A number of classification systems exist for posterior malleolus fractures of the ankle. The reliability of these classification systems remains unclear. The primary aim of this study was to evaluate the reliability of three commonly utilised fracture classification systems of the posterior malleolus. 60 patients across 2 hospitals sustaining an unstable ankle fracture with a posterior malleolus fragment were identified. All patients underwent radiographs and computed tomography of their injured ankle. 9 surgeons including pre-ST3 level, ST3-8 level, and consultant level applied the Haraguchi, Rammelt, and Mason & Molloy classifications to these patients, at two timepoints, at least 4 weeks apart. The order was randomised between assessments. Inter-rater reliability was assessed using Fleiss’ kappa and 95% confidence intervals (CI). Intra-rater reliability was assessed using Cohen's Kappa and standard error (SE). Inter-rater reliability (Fleiss’ Kappa) was calculated for the Haraguchi classification as 0.522 (95% CI 0.490 – 0.553), for the Rammelt classification as 0.626 (95% CI 0.600 – 0.652), and the Mason & Molloy classification as 0.541 (95% CI 0.514 – 0.569). Intra-rater reliability (Cohen's Kappa) was 0.764 (SE 0.034) for the Haraguchi, 0.763 (SE 0.031) for the Rammelt, 0.688 (SE 0.035) for the Mason & Molloy classification. This study reports the inter-rater and intra-rater reliability for three classification systems for posterior malleolus fractures. Based on definitions by Landis & Koch (1977), inter-rater reliability was rated as ‘moderate’ for the Haraguchi and Mason & Molloy classifications; and ‘substantial’ for the Rammelt classification. Similarly, the intra-rater reliability was rated as ‘substantial’ for all three classifications

Virtual mechanical testing is a method for measuring bone healing using finite element models built from computed tomography (CT) scans. Previously, we validated a dual-zone material model for ovine fracture callus that differentiates between mineralized woven bone and soft tissue based on radiodensity. 1. The objective of this study was to translate the dual-zone material model from sheep to two important clinical scenarios: human tibial fractures in early-stage healing and late-stage nonunions. CT scans for N = 19 tibial shaft fractures were obtained prospectively at 12 weeks post-op. A second group of N = 33 tibial nonunions with CT scans were retrospectively identified. The modeling techniques were based on our published method. 2. The dual-zone material model was implemented for humans by performing a cutoff sweep for both the 12-week and nonunion groups. Virtual torsional rigidity (VTR) was calculated as VTR = ML/φ [N-m. 2. /°], where M is the moment reaction, L is the diaphyseal segment length, and φ is the angle of twist. As the soft tissue cutoff was increased, the rigidity of the clinical fractures decreased and soft tissue located within the fracture gaps produced higher strains that are not predicted without the dual zone approach. The structural integrity of the nonunions varied, ranging from very low rigidities in atrophic cases to very high rigidities in highly calcified hypertrophic cases, even with dual-zone material modeling. Human fracture calluses are heterogeneous, comprising of woven bone and interstitial soft tissue. Use of a dual-zone callus material model may be instrumental in identifying delayed unions during early healing when callus formation is minimal and/or predominantly fibrous with little mineralization. ACKNOWLEDGEMENTS:. This work was supported by the National Science Foundation (NSF) grant CMMI-1943287

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

Cartilage diseases have a significant impact on the patient's quality of life and are a heavy burden for the healthcare system. Better understanding, early detection and proper follow-up could improve quality of life and reduce healthcare related costs. Therefore, the aim of this study was to evaluate if difference between osteoarthritic (OA) and non-osteoarthritic (non-OA) knees can be detected quantitatively on cartilage and subchondral bone levels with advanced but clinical available imaging techniques. Two OA (mean age = 88.3 years) and three non-OA (mean age = 51.0 years) human cadaveric knees were scanned two times. A high-resolution peripheral quantitative computed tomography (HR-pQCT) scan (XtremeCT, Scanco Medical AG, Switzerland) was performed to quantify the bone microstructure. A contrast-enhanced clinical CT scan (GE Revolution Evo, GE Medical Systems AG, Switzerland) was acquired with the contrast agent Visipaque 320 (60 ml) to measure cartilage. Subregions dividing the condyle in four parts were identified semi-automatically and the images were segmented using adaptive thresholding. Microstructural parameters of subchondral bone and cartilage thickness were quantified. The overall cartilage thickness was reduced by 0.27 mm between the OA and non-OA knees and the subchondral bone quality decreased accordingly (reduction of 33.52 % in BV/TV in the layer from 3 to 8 mm below the cartilage) for the femoral medial condyle. The largest differences were observed at the medial part of the femoral medial condyle both for cartilage and for bone parameters, corresponding to clinical observations. Subchondral bone microstructural parameters and cartilage thickness were quantified using in vivo available imaging and apparent differences between the OA and non-OA knees were detected. Those results may improve OA follow-up and diagnosis and could lead to a better understanding of OA. However, further in vivo studies are needed to validate these methods in clinical practice

Introduction. In tissue engineering, the establishment of sufficient vascularization is essential for tissue viability and functionality. Inadequate vascularization disrupts nutrients and oxygen supply. Nonetheless, regenerating intricate vascular networks represents a significant challenge. Consequently, research efforts devoted to preserving and regenerating functional vascular networks in engineered tissues are of paramount importance. The present work aims to validate a decellularisation process with preservation of the vascular network and extracellular matrix (ECM) components in fasciocutaneous flaps. Method. Five vascularized fasciocutaneous flaps from cadaveric donors were carefully harvested from the anterolateral thigh (ALT), preserving the main perforator of the fascia lata. The entire ALT flap underwent decellularization by perfusion using a clinically validated chemical protocol. Fluoroscopy and computed tomography (CT) were used to analyze the persistence of the vascular network within the flap, pre- and post-decellularization. Histological analysis, including hematoxylin and eosin staining, and quantitative DNA assessment evaluated decellularization efficacy. Further qualitative (immunohistochemistry, IHC) and quantitative analyses were conducted to assess the preservation of ECM components, such as collagen, glycosaminoglycans, and elastin. Result. On average, the ALT flap maintains 82% of the perfusion area (p = 0.094) post-treatment. Histological analysis confirmed decellularization efficacy and revealed structural rearrangement. Paired analysis revealed a significant decrease in DNA levels (<14.8 ng/mg of dry weight, p****< 0.0001) and well-maintained ECM. IHC indicated the persistence of elastine, collagen IV and laminin. Quantitative analysis confirmed elastin (p = 0.44) and collagen persistence (+74%, p*** = 0.001, albeit with a decrease in matrix glycosaminoglycans (-41%, p*** = 0.01). Conclusion. Decellularization effectively removed cells, while preserving the ECM overall and maintaining some vascular network integrity. Yet, further study is needed to validate these findings, involving microCT examination of the vascular network and its ability to support cell colonization and viability

Introduction. Achieving an appropriate primary stability after implantation is a prerequisite for the long-term viability of a dental implant. Virtual testing of the bone-implant construct can be performed with finite element (FE) simulation to predict primary stability prior to implantation. In order to be translated to clinical practice, such FE modeling must be based on clinically available imaging methods. The aim of this study was to validate an FE model of dental implant primary stability using cone beam computed tomography (CBCT) with ex vivo mechanical testing. Method. Three cadaveric mandibles (male donors, 87-97 years old) were scanned by CBCT. Twenty-three bone samples were extracted from the bones and conventional dental implants (Ø4.0mm, 9.5mm length) were inserted in each. The implanted specimens were tested under quasi-static bending-compression load (cf. ISO 14801). Sample-specific homogenized FE (hFE) models were created from the CBCT images and meshed with hexahedral elements. A non-linear constitutive model with element-wise density-based material properties was used to simulate bone and the implant was considered rigid. The experimental loading conditions were replicated in the FE model and the ultimate force was evaluated. Result. The experimental ultimate force ranged between 67 N and 789 N. The simulated ultimate force correlated better with the experimental ultimate force (R. 2. =0.71) than the peri-implant bone density (R. 2. =0.30). Conclusion. The developed hFE model was demonstrated to provide stronger prediction of primary stability than peri-implant bone density. Therefore, hFE Simulations based on this clinically available low-radiation imaging modality, is a promising technology that could be used in future as a surgery planning tool to assist the clinician in evaluating the load-bearing capacity of an implantation site. Acknowledgements. Funding: EU's Horizon 2020 grant No: 953128 (I-SMarD). Dental implants: THOMMEN Medical AG

There is currently no commercially available and clinically successful treatment for scapholunate interosseous ligament rupture, the latter leading to the development of hand-wrist osteoarthritis. We have created a novel biodegradable implant which fixed the dissociated scaphoid and lunate bones and encourages regeneration of the ruptured native ligament. To determine if scaphoid and lunate kinematics in cadaveric specimens were maintained during robotic manipulation, when comparing the native wrist with intact ligament and when the implant was installed. Ten cadaveric experiments were performed with identical conditions, except for implant geometry that was personalised to the anatomy of each cadaveric specimen. Each cadaveric arm was mounted upright in a six degrees of freedom robot using k-wires drilled through the radius, ulna, and metacarpals. Infrared markers were attached to scaphoid, lunate, radius, and 3rd metacarpal. Cadaveric specimens were robotically manipulated through flexion-extension and ulnar-radial deviation by ±40° and ±30°, respectively. The cadaveric scaphoid and lunate kinematics were examined with 1) intact native ligament, 2) severed ligament, 3) and installed implant. Digital wrist models were generated from computed tomography scans and included implant geometry, orientation, and location. Motion data were filtered and aligned relative to neutral wrist in the digital models of each specimen using anatomical landmarks. Implant insertion points in the scaphoid and lunate over time were then calculated using digital models, marker data, and inverse kinematics. Root mean squared distance was compared between severed and implant configurations, relative to intact. Preliminary data from five cadaveric specimens indicate that the implant reduced distance between scaphoid and lunate compared to severed configuration for all but three trials. Preliminary results indicate our novel implant reduced scapho-lunate gap caused by ligament transection. Future analysis will reveal if the implant can achieve wrist kinematics similar to the native intact wrist

Applications of weightbearing computed tomography (WBCT) imaging in the foot and ankle have emerged over the past decade. However, the potential diagnostic benefits are scattered across the literature, and a concise overview is currently lacking. Therefore, we aimed to systematically review all reported diagnostic applications per anatomical region in the foot and ankle. A systematic literature search was performed in the electronic databases PubMed, EMBASE, Cochrane Library, and Web of Science. Search terms consisted of “weightbearing/standing CT and ankle, hind-, mid- or forefoot”. English language studies analyzing the diagnostic applications of WBCT were included. Studies were excluded if they simulated weightbearing CT, described normal subjects, included cadaveric samples or samples were case reports. The modified Methodological Index for Non-Randomized Studies (MINORS) was applied for quality assessment. The added value was defined as the review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and registered in the Prospero database (CRD42019106980). A total of 48 studies (prospective N=8, retrospective N=36, cohort study N=1, diagnostic N=2, prognostic comparative study N=1) were found to be eligible for review. The following diagnostic applications were identified per anatomical area in the foot: ankle (osteoarthritis N=5, ligament injury N=6); hindfoot (deformity N=9); midfoot (Lisfranc injury N=2, flatfoot deformity N=13, osteoarthritis N=1); forefoot (hallux valgus N=12). The identified studies contained diagnostic applications that could not be used on plain radiographs. The mean MINORS equaled 10.1 on a total of 16 (range: 8 to 12). Diagnostic applications of weightbearing CT imaging are most frequently studied in hindfoot deformity, but other area's areas are on the rise. Post-processing of images was identified as the main added value compared to WBRX. However, the findings should be interpreted with caution as the average quality score was moderate. Therefore, future prospective studies are warranted to consolidate the role of WBCT in diagnostic and therapeutic algorithms

Introduction. Functional Spine Units (FSUs) play a vital role in understanding biomechanical characteristics of the spine, particularly bone fracture risk assessment. While established models focus on simulating axial compression of individual bones to assess fracture load, recent models underscore the importance of understanding fracture load within FSUs, offering a better representation of physiological conditions. Despite the limited number of FSU fracture studies, they predominantly rely on a linear material model with an annulus fibrosus Young's modulus set at 500 MPa, significantly higher than stiffness values (ca. 4 MPa) utilized in other FSU and spine section biomechanical models. Thus, this study aims to study the effect of varying annulus fibrosus stiffness on FSU fracture load, aiming to identify physiologically relevant biomechanical parameters. Method. Subject-specific geometry and material properties of bones were derived from computed tomography (CT) image data of five human cadaveric FSU specimens. The annulus fibrosus and nucleus pulposus were manually recreated and assigned linear elastic material properties. By subjecting the model to axial compression, the fracture load of the FSU was deduced from the peak of the force-displacement graph. To explore the effect of stiffness of the annulus fibrosus on simulated fracture load, we conducted a parameter study, varying stiffness values from the high 500 MPa to a more physiologically relevant 25 MPa, aiming to approximate values applied in FSU kinematic models while achieving bone fracture. Result. Significant reductions in fracture load were observed, ranging from 23% to 46%, as annulus stiffness decreased from 500MPa to 25MPa. Additionally, a discernible, gradual decline in fracture load was observed with a decrease in stiffness values. Conclusion. The stiffness of the annulus fibrosus significantly influences the simulated fracture load of an FSU. Future investigations should prioritize biomechanically accurate modeling of the intervertebral disc, ensuring alignment with experimental findings regarding FSU fracture load while maintaining biomechanical fidelity

Introduction. Pedicle screw loosening in posterior instrumentation of thoracolumbar spine occurs up to 60% in osteoporotic patients. These complications may be alleviated using more flexible implant materials and novel designs that could be optimized with reliable computational modeling. This study aimed to develop and validate non-linear homogenized finite element (hFE) simulations to predict pedicle screw toggling. Method. Ten cadaveric vertebral bodies (L1-L5) from two female and three male elderly donors were scanned with high-resolution peripheral quantitative computed tomography (HR-pQCT, Scanco Medical) and instrumented with pedicle screws made of carbon fiber-reinforced polyether-etherketone (CF/PEEK). Sample-specific 3D-printed guides ensured standardized instrumentation, embedding, and loading procedures. The samples were biomechanically tested to failure in a toggling setup using an electrodynamic testing machine (Acumen, MTS) applying a quasi-static cyclic testing protocol of three ramps with exponentially increasing peak (1, 2 and 4 mm) and constant valley displacements. Implant-bone kinematics were assessed with a stereographic 3D motion tracking camera system (Aramis SRX, GOM). hFE models with non-linear, homogenized bone material properties including a strain-based damage criterion were developed based on intact HR-pQCT and instrumented 3D C-arm scans. The experimental loading conditions were imposed, the maximum load per cycle was calculated and compared to the experimental results. HR-pQCT-based bone volume fraction (BV/TV) around the screws was correlated with the experimental peak forces at each displacement level. Result. The nonlinear hFE models accurately (slope = 1.07, intercept = 0.2 N) and precisely (R. 2. = 0.84) predicted the experimental peak forces at each displacement level. BV/TV alone was a weak predictor (R. 2. <0.31). Conclusion. The hFE models enable fast design iterations aiming to reduce the risk of screw loosening in low-density vertebrae. Improved flexible implant designs are expected to contribute to reduced complication rates in osteoporotic patients

Introduction. Patient-specific biomechanical modeling using Finite Element Analysis (FEA) is pivotal for understanding the structural health of bones, optimizing surgical procedures, assessing outcomes, and validating medical devices, aligning with guidance issued by standards and regulatory bodies. Accurate mapping of image-to-mesh-material is crucial given bone's heterogeneous composition. This study aims to rigorously assess mesh convergence and evaluate the sensitivity of material grouping strategies in quantifying bone strength. Method. Subject-specific geometry and nonlinear material properties were derived from computed tomography (CT) scan data of one cadaveric human vertebral body. Linear tetrahedral elements with varying edge lengths between 2mm and 0.9mm were then generated to study the mesh convergence. To compare the effectiveness of different grouping strategies, three approaches were used: Modulus Gaping (a user-defined absolute threshold of Young's modulus ranging from 500 MPa to 1 MPa), Percentual Thresholding (relative parameter thresholds ranging from 50% to 1%), and Adaptive clustering (unsupervised k-means-based clustering ranging from 10 to 200 clusters). Adaptive clustering enables a constant number of unique material properties in cross-specimen studies, improving the validity of results. Result. Mesh convergence was evaluated via fracture load and reached at a 1mm mesh size across grouping strategies. All strategies exhibit minimal deviation (within 5%) from individually assigned material parameters, except Modulus Gaping, with a 500 MPa threshold (32% difference). Computational efficiency, measured by runtime, significantly improved with grouping strategies, reducing computational cost by 82 to 94% and unique material count by up to 99%. Conclusion. Different grouping strategies offer comparable mesh convergence, highlighting their potential to reduce computational complexity while maintaining accuracy in the biomechanical modeling of bones and suggesting a more efficient approach than individual element materials. The higher efficiency of FEA may increase its applicability in clinical settings with limited computational resources. Further studies are needed to refine grouping parameters and assess their suitability across different subjects

Stand-alone anterior lumbar interbody fusion (ALIF) provides the opportunity to avoid supplemental posterior fixation. This may reduce morbidity and complication rate, which is of special interest in patients with reduced bone mineral density (BMD). This study aims to assess immediate biomechanical stability and radiographic outcome of a stand-alone ALIF device with integrated screws in specimens of low BMD. Eight human cadaveric spines (L4-sacrum) were instrumented with SynFix-LR™ (DePuy Synthes) at L5/S1. Quantitative computed tomography was used to measure BMD of L5 in AMIRA. Threshold values proposed by the American Society of Radiology 80 and 120 mg CaHa/mL were used to differentiate between Osteoporosis, Osteopenia, and normal BMD. Segmental lordosis, anterior and posterior disc height were analysed on pre- and postoperative radiographs (Fig 1). Specimens were tested intact and following instrumentation using a flexibility protocol consisting of three loading cycles to ±7.5 Nm in flexion-extension, lateral bending, and axial rotation. The ranges of motion (ROM) of the index level were assessed using an optoelectronic system. BMD ranged 58–181mg CaHA/mL. Comparison of pre- and postoperative radiographs revealed significant increase of L5/S1 segmental lordosis (mean 14.6°, SD 5.1, p < 0.001) and anterior disc height (mean 5.8mm, SD 1.8, p < 0.001), but not posterior disc height. ROM of 6 specimens was reduced compared to the intact state. Two specimens showed destructive failure in extension. Mean decrease was most distinct in axial rotation up to 83% followed by flexion-extension. ALIF device with integrated screws at L5/S1 significantly increases segmental lordosis and anterior disc height without correlation to BMD. Primary stability in the immediate postoperative situation is mostly warranted in axial rotation. The risk of failure might be increased in extension for some patients with reduced lumbar BMD, therefore additional posterior stabilization could be considered. For any figures or tables, please contact the authors directly

Introduction. This study aimed to evaluate the effectiveness of a novel intraoperative navigation platform for total knee arthroplasty (TKA) in restoring native knee joint kinematics and strains in the medial collateral ligament (MCL) and lateral collateral ligament (LCL) during squatting motions. Method. Six cadaver lower limbs underwent computed tomography scans to design patient-specific guides. Using these scans, bony landmarks and virtual single-line collateral ligaments were identified to provide intraoperative real-time feedback, aided in bone resection, implant alignment, tibiofemoral kinematics, and collateral ligament elongations, using the navigation platform. The specimens were subjected to squatting (35°-100°) motions on a physiological ex vivo knee simulator, maintaining a constant 110N vertical ankle load regulated by active quadriceps and bilateral hamstring actuators. Subsequently, each knee underwent a medially-stabilized TKA using the mechanical alignment technique, followed by a retest under the same conditions used preoperatively. Using a dedicated wand, MCL and LCL insertions—anterior, middle, and posterior bundles—were identified in relation to bone-pin markers. The knee kinematics and collateral ligament strains were analyzed from 3D marker trajectories captured by a six-camera optical system. Result. Both native and TKA conditions demonstrated similar patterns in tibial valgus orientation (Root Mean Square Error (RMSE=1.7°), patellar flexion (RMSE=1.2°), abduction (RMSE=0.5°), and rotation (RMSE=0.4°) during squatting (p>0.13). However, a significant difference was found in tibial internal rotation between 35° and 61° (p<0.045, RMSE=3.3°). MCL strains in anterior (RMSE=1.5%), middle (RMSE=0.8%), and posterior (RMSE=0.8%) bundles closely matched in both conditions, showing no statistical differences (p>0.05). Conversely, LCL strain across all bundles (RMSE<4.6%) exhibited significant differences from mid to deep flexion (p<0.048). Conclusion. The novel intraoperative navigation platform not only aims to achieve planned knee alignment but also assists in restoring native knee kinematics and collateral ligament behavior through real-time feedback. Acknowledgment. This study was funded by Medacta International (Castel San Pietro, Switzerland)

Introduction. Intraoperative navigation systems for lumbar spine surgery allow to perform preoperative planning and visualize the real-time trajectory of pedicle screws. The aim of this study was to evaluate the deviation from preoperative planning and the correlations between screw deviation and accuracy. Method. Patients affected by degenerative spondylolisthesis who underwent posterior lumbar interbody fusion using intraoperative 3D navigation since April 2022 were included. Intraoperative cone-beam computed tomography (CBCT) was performed before screw planning and following implantation. The deviation from planning was calculated as linear, angular, and 3D discrepancies between planned and implanted screws. Accuracy and facet joint violation (FJV) were evaluated using Gertzbein-Robbins system (GRS) and Yson classification, respectively. Statistical analysis was performed using SPSS version28. One-way ANOVA followed by Bonferroni post-hoc tests were performed to evaluate the association between GRS, screw deviation and vertebral level. Statistical significance was set at p<0.05. Result. This study involved 34 patients, for a total of 154 pedicle screws. Mean age was 62.6±8.9 years. The mean two-dimensional screw tip deviation in mediolateral (ML), craniocaudal (CC), and anteroposterior (AP) was 2.6±2.45mm, 1.6±1.7mm, and 3.07±2.9mm, respectively. The mean screw tip 3D deviation was 5±3.3mm. The mean two-dimensional screw head deviation in ML, CC and AP was 1.83±1.8mm, 1.7±1.67mm and 3.6±3.1mm, respectively. The mean screw head 3D deviation was 4.94±3.2mm. 98% of screws were clinically acceptable (grade A+B), and grade 0 for FJV. Significant results were found between GRS and ML (p=0.005), AP (p=0.01) and 3D (p=0.003) tip deviations, and between GRS and AP and 3D head deviations (both p=0). Moreover, a significant correlation was found between GRS and vertebral level (p=0). Conclusion. Our results showed a reasonable rate of discrepancy between planned and positioned screws. However, accuracy was clinically acceptable in almost all cases. Therefore, pedicle screw fixation using intraoperative CBCT, 3D navigation and screw planning is safe and accurate

Bone metastases radiographically appear as regions with high (i.e. blastic metastases) or low (i.e. lytic metastases) bone mineral density. The clinical assessment of metastatic features is based on computed tomography (CT) but it is still unclear if the actual size of the metastases can be accurately detected from the CT images and if the microstructure in regions surrounding the metastases is altered (Nägele et al., 2004, Calc Tiss Int). This study aims to evaluate (i) the capability of the CT in evaluating the metastases size and (ii) if metastases affect the bone microstructure around them. Ten spine segments consisted of a vertebra with lytic or mixed metastases and an adjacent control (radiologically healthy) were obtained through an ethically approved donation program. The specimens were scanned with a clinical CT (AquilionOne, Toshiba: slice thickness:1mm, in-plane resolution:0.45mm) to assess clinical metastatic features and a micro-CT (VivaCT80, Scanco, isotropic voxel size:0.039mm) to evaluate the detailed microstructure. The volume of the metastases was measured from both CT and micro-CT images (Palanca et al., 2021, Bone) and compared with a linear regression. The microstructural alteration around the metastases was evaluated in the volume of interest (VOI) defined in the micro-CT images as the volume of the vertebral body excluding the metastases. Three 3D microstructural parameters were calculated in the VOI (CTAn, Bruker SkyScan): Bone Volume Fraction (BV/TV), Trabecular Thickness (Tb.Th.), Trabecular Spacing (Tb.Sp.). Medians of each parameter were compared (Kruskal-Wallis, p=0.05). One specimen was excluded as it was not possible to define the size of the metastases in the CT scans. A strong correlation between the volume obtained from the CT and micro-CT images was found (R2=0.91, Slope=0.97, Intercept=2.55, RMSE=5.7%, MaxError=13.12%). The differences in BV/TV, Tb.Th. and Tb.Sp. among vertebrae with lytic and mixed metastases and control vertebrae were not statistically significant (p-value>0.6). Similar median values of BV/TV were found in vertebrae with lytic (13.2±2.4%) and mixed (12.8±9.8%) metastases, and in controls (13.0±10.1%). The median Tb.Th. was 176±18 ∓m, 179±43 ∓m and 167±91 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. The median Tb. Sp. was 846±26 ∓m, 849±286 ∓m and 880±116 ∓m in vertebrae with lytic and mixed metastases and control vertebrae, respectively. In conclusion, the size of vertebral metastases can be accurately assess using CT images. The 3D microstructural parameters measured were comparable with those reported in the literature for healthy vertebrae (Nägele et al., 2004, Calc Tiss Int, Sone et al., 2004, Bone) and showed how the microstructure of the bone tissue surrounding the lesion is not altered by the metastases

Osteoarthritis (OA) is a degenerative disease that lacks regenerative treatment options. Current research focuses on mesenchymal stem cells (MSCs) and Platelet-Rich Plasma (PRP) as regenerative therapies, but extracellular vesicles (EVs) have shown to be more advantageous. This study compares the regenerative potential of human umbilical cord MSC-derived EVs (cEVs) and platelet-derived EVs (pEVs) in ex vivo and in vivo OA models. In the ex vivo study, OA conditions were induced in human cartilage explants, which were then treated either with pEVs or cEVs. Results showed a higher content of DNA and collagen in the pEVs group compared to control and cEVs groups, suggesting that pEVs could be a potential alternative to cEVs. In the in vivo study, an OA model was established in the knee joints of rats through MIA (monoiodoacetate) injection and then treated either with pEVs or cEVs. Results showed that pEVs-treated knee joints had better subchondral bone integrity and greater OA reversion, particularly in female rats, indicating that pEVs are a viable regeneration treatment for OA and outperform cEVs in terms of efficacy. Overall, the study demonstrates the potential of EVs as a regenerative treatment for OA, with pEVs showing promising results in both ex vivo and in vivo models. The use of pEVs in clinical practice could provide a faster path to translation due to the established use of platelet concentrates in therapeutics. However, further studies are needed to fully evaluate the potential of pEVs for OA treatment and to elucidate the mechanisms behind their regenerative effects. Acknowledgments: The authors thank Dr Fernando Hierro (UIB) for their technical contribution with TEM, Mª Trinidad García (UIB) for the access to radioactivity facilities, Aina Arbós (IUNICS) for her contribution in the histology staining, María Tortosa (IdISBa) for her assistance with the animal care and ADEMA School of Dentistry for the access to the cone beam computed tomography (CBCT). Funding: This research was funded by Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, co-funded by the ESF European Social Fund and the ERDF European Regional Development Fund (MS16/00124; CP16/00124), PROGRAMA JUNIOR del proyecto TALENT PLUS, construyendo SALUD, generando VALOR (JUNIOR01/18), financed by the sustainable tourism tax of the Balearic Islands; the Direcció General d'Investigació and Conselleria d'Investigació, Govern Balear (FPI/2046/2017); the Mecanisme de Recuperació i Resiliència, intended to execute research projects of «Noves polítiques públiques per a un mercat de treball dinàmic, resilient i inclusiu», collected in Pla de Recuperació, Transformació i Resiliència, financed by European Union-Next Generation EU and driven by SOIB and Conselleria de Fons Europeus, Universitat i Cultura i la Conselleria de Model Econòmic, Turisme i Treball (NG0421) and the grant SYN20/03 from IdISBa

Abstract. Objectives. This abstract provides an update on the Open Ankle Models being developed at the University of Bath. The goal of this project is to create three fully open-source finite element (FE) ankle models, including bones, ligaments, and cartilages, appropriate musculoskeletal loading and boundary conditions, and heterogeneous material property distribution for a standardised representation of ankle biomechanics and pre-clinical ankle joint analysis. Methods. A computed tomography (CT) scan data (pixel size of 0.815 mm, and slice thickness of 1 mm) was used to develop the 3D geometry of the bones (tibia, talus, calcaneus, fibula, and navicular). Each bone was given the properties of a heterogeneous elastic material based on the CT greyscale. The density values for each bone element were calculated using a linear empirical relation, ρ= 0.0405 + (0.000918) HU and then power law equations were utilised to get the Young's Modulus value for each bone element [1]. At the bone junction, a thickness of cartilage ranging from 0.5–1 mm, and was modelled as a linear material (E=10 MPa, ν=0.4 [2]). All ligament insertions and positions were represented by four parallel spring elements, and the ligament stiffness and material attributes were applied in accordance with the published literature [2]. The ankle model was subjected to static loading (balance standing position). Four noded tetrahedral elements were used for the discretization of bones and cartilages. All degrees of freedom were restricted at the proximal ends of the tibia and fibula. The ground reaction forces were applied at the underneath of the calcaneus bone. The interaction between the cartilages and bones was modelled using an augmented contact algorithm with a sliding elastic contact between each cartilage. A tied elastic contact was used between the cartilages and the bone. FEbio 2.1.0 (University of Utah, USA) was used to construct the open-source ankle model. Results. When the double-legged stance phase loading condition was taken into consideration, stress at the antero-medial tibial wall (ranged from 1 to 7 MPa) was found to be similar to the prior work [2], indicating bulk of the load transfer was through this region. The maximum principal strain was predicted at the different regions on bones around the ankle joint. The proximal surface of the talus, and tibial distal surface were shown to have the highest maximum principal strains followed by antero-medial walls of the tibia bone, at the proximal location. Conclusions. The present open 3D FE model of the ankle will assist researchers in better understanding ankle biomechanics, precisely predicting load transfer, and examining the ankle to address unmet clinical needs for this joint. The results of the current investigation are realistic in terms of load transfer and stress-strain distribution across the ankle joint and well comparable to those reported in the literature [2]. However, sensitivity and ankle instability simulations will be performed in future work to investigate the model's reliability and robustness. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Introduction and Objective. The geometry of the proximal tibia and distal femur is intimately linked with the biomechanics of the knee and it is to be considered in total knee arthroplasty (TKA) component positioning. The aim of the present study was to evaluate the proximal tibial torsion in relation to the flexion-extension axis of the knee in healthy and pathological cohort affected by knee osteoarthritis (OA). Materials and Methods. We retrospectively analyzed computed tomography scans of OA knee of 59 patients prior to TKA and non-arthritic knee of 39 patients as control. Posterior condylar angle (PCA), femoral tibial torsion (TEAs-PTC and TEAs-PTT), proximal tibial torsion (PTC-PTT and PCAx-PTC) and distance between tibial tuberosity and the trochlear groove (TT-TG) were measured. Results. No differences were found for gender, age, TG-TT and PCAn angles. Statistically significant differences were found for all the other angles considered. Significant relation was found between Tibial Torsion and TEA-PTT angles, between PCAx-PTC and TEA-PTC, between TEA-PTT and TEA-PTC and between PCAx-PTC and TEA-PTT. All measures, except TG-TT and PCAn angles, showed high validity (AUC > 75%) in detecting OA, with TEA-PTT displaying the highest validity with an AUC of 94.38%. Conclusions. This is the first study to find significant differences in terms of proximal tibia geometry and anatomy between non arthritic and OA knees. It is conceivable that such anatomy could be implicated in the development of OA. Based on our data, the TEAs is a valid reference for correct positioning of tibial component in TKA. Indeed, setting the tibial component parallel to TEAs makes the prosthetic knee more similar to the native non-arthritic knee

Abstract. Objectives. High tibial osteotomy for knee realignment is effective at relieving symptoms of knee osteoarthritis but the operation is surgically challenging. A new personalised treatment with simpler surgery using pre-operatively planned measurements from computed tomography (CT) imaging and 3D-printed implants and instrumentation has been designed and is undergoing clinical trial. The aim of this study was to evaluate the early clinical results of a preliminary pilot study evaluating the safety of this new personalised treatment. Methods. The single-centre prospective clinical trial is ongoing (IRCCS Istituto Ortopedico Rizzoli; IRB-0013355; ClinicalTrials.gov NCT04574570), with recruitment completed and all patients having received the novel custom surgical treatment. To preserve the completeness of the trial reporting, only surgical aspects were evaluated in the present study. Specifically, the length of the implanted osteosynthesis screws was considered, being determined pre-operatively eliminating intraoperative measurements, and examined post-operatively (n=7) using CT image processing (ScanIP, Synopsys) and surface distance mapping. The surgical time, patient discharge date and ease of wound closure were recorded for all patients (n=25). Results. Over the study period the average surgical time (skin incision to suture) reduced from 54 to 31 minutes (range: 17–62, n=25). It was noted that wound closure was easier than the conventional surgery due to the lower profile of the implant. Over seventy percent of patients were discharged day 2 post-op. The position, orientation and length of all screws matched the pre-operative configuration to within approximately 1mm. Conclusions. The early trial results are promising from a clinical perspective. It was evident that surgical time was saved because no intraoperative screw length measurements were required, and the use of custom instrumentation significantly reduced the surgical inventory. The reduced invasiveness and ease of surgery may contribute to faster patient recovery compared to conventional techniques. The full trial results will be reported later this year. Declaration of Interest. (a) fully declare any financial or other potential conflict of interest

Abstract. Introduction. Osteoarthritis (OA) is one of the lead causes of pain and disability in adults. Bone marrow lesions (BMLs) are one feature of subchondral bone involvement in OA. MRI images suggest changes in tissue content and properties in the affected regions however, it is not known if this alters the mechanical behavior of the bone, which could in turn affect OA progression. The aim of this study was to characterize the mechanical properties of BMLs, using a combined experimental and computational approach. Methods. Six human cadaveric patellae from donors aged 56–76 were used in this study; all exhibited BML regions under MRI. Bone plugs were taken from non-BML (n = 6) and BML (n = 7) regions within the patellae, with guidance from the MRI. The plugs were imaged at 82µm resolution using micro computed tomography (µCT) and tested under uniaxial compression. Finite element (FE) models were created for each plug from the µCT scans and morphological properties such as bone volume fraction (BV/TV) were also determined. The relationship between bone volume fraction and apparent modulus was investigated for both sample groups. Results. The BV/TV range was similar for the BML and non-BML groups (0.25–0.46 and 0.18–0.44) From the experimental tests, a moderate positive correlation was found between BV/TV and apparent modulus in the no BML group (r= 0.57) while no correlation was found in the BML group (r = −0.02). From the FE results, a different relationship between BV/TV and element elastic modulus was found for the BML and non-BML groups. Conclusions. The results of this study show that in regions of bone containing BMLs, bone volume fraction does not predict overall apparent modulus and has different relationship to local modulus, suggesting the BML associated tissue structural changes affect mechanical behavior. Funders: EPSRC