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.