001, d= −1.81 to −1.04) regions.

Findings highlight morphological features in distal ST not identified by traditional discrete morphology measures. ST shape was most different in the distal region of the muscle, despite deficits in CSA and volume being most pronounced in proximal and middle regions. ST shape following ACLR may affect force transmission and distribution within the hamstrings and contribute to persistent deficits in knee flexor and internal rotator strength.

Dislocation is one of the most common complications in total hip arthroplasty (THA) and is primarily driven by bony or prosthetic impingement. The aim of this study was two-fold. First, to develop a simulation that incorporates the functional position of the femur and pelvis and instantaneously determines range of motion (ROM) limits. Second, to assess the number of patients for whom their functional bony alignment escalates impingement risk.

468 patients underwent a preoperative THA planning protocol that included functional x-rays and a lower limb CT scan. The CT scan was segmented and landmarked, and the x-rays were measured for pelvic tilt, femoral rotation, and preoperative leg length discrepancy (LLD). All patients received 3D templating with the same implant combination (Depuy; Corail/Pinnacle). Implants were positioned according to standardised criteria.

Each patient was simulated in a novel ROM simulation that instantaneously calculates bony and prosthetic impingement limits in functional movements. Simulated motions included flexion and standing-external rotation (ER). Each patient's ROM was simulated with their bones oriented in both functional and neutral positions.

13% patients suffered a ROM impingement for functional but not neutral extension-ER. As a result, 48% patients who failed the functional-ER simulation would not be detected without consideration of the functional bony alignment. 16% patients suffered a ROM impingement for functional but not neutral flexion. As a result, 65% patients who failed the flexion simulation would not be detected without consideration of the functional bony alignment.

We have developed a ROM simulation for use with preoperative planning for THA surgery that can solve bony and prosthetic impingement limits instantaneously. The advantage of our ROM simulation over previous simulations is instantaneous impingement detection, not requiring implant geometries to be analysed prior to use, and addressing the functional position of both the femur and pelvis.

Knee swelling is common after injury or surgery, resulting in pain, restricted range of movement and limited mobility. Accurately measuring knee swelling is critical to assess recovery. However, current measurement methods are either unreliable or expensive [1,2]. Therefore, a new measurement method is developed. This wearable (the ‘smart brace’) has shown the ability to distinguish a swollen knee from a not swollen knee using multi-frequency-bio impedance analysis (MF-BIA) [3].

This study aimed to determine the accuracy of this smart brace. The study involved 25 usable measurements on patients treated for unilateral knee osteoartritis with a 5mL injection of Lidocaïne + DepoMedrol (1:4). MF-BIA measurements were taken before and after the injection, both on the treated and untreated knee. The smart brace accurately measured the effect of the injection by a decrease in resistance of up to 2.6% at 100kHz (p<0.01), where commonly used gel electrodes were unable to measure the relative difference. Remarkably, both the smart brace and gel electrodes showed a time component in the MF-BIA measurements.

To further investigate this time component, 10 participants were asked to lie down for 30 minutes, with measurements taken every 3 minutes using both gel electrodes and the smart brace on both legs. The relative change between each time step was calculated to determine changes over time. The results showed presence of a physiological aspect (settling of knee fluids), and for the brace also a mechanical aspect (skin-electrode interface) [4]. The mechanical aspect mainly interfered with reactance values.

Overall, the smart brace is a feasible method for quantitatively measuring knee swelling as a relative change over time. However, the skin-electrode interface should be improved for reliable measurements at different moments in time. The findings suggest that the smart brace could be a promising tool for monitoring knee swelling during rehabilitation.

Our previous rat study demonstrated an ex vivo-created “Biomimetic Hematoma” (BH) that mimics the intrinsic structural properties of normal fracture hematoma, consistently and efficiently enhanced the healing of large bone defects at extremely low doses of rhBMP-2 (0.33 μg). The aim of this study was to determine if an extremely low dose of rhBMP-2 delivered within BH can efficiently heal large bone defects in goats.

Goat 2.5 cm tibial defects were stabilized with circular fixators, and divided into groups (n=2-3): 2.1 mg rhBMP-2 delivered on an absorbable collagen sponge (ACS); 52.5 μg rhBMP-2 delivered within BH; and an empty group. BH was created using autologous blood with a mixture of calcium and thrombin at specific concentrations. Healing was monitored with X-rays. After 8 weeks, femurs were assessed using microCT.

Using 2.1 mg on ACS was sufficient to heal 2.5 cm bone defects. Empty defects resulted in a nonunion after 8 weeks. Radiographic evaluation showed earlier and more robust callus formation with 97.5 % (52.5 μg) less of rhBMP-2 delivered within the BH, and all tibias were fully bridged at 3 weeks. The bone mineral density was significantly higher in defects treated with BH than with ACS. Defects in the BH group had smaller amounts of intramedullary and cortical trabeculation compared to the ACS group, indicating advanced remodeling.

The results confirm that the delivery of rhBMP-2 within the BH was much more efficient than on an ACS. Not only did the large bone defects heal consistently with a 40x lower dose of rhBMP-2, but the quality of the defect regeneration was also superior in the BH group. These findings should significantly influence how rhBMP-2 is delivered clinically to maximize the regenerative capacity of bone healing while minimizing the dose required, thereby reducing the risk of adverse effects.

Iliopsoas tendonitis occurs in up to 30% of patients after hip resurfacing arthroplasty (HRA) and is a common reason for revision. The primary purpose of this study was to validate our novel computational model for quantifying iliopsoas impingement in HRA patients using a case-controlled investigation. Secondary purpose was to compare these results with previously measured THA patients.

We conducted a retrospective search in an experienced surgeon's database for HRA patients with iliopsoas tendonitis, confirmed via the active hip flexion test in supine, and control patients without iliopsoas tendonitis, resulting in two cohorts of 12 patients. The CT scans were segmented, landmarked, and used to simulate the iliopsoas impingement in supine and standing pelvic positions. Three discrete impingement values were output for each pelvic position, and the mean and maximum of these values were reported. Cup prominence was measured using a novel, nearest-neighbour algorithm.

The mean cup prominence for the symptomatic cohort was 10.7mm and 5.1mm for the asymptomatic cohort (p << 0.01). The average standing mean impingement for the symptomatic cohort was 0.1mm and 0.0mm for the asymptomatic cohort (p << 0.01). The average standing maximum impingement for the symptomatic cohort was 0.2mm and 0.0mm for the asymptomatic cohort (p << 0.01). Impingement significantly predicted the probability of pain in logistic regression models and the simulation had a sensitivity of 92%, specificity of 91%, and an AUC ROC curve of 0.95.

Using a case-controlled investigation, we demonstrated that our novel simulation could detect iliopsoas impingement and differentiate between the symptomatic and asymptomatic cohorts. Interestingly, the HRA patients demonstrated less impingement than the THA patients, despite greater cup prominence. In conclusion, this tool has the potential to be used preoperatively, to guide decisions about optimal cup placement, and postoperatively, to assist in the diagnosis of iliopsoas tendonitis.

In the unstable patellofemoral joint (PFJ), the patella will articulate in an abnormal manner, producing an uneven distribution of forces. It is hypothesised that incongruency of the PFJ, even without clinical instability, may lead to degenerative changes. The aim of this study was to record the change in joint contact area of the PFJ after stabilisation surgery using an established and validated MRI mapping technique.

A prospective MRI imaging study of patients with a history of PFJ instability was performed. The patellofemoral joints were imaged with the use of an MRI scan during active movement from 0° through to 40° of flexion. The congruency through measurement of the contact surface area was mapped in 5-mm intervals on axial slices. Post-stabilisation surgery contact area was compared to the pre-surgery contact area.

In all, 26 patients were studied. The cohort included 12 male and 14 female patients with a mean age of 26 (15-43). The greatest mean differences in congruency between pre- and post-stabilised PFJs were observed at 0-10 degrees of flexion (0.54 cm² versus 1.18 cm², p = 0.04) and between 11° and 20° flexion (1.80 cm² versus 3.45 cm²; p = 0.01).

PFJ stabilisation procedures increase joint congruency. If a single axial series is to be obtained on MRI scan to compare the pre- and post-surgery joint congruity, the authors recommend 11° to 20° of tibiofemoral flexion as this was shown to have the greatest difference in contact surface area between pre- and post-operative congruency.

Macrophages play a critical role in innate immunity by promoting or inhibiting tissue inflammation and repair. Classically, macrophages can differentiate into either pro-inflammatory (M1) or pro-reparative (M2) phenotypes in response to various stimuli. Therefore, this study aimed to address how extracellular vesicles (EVs) derived from polarized macrophages can affect the inflammatory response of tendon cells.

For that purpose, human THP-1 cells were stimulated with lipopolysaccharide (LPS), and interleukins -4 and -13 (IL- 4, IL-13), to induce macrophages polarization into M1, M2, and hybrid M1/M2 phenotypes. Subsequently, the EVs were isolated from the culture medium by ultracentrifugation. The impact of these nanovesicles on the inflammation and injury scenarios of human tendon-derived cells (hTDCs), which had previously been stimulated with interleukin- 1 beta (IL-1ß) to mimic an inflammatory scenario, was assessed.

We were able to isolate three different nanovesicles populations, showing the typical shape, size and surface markers of EVs. By extensively analyzing the proteomic expression profiles of M1, M2, and M1/M2, distinct proteins that were upregulated in each type of macrophage-derived EVs were identified. Notably, most of the detected pro- inflammatory cytokines and chemokines had higher expression levels in M1-derived EVs and were mostly absent in M2-derived EVs. Hence, by acting as a biological cue, we observed that M2 macrophage-derived EVs increased the expression of the tendon-related marker tenomodulin (TNMD) and tended to reduce the presence of pro-inflammatory markers in hTDCs. Overall, these preliminary results show that EVs derived from polarized macrophages might be a potential tool to modulate the immune system responses becoming a valuable asset in the tendon repair and regeneration fields worthy to be further explored.

Iliopsoas impingement occurs in between 5-30% of patients after hip arthroplasty and has been thought to only be caused by an oversized cup, cup malpositioning, or the depth of the psoas valley. However, no study has associated the relationship between preoperative measurements with the risk of impingement. This study sought to assess impingement between the iliopsoas and acetabular cup using a novel validated model to determine the risk factors for iliopsoas impingement.

413 patients received lower limb CT scans and lateral x-rays that were segmented, landmarked, and measured using a validated preoperative planning protocol. Implants were positioned according to the preference of ten experienced surgeons. The segmented bones were transformed to the standing reference frame and simulated with a novel computational model that detects impingement between the iliopsoas and acetabular cup. Definitions of patients at-risk and not at-risk of impingement were defined from a previous validation study of the simulation. At-risk patients were propensity score matched to not at-risk patients.

21% of patients were assessed as being at-risk of iliopsoas impingement. Significant differences between at-risk patients and not at-risk patients were observed in standing pelvic tilt (p << 0.01), standing femoral internal rotation (p << 0.01), medio-lateral centre-of-rotation (COR) change (p << 0.01), supine cup anteversion (p << 0.01), pre- to postoperative cup offset change (p << 0.001), postoperative gross offset (p = 0.009), and supero-inferior COR change (p = 0.02).

Impingement between the iliopsoas and acetabular cup is under-studied and may be more common than is published in the literature. Previously it has been thought to only be related to cup size or positioning. However, we have observed significant differences between at-risk and not at-risk patients in additional measurements. This indicates that its occurrence is more complex than simply being related to cup position.

A Morel-Lavallee lesion (MLL) is a benign cystic lesion that occurs due to injury to the soft-tissue envelope's perforating vascular and lymphatic systems, resulting in a distinctive hemolymphatic fluid accumulation between the tissue layers. The MLL has the potential to make a significant impact on the treatment of orthopaedic injuries.

A 79-year-old male patient community ambulatory with assisting aid (cane) known case of Diabetes mellitus, hypertension, bronchial asthma and ischemic heart disease. He was brought to the Emergency, complaining of right hip discomfort and burning sensation for the last 5 days with no history of recent trauma at all. Patient had history of right trochanteric femur fracture 3 years ago, treated with DHS in a privet service. Clinical and Radiological assessment showed that the patient mostly has acute MLL due to lag screw cut out. We offered the patient the surgical intervention, but he refused despite explaining the risks of complications if not treated and preferred to receive the conservative treatment. Compression therapy management explained to him including biker's shorts (instructed to be worn full-time a day) and regular follow up in clinic. Symptom's improvement was reported by the patient in the subsequent visits.

In the polytrauma patient, a delayed diagnosis of these lesions is conceivable due to the presence of more visible injuries. It's located over the greater trochanter more commonly, but sometimes in other areas such as the lower lumbar region, the thigh, or the calf. Incorrect or delayed diagnosis and care can have unfavorable outcomes such as infection, pseudocyst development, and cosmetologically deformity. Magnetic resonance imaging (MRI) and ultrasound will aid in MLL diagnosis. However, the effectiveness of MLL therapy remains debatable.

We strongly believe that the MLL caused due to tangential shear forces applied to the soft tissue leads to accumulation of the blood and/or lymph between the subcutaneous and overlying fascia and it often misdiagnosed due to other distracting injuries. Nontheless, in our case we reported MLL occur due to internal pressure on the fascia caused by cut out of DHS lag screw.

While clinically important improvements in Oxford Shoulder Scores have been defined for patients with general shoulder problems or those undergoing subacromial decompression, no threshold has been reported for classifying improvement after shoulder replacement surgery. This study aimed to establish the minimal clinically important change (MCIC) for the Oxford Shoulder Score in patients undergoing primary total shoulder replacement (TSR).

Patient-reported outcomes data were sourced from the Australian Orthopaedic Association National Joint Replacement Registry Patient-Reported Outcome Measures Program. These included pre- and 6-month post-operative Oxford Shoulder Scores and a rating of patient-perceived change after surgery (5-point scale ranging from ‘much worse’ to ‘much better’). Two anchor-based methods (using patient-perceived improvement as the anchor) were used to calculate the MCIC: 1) mean change method; and 2) predictive modelling, with and without adjustment for the proportion of improved patients.

The analysis included 612 patients undergoing primary TSR who provided pre- and post-operative data (58% female; mean (SD) age 70 (8) years). Most patients (93%) reported improvement after surgery. The MCIC derived from the mean change method was 6.8 points (95%CI 4.7 to 8.9). Predictive modelling produced an MCIC estimate of 11.6 points (95%CI 8.9 to 15.6), which reduced to 8.7 points (95%CI 6.0 to 12.7) after adjustment for the proportion of improved patients.

For patient-reported outcome measures to provide valuable information that can support clinical care, we need to understand the magnitude of change that matters to patients. Using contemporary psychometric methods, this analysis has generated MCIC estimates for the Oxford Shoulder Score. These estimates can be used by clinicians and researchers to interpret important changes in pain and function after TSR from the patient's perspective. We conclude that an increase in Oxford Shoulder Scores of at least 9 points can be considered a meaningful improvement in shoulder-related pain and function after TSR.

Human error is usually evaluated using statistical descriptions during radiographic annotation. The technological advances popularized the “non-human” landmarking techniques, such as deep learning, in which the error is presented in a confidence format that is not comparable to that of the human method. The region-based landmark definition makes an arbitrary “ground truth” point impossible. The differences in patients’ anatomies, radiograph qualities, and scales make the horizontal comparison difficult. There is a demand to quantify the manual landmarking error in a probability format.

Taking the measurement of pelvic tilt (PT) as an example, this study recruited 115 sagittal pelvic radiographs for the measurement of two PTs. We proposed a method to unify the scale of images that allows horizontal comparisons of landmarks and calculated the maximum possible error using a density vector. Traditional descriptive statistics were also applied.

All measurements showed excellent reliabilities (intraclass correlation coefficients > 0.9). Eighty-four measurements (6.09%) were qualified as wrong landmarks that failed to label the correct locations. Directional bias (systematic error) was identified due to cognitive differences between observers. By removing wrong labels and rotated pelves, the analysis quantified the error density as a “good doctor” performance and found 6.77°-11.76° maximum PT disagreement with 95% data points.

The landmarks with excellent reliability still have a chance (at least 6.09% in our case) of making wrong landmark decisions. Identifying skeletal contours is at least 24.64% more accurate than estimating landmark locations. The landmark at a clear skeletal contour is more likely to generate systematic errors. Due to landmark ambiguity, a very careful surgeon measuring PT could make a maximum 11.76° random difference in 95% of cases, serving as a “good doctor benchmark” to qualify good landmarking techniques.

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.

Source of the study: University of Auckland, Auckland, New Zealand and University of Otago, Christchurch, New Zealand

The Oxford Knee Score (OKS) is a 12-item questionnaire used to track knee arthroplasty outcomes. Validation of such patient reported outcome measures is typically anchored to a single question based on patient ‘satisfaction’, however risk of subsequent revision surgery is also an important outcome measure. The OKS can predict subsequent revision risk within two years, however it is not known which item(s) are the strongest predictors. Our aim was to identify which questions were most relevant in the prediction of subsequent knee arthroplasty revision risk.

All primary TKAs (n=27,708) and UKAs (n=8,415) captured by the New Zealand Joint Registry between 1999 and 2019 with at least one OKS response at six months, five years or ten years post-surgery were included. Logistic regression and receiver operating characteristics (ROC) curves were used to assess prediction models at six months, five years and ten years.

Q1 ‘overall pain’ was the strongest predictor of revision within two years (TKA: 6 months, odds ratio (OR) 1.37; 5 years, OR 1.80; 10 years, OR 1.43; UKA: 6 months, OR 1.32; 5 years, OR 2.88; 10 years, OR 1.85; all p<0.05). A reduced model with just three questions (Q1, Q6 ‘limping when walking’, Q10 ‘knee giving way’) showed comparable or better diagnostic ability with the full OKS (area under the curve (AUC): TKA: 6 months, 0.77 vs. 0.76; 5 years, 0.78 vs. 0.75; 10 years, 0.76 vs. 0.73; UKA: 6 months, 0.80 vs. 0.78; 5 years: 0.81 vs. 0.77; 10 years, 0.80 vs. 0.77).

The three questions on overall knee pain, limping when walking, and knee ‘giving way’ were the strongest predictors of subsequent revision within two years. Attention to the responses for these three key questions during follow-up may allow for prompt identification of patients most at risk of revision.

Back pain is a leading cause of disability worldwide and it is primarily considered to be triggered by intervertebral disc (IVD) degeneration (IVDD). Current treatments may improve pain and mobility, but carry high costs and fail to address IVD repair or regeneration. As no effective therapeutic approach has been proposed to restore inflamed and degenerated IVDs, there is the urgent need to clarify the key pathomechanism of IVDD, the involvement of inflammation, particularly complement activation in matrix catabolism, and how to target them towards tissue repair/regeneration. Mesenchymal stem cell (MSC)-based therapies have become the focus of several regenerative IVD studies. Although patients in clinical trials reported less pain after cell therapy, the long-term success of cell engraftment is unclear due to the hostile IVD environment. The mechanism-of-action of MSCs is mostly dependent on the secreted soluble factors. Moreover, priming of MSC with interleukin (IL)-1β modulates the secretome content, improving its anti-inflammatory and regenerative effect on IVDD organ culture models. MSC-derived extracellular vesicles (EVs) have also been shown to modulate human IVD cells towards a healthy IVD phenotype in vitro. However, the mechanisms involved in the effect of secretome and EVs, particularly with regard to immunomodulation and matrix metabolism, are not fully understood. Our work investigates the effects of secretome and EVs secreted by IL-1β-primed MSCs to impair IVD matrix degradation and/or improve matrix formation in IVDD.

Mechanical loading is important to maintain the homeostasis of the intervertebral disc (IVD) under physiological conditions but can also accelerate cell death and tissue breakdown in a degenerative state. Bioreactor loaded whole organ cultures are instrumental for investigating the effects of the mechanical environment on the IVD integrity and for preclinical testing of new therapies under simulated physiological conditions. Thereby the loading parameters that determine the beneficial or detrimental reactions largely depend on the IVD model and its preparation. Within this symposium we are discussing the use of bovine caudal IVD culture models to reproduce tissue inflammation or matrix degradation with or without bioreactor controlled mechanical loading. Furthermore, the outcome parameters that define the degenerative state of the whole IVD model will be outlined. Besides the disc height, matrix integrity, cell viability and phenotype expression, the tissue secretome can provide indications about potential interactions of the IVD with other cell types such as neurons. Finally, a novel multiaxial bioreactor setup capable of mimicking the six degrees-of-freedom loading environment of IVDs will be introduced that further advances the relevance of preclinical ex-vivo testing.

Worldwide, tendon disorders are one of the main causes of disability that decrease the quality of life of individuals and represent a substantial economic burden on society. Currently, the main therapies used for tendon injuries are not able to restore tendon functionality, and due to tendons' hypovascular and hypocellular nature, they present a reduced healing capacity, which also limits the success of the available therapies. In order to discover new therapies, extracellular vesicles (EVs), key players in cell-cell communication, have been widely explored for tissue engineering and regenerative medicine applications. Thus, the aim of this study is to assess the role of EVs derived from platelets in stem cell tenogenic commitment using a bioengineered tendon in vitro model for potential use as tendon therapeutic agents. Biomimetic platelet-derived EVs were produced by freeze-thaw cycles of platelets and isolation at different centrifugation speed. To recreate the architecture of tendons, a 3D system consisting of electrospun anisotropic nanofiber scaffolds coated with collagen encapsulating human adipose stem cells (hASCs) and different types of platelet-derived EVs, were produced. Then, the influence of the tendon-mimetic constructs and the distinct EVs populations in the hASCs tenogenic differentiation were assessed over culture time. We observed that the hASCs on the nanofibrous tendon scaffolds, show high cytoskeleton anisotropic organization that is characteristic of tenocytes. Moreover, acting as biological cues, platelet-derived EVs boosted hASCs tenogenic commitment, supported by the increased gene expression of tendon-related markers (SCX and TNMD). Additionally, EVs enhanced the deposition of tendon like extracellular matrix (ECM), as evidenced by the increased gene expression of ECM-related markers such as COL1, COL3, DCN, TNC, and MMP-3, which are fundamental for ECM synthesis and degradation balance. Moreover, EVs induced lower collagen matrix contraction on hASCs, which has been related with lower myofibroblast differentiation. Overall, the results revealed that EVs are capable of modulating stem cells' behavior boosting their tenogenic commitment, through the increased expression of healthy tendon cell markers, potentiating ECM deposition and decreasing cell contractility. Therefore, platelet EVs are a promising biochemical tool, worthy to be further explored, as paracrine signaling that might potentiate tendon repair and regeneration.

Recent researches indicate that both M1 and M2 macrophages play vital roles in tissue repair and foreign body reaction processes. In this study, we investigated the dynamics of M1 macrophages in the induced membrane using a mouse femur critical-sized bone defect model.

The Masquelet method (M) and control (C) groups were established using C57BL/6J male mice (n=24). A 3mm-bone defect was created in the right femoral diaphysis followed by a Kirschner wire fixation, and a cement spacer was inserted into the defect in group M. In group C, the bone defect was left uninserted. Tissues around the defect were harvested at 1, 2, 4, and 6 weeks after surgery (n=3 in each group at each time point). Following Hematoxylin and eosin (HE) staining, immunohistochemical staining (IHC) was used to evaluate the CD68 expression as a marker of M1 macrophage. Iron staining was performed additionally to distinguish them from hemosiderin-phagocytosed macrophages.

In group M, HE staining revealed a hematoma-like structure, and CD68-positive cells were observed between the spacer and fibroblast layer at 1 week. The number of CD68-positive cells decreased at 2 weeks, while they were observed around the new bone at 4 and 6 weeks. In group C, fibroblast infiltration and fewer CD68-positive cells were observed in the bone defect without hematoma-like structure until 2 weeks, and no CD68-positive cells were observed at 4 and 6 weeks. Iron staining showed hemosiderin deposition in the surrounding area of the new bone in both groups at 4 and 6 weeks. The location of hemosiderin deposition was different from that of macrophage aggregation.

This study suggests that M1 macrophage aggregation is involved in the formation of induced membranes and osteogenesis and may be facilitated by the presence of spacers.

The aim of the ongoing projects was to demonstrate the efficacy of autologous bone marrow derived stem cells (MSC) combined with biomaterial to induced new bone formation in a randomized multicenter controlled clinical trial.

Patients with a need for bone reconstruction of residual edentulous ridges in both the mandible and maxilla due to bone defects with a vertical loss of alveolar bone volume and/or knife edge ridges (≤ than 4,5 mm) unable to provide adequate primary stabilization for dental implants were included in the clinical study. Autologous bone marrow MSC were expanded, loaded on BCP and used to augment the alveolar ridges. After five months bone biopsies were harvested at the implant position site and implants were installed in the regenerated bone. The implants were loaded after 8–12 weeks. Safety, efficacy, quality of life and success/survival were assessed. Five clinical centers, 4 different countries participated. Bone grafts harvested from the ramus of the mandibles were used as control in the projects.

Utility score is a preference-based measure of general health state – where 0 is equal to death, and 1 is equal to perfect health. To understand a patient's smallest perceptible change in utility score, the minimal clinically important difference (MCID) can be calculated. However, there are multiple methods to calculate MCID with no consensus about which method is most appropriate. The aim of this study is to calculate MCID values for the Veterans-RAND 12 (VR12) utility score using varying methods. Our hypothesis is that different methods will yield different MCID values.

A tertiary institutional registry (SMART) was used as the study cohort. Patients who underwent unilateral TKA for osteoarthritis from January 2012 to January 2020 were included. Utility score was calculated from VR12 responses using the standardised Brazier's method. Distribution and anchor methods were used for the MCID calculation. For distribution methods, 0.5 standard deviations of the baseline and change scores were used. For anchor methods, the physical and emotional anchor questions in the VR12 survey were used to benchmark utility score outcomes. Anchor methods included mean difference in change score, mean difference in 12 month score, and receiver operating characteristics (ROC) analysis with the Youden index.

Complete case analysis of 1735 out of 1809 eligible patients was performed. Significant variation in the MCID estimates for VR12 utility score were reported dependent on the calculation method used. The MCID estimate from 0.5 standard deviations of the change score was 0.083. The MCID estimate from the ROC analysis method using physical or emotional anchor question improvement was 0.115 (CI95 0.08-0.14; AUC 0.656).

Different MCID calculation methods yielded different MCID values. Our results suggest that MCID is not an umbrella concept but rather many distinct concepts. A general consensus is required to standardise how MCID is defined, calculated, and applied in clinical practice.

In cartilage tissue engineering (TE),new solutions are needed to effectively drive chondrogenic differentiation of mesenchymal stromal cells in both normal and inflammatory milieu. Ultrasound waves represent an interesting tool to facilitate chondrogenesis. In particular, low intensity pulsed ultrasound (LIPUS)has been shown to regulate the differentiation of adipose mesenchymal stromal cells. Hydrogels are promising biomaterials capable of encapsulating MSCs by providing an instructive biomimetic environment, graphene oxide (GO) has emerged as a promising nanomaterial for cartilage TE due to its chondroinductive properties when embedded in polymeric formulations, and piezoelectric nanomaterials, such as barium titanate nanoparticles (BTNPs),can be exploited as nanoscale transducers capable of inducing cell growth/differentiation. The aim of this study was to investigate the effect of dose-controlled LIPUS in counteracting inflammation and positively committing chondrogenesis of ASCs embedded in a 3D piezoelectric hydrogel.

ASCs at 2*10⁶ cells/mL were embedded in a 3D VitroGel RGD^® hydrogel without nanoparticles (Control) or doped with 25 µg/ml of GO nanoflakes and 50 µg/ml BTNPs.The hydrogels were exposed to basal or inflammatory milieu (+IL1β 10ng/ml)and then to LIPUS stimulation every 2 days for 10 days of culture. Hydrogels were chondrogenic differentiated and analyzed after 2,10 and 28 days. At each time point cell viability, cytotoxicity, gene expression and immunohistochemistry (COL2, aggrecan, SOX9, COL1)and inflammatory cytokines were evaluated.

Ultrasound stimulation significantly induced chondrogenic differentiation of ASCs loaded into 3D piezoelectric hydrogels under basal conditions: COL2, aggrecan and SOX9 were significantly overexpressed, while the fibrotic marker COL1 decreased compared to control samples. LIPUS also has potent anti-inflammatory effects by reducing IL6 and IL8 and maintaining its ability to boost chondrogenesis.

These results suggest that the combination of LIPUS and piezoelectric hydrogels promotes the differentiation of ASCs encapsulated in a 3D hydrogel by reducing the inflammatory milieu, thus representing a promising tool in the field of cartilage TE.

Acknowledgements: This work received funding from the European Union's Horizon 2020 research and innovation program, grant agreement No 814413, project ADMAIORA (AdvanceD nanocomposite MAterIals for in situ treatment and ultRAsound-mediated management of osteoarthritis).

Management of ankle arthritis in young patients is challenging. Although ankle arthrodesis gives consistent pain relief, it leads to loss of function and adjacent joint arthritis. Ankle joint distraction (AJD) has been shown to give good outcomes in adults with osteoarthritis or post-traumatic arthritis. The efficacy in children or young adults and those with juvenile idiopathic arthritis is less well evidenced.

Clinical notes and radiographs of all patients (n=6) managed with AJD in one tertiary referral centre were retrospectively reviewed. Radiographs were taken pre-surgery, intra-operatively, 1 month following frame removal and at the last follow up, tibiotalar joint space was assessed using ImageJ software. Measurements were taken at the medial, middle and lateral talar dome using frame components as reference. Radiographic data for patients with a good clinical outcome was compared with those who did not.

At time of surgery mean age was 16.1 years (12 – 25 years). Mean follow up was 3.4 years (1.5 – 5.9 years). Indications were juvenile idiopathic arthritis (4) post-traumatic (1) and post-infective arthritis (1). Three patients at last follow up had a good clinical outcome. Two patients required revision to arthrodesis (1.3 and 2.4 years following distraction). One patient had spontaneous fusion. One patient required oral antibiotics for pin site infection.

Inter-observer reliability was 95%. Mean joint space was 1.17mm (SD = 0.87mm) pre-operatively which increased to 6.72mm (SD = 2.23mm) at the time of distraction and 2.09mm (SD = 1.14mm) at the time of removal. At one-year follow up, mean joint space was 1.96mm (SD = 1.97mm).

Outcomes following AJD in this population are variable although significant benefits were demonstrated for 50% of the patients in this series. Radiographic joint space preoperatively did not appear to be associated with need for arthrodesis. Further research in larger groups of young patients is required.

Recent studies suggested that both the soluble protein of the mesenchymal stromal cell (MSC) secretome, as well as the secreted extracellular vesicles (EVs) promote bone regeneration. However, there is limited knowledge of the changes in MSC secretome vesicular fraction during aging. We therefore aimed to characterize the release profiles and cargo of EVs from MSCs of different chronological ages.

Conditioned medium (CM) was collected from 13 bone marrow MSC strains (20-89 years) and from one MSC strain derived from human induced pluripotent stem cells (iPSCs). The EV-containing fraction was enriched with ultracentrifugation. The number of particles in the CM was evaluated by nanoparticle tracking analysis (NTA), and the number of EVs was evaluated by flow cytometry (FC) after staining with cell-mask-green and anti-CD81 antibody. EV cargo analysis was conducted using next-generation sequencing (NGS).

Our data confirmed the release of EVs from all MSC strains used in the study. There were no correlations between the number of particles and the number of EVs released in the CM, and between the number of EVs released and the strain age. Nevertheless, some of the lowest concentrations of EVs were found in the CM of strains over 70 years of age, which exhibited a low/absent chondrogenic and osteogenic differentiation potential. In contrast, iPSC-MSCs, which exhibited a high growth and three-lineage differentiation potential, released a similar amount of EVs as the best performing bone marrow MSC strain. NGS analysis identified several microRNAs that were significantly enriched in EVs of young MSC strains exhibiting low senescence, and those that were enriched in EVs of strains exhibiting high differentiation potentials. Gender had no influence on microRNA profiles in EVs or releasing MSCs.

Taken together, our data provides new insights into the properties of MSC vesicular secretome and its therapeutic potential during aging.

Multiple biochemical biomarkers have been previously investigated for the diagnosis, prognosis and response to treatment of articular cartilage damage, including osteoarthritis (OA). Synovial fluid (SF) biomarker measurement is a potential method to predict treatment response and effectiveness. However, the significance of different biomarkers and their correlation to clinical outcomes remains unclear. This systematic review evaluated current SF biomarkers used in investigation of cartilage degeneration or regeneration in the knee joint and correlated these biomarkers with clinical outcomes following cartilage repair or regeneration interventions.

PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials, and Embase databases were searched. Studies evaluating SF biomarkers and clinical outcomes following cartilage repair intervention were included. Two researchers independently performed data extraction and QUADAS-2 analysis. Biomarker inclusion, change following intervention and correlation with clinical outcome was compared.

9 studies were included. Study heterogeneity precluded meta-analysis. There was significant variation in sampling and analysis. 33 biomarkers were evaluated in addition to microRNA and catabolic/anabolic ratios. Five studies reported on correlation of biomarkers with six biomarkers significantly correlated with clinical outcomes following intervention. However, correlation was only demonstrated in isolated studies.

This review demonstrates significant difficulties in drawing conclusions regarding the importance of SF biomarkers based on the available literature. Improved standardisation for collection and analysis of SF samples is required. Future publications should also focus on clinical outcome scores and seek to correlate biomarkers with progression to further understand the significance of identified markers in a clinical context.

Degeneration of the intervertebral disc (IVD), and subsequent low back pain, is an almost inevitable cause of disability. The underlying mechanisms are complex and current therapeutic strategies mainly focus on symptomatic relief rather than on the intrinsic regeneration of the IVD. This talk will provide an overview of special anatomical features and the composition of the IVD as well as its cellular microenvironment. Selected promising conceptional regenerative approaches will be discussed.

The quest for optimal treatment of acute distal tibiofibular syndesmotic disruptions is still in progress. Using suture-button repair devices is one of the dynamic stabilization options, however, they may not be always appropriate for stabilization of length-unstable syndesmotic injuries. Recently, a novel screw-suture repair system was developed to address such issues. The aim of this study was to investigate the performance of the novel screw-suture repair system in comparison to a suture-button stabilization of unstable syndesmotic injuries.

Eight pairs of human cadaveric lower legs were CT scanned under 700 N single-leg axial loading in five foot positions – neutral, 15° external/internal rotation and 20° dorsi-/plantarflexion – in 3 different states: (1) pre-injured (intact); (2) injured, characterized by complete syndesmosis and deltoid ligaments cuts simulating pronation-eversion injury types III and IV as well as supination-eversion injury type IV according to Lauge-Hansen; (3) reconstructed, using a screw-suture (FIBULINK, Group 1) or a suture-button (TightRope, Group 2) implants for syndesmotic stabilization, placed 20 mm proximal to the tibia plafond. Following, all specimens were: (1) biomechanically tested over 5000 cycles under combined 1400 N axial and ±15° torsional loading; (2) rescanned. Clear space (diastasis), anterior tibiofibular distance, talar dome angle and fibular shortening were measured radiologically from CT scans. Anteroposterior (AP), axial, mediolateral and torsional movements at the distal tibiofibular joint level were evaluated biomechanically via motion tracking.

In each group clear space increased significantly after injury (p ≤ 0.004) and became significantly smaller in reconstructed compared with both pre-injured and injured states (p ≤ 0.041). In addition, after reconstruction it was significantly smaller in Group 1 compared to Group 2 (p < 0.001). AP and axial movements were significantly smaller in Group 1 compared with Group 2 (p < 0.001). No further significant differences were identified/detected between the groups (p ≥ 0.113).

Although both implant systems demonstrate ability for stabilization of unstable syndesmotic injuries, the screw-suture reconstruction provides better anteroposterior translation and axial stability of the tibiofibular joint and maintains it over time under dynamic loading. Therefore, it could be considered as a valid option for treatment of syndesmotic disruptions.

The anterior cruciate ligament (ACL) is the connective tissue located at the end of long bones providing stability to the knee joint. After tear or rupture clinical reconstruction of the tissue remains a challenge due to the particular mechanical properties required for proper functioning of the tissue. The outstanding mechanical properties of the ACL are characterized by a viscoelastic behavior responsible of the dissipation of the loads that are transmitted to the bone. These mechanical properties are the result of a very specialized graded extracellular matrix that transitions smoothly between the heterotypic cells, stiffness and composition of the ACL and the adjacent bone. Thus, mimicking the zonal biochemical composition, cellular phenotype and organization are key to reset the proper functioning of the ACL.

We have previously shown how the biochemical composition presented to cells in electrospun scaffolds results in haptokinesis, reverting contact-guidance effects.^[1] Here, we demonstrate that contact guidance can also be disrupted by structural parameters in aligned wavy scaffolds. The presentation of a wavy fiber arrangement affected the cell organization and the deposition of a specific ECM characteristic of fibrocartilage. Cells cultured in wavy scaffolds grew in aggregates, deposited an abundant ECM rich in fibronectin and collagen II, and expressed higher amounts of collagen II, X and tenomodulin as compared to aligned scaffolds. In-vivo implantation in rabbits of triphasic scaffolds accounting for aligned-wavy-aligned zones showed a high cellular infiltration and the formation of an oriented ECM, as compared to traditional aligned scaffolds.^[2]

Odontoid fracture of the second cervical vertebra (C2) is the most common spinal fracture type in elderly patients. However, very little is known about the biomechanical fracture mechanisms, but could play a role in fracture prevention and treatment. This study aimed to investigate the biomechanical competence and fracture characteristics of the odontoid process.

A total of 42 human C2 specimens (14 female and 28 male, 71.5 ± 6.5 years) were scanned via quantitative computed tomography, divided in 6 groups (n = 7) and subjected to combined quasi-static loading at a rate of 0.1 mm/s until fracturing at inclinations of −15°, 0° and 15° in sagittal plane, and −50° and 0° in transverse plane. Bone mineral density (BMD), specimen height, fusion state of the ossification centers, stiffness, yield load, ultimate load, and fracture type according to Anderson and d'Alonzo were assessed.

While the lowest values for stiffness, yield, and ultimate load were observed at load inclination of 15° in sagittal plane, no statistically significant differences could be observed among the six groups (p = 0.235, p = 0.646, and p = 0.505, respectively). Evaluating specimens with only clearly distinguishable fusion of the ossification centers (n = 26) reveled even less differences among the groups for all mechanical parameters. BMD was positively correlated with yield load (R² = 0.350, p < 0.001), and ultimate load (R² = 0.955, p < 0.001), but not with stiffness (p = 0.070). Type III was the most common fracture type (23.5%).

These biomechanical outcomes indicate that load direction plays a subordinate role in traumatic fractures of the odontoid process in contrast to BMD which is a strong determinant of stiffness and strength. Thus, odontoid fractures appear to result from an interaction between load magnitude and bone quality.

The use of mesenchymal stem cell (MSCs) for intervertebral disc (IVD) regeneration has been extensively explored in the last two decades. MSCs are potent cell types that can be easily and safely harvested due to their abundancy and availability. Moreover, they are characterized by the capacity to differentiate towards IVD cells as well as release growth factors to support resident cell metabolism and recruit local progenitor cells to induce endogenous repair of degenerated IVDs. This talk will outline the characteristics of the main MSC sources and their effect towards IVD regeneration based on available preclinical and clinical evidence. In addition, innovative aspects of MSC-derived cell-free therapies will also be discussed.

The biological understanding for the disease progression osteoarthritis (OA) has uncovered specific biomarkers from either synovial fluid, articular chondrocytes or synoviocytes that can be used to diagnose the disease. Examples of these biomarkers include interleukin-1β (IL-1β) or collagen II fragments (1, 2). In parallel, isolation of chondrocytes or bone marrow derived mesenchymal stromal cells (MSCs) has yielded cell-based strategies that have shown long- term beneficial effects in a specific cohort of patients, specifically in traumatic cartilage lesions (2). This latter finding shows that patient stratification of OA is an important tool to both match patients for a specific treatment and to develop novel therapies, especially disease modifying drugs. In order to create disease stage specific therapies, the use of next generation analysis tools such as RNAseq and metabolomics, has the potential to decipher specific cellular and molecular endotypes. Alongside greater understanding of the clinical phenotype (e.g. imaging, pain, co- morbidities), therapies can be designed to alleviate the symptoms of OA at specific points of the disease in patients. This talk will outline the current biological understanding of OA and discuss how patient stratification could assist in the design of innovative therapies for the disease.

Acknowledgements: This presentation was supported by the COST action, CA21110 – Building an open European Network on Osteoarthritis Research (NetwOArk)

In healthy subjects, respiratory maximal volumes are highly dependent on the sagittal range of motion of the T7-T10 segment. In AIS, the abolition of T7-T10 dynamics related to the stiffness induced by the apex region in Lenke IA curves could harm ventilation during maximal breathing. The aim of this study was to analyze the dynamics of the thoracic spine during deep breathing in AIS patients and in healthy matched controls. This is a cross-sectional, case-control study. 20 AIS patients (18 girls, Cobb angle, 54.7±7.9°; Risser 1.35±1.2) and 15 healthy volunteers (11 girls) matched in age (12.5 versus 15.8 yr. mean age) were included. In AIS curves, the apex was located at T8 (14) and T9 (6). Conventional sagittal radiographs of the whole spine were performed at maximal inspiration and exhalation. The ROM of each spinal thoracic functional segment (T1-T7, T7-T10, T10-T12) and the global T1-T12 ROM were measured. In healthy subjects, the mean T1-T12 ROM during forced breathing was 16.7±3.8. AIS patients showed a T1-T12 ROM of 1.1±1.5 (p<0.05), indicating a sagittal stiffness of the thoracic spine. A wide T7-T10 ROM (15.3±3.0) was found in healthy controls (91.6% of the T1–T12 ROM). AIS patients showed only 0.4±1.4 ROM at T7-T10 (36.4% of the T1-T12 ROM) (p<0.001). There was a significant positive correlation between the magnitude of T7-T10 kyphosis in maximal exhalation and both FVC (% of predicted FVC) and FEV1. In conclusion, Lenke 1A AIS patients show a restriction of the thoracic spine motion with an almost complete abolition of T7-T10 ROM, a crucial segment for deep breathing. T7-T10 stiffness could explain the ventilatory limitations found in AIS patients.

Tip-apex distance (TAD) has long been discussed as a metric for determining risk of failure in fixation of peritrochanteric hip fractures. This study seeks to investigate risk factors including TAD for hospital readmission one year after hip fixation surgery.

A retrospective review of proximal hip fractures treated with single screw intramedullary devices between 2016 and 2020 was performed at a 327 bed regional medical center. Patients included had a postoperative follow-up of at least twelve months or surgery-related complications developing within that time.

44 of the 67 patients in this study met the inclusion criteria with adequate follow-up post-surgery. The average TAD in our study population was 19.57mm and the average one year readmission rate was 15.9%. 3 out of 6 patients (50%) with a TAD > 25mm were readmitted within one year due to surgery-related complications. In contrast, 3 out of 38 patients (7.9%) with a TAD < 25mm were readmitted within one year due to surgery-related complications (p=0.0254). Individual TAD measurements, averaging 22.05mm in patients readmitted within one year of surgery and 19.18mm in patients not readmitted within one year of surgery were not significantly different between the two groups (p=0.2113).

Our data indicate a significant improvement in hospital readmission rates up to one year after hip fixation surgery in patients with a TAD < 25mm with a decrease in readmissions of over 40% (50% vs 7.9%). This result builds upon past investigations by extending the follow-up time to one year after surgery and utilizing hospital readmissions as a metric for surgical success. With the well-documented physical and financial costs of hospital readmission after hip surgery, our study highlights a reduction of TAD < 25mm as an effective method of improving patient outcomes and reducing financial costs to patients and medical institutions.

Osteoarthritis (OA) is the most common degenerative joint disorder. Its multifactorial etiology includes age, sex, joint overloading, genetic or nervous influences. In particular, the autonomic nervous system is increasingly gaining in importance. Its two branches, the sympathetic (SNS) and parasympathetic nervous system, are well-balanced under healthy conditions. OA patients seem to be prone to an autonomic imbalance and therefore, we analyzed their autonomic status.

More than 200 participants including patients with early and late stage knee OA (before and 1 year after knee replacement surgery) and healthy probands (age-matched) were analyzed. Heart rate variability was measured via electrocardiogram to assess long-term sympathetic (low-frequency=LF) and parasympathetic (high-frequency=HF, pRR50) activities or general variability (RMSSD, SDRR). Serum cortisol concentrations were measured by ELISA. Perceived chronic stress (PSQ) was assessed via questionnaire. Multivariant regression was performed for data analysis. LF/HF value of early OA was slightly increased compared to healthy controls but significantly higher compared to late OA patients before (p>0.05) and after TKR (p>0.01). HF in late OA patients before TKR was significantly decreased compared to patients after TKR (p>0.001) or healthy controls (p>0.05). Healthy probands exhibited the highest SDRR values, early OA patients had slightly lower levels and late OA patients before TKR displayed significantly reduced SDRR (p>0.001). The same differences were observed in pRR50 and RMSSD. Serum cortisol concentrations and PSQ scores increased in late OA patients before TKR. At the time point of TKR, women with beta blocker medication had significantly higher age (71 ± 9 years) than those without (63 ± 12 years)(p>0.01). An autonomic dysfunction with sympathetic dominance occurs in OA patients. The fact that beta blocker medication in women delayed the need of TKR indicates that SNS inhibition might counteract OA. Future therapeutic interventions for OA should consider a systemic approach with special regard on the ANS.

Translational models for OA have used a variety of small (mouse, rat) and large (sheep, pig) animal models to evaluate the efficacy of a specific therapy. Clinical trials based on the results of these animal models have yielded mixed results with respect to the treatment of the disease. Due to greater stringency in EU regulations in the use of animal models for research, ex vivo models of OA (e.g. cartilage explants, bioreactors) are being developed to mimic human joint motion as well as the inflammatory milieu (e.g. IL-1β) that can be used to understand efficacy of therapy in a physiological environment. The development of these models can enable therapies to undergo clinical trials in patients without the necessity for long-term animal studies. This presentation will describe the state of the art in this field and will discuss whether there is potential to speed up translation from bench to bedside in the future.

The HIPGEN study funded under EU Horizon 2020 (Grant 7792939) has the aim to investigate the potential of the first regenerative cell therapy for the improvement of recovery after muscle injury in hip fracture patients. For this aim we intramuscularly injected placental derived mesenchymal stromal cells during hip fracture arthroplasty. Despite not having reached the primary endpoint, which was the Short Physical Performance Battery, we could observe an increase in abductor muscle strength and a faster return to balance looking at symmetry in insole measurements during follow up.

Bone regeneration is a complex but very well organized process in which the immune system has a decisive role. The adaptive immune system and its experience level (percentage of effector and memory T cells) has been proven to influence the healing cascade especially in the early healing phases. This opens the possibility of an early intervention to enhance bone healing during the primary clinical treatment. Patients stratified for possible delayed bone healing could benefit from immunomodulatory treatment approaches. In pre-clinical studies cells and signaling molecules have been identified that could represent promising candidates to help patients in need.

To describe clinical situations for use of modified VAC in POC based on: diagnosis, comorbidities, BMI, wound size in cm, days following trauma when VAC was first applied, total duration of uninterrupted use, frequency of change, settings, bacterial growth, outcomes

To report the outcomes of mVAC use in POC within 6 months to help improve and standardize its application in the institution

This study involves data gathering from inpatients handled by orthopedic surgeons in training and subspecialty rotations in POC. The data collected are highly dependent on the doctors-in-charge's complete charting, thorough reporting and accurate documentation. Modified Vacuum Assisted Closure (mVAC) is used frequently in this study and is defined as a form of revised, adapted and reformed use of VAC based on available materials in the involved institution. The materials that are included are, but not limited to the following: sterile Uratex™ blue foam, nasogastric or suction tubing, phlegm suction machine, Bactigras™ and Opsite™ or Ioban™.

A total of 58 patients were included in the study. The average age of the population was 35 and are predominantly male. The most common mechanism of injury was motorcycle accident and 37 of the patients were diagnosed with an open fracture of the lower extremity with open tibia fractures (22) being the most common. Average wound area measured was 24.12 cm³. All patients yield a bacteria growth with e. coli being the most frequent. Average during of uninterrupted use was 39 days. Of the 58 included in the study, 8 patients underwent STSG, 2 had a flap coverage surgery, 4 patients eventually underwent amputation and 33 with complete resolution of soft tissue defect after conversion to biologic dressing post-mVAC. The rest of the population were still ongoing mVAC at the end of the study.

mVAC is an alternative temporary medium for soft tissue coverage for cases with or without concomitant fractures. mVAC promotes removal of exudate from the wound, supports wound apposition and granulation bed proliferation. Usage mVAC helps prepare for skin coverage procedure and on some cases leads to full resolution of defect.

The rotator cuff tendinopathy is one of the most common shoulder problems leading to full-thickness rotator cuff tendon tear and, eventually, to degenerative arthritis. Recent research on rotator cuff tendon degeneration has focused on its relationship to cell death. The types of cell death known to be associated with rotator cuff tendon degeneration are apoptosis, necrosis, and autophagic cell death. The increased incidence of cell death in degenerative tendon tissue may affect the rates of collagen synthesis and repair, possibly weakening tendon tissue and increasing the risk of tendon rupture. The biomolecular mechanisms of the degenerative changes leading to apoptotic cell death in rotator cuff tenofibroblasts have been identified as oxidative-stress-related cascade mechanisms. Furthermore, apoptosis, necrosis, and autophagic cell death are all known to be mediated by oxidative stress, a condition in which ROS (reactive oxygen species) are overproduced. Lower levels of oxidative stress trigger apoptosis; higher levels mediate necrosis. Although the signaltransduction pathway leading to autophagy has not yet been fully established, ROS are known to be essential to autophagy. A neuronal theory regarding rotator cuff degeneration has been developed from the findings that glutamate, a neural transmitter, is present in increased concentrations in tendon tissues with tendinopathy and that it induces rat supraspinatus tendon cell death. Recent studies have reported that hypoxia involved in rotator cuff tendon degeneration. Because antioxidants are known to scavenge for intracellular ROS, some studies have been conducted to determine whether antioxidants can reduce cell death in rotator cuff tendon-origin fibroblasts. The first study reported that an antioxidant has the ability to reduce apoptosis in oxidative-stressed rotator cuff tenofibroblasts. The second study reported that antioxidants have both antiapoptotic effects and antinecrotic effects on rotator cuff tendon-origin fibroblasts exposed to an oxidative stimulus. The third study reported that an antioxidant has antiautophagic-cell-death effects on rotator cuff tendon-origin fibroblasts exposed to an oxidative stimulus. The fourth study reported that glutamate markedly increases cell death in rotator cuff tendonorigin fibroblasts. The glutamate-induced cytotoxic effects were reduced by an antioxidant, demonstrating its cytoprotective effects against glutamate-induced tenofibroblast cell death. The fifth study reported that hypoxia significantly increases intracellular ROS and apoptosis. The hypoxia-induced cytotoxic effects were markedly attenuated by antioxidants, demonstrating their cytoprotective effects against hypoxia-induced tenofibroblast cell death. In conclusion, antioxidants have cytoprotective effects on tenofibroblasts exposed in vitro to an oxidative stressor, a neurotransmitter, or hypoxia. These cytoprotective effects result from antiapoptotic, antinecrotic, and antiautophagic actions involving the inhibition of ROS formation. These findings suggest that antioxidants may have therapeutic potential for rotator cuff tendinopathy. Further studies must be conducted in order to apply these in vitro findings to clinical situations.

Osteoarthritis (OA) is the most common joint disease, affecting approximately 16% of the adult population worldwide. The chronic inflammation in the joint leads to the breakdown of cartilage, which leads to permanent pain and limitations in everyday life at an early stage of the disease. To date, there is no therapy that can interrupt the inflammatory state or reverse cartilage damage. The PROTO consortium (funded by the EU Horizon Europe program, Grant 101095635) aims to prevent the development of OA by correcting a pathological biomechanical pattern by a digital training intervention and to treat early stage OA with an innovative allogeneic cell therapy.

More and more evidences showed that cartilage harbored local progenitor cells that could differentiate toward osteoblast, chondrocyte, and adipocyte. However, our previous results showed that osteoarthritis derived chondroprogenitor cells (OA-CPC) exhibited strong osteogenic potential even in chondrogenic condition. How to promote their chondrogenic potential is the key for cartilage repair and regeneration in osteoarthritis. Recently, lipid availability was proved to determine skeletal progenitor fate. Therefore, we aim to determine whether lipid inhibition under 3D culture condition could enhance OA-CPC chondrogenesis. Moreover, glucose concentration was also evaluated for chondrogenic capacity. Although there are many researches showed that lower glucose promotes chondrogenesis, in our results, we found that OA-CPC in high concentration of glucose (4.5g/L) with lipid inhibitor (GW1100) showed strongest chondrogenic potential, which could form largest cell pellet with strong proteoglycan staining, COL II expression and no COL I expression. Besides, COL2A1 was increased and COL10A1 was decreased significantly by GW1100 under high glucose condition in 2D culture. Interestingly, although the expression level of MMP13 was not changed by GW1100 at RNA and protein level, less MMP13 protein secreted out of cell nuclear. In summary, we estimated that higher glucose and lower lipid supplies benefit OA-CPC chondrogenesis and cartilage repair.

Knee joint distraction (KJD) has been associated with clinical and structural improvement and synovial fluid (SF) marker changes. However, structural changes have not yet been shown satisfactorily in regular care, since radiographic acquisition was not fully standardized. AI-based modules have shown great potential to reduce reading time, increase inter-reader agreement and therefore function as a tool for treatment outcome assessment. The objective was to analyse structural changes after KJD in patients using this AI-based measurement method, and relate these changes to clinical outcome and SF markers.

20 knee OA patients (<65 years old) were included in this study. KJD treatment was performed using an external fixation device, providing 5 mm distraction for 6 weeks. SF was aspirated before, during and immediately after treatment. Weight-bearing antero-posterior knee radiographs and WOMAC questionnaires were collected before and ~one year after treatment. Radiographs were analysed with the Knee Osteoarthritis Labelling Assistant (KOALA, IB Lab GmbH, Vienna, Austria), and 10 pre-defined biomarker levels in SF were measured by immunoassay. Radiographic one-year changes were analysed and linear regression was used to calculate associations between changes in standardized joint space width (JSW) and WOMAC, and changes in JSW and SF markers.

After treatment, radiographs showed an improvement in Kellgren-Lawrence grade in 7 of 16 patients that could be evaluated; 3 showed a worsening. Joint space narrowing scores and continuous JSW measures improved especially medially. A greater improvement in JSW was significantly associated with a greater improvement in WOMAC pain (β=0.64;p=0.020). A greater increase in MCP1 (β=0.67;p=0.033) and lower increase in TGFβ1 (β=-0.787;p=0.007) were associated with JSW improvement.

Despite the small number of patients, also in regular care KJD treatment shows joint repair as measured automatically on radiographs, significantly associated with certain SF marker change and even with clinical outcome.

In relation to regenerative therapies in osteoarthritis and cartilage repair, mesenchymal stromal cells (MSCs) have immunomodulatory functions and influence macrophage behaviour. Macrophages exist as a spectrum of pro-(M1) and anti-(M2) inflammatory phenotypic subsets. In the context of cartilage repair, we investigated MSC-macrophage crosstalk, including specifically the priming of cartilage cells by macrophages to achieve a regenerative rather than fibrotic outcome. Human monocytes were isolated from blood cones and differentiated towards M1 and M2 macrophages. Monocytes (Mo), M1 and M2 macrophages were cultured directly and indirectly (trans-well system) with human bone marrow derived MSCs. MSCs were added during M1 polarisation and separately to already induced M1 cells. Outcomes (M1/M2 markers and ligands/receptors) were evaluated using RT-qPCR and flow cytometry. Influence on chondrogenesis was assessed by applying M1 and M2 macrophage conditioned media (CM) sequentially to cartilage derived cells (recapitulating an acute injury environment). RT-qPCR was used to evaluate chondrogenic/fibrogenic gene transcription. The ratio of M2 markers (CD206 or CD163) to M1 markers (CD38) increased when MSCs were added to Mo/M1 macrophages, regardless of culture system used (direct or indirect). Pro-inflammatory markers (including TNFβ) decreased. CXCR2 expression by both M1 macrophages and MSCs decreased when MSCs were added to differentiated M1 macrophages in transwell. When adding initially M1 CM (for 12 hours) followed by M2 CM (for 12 hours) sequentially to chondrocytes, there was a significant increase of Aggrecan and Collagen type 2 gene expression and decrease in fibroblastic cell surface markers (PDPN/CD90). Mo/M1 macrophages cultured with MSCs, directly or indirectly, are shifted towards a more M2 phenotype. Indirect culture suggests this effect can occur via soluble signaling mediators. Sequential exposure of M1CM followed by M2CM to chondrocytes resulted in increased chondrogenic and reduced fibrotic gene expression, suggesting that an acute pro-inflammatory stimulus may prime chondrocytes before repair.

3D accurate measurements of the skeletal structures of the foot, in physiological and impaired subjects, are now possible using Cone-Beam CT (CBCT) under real-world loading conditions. In detail, this feature allows a more realistic representation of the relative bone-bone interactions of the foot as they occur under patient-specific body weight conditions. In this context, varus/valgus of the hindfoot under altered conditions or the thinning of plantar tissues that occurs with advancing age are among the most complex and interesting to represent, and numerous measurement proposals have been proposed. This study aims to analyze and compare these measurements from CBCT in weight-bearing scans in a clinical population. Sixteen feet of diabetic patients and ten feet with severe adult flatfoot acquired before/after corrective surgery underwent CBCT scans (Carestream, USA) while standing on the leg of interest. Corresponding 3D shapes of each bone of the shank and hindfoot were reconstructed (Materialise, Belgium). Six different techniques found in the literature were used to calculate the varus/valgus deformity, i.e., the inclination of the hindfoot in the frontal plane of the shank, and the distance between the ground and the metatarsal heads was calculated along with different solutions for the identification of possible calcifications. Starting with an accurate 3D reconstruction of the skeletal structures of the foot, a wide range of measurements representing the same angle of hindfoot alignment were found, some of them very different from each other. Interesting correlations were found between metatarsal height and subject age, significant in diabetic feet for the fourth and fifth metatarsal bones. Finally, CBCT allows 3D assessment of foot deformities under loaded conditions. The observed traditional measurement differences and new measurement solutions suggest that clinicians should consider carefully the anatomical and functional concepts underlying measurement techniques when drawing clinical and surgical conclusions.

Residual tumor cells left in the bone defect after malignant bone tumor resection can result in local tumor recurrence and high mortality. Therefore, ideal bone filling materials should not only aid bone reconstruction or regeneration, but also exert local chemotherapeutic efficacy. However, common bone substitutes used in clinics are barely studied in research for local delivery of chemotherapeutic drugs. Here, we aimed to use facile manufacturing methods to render polymethylmethacrylate (PMMA) cement and ceramic granules suitable for local delivery of cisplatin to limit bone tumor recurrence.

Porosity was introduced into PMMA cement by adding 1-4% carboxymethylcellulose (CMC) containing cisplatin, and chemotherapeutic activity was rendered to two types of granules via adsorption. Then, mechanical properties, porosity, morphology, drug release kinetics, ex vivo reconstructive properties of porous PMMA and in vitro anti-cancer efficacy against osteosarcoma cells were assessed. Morphologies, molecular structures, drug release profiles and in vitro cytostatic effects of two different drug-loaded granules on the proliferation of metastatic bone tumor cells were investigated.

The mechanical strengths of PMMA-based cements were sufficient for tibia reconstruction at CMC contents lower than 4% (≤3%). The concentrations of released cisplatin (12.1% and 16.6% from PMMA with 3% and 4% CMC, respectively) were sufficient for killing of osteosarcoma cells, and the fraction of dead cells increased to 91.3% within 7 days. Functionalized xenogeneic granules released 29.5% of cisplatin, but synthetic CaP granules only released 1.4% of cisplatin over 28 days. The immobilized and released cisplatin retained its anti-cancer efficacy and showed dose-dependent cytostatic effects on the viability of metastatic bone tumor cells.

Bone substitutes can be rendered therapeutically active for anticancer efficacy by functionalization with cisplatin. As such, our data suggest that multi-functional PMMA-based cements and cisplatin-loaded granules represent viable treatment options for filling bone defects after bone tumor resection.

Introduction

With advances in mobile application, digital health is being increasingly used for remote and personalised care. Patient education, self-management and tele communication is a crucial factor in optimising outcomes.

BACKGROUND

Theatre-listed trauma patients routinely require two ‘group and save’ blood-bank samples, in case they need perioperative transfusion. The Welsh Blood Service (WBS) need patients to have one recorded sample from any time in the last 10 years. A second sample, to permit cross-matching and blood issuing, must be within 7 days of transfusion (or within 48 hours if the patient is pregnant, or has been transfused within the last 3 months). The approximate cost of processing a sample is £15.00.

Results in patients undergoing total hip arthroplasty (THA) for femoral head osteonecrosis (ON) when compared with primary osteoarthritis (OA) are controversial. Different factors like age, THA type or surgical technique may affect outcome. We hypothesized that patients with ON had an increased revision rate compared with OA. We analysed clinical outcome, estimated the survival rate for revision surgery, and their possible risk factors, in two groups of patients.

In this retrospective cohort analysis of our prospective database, we assessed 2464 primary THAs implanted between 1989 and 2017. Patients with OA were included in group 1, 2090 hips; and patients with ON in group 2, 374 hips. In group 2 there were more men (p<0.001), patients younger than 60 years old (p<0.001) and with greater physical activity (p<0.001). Patients with lumbar OA (p<0.001) and a radiological acetabular shape type B according to Dorr (p<0.001) were more frequent in group 1. Clinical outcome was assessed according to the Harris Hip Score and radiological analysis included postoperative acetabular and femoral component position and hip reconstruction. Kaplan-Meier survivorship analysis was used to estimate the cumulative probability of not having revision surgery for different reasons. Univariate and multivariate Cox regression models were used to assess risk factors for revision surgery.

Clinical improvement was better in the ON at all intervals. There were 90 hips revised, 68 due to loosening or wear, 52 (2.5%) in group 1, and 16 (4.3%) in group 2. Overall, the survival rate for revision surgery for any cause at 22 years was 88.0 % (95% CI, 82-94) in group 1 and 84.1% (95% CI, 69 – 99) in group 2 (p=0.019). Multivariate regression analysis showed that hips with conventional polyethylene (PE), compared with highly-cross linked PEs or ceramic-on-ceramic bearings, (p=0.01, Hazard Ratio (HR): 2.12, 95% CI 1.15-3.92), and cups outside the Lewinnek´s safe zone had a higher risk for revision surgery (p<0.001, HR: 2.57, 95% CI 1.69-3.91).

Modern highly-cross linked PEs and ceramic-on-ceramic bearings use, and a proper surgical technique improved revision rate in patients undergoing THA due to ON compared with OA.

The current procedures being applied in the clinical setting to address osteoporosis-related delayed union and nonunion bone fractures have been found to present mostly suboptimal outcomes. As a result, bone tissue engineering (BTE) solutions involving the development of implantable biomimetic scaffolds to replace damaged bone and support its regeneration are gaining interest. The piezoelectric properties of the bone tissue, which stem primarily from the significant presence of piezoelectric type I collagen fibrils in the tissue's extracellular matrix (ECM), play a key role in preserving the bone's homeostasis and provide integral assistance to the regeneration process. However, despite their significant potential, these properties of bone tend to be overlooked in most BTE-related studies. In order to bridge this gap in the literature, novel hydroxyapatite (HAp)-filled osteoinductive and piezoelectric poly(vinylidene fluoride-co-tetrafluoroethylene) (PVDF-TrFE) electrospun nanofibers were developed to replicate the bone's fibrous ECM composition and electrical features. Different HAp nanoparticle concentrations (1–10%, wt%) were tested to assess their effect on the physicochemical and biological properties of the resulting fibers. The fabricated scaffolds displayed biomimetic collagen fibril-like diameters, while also presenting mechanical features akin to type I collagen. The increase in HAp presence was found to enhance both surface and piezoelectric properties of the fibers, with an improvement in scaffold wettability and increase in β-phase nucleation (translating to increased piezoelectricity) being observed. The HAp-containing scaffolds also exhibited an augmented bioactivity, with a more comprehensive surface mineralization of the fibers being obtained for the scaffolds with the highest HAp concentrations. Improved osteogenic differentiation of seeded human mesenchymal stem/stromal cells was achieved with the addition of HAp, as confirmed by an increased ALP activity, calcium deposition and upregulated expression of key osteogenic markers. Overall, our findings highlight, for the first time, the potential of combining PVDF-TrFE and HAp to develop electroactive and osteoinductive nanofibers for BTE.

Acknowledgements: The authors thank FCT for funding through the projects InSilico4OCReg (PTDC/EME-SIS/0838/2021), OptiBioScaffold (PTDC/EME-SIS/4446/2020) and BioMaterARISES (EXPL/CTM-CTM/0995/2021), the PhD scholarship (2022.10572.BD) and to the research institutions iBB (UIDB/04565/2020 and UIDP/04565/2020) and Associate Laboratory i4HB (LA/P/0140/2020).

Aims

The microbiological detection of microorganisms plays a crucial role in the diagnosis as well as in the targeted systemic and local antibiotic therapy of periprosthetic infections (PJI). Despite extensive efforts to improve the sensitivity of current culture methods, the rate of culture-negative infections is approximately 10–20% of all PJI. This study investigates an preanalytical algorithm (culture collection and direct processing in the OR) to potentially increasing culture yield in patients with PJI.

Aim

The aim of this study was to investigate the clinical relevance of an isolated positive sonication fluid culture (SFC) in patients who underwent revision surgery of a prosthetic joint. We hypothesized that cases with a positive SFC have a higher rate of infection and prosthesis failure during follow-up compared to controls with a negative SFC.

Background

Advice and education are considered vital components of back pain care within national guidelines. However, a recent systematic review only found low grade evidence for a small average effect. They also reported wide heterogeneity in intervention design and delivery. This review aimed to understand why intervention design varied and what limited effectiveness by examining the underlying theoretical foundations of the studies from that review.

Traditionally, sports Injuries have been sub-optimally managed through Emergency Departments (ED) in the public health system due to a lack of adequate referral processes. Fractures are ruled out through plain radiographs followed by a reactive process involving patient initiated further follow up and investigation. Consequently, significant soft tissue and chondral injuries can go undiagnosed during periods in which early intervention can significantly affect natural progression. The purpose of this quality improvement project was to assess the efficacy of an innovative Sports Injury Pathway introduced to detect and treat significant soft tissue injuries.

A Sports Injury Pathway was introduced at Fiona Stanley Hospital (WA, Australia) in April 2019 as a collaboration between the ED, Physiotherapy and Orthopaedic Departments. ED practitioners were advised to have a low threshold for referral, especially in the presence of a history of a twisting knee injury, shoulder dislocation or any suggestion of a hip tendon injury. All referrals were triaged by the Perth Sports Surgery Fellow with early follow-up in our Sports Trauma Clinics with additional investigations if required. A detailed database of all referrals was maintained, and relevant data was extracted for analysis over the first 3 years of this pathway.

570 patients were included in the final analysis. 54% of injuries occurred while playing sport, with AFL injuries constituting the most common contact-sports injury (13%). Advanced Scope Physiotherapists were the largest source of referrals (60%). A total of 460 MRI scans were eventually ordered comprising 81% of total referrals. Regarding Knee MRIs, 86% identified a significant structural injury with ACL injuries being the most common (33%) followed by isolated meniscal tears (16%) and multi-ligament knee injuries (11%). 95% of Shoulder MRI scans showed significant pathology. 39% of patients required surgical management, and of these 50% were performed within 3 months from injury.

The Fiona Stanley Hospital Sports Injury Pathway has demonstrated its clear value in successfully diagnosing and treating an important cohort of patients who present to our Emergency Department. This low threshold/streamlined referral pathway has found that the vast majority of these patients suffer significant structural injuries that may have been otherwise missed, while providing referring practitioners and patients access to prompt imaging and high-quality Orthopaedic sports trauma services. We recommend the implementation of a similar Sports Injury Pathway at all secondary and tertiary Orthopaedic Centres.

Children with osteogenesis imperfecta (OI) frequently present with coxa vara (CV). Skeletal fragility, severe deformity and limited fixation options make this a challenging condition to correct surgically. Our study aimed to determine the efficacy of the Fassier technique to correct CV and determine the complication rate.

Retrospective, descriptive case series from a tertiary hospital. We retrospectively reviewed records of a cohort of eight children (four females, 12 hips) with OI (6/8 Sillence type III, 2/8 type IV) who had surgical treatment with Fassier technique for CV between 2014 and 2020.

Inclusion Criteria: All patients with CV secondary to OI treated surgically with Fassier technique.

Exclusion Criteria: Patients older than 18 years; Patients with CV treated non-operatively or by surgical technique different to Fassier technique.

Data relating to the following parameters was collected and analyzed: demographic data, pre- and postoperative neck shaft angle (NSA), complications and NSA at final follow-up.

The mean age at operation was 5.8 years (range 2–10). The mean NSA was corrected from 96.8° preoperatively to 137º postoperatively. At a mean follow-up of 38.6 months, the mean NSA was maintained at 133°, and 83% (10/12) of hips had an NSA that remained greater than 120°. There was a 42% (5/12) complication rate: three Fassier–Duval rods failed to expand after distal epiphyseal fixation was lost during growth; one Rush rod migrated through the lateral proximal femur cortex with recurrent coxa vara; and one Rush rod migrated proximally and required rod revision.

The Fassier technique effectively corrected CV in children with moderate and progressively deforming OI. The deformity correction was maintained in the short term. The complication rate was high, but mainly related to the failed expansion of the Fassier–Duval rods.

Local anatomical abnormalities vary in congenital hip disease patients. Authors often present early to mid-term total hip arthroplasty clinical outcomes using different techniques and implants randomly on patients with different types of the disease, making same conclusions difficult.

We report long term outcomes (13 to 23 years) of the treatment of low and high dislocation cases (separately) with total hip arthroplasty using TM technology acetabular cups (Implex initially and then Zimmer) and short fluted conical (Zimmer) femoral stems.

From 2000 to 2010, 418 congenital hip disease hip joints were treated in our department with total hip arthroplasty. According to Hartofilakidis et al's classification, 230 hips had dysplasia, 101 low dislocation, (group A) and 87 high dislocation (group B). Pre-operative and post-operative values, at regular intervals, of HHS, SF-12, WOMAC, OHS and HOOS were available for all patients. Patient, surgeon and implant related failures and complications were recorded for all patients.

In all cases an attempt was made to restore hip center of rotation. In group A the average lengthening was 2.8 cm (range: 1 to 4.2) and in group B 5.7 cm (range: 4.2 to 11). In both groups, no hips were revised due to aseptic loosening of either the acetabular cup or the femoral stem. In group A, a cumulative success rate of 95.6% (95% confidence interval, 92.7% – 97.4%) and in group B a cumulative success rate of 94.8% (95% confidence interval, 92.6%–96.9%) was recorded, at 20 years, with revision for any reason as an end point. No s.s. differences were found between groups when mean values of HHS, SF-12, WOMAC and OKS were compared.

Satisfactory long-term clinical outcomes can be achieved in treating different types of congenital hip disease when appropriate surgical techniques combined with “game changing” implants are used.

Abstract

Abstract

The purpose was to determine the lifetime risk of re-operation due to specific complications related to dual mobility using re-operation as a competing risk, excluding loosening, periprosthetic fracture, and infection.

1503 mono-block dual mobility total hip arthroplasty (DM-THAs). Defining the re-operation when anesthesia (for dislocation) and revision when the implant changed. Surgery (801 for primary, 702 for revision with 201 for recurrent dislocation and 501 for loosening) performed between 1990 and 2020 in average 81-year-old (range 50–102) patients, with 522 living patients at 10 years follow-up.

During the first month, outer dislocation (60 cases; 4%) was the cause re-operation (1% among primary and 6 % among revisions). Twenty-four intra-prosthetic dislocations (IPD) were an iatrogenic consequence of a failed closed reduction (reduction maneuver dissociating the inner head) with 1.6% revision.

Between 1 month and 1 year, 22 new outer dislocations, while 25 of the 60 “first month” dislocations had recurrent dislocation. Fifteen other IPDs as iatrogenic consequences were observed. At one year, the cumulative revision was 3% (49 of 82 dislocations).

Between 1- 10-year FU, 132 other dislocations, and 45 other revisions for dislocations were observed. Corrosion was another cause of revision (37 cases): between the cobalt-chromium shell and the femoral neck (23 hips), or 14 crevice corrosion between the trunnion and the metal head (trunnion damage).

In summary, at 10-year: dislocation first cause of re-operation (214 anesthesia, 14%), while among 131 revisions (8.9 %) the 55 iatrogenic intra-prosthetic dislocations were the first revision cause before 39 recurrent dislocations and 37 corrosions.

The 522 patients followed ten years or more had a 15% risk revision due to DM specific complications during their lifetime and 10% more risk associated with loosening (6%), periprosthetic fracture (2%) and infection (2%).

Complex regional pain syndrome type 1 (CRPS-I) is a devastating complication that can occur after limb extremity injuries. The effectiveness of vitamin C in preventing CRPS-I incidence is debatable. Therefore, we conducted a systematic review and meta-analysis to assess the role of vitamin C in CRPS-I prevention and its effect on pain score, functional outcomes and complications rate after wrist, ankle, and foot fractures.

We searched Medline, Embase, the Cochrane Library, Clinicaltrial.gov, and Google Scholar from infinity to May 2021 for relevant studies comparing the incidence of CRPS-I with administration of perioperative vitamin C versus placebo after wrist, ankle, and foot fractures. Continuous data such as functional outcomes and pain scores were pooled as mean differences (MD), whist dichotomous variables such as the incidence of CRPS-I and complications were pooled as odds ratios (OR), with 95% confidence interval (CI). Data analyses was done using R software (meta package, version 4.9-0) for Windows.

Eight studies, including two quasi-experimental studies, were included. The timeframe for vitamin C administration ranged from 42 to 50 days post-injury and/or surgical fixation and the dosage was either 500 mg or 1000 mg. The results showed that vitamin C was associated with a lower rate of CRPS-I relative to a placebo (OR 0.33, 95% CI [0.17, 0.63]). No significant difference was found between vitamin C and placebo in terms of complications (OR 1.90, 95% CI [0.99, 3.65]), functional outcomes (MD 6.37, 95% CI [-1.40, 14.15]), and pain scores (MD −0.14, 95% CI [-1.07, 0.79]).

The findings demonstrate that when compared to placebo, at least 42 days of vitamin C prophylaxis is associated with prevention of CRPS-I following wrist, ankle, and foot fractures, irrespective of vitamin C dosage or fracture type. No significant differences were found with secondary outcomes.

Ankle fractures represent the third most common fragility fracture seen in elderly patients following hip and distal radius fractures. Non-operative management of these see complication rates as high as 70%. Open reduction and internal fixation (ORIF) has complication rates of up to 40%. With either option, patients tend to be managed with a non-weight bearing period of six weeks or longer. An alternative is the use of a tibiotalocalcaneal (TTC) nail. This provides a percutaneous treatment that enables the patient to mobilise immediately. This case-series explores the efficacy of this device in a broad population, including the highly comorbid and cognitively impaired.

We reviewed patients treated with TTC nail for acute ankle fractures between 2019 and 2022. Baseline and surgical data were collected. Clinical records were reviewed to record any post-operative complication, and post-operative mobility status and domicile. 24 patients had their ankle fracture managed with TTC nailing. No intra-operative complications were noted. There were six (27%) post-operative complications; four patients had loosening of a distal locking screw, one significant wound infection necessitating exchange of nail, and one pressure area from an underlying displaced fracture fragment. All except three patients returned to their previous domicile. Just over two thirds of patients returned to their baseline level of mobility.

This case-series is one of the largest and is also one of the first to include cognitively impaired patients. Our results are consistent with other case-series with a favourable complication rate when compared with ORIF in similar patient groups. The use of a TTC nail in the context of acute, geriatric ankle trauma is a simple and effective treatment modality. This series shows acceptable complication rates and the majority of patients are able to return to their baseline level of mobility and domicile.

Distal radius fractures are common in South Africa. Accurate, decisive radiographic parameter interpretation is key in appropriate management. Digital radiographic facilities are rare in the public setting and goniometer usage is known to be low, thus, visual estimates are the primary form of radiographic assessment. Previous research associated orthopaedic experience with accuracy of distal radius fracture parameter estimation but, oftentimes, doctors treating orthopaedic patients are not experienced in orthopaedics.

A cross-sectional questionnaire including four distal radius fracture radiographs administered to 149 orthopaedic doctors at three Johannesburg teaching hospitals. Participants grouped into ranks of: consultants (n=36), registrars (n=41), medical officers (n=20) and interns (n=52). Participants visually estimated values of distal radius fracture parameters, stated whether they would accept the position of the fractures and stated their percentage of routine usage of goniometers in real practice.

The registrar group was most accurate in visually estimating radial height, whilst the interns were least accurate (p=0.0237). The consultant, registrar and medical officer groups were equally accurate in estimating radial inclination whilst the intern group was the least accurate (p<0.0001). The consultant and registrar group were equally accurate at estimating volar tilt, whilst the medical officer and intern groups were least accurate (p<0.0001). The Gwet's AC agreement was 0.1612 (p=0.047) for acceptance of position of the first radiograph, 0.8768 (p<0.0001) for the second, 0.8884 (p<0.0001) for the third and 0.8064 (p<0.0001) for the fourth. All groups showed no difference in goniometer usage, using them largely 0–25% of practice (p=0.1937).

The study found that accuracy in visual estimations of distal radius fracture parameters was linked to orthopaedic experience but not linked to routine practice goniometer usage, which was minimal across all groups. Inter-rater agreement on acceptability of fracture position is potentially dependent on severity of deviation from acceptable parameters.

There is a paucity of mid-term data on modular dual-mobility (MDM) constructs versus large (≥40 mm) femoral heads (LFH) in revision total hip arthroplasties (THAs). The purpose of this study was to update our prior series at 10 years, with specific emphasis on survivorships free of re-revision for dislocation, any re-revision, and dislocation.

We identified 300 revision THAs performed at a single tertiary care academic institution from 2011 to 2014. Aseptic loosening of the acetabular component (n=65), dislocation (n=59), and reimplantation as part of a two-stage exchange protocol (n=57) were the most common reasons for index revision. Dual-mobility constructs were used in 124 cases, and LFH were used in 176 cases. Mean age was 66 years, mean BMI was 31 kg/m², and 45% were female. Mean follow-up was 7 years.

The 10-year survivorship free of re-revision for dislocation was 97% in the MDM cohort and 91% in the LFH cohort with a significantly increased risk of re-revision for dislocation in the LFH cohort (HR 5.2; p=0.03). The 10-year survivorship free of any re-revision was 90% in the MDM cohort and 84% in the LFH cohort with a significantly increased risk of any re-revision in the LFH cohort (HR 2.5; p=0.04). The 10-year survivorship free of any dislocation was 92% in the MDM cohort and 87% in the LFH cohort. There was a trend towards an increased risk of any dislocation in the LFH cohort (HR 2.3; p=0.06).

In this head-to-head comparison, revision THAs using MDM constructs had a significantly lower risk of re-revision for dislocation compared to LFH at 10 years. In addition, there was a trend towards lower risk of any dislocation.

Level of Evidence: IV

Fractures of the distal radius are common, and form a considerable proportion of the trauma workload. We conducted a study to examine the patterns of injury and treatment for adult patients presenting with distal radius fractures to a major trauma centre serving an urban population.

We undertook a retrospective cohort study to identify all patients treated at our major trauma centre for a distal radius fracture between 1 June 2018 and 1 May 2021. We reviewed the medical records and imaging for each patient to examine patterns of injury and treatment. We undertook a binomial logistic regression to produce a predictive model for operative fixation or inpatient admission.

Overall, 571 fractures of the distal radius were treated at our centre during the study period. A total of 146 (26%) patients required an inpatient admission, and 385 surgical procedures for fractures of the distal radius were recorded between June 2018 and May 2021. The most common mechanism of injury was a fall from a height of one metre or less. Of the total fractures, 59% (n = 337) were treated nonoperatively, and of those patients treated with surgery, locked anterior-plate fixation was the preferred technique (79%; n = 180).

The epidemiology of distal radius fractures treated at our major trauma centre replicated the classical bimodal distribution described in the literature. Patient age, open fractures, and fracture classification were factors correlated with the decision to treat the fracture operatively. While most fractures were

Abstract

Atypical femoral fracture non-union (AFFNU) is both, rare (3–5 per 1000 proximal femur fractures) and difficult to treat. Lack of standardised guidelines leads to a variability in fixation constructs, use of bone grafting and restricted weight bearing protocols, which are not evidence based. We hypothesised that there is no change in union rates without the use of bone grafting and immediate weight bearing post-operatively does not lead to increased complications.

The purpose of this study is to assess the long term results of combined ACL reconstruction and unicompartmental knee replacements (UKR). These patients have been selected for this combined operation due to their combination of instability symptoms from an absent ACL and unicompartmental arthritis.

Retrospective review of 44 combined UKR and ACL reconstruction by a single surgeon. Surgeries included both medial and lateral UKR combined with either revision ACL reconstruction or primary ACL reconstruction. Patient reported outcomes were obtained preoperatively, at one year, 5 years and 10 years. Revision rate was followed up over 13 years for a mean of 7.4 years post-surgery.

The average Oxford score at one year was 43 with an average increase from pre-operation to 1 year post operation of 15. For the 7 patients with 10 year follow up average oxford score was 42 at 1 year, 43 at 5 years and 45 at 10 years.

There were 5 reoperations. 2 for revision to total knee arthroplasty and 1 for an exchange of bearing due to wear. The other 2 were the addition of another UKR. For those requiring reoperation the average time was 8 years.

Younger more active patients presenting with ACL deficiency causing instability and unicompartmental arthritis are a difficult group to manage. Combining UKR and ACL reconstruction has scant evidence in regard to long term follow up but is a viable option for this select group. This paper has one of the largest cohorts with a reasonable follow up averaging 7.4 years and a revision rate of 11 percent.

Combined unilateral knee replacements and ACL reconstruction can be a successful operation for patients with ACL rupture causing instability and unicompartmental arthritis.

Abstract

Approximately 20% of primary and revision Total Knee Arthroplasty (TKA) patients require multiple revisions, which are associated with poor survivorship, with worsening outcomes for subsequent revisions. For revision surgery, either endoprosthetic replacements or metaphyseal sleeves can be used for the repair, however, in cases of severe defects that are deemed “too severe” for reconstruction, endoprosthetic replacement of the affected area is recommended. However, endoprosthetic replacements have been associated with high complication rates (high incidence rates of prosthetic joint infection), while metaphyseal sleeves have a more acceptable complication profile and are therefore preferred. Despite this, no guidance exists as to the maximal limit of bone loss, which is acceptable for the use of metaphyseal sleeves to ensure sufficient axial and rotational stability. Therefore, this study assessed the effect of increasing bone loss on the primary stability of the metaphyseal sleeve in the proximal tibia to determine the maximal bone loss that retains axial and rotational stability comparable to a no defect control.

Aim

Diagnosis of periprosthetic shoulder infections (PSI) is difficult as they are mostly caused by low-virulent bacteria and patients do not show typical infection signs, such as elevated blood markers, wound leakage, or red and swollen skin. Ultrasound-guided biopsies for culture may therefore be an alternative for mini-open biopsies as less costly and invasive method. The aim of this study was to determine the diagnostic value and reliability of ultrasound-guided biopsies for cultures alone and in combination polymerase chain reaction (PCR), and/or synovial markers for preoperative diagnosis of PSI in patients undergoing revision shoulder surgery.

Introduction

Angular deformities of the distal femur can be corrected by opening, closing and neutral wedge techniques. Opening wedge (OW) and closing wedge (CW) are popular and well described in the literature. CW and OW techniques lead to leg length difference whereas the advantage of neutral wedge (NW) technique has several unique advantages. NW technique maintains limb length, wedge taken from the closing side is utilised on the opening side and since the angular correction is only half of the measured wedge on either side, translation of distal fragment is minimum. Leg lengths are not altered with this technique hence a useful technique in large deformities. We found no reports of clinical outcomes using NW technique. We present a technique of performing external fixator assisted NW correction of large valgus and varus deformities of distal femur and dual plating and discuss the results.

Abstract

Obesity is a common in individuals undergoing arthroplasty, and the potential for weight loss with improved mobility may be expected by some. The aim of this study was 1. determine the proportion that achieved weight loss after hip or knee arthroplasty, and 2. examine the effect of obesity on patient reported outcomes (PROMS) and satisfaction with surgery.

Participants underwent primary TKA or THA between July 2015 and December 2020 and consented to participation in a research database with baseline PROMS, including weight, BMI, Oxford Knee, or Hip Score, and EQ5D. Participants repeated PROMS at 12 months after surgery with additional questions regarding satisfaction with surgery.

3449 patients completed PROMS 1 year after arthroplasty with weight and BMI. There were 1810 THA and 1639 TKA procedures. The mean baseline BMI was higher in TKA (29.8, SD 5.2) compared to THA (27.7, SD 5.0), p=0.001. A higher proportion of TKA were classified as obese class 1 (29% TKA, 19% THA), obese class 2 (11% TKA and 6% THA), and obese class 3 (5% TKA and 2% THA), p=0.001. The mean weight loss after 1 year was 0.4kg and 0.9kg in obese THA subjects and TKA subjects respectively. In the obese >5kg weight loss was achieved in 13% of TKA and 7% of THA (p=0.001). Obese experienced equivalent improvement in Oxford scores, compared to non-obese subjects. Satisfaction with surgery was reported by 95% of THA and 91% of TKA subjects with no significant differences between BMI group grades (p=0.491 THA and p=0.473 TKA).

Preoperative obesity was observed in 44% of TKA and 27% of THA subjects. In the obese only 1 in 10 subjects lost 5kg or more over 12 months. Obese patients experienced equivalent improvements in outcome after arthroplasty and rates of satisfaction with surgery to the non-obese.

Glutamate regulates the expression of apoptosis-related genes and triggers the apoptosis of fibroblasts in rotator cuff tendons. Subacromial bursitis is always accompanied by symptomatic rotator cuff tear (RCT). However, no study has been reported on the presence of glutamate in subacromial bursa and on its involvement of shoulder pain in patients who had RCT. The purposes of this study were to determine whether the glutamate expression in subacromial bursa is associated with the presence of RCT and with the severity of shoulder pain accompanying RCT.

Subacromial bursal tissues were harvested from patients who underwent arthroscopic rotator cuff tendon repair or glenoid labral repair with intact rotator cuff tendon. Glutamate tissue concentrations were measured, using a glutamate assay kit. Expressions of glutamate and its receptors in subacromial bursae were histologically determined. The sizes of RCT were determined by arthroscopic findings, using the DeOrio and Cofield classification. The severity of shoulder pain was determined, using visual analog scale (VAS). Any associations between glutamate concentrations and the size of RCT were evaluated, using logistic regression analysis. The correlation between glutamate concentrations and the severity of pain was determined, using the Pearson correlation coefficient. Differences with a probability <0.05 were considered statistically significant.

Glutamate concentrations showed significant differences between the torn tendon group and the intact tendon group (P = 0.009). Concentrations of glutamate significantly increased according to increases in tear size (P < 0.001). In histological studies, the expressions of glutamate and of its ionotropic and metabotropic receptors have been confirmed in subacromial bursa. Glutamate concentrations were significantly correlated with pain on VAS (Rho=0.56 and P =0.01).

The expression of glutamate in subacromial bursa is significantly associated with the presence of RCT and significantly correlated with its accompanying shoulder pain.

Acknowledgements: This research was supported by the Basic Science Research Program, through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A3A01018955 and 2017R1D1A1B03035232).

ZrN-multilayer coating is clinically well established in total knee arthroplasty [1–3] and has demonstrated significant reduction in polyethylene wear and metal ion release [4,5].

The goal of our study was to analyze the biotribological behaviour of the ZrN-multilayer coating on a polished cobalt-chromium cemented hip stem.

CoCr28Mo6 alloy hip stems with ZrN-multilayer coating (CoreHip®AS) were tested versus an un-coated version. In a worst-case-scenario the stems with ceramic heads have been tested in bovine serum in a severe cement interface debonding condition under a cyclic load of 3,875 N for 15 million cycles. After 1, 3, 5, 10 & 15 million cycles the surface texture was analysed by scanning-electron-microscopy (SEM) and energy-dispersive x-ray (EDX). Metal ion concentration of Co,Cr,Mo was measured by inductively coupled plasma mass spectroscopy (ICP-MS) after each test interval.

Based on SEM/EDX analysis, it has been demonstrated that the ZrN-multilayer coating keeps his integrity over 15 million cycles of severe stem cemented interface debonding without any exposure of the CoCr28Mo6 substrate.

The ZrN-multilayer coated polished cobalt-chromium cemented hip stem has shown a reduction of Co & Cr metal ion release by two orders of a magnitude, even under severe stem debonding and high interface micro-motion conditions.

ZrN-multilayer coating on polished cobalt-chromium cemented hip stems might be a suitable option for further minimisation of Co & Cr metal ion release in total hip arthroplasty. Clinical evidence has to be proven during the next years.

An increased number of neutrophils (NEUs) has long been associated with infections in the knee joints; their contribution to knee osteoarthritis (KOA) pathophysiology remains largely unexplored. This study aimed to compare the phenotypic and functional characteristics of synovial fluid (SF)-derived NEUs in KOA and knee infection (INF).

Flow cytometric analysis, protein level measurements (ELISA), NEU oxidative burst assays, detection of NEU phagocytosis (pHrodo^TM Green Zymosan Biparticles^TM Conjugate for Phagocytosis), morphological analysis of the SF-derived/synovial tissue NEUs, and cultivation of human umbilical vein endothelial cells (HUVECs) using SF supernatant were used to characterise NEUs functionally/morphologically.

Results: Compared with INF NEUs, KOA NEUs were characterised by a lower expression of CD11b, CD54 and CD64, a higher expression of CD62L, TLR2 and TLR4, and lower production of inflammatory mediators and proteases, except CCL2.

Functionally, KOA NEUs displayed an increased production of radical oxygen species and phagocytic activity compared with INF NEUs. Morphologically, KOA and INF cells displayed different cell sizes and morphology, histological characteristics of the surrounding synovial tissues and influence on endothelial cells. KOA NEUs were further subdivided into two groups: SF containing <10% and SF with 10%–60% of NEUs. Analyses of two KOA NEU subgroups revealed that NEUs with SF <10% were characterised by 1) higher CD54, CD64, TLR2 and TLR4 expression on their surface; 2) higher concentrations of TNF-α, sTREM-1, VILIP-1, IL-1RA and MMP-9 in SFs.

Our findings reveal a key role for NEUs in the pathophysiology of KOA, indicating that these cells are morphologically and functionally different from INF NEUs. Further studies should explore the mechanisms that contribute to the increased number of NEUs and their crosstalk with other immune cells in KOA.

This study was supported by the Ministry of Health of the Czech Republic (NU20-06-00269; NU21-06-00370).

Osteoarthritis, the most common degenerative joint disease, significantly impairs life quality and labor capability of patients. Synovial inflammation, initiated by HMGB1 (High mobility group box 1)-induced activation of macrophage, precedes other pathological changes. As an upstream regulator of NF-κB (nuclear factor-kappa B) and MAPK (mitogen-activated protein kinase) signaling pathway, TAK1 (TGF-β activated kinase 1) participates in macrophage activation, while its function in osteoarthritis remains unveiled. This study aims to investigate the role of TAK1 in the pathogenesis of osteoarthritis via both in vitro and in vivo approaches.

We performed immunohistochemical staining for TAK1 in synovial tissue, both in osteoarthritis patients and healthy control. Besides, immunofluorescence staining for F4/80 as macrophage marker and TAK1 were conducted as well. TAK1 expression was examined in RAW264.7 macrophages stimulated by HMGB1 via qPCR (Quantitative polymerase chain reaction) and Western blotting, and the effect of TAK1 inhibitor (5z-7 oxozeaenol) on TNF-α production was evaluated by immunofluorescence staining. Further, we explored the influence of intra-articular shRNA (short hairpin RNA) targeting TAK1 on collagenase-induced osteoarthritis in mice.

Immunohistochemical staining confirmed significant elevation of TAK1 in osteoarthritic synovium, and immunofluorescence staining suggested macrophages as predominant residence of TAK1. In HMGB1-stimulated RAW264.7 macrophages, TAK1 expression was up-regulated both in mRNA and protein level. Besides, TAK1 inhibitor significantly impairs the production of TNF-α by macrophages upon HMGB1 stimulation. Moreover, intra-articular injection of lentivirus loaded with shRNA targeting TAK1 (sh-TAK1) reduced peri-articular osteophyte formation in collagenase-induced osteoarthritis in mice.

TAK1 exerts a potent role in the pathogenesis of osteoarthritis by mediating the activation of macrophages.

Energy storing tendons such as the human Achilles and equine superficial digital flexor tendon (SDFT) are prone to age-related injury. Tendons have poor healing capacity and a lack of effective treatments can lead to ongoing pain, reduced function and re-injury. It is therefore important to identify the mechanisms underpinning age-related tendinous changes in order to develop more effective treatments. Our recent single cell sequencing data has shown that tendon cell populations have extensive heterogeneity and cells housed in the tendon interfascicular matrix (IFM) are preferentially affected by ageing. There is, however, a lack of established surface markers for cell populations in tendon, limiting the capacity to isolate distinct cell populations and study their contribution to age-related tendon degeneration. Here, we investigate the presence of the cell surface proteins MET proto-oncogene (MET), integrin subunit alpha 10 (ITGA10), fibroblast activation protein alpha (FAP) and platelet derived growth factor receptor alpha (PDGFRA) in the equine SDFT cell populations and their co-localisation with known markers.

Using Western blot we validated the specificity of selected antibodies in equine tissue before performing immunohistochemistry to establish the location of the respective proteins in the SDFT. We subsequently used double labelling immunofluorescence with the established mural cell marker desmin (DES) to distinguish between tenocyte and mural cell populations.

In situ, MET, ITGA10, and FAP presence was found in cells throughout the tendon whereas PDGFRA was present in cells within the IFM. Double labelling immunofluorescence with the mural cell marker DES showed lack of co-localisation between PDGFRA and DES suggesting PDGFRA is labelling an IFM cell population distinct from those associated with blood vessels.

PDGFRA is a promising target for the specific cell sorting of IFM-localised tenocytes, enabling their isolation and subsequent characterisation.

Acknowledgments: The authors acknowledge the Biotechnology and Biological Sciences Research Council (BB/W007282/1) for funding this work.

Occlusal loading and muscle forces during mastication aids in assessment of dental restorations and implants and jaw implant design; however, three-dimensional bite forces cannot be measured with conventional transducers, which obstruct the native occlusion. The aim of this study was to combine accurate jaw kinematics measurements, together with subject-specific computational modelling, to estimate subject-specific occlusal loading and muscle forces during mastication.

Motion experiments were performed on one male participant (age: 39yrs, weight: 82kg) with healthy dentition. Two low-profile magnetic sensors were fixed to the participant's teeth and the two dental arches digitised using an intra-oral scanner. The participant performed ten continuous of chewing on a polyurethane rubber sample of known material properties, followed by maximal compression (clenching). This was repeated at the molars, premolars of both the left and right sides, and central incisors. Jaw motion was simultaneously recorded from the sensors, and finite element modelling used to estimate bite force. Specifically, simulations of chewing and biting were performed by driving the model using the measured kinematics, and bite force magnitude and direction quantified. Muscle forces were then evaluated using a rigid-body musculoskeletal model of the patient's jaw.

The first molars generated the largest bite forces during chewing (left: 309 N, right: 311 N) and maximum-force biting (left: 496 N, right: 495 N). The incisors generated the smallest bite forces during chewing (75 N) and maximum-force biting (114 N). The anterior temporalis and superficial masseter muscles had the largest contribution to maximum bite force, followed by the posterior temporalis and medial pterygoid muscles.

This study presents a new method for estimating dynamic occlusal loading and muscle forces during mastication. These techniques provide new knowledge of jaw biomechanics, including muscle and occlusal loading, which will be useful in surgical planning and jaw implant design.

Intramedullary nails (IMNs) are the current gold standard for treatment of long bone diaphyseal and selected metaphyseal fractures. Their design has undergone many revisions to improve fixation techniques, conform to the bone shape with appropriate anatomic fit, reduce operative time and radiation exposure, and extend the indication of the same implant for treatment of different fracture types with minimal soft tissue irritation.

The IMNs are made or either titanium alloy or stainless steel and work as load-sharing internal splints along the long bone, usually accommodating locking elements – screws and blades, often featuring angular stability and offering different configurations for multiplanar fixation – to secure secondary fracture healing with callus formation in a relative-stability environment. Bone cement augmentation of the locking elements can modulate the construct stiffness, increase the surface area at the bone-implant interface, and prevent cut-through of the locking elements.

The functional requirements of IMNs are related to maintaining fracture reduction in terms of length, alignment and rotation to enhance fracture healing. The load distribution during patient's activities is along the entire bone-nail interface, with nail length and anatomic fit being important factors to avoid stress risers.

Stratification is required to ensure that only those patients likely to benefit, receive Autologous Chondrocyte Implantation (ACI); ideally by assessing a biomarker in the blood. This study aimed to assess differences in the plasma proteome of individuals who respond well or poorly to ACI.

Isobaric tag for relative and absolute quantitation (ITRAQ) mass spectrometry and label-free proteomics analyses were performed in tandem as described previously by our group (Hulme et al., 2017; 2018; 2021) using plasma collected from ACI responders (n=10) compared with non-responders (n=10) at each stage of surgery (Stage I, cartilage harvest and Stage II, cell implantation).

iTRAQ using pooled plasma detected 16 proteins that were differentially abundant at baseline in ACI responders compared with non-responders (n=10) (≥±2.0 fold; p<0.05). Responders demonstrated a mean Lysholm (patient reported functional score from 0–100) improvement of 33±13 and non-responders a mean worsening of −13±13 points. The most pronounced plasma proteome shift was seen in response to Stage I surgery in ACI non-responders, with 48 proteins being differentially abundant between the two surgical procedures. We have previously noted this marked shift in response to initial surgery in the SF of ACI non-responders, several of these proteins were associated with the Acute Phase Response. One of these proteins, clusterin, could be confirmed in patients’ plasma using an independent immunoassay using individual samples. Label-free proteomic data from individual samples identified only cartilage acidic protein-1 (known to associate with osteoarthritis progression) to be significantly more abundant at Stage I in the plasma of non-responders.

This study indicates that proteins can be identified within the plasma that have potential use in ACI patient stratification. Further work is required to validate the findings of this discovery-phase work in larger ACI cohorts.

Periprosthetic joint infections (PJI) are one of the most common reasons for orthopedic revision surgeries. In previous studies, it has been shown that silver modification of titanium (Ti-6Al-4V) surfaces by PMEDM (powder mixed electrical discharge machining) has an antibacterial effect on Staphylococcus aureus adhesion. Whether this method also influences the proliferation of bacteria has not been investigated so far. Furthermore, the effect is only limitedly investigated on the ossification processes. Therefore, the aim of this work is to investigate the antibacterial effect as well as the in vitro ossification process of PMEDM machined surfaces modified by integration of silver.

In this study, we analyzed adhesion and proliferation of S. aureus in comparison to of surface roughness, silver content and layer thickness of the silver-integrated-PMEDM surfaces (N = 5). To test the in vitro ossification, human osteoblasts (SaOs-2) and osteoclasts (differentiated from murine-bone-marrow-macrophages) were cultured on the silver surfaces (N = 3).

We showed that the attachment of S. aureus on the surfaces was significantly lower than on the comparative control surfaces of pure Ti-6Al-4V without incorporated silver, independently of the measured surface properties. Bacterial proliferation, however, was not affected by the silver content. No influence on the in vitro ossification was observed, whereas osteoclast formation was drastically reduced on the silver-modified surfaces.

We showed that 1 to 3% of silver in the surface layer significantly reduced the adhesion of S. aureus, but not the proliferation of already attached bacteria. At the same time, no influence on the in vitro ossification was observed, while no osteoclasts were formed on the surface. Therefore, we state that PMEDM with simultaneous silver modification of the machined surfaces represents a promising technology for endoprostheses manufacturing to reduce infections while at the same time optimizing bone ingrowth.

Treatment of posterior malleolar (PM) ankle fractures remain controversial. Despite increasing recommendation for small PM fragment fixation, high quality evidence demonstrating improved clinical outcomes over the unfixated PM is limited. We describe the medium-to-long term clinical and radiographical outcomes in younger adult patients with PM ankle fractures managed without PM fragment fixation.

A retrospective cohort study of patients aged 18-55 years old admitted under our orthopaedic unit between 1st of April 2009 and 31st of October 2013 with PM ankle fractures was performed. Inclusion criteria were that all patients must mobilise independently pre-trauma, have no pre-existing ankle pathologies, and had satisfactory bimalleolar and syndesmotic stabilisation. Open fractures, talar fractures, calcaneal fractures, pilon fractures, subsequent re-injury and major complications were excluded. All PM fragments were unfixated. Clinical outcomes were evaluated using Foot and Ankle Ability Measure (FAAM) with activities of daily living (ADL) and sports subscale, visual analogue scale (VAS) and patient satisfaction ratings. Osteoarthrosis was assessed using modified Kellgren-Lawrence scale on updated weightbearing ankle radiographs.

61 participants were included. Mean follow-up was 10.26 years. Average PM size was 16.19±7.39%. All participants were evaluated for clinical outcomes, demonstrating good functional outcomes (FAAM-ADL 95.48±7.13; FAAM-Sports 86.39±15.52) and patient satisfaction (86.16±14.42%), with minimal pain (VAS 1.13±1.65). Radiographical outcomes were evaluated in 52 participants, showing no-to-minimal osteoarthrosis in 36/52 (69.23%), mild osteoarthrosis in 14/52 (26.92%) and moderate osteoarthrosis in 2/52 (3.85%). Clinical outcomes were not associated with PM fragment size, post-reduction step-off, dislocation, malleoli fractured or syndesmotic injury. PM step-off and dislocation were associated with worse radiographical osteoarthrosis. Other published medium-to-long term studies reported overall good outcomes, with no differences after small fragment fixation.

The unfixated smaller posterior malleolus fragment demonstrated overall satisfactory clinical and radiographical outcomes at 10-year follow-up and may be considered a valid treatment strategy.

Anterior approach total hip arthroplasty (AA-THA) has a steep learning curve, with higher complication rates in initial cases. Proper surgical case selection during the learning curve can reduce early risk. This study aims to identify patient and radiographic factors associated with AA-THA difficulty using Machine Learning (ML).

Consecutive primary AA-THA patients from two centres, operated by two expert surgeons, were enrolled (excluding patients with prior hip surgery and first 100 cases per surgeon). K- means prototype clustering – an unsupervised ML algorithm – was used with two variables - operative duration and surgical complications within 6 weeks - to cluster operations into difficult or standard groups.

Radiographic measurements (neck shaft angle, offset, LCEA, inter-teardrop distance, Tonnis grade) were measured by two independent observers. These factors, alongside patient factors (BMI, age, sex, laterality) were employed in a multivariate logistic regression analysis and used for k-means clustering. Significant continuous variables were investigated for predictive accuracy using Receiver Operator Characteristics (ROC).

Out of 328 THAs analyzed, 130 (40%) were classified as difficult and 198 (60%) as standard. Difficult group had a mean operative time of 106mins (range 99–116) with 2 complications, while standard group had a mean operative time of 77mins (range 69–86) with 0 complications. Decreasing inter-teardrop distance (odds ratio [OR] 0.97, 95% confidence interval [CI] 0.95–0.99, p = 0.03) and right-sided operations (OR 1.73, 95% CI 1.10–2.72, p = 0.02) were associated with operative difficulty. However, ROC analysis showed poor predictive accuracy for these factors alone, with area under the curve of 0.56. Inter-observer reliability was reported as excellent (ICC >0.7).

Right-sided hips (for right-hand dominant surgeons) and decreasing inter-teardrop distance were associated with case difficulty in AA-THA. These data could guide case selection during the learning phase. A larger dataset with more complications may reveal further factors.

Adult Spine Deformity (ASD) is a degenerative condition of the adult spine leading to altered spine curvatures and mechanical balance. Computational approaches, like Finite Element (FE) Models have been proposed to explore the etiology or the treatment of ASD, through biomechanical simulations. However, while the personalization of the models is a cornerstone, personalized FE models are cumbersome to generate. To cover this need, we share a virtual cohort of 16807 thoracolumbar spine FE models with different spine morphologies, presented in an online user-interface platform (SpineView). To generate these models, EOS images are used, and 3D surface spine models are reconstructed. Then, a Statistical Shape Model (SSM), is built, to further adapt a FE structured mesh template for both the bone and the soft tissues of the spine, through mesh morphing. Eventually, the SSM deformation fields allow the personalization of the mean structured FE model, leading to generate FE meshes of thoracolumbar spines with different morphologies. Models can be selectively viewed and downloaded through SpineView, according to personalized user requests of specific morphologies characterized by the geometrical parameters: Pelvic Incidence; Pelvic Tilt; Sacral Slope; Lumbar Lordosis; Global Tilt; Cobb Angle; and GAP score. Data quality is assessed using visual aids, correlation analyses, heatmaps, network graphs, Anova and t-tests, and kernel density plots to compare spinopelvic parameter distributions and identify similarities and differences. Mesh quality and ranges of motion have been assessed to evaluate the quality of the FE models. This functional repository is unique to generate virtual patient cohorts in ASD.

Acknowledgements: European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828)

There is an evolving body of evidence that demonstrates the role of epigenetic mechanisms, such as DNA-methylation in the pathogenesis of OA. This systematic review aims to summarize the current evidence of DNA methylation and its influence on the pathogenesis of OA.

A pre-defined protocol in alignment with the PRISMA guidelines was employed to systematically review eight bibliographic databases, to identify associations between DNA-methylation of articular chondrocytes and osteoarthritis. A search of Medline (Ovid), Embase, Web-of-Science, Scopus, PubMed, Cinahl (EBSCOhost), Cochrane Central and Google Scholar was performed between 1st January 2015 to 31st January 2021. Data extraction was performed by two independent reviewers.

During the observation period, we identified 15 gene specific studies and 24 genome wide methylation analyses. The gene specific studies mostly focused on the expression of pro-inflammatory markers, such as IL8 and MMP13 which are overexpressed in OA chondrocytes. DNA hypomethylation in the promoter region resulted in overexpression, whereas hypermethylation was seen in non-OA chondrocytes. Others reported on the association between OA risk genes and the DNA methylation pattern close to RUNX2, which is an important OA signal. The genome wide methylation studies reported mostly on differentially methylated regions comparing OA chondrocytes and non-OA chondrocytes. Clustering of the regions identified genes that are involved in skeletal morphogenesis and development. Differentially methylated regions were seen in hip OA and knee OA chondrocytes, and even within different regions of an OA affected knee joint, differentially methylated regions were identified depending on the disease stage.

This systematic review demonstrates the growing evidence of epigenetic mechanisms, such as DNA methylation, in the pathogenesis of OA. In recent years, there has been a focus on the interplay between OA risk genes and DNA methylation changes which revealed a reactivation of genes responsible for endochondral ossification during development. These are important findings and may help to identify eventual future therapeutic targets. However, the current body of literature is mostly showing the differences in DNA methylation of OA chondrocytes and non-OA chondrocytes, but a true longitudinal analysis demonstrating the DNA methylation changes actually happening is still not available.

While high-performance ceramics like alumina and zirconia exhibit excellent wear resistance, they provide poor osseointegration capacity. As osseointegration is crucial for non-cemented joint prostheses, new techniques have been successfully developed for biofunctionalizing high-performance ceramic surfaces. Stable cell adhesion can be achieved by covalently bound specific peptides. In this study we investigate the effect of sterilization processes on organo-chemically functionalized surfaces.

To enhance the performance of alumina-toughened zirconia ceramics (ATZ), a 3-aminopropyldiisopropylethoxysilane (APDS) monolayer was applied and coupled with cyclo-RGD peptides (cRGD) by using bifunctional crosslinker bis(sulfosuccinimidyl)suberat (BS³). The samples were sterilized using e-beam or gamma-sterilization at 25 kGy, either before or after biofunctionalization with cRGD. Functionalization stability was investigated by contact angle measurements. The functionality of cRGD after sterilization was demonstrated using proliferation tests and cytotoxicity assays. Immunofluorescence staining (pFAK, Actin, DAPI) was conducted to evaluate the adhesion potential between the samples and human mesenchymal stem cells (hMSCs).

Functionalized samples before and after sterilization showed no significant difference regarding their contact angles. A proliferation test demonstrated that the cells on functionalized samples proliferate significantly more than on untreated samples before and after sterilization. hMSCs showed a significant higher proliferation on gamma sterilized samples compared to all other groups after 14 days. It was confirmed that the samples did not exhibit cytotoxic behavior before or after sterilization. Fluorescence microscopy demonstrated that both, cells on sterilized and on non-sterilized samples, expressed high levels of pFAK-Y397.

The investigated functionalization enables improved adhesion and proliferation of hMSCs and is stable against the investigated sterilization processes. This is of importance as the option of having a sterile product enables the start of the translation of this biofunctional coating towards preclinical and subsequently first-in-man applications.

Acknowledgments: We acknowledge the financial support of the Federal Ministry of Education and Research, BMBF (13GW0452A-C).

Contemporary indications for unicompartmental knee replacement (UKR) include bone on bone radiographic changes in the medial compartment with relatively preserved lateral and patellofemoral compartments. The role of MRI in identifying candidates for UKR is commonplace. The aim of this study was to assess the relationship between radiographic and MRI pre-operative grade and outcome following UKR.

A retrospective analysis of medial UKR patients from 2017 to 2021. Inclusion criteria were medial UKR for osteoarthritis with pre-operative and post-operative Oxford Knee Scores (OKS), pre-operative radiographs and MRI.

89 patients were included. Whilst all patients had grade 4 ICRS scores on MRI, 36/89 patients had grade 3 KL radiographic scores in the medial compartment, 50/89 had grade 4 KL scores on the medial compartment. Grade 3 KL with grade 4 IRCS medial compartment patients had a mean OKS change of 17.22 (Sd 9.190) meanwhile Grade 4 KL had a mean change of 17.54 (SD 9.001), with no statistical difference in the OKS change score following UKR between these two groups (p=0.873). Medial bone oedema was present in all but one patient. Whilst lateral compartment MRI ICRS scores ranged from 1 to 4 there was no association with MRI score of the lateral compartment and subsequent change in oxford score (P value 0.458). Patellofemoral Compartment (PFC) MRI ICRS ranged from 0 to 4. There was no association between PFC ICRS score and subsequent change in oxford knee score (P value .276)

Radiographs may under report severity of some medial sided knee osteoarthritis. We conclude that in patients with grade 3 KL score that would normally not be considered for UKR, pre-operative MRI might identify grade 4 ICRS scores and this subset of patients have equivalent outcomes to patients with radiographic Grade 4 KL medial compartment osteoarthritis.

Osteoarthritis (OA) of the knee joint is a complex peripheral joint disorder with multiple risk factors. We aimed to examine the relationship between the grade of knee OA and anterior thigh length (ATL).

A total of 64 geriatric patients who had no total hip or knee replacement with a BMI of ≥30 were evaluated. Patients' OA severity was determined by two independent experts from bilateral standing knee radiographs according to the Kellgren-Lawrence (KL) grade. Joint cartilage structure was assessed using ultrasonography (US). The ATL, the gastrocnemius medialis (GC), the rectus femoris (RF) and the rectus abdominis (RA) skeletal muscle thicknesses as well as the RF cross-sectional area (CSA) were measured with US. Sarcopenia was diagnosed using the handgrip strength (HGS), 5× sit-to-stand test (5xSST) and bioelectrical impedance analysis.

The median (IQR) age of participants was 72 (65–88) years. Seventy-one per cent of the patients (n=46) were female. They were divided into the sarcopenic obese (31.3 %) and the non-sarcopenic obese (68.8%) groups. KL grade of all patients correlated negatively with the ATL (mm) and the thickness of GC (mm) (r= -0,517, p<0.001 and r= -0.456, p<0.001, respectively). In the sarcopenic obese and the non-sarcopenic obese groups, KL grade of the all patients was negatively correlated with ATL (mm) and thickness of GC (mm) (r= -0,986, p<0.001; r= -0.456, p=0.05 and r= -0,812, p=0.002; r= −0,427, p=0.006). KL grade negatively correlated with the RF thickness in the sarcopenic obese group (r= -0,928, p=0.008).

In conclusion, OA risk may decrease as the lower extremity skeletal muscle mass increases.

Acknowledgments: Feza Korkusuz MD is a member of the Turkish Academy of Sciences (TÜBA).

The incisura fibularis (IF) provides intrinsic stability to the ankle joint complex by interlocking the distal tibia and fibula. Despite a high frequency of ligamentous ankle injuries, scant attention has been given to the morphology of the IF morphology incisura fibularis in the onset and development of these lesions. Therefore, we systematically reviewed the relation between ligamentous ankle disorders and the morphometrics of the IF.

A systematic literature search was conducted on following databases: PubMed, Embase and Web of Science. Search terms consisted of ‘ankle trauma’, ‘ankle injury’, ‘ankle sprain’, ‘ankle fracture’, ‘tibiofibular’, ‘fibular notch’, ‘fibular incisura’, ‘incisura fibularis’, ‘morphometric analysis’, ‘ankle syndesmosis’, ‘syndesmotic stability’. The evaluation instrument developed by Hawker et al. was used to assess the quality of the selected studies. This protocol was performed according to the PRISMA guidelines and is registered on PROSPERO (CRD42021282862).

Nineteen studies were included and consisted of prospective cohort (n=1), retrospective comparative (n=10), and observational (n=8) study design. Comparative studies have found certain morphological characteristics in patients with ankle instability. Several studies (n=5) have correlated a shallow IF depth with a higher incidence of ankle injury. A significant difference has also been found concerning the incisura height and angle (n=3): a shorter incisura and more obtuse angle have been noted in patients with ankle sprains. The mean Hawker score was 28 out of 36 (range=24-31).

A shallower IF is associated with ligamentous ankle lesions and might be due to a lower osseous resistance against tibiofibular displacement. However, these results should be interpreted in light of moderate methodological quality and should always be correlated with clinical findings. Further prospective studies are needed to further assess the relation between the incisura morphometrics and ligamentous disorders of the ankle joint.

Keywords: ankle instability, ankle injury, incisura fibularis, fibular notch, tibiofibular morphometrics, ankle syndesmosis

Knee osteoarthritis (KOA) diagnosis is based on symptoms, assessed through questionnaires such as the WOMAC. However, the inconsistency of pain recording and the discrepancy between joint phenotype and symptoms highlight the need for objective biomarkers in KOA diagnosis. To this end, we study relationships among clinical and molecular data in a cohort of women (n=51) with Kellgren-Lawrence grade 2–3 KOA through Support Vector Machine (SVM) and a regulation network model (RNM). Clinical descriptors (i.e., pain catastrophism (CA); depression (DE); functionality (FU); joint pain (JP); rigidity (RI); sensitization (SE); synovitis (SY)) are used to classify patients. A Youden's test is performed for each classifier to determine optimal binarization thresholds for the descriptors. Thresholds are tested against patient stratification according to baseline WOMAC data from the Osteoarthritis Initiative, and the mean accuracy is 0.97. For our cohort, the data used as SVM inputs are KOA descriptors, synovial fluid (SL) proteomic measurements (n=25), and transcription factors (TF) activation obtained from RNM [2] stimulated with the SL measurements. The relative weights after classification reflect input importance. The performance of each classifier is evaluated through AUC-ROC analysis. The best classifier with clinical data is CA (AUC = 0.9), highly influenced by FU and SE, suggesting that kinesophobia is involved in pain perception. With SL input, leptin strongly influences every classifier, suggesting the importance of low-grade inflammation. When TF are used, the mean AUC is limited to 0.608, which can be related to the pleomorphic behaviour of osteoarthritic chondrocytes. Nevertheless, FU has an AUC of 0.7 with strong importance of FOXO downregulation. Though larger and longitudinal cohorts are needed, this unique combination of SVM and RNM shall help to map objectively KOA descriptors.

Acknowledgements: Catalan & Spanish governments 2020FI_b00680; STRATO-PID2021126469ob-C21-2, European Commission (MSCA-TN-ETN-2020-Disc4All-955735, ERC-2021-CoG-O-Health-101044828). ICREA Academia.

Meniscus tears have been treated using partial meniscectomy to relieve pain in patients, although this leads to the onset of early osteoarthritis (OA). Cell-based therapies can help preserve the meniscus, although the presence of inflammatory cytokines compromises clinical outcomes. Anti-inflammatory drugs (e.g. celecoxib), can help to reduce pain in patients and in vitro studies suggest a beneficial effect on cytokine inhibited matrix content. Previously, we have demonstrated that the inhibitory effects of IL-1β can be countered by culture under low oxygen tension or physioxia. The present study sought to understand whether physioxia, celecoxib or combined application can counter the inhibitory effects IL-1β inhibited meniscus cells.

Human avascular and vascular meniscus cells (n =3) were isolated and expanded under 20% (hyperoxia) or 2% (physioxia) oxygen. Cells were seeded into collagen scaffolds (Geistlich, Wolhusen) and cultured for 28 days either in the presence of 0.1ng/mL IL-1β, 5µg/mL celecoxib or both under their expansion oxygen conditions. Histological (DMMB, collagen I and collagen II immunostaining), GAG content and gene expression analysis was evaluated for the scaffolds.

Under hyperoxia, meniscus cells showed a significant reduction in GAG content in the presence of IL-1β (*p < 0.05). Celecoxib alone did not significantly increase GAG content in IL-1β treated cultures. In contrast, physioxic culture showed a donor dependent increase in GAG content in control, IL-1β and celecoxib treated cultures with corresponding histological staining correlating with these results. Additionally, gene expression showed an upregulation in COL1A1, COL2A1 and ACAN and a downregulation in MMP13 and ADAMTS5 under physioxia for all experimental groups.

Physioxia alone had a stronger effect in countering the inhibitory effects of IL-1β treated meniscus cells than celecoxib under hyperoxia. Preconditioning meniscus cells under physioxia prior to implantation has the potential to improve clinical outcomes for cell-based therapies of the meniscus.

The incidence of PJI in knee replacements is 2.8% and slightly lower with hip replacement surgery. PJI make up 15% (or even more) of knee revisions. To combat PJI, antibiotic laden bone cement has been used for many decades, but antibiotic stewardship dictates more prudent management of antimicrobials. Projected increase in infection rate, due to increased surgery and latent infection to be almost 5-fold up to 2035.

Biofilm is a complex structure of bacteria and polysaccharide matrix and, is recognised as a major component in PJI and other orthopaedic infections.

Biofilm is responsible for high incidence of resistance to antimicrobials and ineffective host immune response.

Total knee arthroplasty is one of the most common surgeries. About 92% of all implanted knee endorposthesis in 2020 were manufactured from uncoated CoCrMo articulating on ultra-high-molecular-weight polyethylene. All articluations generate wear particles and subsequent emission of metal ions due to the mechanical loading. These wear particles cause diverse negative reactions in the surrounding tissues and can lead to implant loosening. Coating technologies might offer the possibility to reduce this wear. Therefore, we investigated the applicability of tetrahedral amorphous carbon (ta-C) coating on CoCrMo alloy.

Polished specimens made of CoCrMo wrought alloy according to ISO 5832-12 were coated with ta-C coatings with different layer structure using pulsed laser deposition (PLD). This process allows the deposition of ta-C coatings with low internal stress using an additional relaxation laser. Surface quality and mechanical properties of the coating were characterised using optical surface measurements (NanoFocus μsurf expert, NanoFocus AG) and a nanoindentation tester NHT³ (Anton Paar GmbH). Scratch tests were performed on Micro Scratch Tester MST³ (Anton Paar TriTec SA) to define the coating adhesion. Pin-on-plate tribological tests, with a polyethylene ball sliding on the ta-C-coated plate under a defined load according to ISO 14243-1 were performed using a linear tribometer (Anton Paar GmbH) to evaluate the tribological and wear properties.

The ta-C coatings showed a mean roughness Ra of 5-20 nm and a hardness up to 60 GPa (n=3). The adhesion of the ta-C coatings (n=3) was comparable to the commercial coatings like TiN and TiNbN. The pin-on-plate tests showed an improvement of tribological properties in comparison with the polished uncoated CoCrMo specimens (n=3).

The ta-C coatings applied by DLP technology show increased hardness compared to the base material and sufficient adhesion. Further research will be needed to investigate the optimal coating strategy for implant coating.

Introduction

Patellofemoral instability is one of the most common presentations to a children's orthopaedic clinic. Recurrent patellar dislocations and instability episodes are painful, disabling and increase the risk of irreversible chondral damage. The medial patellofemoral ligament is the primary static stabiliser to prevent lateral dislocation of the patella and is almost always torn or attenuated in these cases. Reconstruction of this ligament is commonly performed using autologous hamstring tendon however there has been some interest recently in use of quadriceps tendon as a graft. Children with patellar instability also present unique challenges due to the small size of the patella and the presence of open growth plates which may require adaptations to the common techniques.

Abstract

The triangular fibrocartilage complex (TFCC) is a known stabiliser of the distal radioulnar joint (DRUJ). An injury to these structures can result in significant disability including pain, weakness and joint stiffness. The contribution each of its components makes to the stability of the TFCC is not well understood. This study was undertaken to investigate the role of the individual ligaments of the TFCC and their contribution to joint stability.

The study was undertaken in two parts. 30 cadaveric forearms were studied in each group. The ligaments of the TFCC were progressively sectioned and the resulting effect on the stability of the DRUJ was measured. A custom jig was created to apply a 20N force through the distal radius, with the ulna fixed.

Experiment one measured the effect on DRUJ translation after TFCC sectioning. Experiment two added the measurement of rotational instability.

Part one of the study showed that complete sectioning of the TFCC caused a mean increase in translation of 6.09(±3) mm. Sectioning the palmar radioulnar ligament of the TFCC caused the most translation.

Part two demonstrated a change in rotation with a mean of 18 (± 6) degrees following sectioning of the TFCC. There was a progressive increase in rotational instability until the palmar radioulnar ligament was also sectioned.

Linear translation consistently increased after sectioning all of the TFCC ligaments, confirming its importance for DRUJ stability. Sectioning of the palmar radioulnar ligament most commonly caused the greatest degree of translation. This suggests injury to this ligament would more likely result in a greater degree of translational instability. The increase in rotation also suggests that this type of instability would be symptomatic in a TFCC injury.

Aim

Bacteriophages are remerging as alternative and adjunctive therapy for fracture-related infection (FRI). However, current administration protocols involve prolonged retention of a percutaneous draining tube with potential risk of developing superinfection. In this study, we applied a cocktail of in vitro evolved biofilm-targeting phages for Methicillin-resistant Staphylococcus aureus (MRSA) in a hydrogel platform co-delivering vancomycin. In vitro synergy and antibiofilm activity was assessed and a subsequent in vivo study was performed in a mouse FRI model with MRSA.