The preoperative planning of adolescent idiopathic scoliosis (AIS) remains largely debated. We hypothesized that adopting a biomechanical energetic framework could provide valuable insights for exploring the impact of spinal arthrodesis. Using this approach, we conducted a comparative analysis to quantify discrepancies between in silico simulations derived from preoperative radiographs and the actual three-dimensional spinal alignment obtained from post-operative imaging. Fifty-two consecutive patients with Lenke Type 1 AIS (mean age: 16 years; mean thoracic Cobb angle: 52°) who underwent posterior spinal fusion were included in the analysis. All patients had complete biplanar radiographs at three time points: preoperatively, post-operatively and at two-year follow-up. Discrepancies between in silico simulated surgery, calculated using preoperative radiographs and a biomechanical model, and actual clinical outcomes were quantified using two metrics: maximum coronal/sagittal deviations (MaxC/MaxS) from T1 to L5, and a comprehensive predictability factor ( a_c and a_s ) measuring cumulative 3D position discrepancies across 17 vertebral levels, normalized by total spinal length. Mean MaxC was 4.7 mm (SD=4.9) and MaxS was 5.7 mm (SD=3.8). Mean values of 𝐚_c were 3.4 𝐚_s were 4.1

Solid tumors are subjected to mechanical stimuli arising from their growth in confined environments. Growth-induced pressure builds up in tumors such as pancreatic cancer and rises alongside the occurrence of genetic alterations during tumorigenesis. This study aims to understand the so far unknown relationship between genetic alterations and cancer cell behavior under compressive stress. Using isogenic cell lines with engineered p53 mutations, we showed that the p53 background influences cell response to compression. Tumor growth under compression increased in cells harboring a mutated-truncated p53 form. This mutation blocked caspase 3 cleavage and promoted survival and growth through PI3K-AKT activation and dysregulation of c-FOS and FOSB transcription factors network. Mutated-truncated p53 cells displayed a unique behavior and heightened an activation state under compression. Mechanical compression and p53 mutations together drive tumor growth. p53 status could be a biomarker for predicting tumor adaptation to mechanical stress and efficiency of therapies targeting mechanosensitive pathways. Mechanical compression and p53 mutations together enhance cancer cell survival and growth, driving solid tumor progression.

Context Solid tumors are subjected to mechanical stimuli arising from their growth in confined environments. Growth-induced pressure builds up in tumors such as pancreatic cancer and rises alongside the occurrence of genetic alterations during tumorigenesis. This study aims to understand the so far unknown relationship between genetic alterations and cancer cell behavior under compressive stress. Results Using isogenic cell lines with engineered p53 mutations, we showed that the p53 background influences cell response to compression. Tumor growth under compression increased in cells harboring a mutated-truncated p53 form. This mutation blocked caspase 3 cleavage and promoted survival and growth through PI3K-AKT activation and dysregulation of c-FOS and FOSB transcription factors network. Mutated-truncated p53 cells displayed a unique behavior and heightened an activation state under compression. Conclusion Mechanical compression and p53 mutations together drive tumor growth. p53 status could be a biomarker for predicting tumor adaptation to mechanical stress and efficiency of therapies targeting mechanosensitive pathways. Teaser Mechanical compression and p53 mutations together enhance cancer cell survival and growth, driving solid tumor progression. ### Competing Interest Statement The authors have declared no competing interest. Fondation Toulouse Cancer Santé, Mecharesist Inserm Plan Cancer, PressDiagTherapy, MECHAEVO MSCA-ITN/ETN, PIPgen (Project ID: 955534) Fondation ARC, ARCPJA2021060003932, ARCPGA2022120005630_6362-3 Université de Toulouse, https://ror.org/01ahyrz84, Emergence (MECACAN) Cancéropôle Grand Ouest, https://ror.org/03vx94b97, Consortium Emergence MECAMes

We present a novel micromodel technology to explore bacterial biofilm development in porous media flows and demonstrate how it can be used to study the growth/detachment dynamics of Pseudomonas aeruginosa .

The assessment of chemotherapy response in osteosarcoma (OS), based on the average percentage of viable cells, is limited, as it overlooks the spatial heterogeneity of tumor cell response (foci of resistant cells), immune microenvironment, and bone microarchitecture. Despite the resulting positive classification for response to chemotherapy, some patients experience early metastatic recurrence, demonstrating that our conventional tools for evaluating treatment response are insufficient. We studied the interactions between tumor cells, immune cells (lymphocytes, histiocytes, and osteoclasts), and bone extracellular matrix (ECM) in 18 surgical resection samples of OS using multiplex and conventional immunohistochemistry (IHC: CD8, CD163, CD68, and SATB2), combined with multiscale characterization approaches in territories of good and poor response (GRT/PRT) to treatment. GRT and PRT were defined as subregions with <10% and >10% of viable tumor cells, respectively. Local correlations between bone ECM porosity and density of immune cells were assessed in these territories. Immune cell density was then correlated to overall patient survival. Two patterns were identified for histiocytes and osteoclasts. In poor responder patients, CD68 osteoclast density exceeded that of CD163 histiocytes but was not related to bone ECM load. Conversely, in good responder patients, CD163 histiocytes were more numerous than CD68 osteoclasts. For both of them, a significant negative local correlation with bone ECM porosity was found (P < ,01). Moreover, in PRT, multinucleated osteoclasts were rounded and intermingled with tumor cells, whereas in GRT, they were elongated and found in close contact with bone trabeculae. CD8 levels were always low in metastatic patients, and those initially considered good responders rapidly died from their disease. The specific recruitment of histiocytes and osteoclasts within the bone ECM, and the level of CD8 represent new features of OS response to treatment. The associated / (2024) prognostic signatures should be integrated into the therapeutic stratification algorithm of patients after surgery. (c) 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

Postoperative bacterial infections are prevalent complications in both human and veterinary orthopedic surgery, particularly when a biofilm develops. These infections often result in delayed healing, early revision, permanent functional loss, and, in severe cases, amputation. The diagnosis and treatment pose significant challenges, and bacterial biofilm further amplifies the therapeutic difficulty as it confers protection against the host immune system and against antibiotics which are usually administered as a first-line therapeutic option. However, the inappropriate use of antibiotics has led to the emergence of numerous multidrug-resistant organisms, which largely compromise the already imperfect treatment efficiency. In this context, the study of bacterial biofilm formation allows to better target antibiotic use and to evaluate alternative therapeutic strategies. Exploration of the roles played by mechanical factors on biofilm development is of particular interest, especially because cartilage and bone tissues are reactive environments that are subjected to mechanical load. This review delves into the current landscape of biofilm mechanobiology, exploring the role of mechanical factors on biofilm development through a multiscale prism starting from bacterial microscopic scale to reach biofilm mesoscopic size and finally the macroscopic scale of the fracture site or bone-implant interface.

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Quantification of bone tissue heterogeneity and cell distributionpatterns from digital histology: application to osteosarcoma Anthony Mancini, Anne Gomez-Brouchet, Michel Quintard, Sylvie Lorthois, Pascal Swider, Pauline Assemat

The mechanical properties of biological tissues and soft biomaterials are difficult to explore even though they play an important role in mechanobiological responses and organ homeostasis. Limited availability of harvested tissue and careful handling must be considered as well as discrepancies in biomaterial development. We hypothesized that a mixed analytical-experimental modal analysis could be used to determine effective mechanical properties at the mesoscale for hydrated and fragile, poorly available and small-sized biological tissue and biomaterials. Young's modulus E, shear modulus G and Poisson's ratio ν were obtained from the measurement of first two natural frequencies of a set-up associating tested specimen with a cantilever. Tangent modules are calculated using a set of two analytical governing equations in linear vibration framework. A complementary parametric sensitivity analysis was performed. The methodology was evaluated using materials known to be challenging, namely agarose for biomaterials and bone marrow for biological tissues. Frequencies were in the range of 350 Hz and acquisition time of few seconds. Linear responses was checked and solution triplets (E, G, ν ) were (99 ± 10 kPa, 43 ± 0.3 kPa, 0.16 ± 0.1) for agarose and (61 ± 12 kPa, 28 ± 7 kPa, 0.07 ± 0.03) for bone marrow. Comparisons with literature when available, confirmed approach acceptability. Limited influences of boundary conditions, brief experiments and reproducibility can be considered for applications to fragile and rare biomaterials and biological tissues, in addition to conventional characterization methods.

To explore the apparent diffusion coefficients of intervertebral discs in an asymptomatic pediatric cohort. We conducted a prospective MRI study of the lumbar spine from below the thoracolumbar junction to the lumbosacral junction on 12 subjects (mean age 13 y.o.) with no spinal pathology or spinal posture disorder. MRI was carried out using a 1.5 T machine with acquisitions realized both in sagittal and coronal planes. First, disc hydration was determined, and then, diffusion-weighted images were obtained using an SE single-shot echo-planar sequence. Apparent diffusion coefficients (ADC) of anterior annulus fibrosus (AAF), nucleus pulposus (NP) and posterior annulus fibrosus (PAF) were measured in the sagittal plane. Averaged hydration of 0.27 SD 0.03 confirmed the asymptomatic nature of discs. Average scaled values of ADC were 0.46 SD 0.01, 0.22 SD 0.09 and 0.18 SD 0.03 for NP, AAF and PAF, respectively. ADC of NP were almost constant along the spine; PAF values show a slight increase in the thorax-sacrum direction, while AAF values showed a pronounced decrease. Locally, ADC of AAF was higher compared to ADC PAF values below the thoracolumbar junction and it reversed for subjacent discs. In our knowledge, our study provided the first diffusive properties of asymptomatic intervertebral discs in an adolescent cohort. ADC of NP was slightly higher than adults'. ADC evolutions of AAF were correlated with lordosis concavity which pointed out the role of compressive strain on fluid transport properties. This study could furnish information about segment homeostasis for exploration of pediatric spinal pathologies.

Background: Craniosynostosis in newborns is caused by the premature closure of the cranial sutures leading to cranial vault deformity. It results in aesthetic imbalance and developmental disabilities and surgery is frequent during the first months of growth. Our study focused on scaphocephaly defined as the premature closure of the sagittal suture. We hypothesised that the effective mechanical properties of sutures were altered as compared to those of the parietal adjacent tissue considered as control. Methods: The population consisted of seven males and four females (mean age 4.9 months). Sixteen suture samples and thirty-four parietal tissue samples were harvested during corrective surgery and investigated by using three-point bending tests to obtain the structure-stiffness of specimens. An energy model was used to derive the effective Young's modulus. A histological study complemented the experimental protocol. Findings: Fused sutures were thicker than adjacent bone and the natural curvature of sutures did not influence the static mechanical response. The stiffness of stenotic sutures was significantly higher than that of the parietal bone. The effective Young's modulus of stenotic sutures was significantly lower than that of the parietal adjacent tissue. The parietal tissue showed a parallel bone architecture whereas the central stenotic tissue was disorganised with more vascularisation. Interpretation: The stenotic suture differed in structural and mechanical terms from the adjacent bone during calvarial growth in the first year of life. Our study emphasised the alteration of effective tissue properties in craniosynostosis.

The aims of the present study were to compare the biomechanical properties of tibial fixation in hamstring-graft ACL reconstruction using interference screw and a novel combination interference screw and dowel construct. We compared the fixation of 30 (2- and 4-stranded gracilis and semitendinosis tendons) in 15 fresh-frozen porcine tibiae with a biocomposite resorbable interference screw (Group 1) and a screw and dowel construct (Group 2). Each graft was subjected to load-to-failure testing (50 mm/min) to determine maximum load, displacement at failure and pullout strength. There were no significant differences between the biomechanical properties of the constructs. Multivariate analysis demonstrated that combination constructs (β = 140.20, p = 0.043), screw diameter (β = 185, p = 0.006) and 4-strand grafts (β = 51, p = 0.050) were associated with a significant increase in load at failure. Larger screw diameter was associated with increased construct stiffness (β = 20.15, p = 0.020). The screw and dowel construct led to significantly increased fixation properties compared to interference screws alone in a porcine model. Increased screw diameter and utilization of 4-strand ACL grafts also led to improvement in load-to-failure of the construct. However, this is an in vitro study and additional investigations are needed to determine whether the results are reproducible in vivo. Level V; Biomechanical study.

La fixation par endoboutons (EBs) de la butée coracoïdienne réalisée par arthroscopie a été développée afin d’éviter les complications rapportées avec l’utilisation des vis. Néanmoins, peu d’études ont évalué les caractéristiques mécaniques de ces procédés d’ostéosynthèse. L’objectif de notre étude était d’évaluer et de comparer la raideur d’une fixation par vis et par EB. L’hypothèse de départ était que l’endobouton présentait une plus faible raideur que les vis. Des impressions 3D d’une glène et d’un processus coracoïde ont été réalisées à partir d’un scanner de patient présentant une instabilité glénohumérale antérieure avec un défect osseux significatif. Quatre types d’ostéosynthèse de la coracoïde ont été réalisés : vis malléolaires de diamètre 4,5 mm (montage avec 1 et 2 vis) et EB (montage avec 1 et 2 EBs). Trois spécimens par montage ont été placés sur un banc d’essai spécifique. Une compression latéro-médiale de la butée à la vitesse 0,1 mm/s a été appliquée en 3 points (supérieur, central et inférieur). La force résultante ainsi que le déplacement de la butée ont été enregistrés. La raideur moyenne des fixations par 1 vis, 2 vis, 1 EB et 2 EBs étaient respectivement de 158 N/mm (133–179), 249 N/mm (241–259), 10 N/mm (5–13), 14 N/mm (13–15). Il existait une différence significative entre la raideur obtenue dans les groupes vis et EB (p < 0,001). Le montage à 1 EB occasionnait un déplacement supérieur par rapport à 2 EBs lorsque la force appliquée était polaire supérieure ou inférieure. En revanche, la différence n’était pas significative lorsque la contrainte était en position centrale (7,45 vs 6,93 mm ; p = 0,53) La fixation par vis a montré une plus grande raideur, alors que la fixation par EB a montré une détente du montage conduisant à une mobilisation de la butée plus importante. L’intérêt de l’utilisation de 2 EBs réside dans un moindre déplacement en cas de contrainte polaire. Cette étude biomécanique confirme la vulnérabilité mécanique jusqu’à sa consolidation, d’une butée fixée par EB. Étude biomécanique.

Le disque intervertébral (DIV) est formé par l’annulus fibrosus (AF) et le nucleus pulposus (NP) complexe inerte hydraté. La capacité de déformation du DIV, corrélée à celle du NP, dépend de son hydratation. Quand le DIV vieillit, son hydratation diminue, ainsi que ses capacités de déformation. Dans la scoliose idiopathique de l’adolescent, une des hypothèses étiologiques repose sur le DIV, étudié pour le diagnostic et le suivi de cette pathologie. L’hydratation du DIV dépend du genre, de l’âge et du niveau du segment rachidien dans une population pédiatrique asymptomatique. Le corollaire est d’établir un groupe contrôle de patients sains. Une cohorte de patients avec une IRM rachidienne normale a été inclue : 98 patients, âge moyen 13,3 ans. L’évaluation des volumes des disques et de l’hydratation de chaque DIV a été effectuée à partir de séquences IRM T2, en utilisant un logiciel de traitement d’images validé. L’étude portait sur la colonne lombaire, de la jonction thoraco-lombaire à la jonction lombo-sacrée. Il a été admis que l’hydratation du DIV était liée au ratio des volumes NP et AF. Une analyse linéaire mixte multivariée a été utilisée pour explorer le rôle de l’âge, du genre et du niveau segmentaire, sur l’hydratation des disques. L’hydratation du groupe des garçons était globalement plus élevée que celle du groupe des filles sans différence significative. L’hydratation augmentait avec l’âge (+0,005 pour chaque année supplémentaire, p = 0,0213). L’hydratation des DIV semblait plus importante au niveau thoraco-lombaire comparé au niveau lombaire, mais sans différence statistiquement significative. Nous avons établi une base de données incluant l’hydratation de disques lombaires non pathologiques à partir d’IRM, selon l’âge, le sexe et le niveau du segment, avec des intervalles de confiance à 95 %. IV.

The adolescent idiopathic scoliosis (AIS) is a 3D deformity of the spine whose origin is unknown and clinical evolution unpredictable. In this work, a mixed theoretical and numerical approach based on energetic considerations is proposed to study the global spine deformations. The introduced mechanical model aims at overcoming the limitations of computational cost and high variability in physical parameters. The model is constituted of rigid vertebral bodies associated with 3D effective stiffness tensors. The spine equilibrium is found using minimization methods of the mechanical total energy which circumvents forces and loading calculation. The values of the model parameters exhibited in the stiffness tensor are retrieved using a combination of clinical images post-processing and inverse algorithms implementation. Energy distribution patterns can then be evaluated at the global spine scale to investigate given time patient-specific features. To verify the reliability of the numerical methods, a simplified model of spine was implemented. The methodology was then applied to a clinical case of AIS (13-year-old girl, Lenke 1A). Comparisons of the numerical spine geometry with clinical data equilibria showed numerical calculations were performed with great accuracy. The patient follow-up allowed us to highlight the energetic role of the apical and junctional zones of the deformed spine, the repercussion of sagittal bending in sacro-illiac junctions and the significant role of torsion with scoliosis aggravation. Tangible comparisons of output measures with clinical pathology knowledge provided a reliable basis for further use of those numerical developments in AIS classification, scoliosis evolution prediction and potentially surgical planning.

Introduction: Arthroscopic coracoid bone-block fixation by Endobutton was developed to avoid the complications associated with screwing. However, few studies have assessed the mechanical characteristics of the two. The aim of the present study was to assess and compare fixation rigidity by screw versus Endobutton. The study hypothesis was that rigidity is lower with Endobutton than with screws. Material and method: 3D print-outs of a glenoid and a coracoid process were obtained from CT scans of a patient showing anterior shoulder instability with significant bone defect. Four types of coracoid fixation were implemented: 1 or 2 4.5 mm malleolar screws, and 1 or 2 Endobuttons. Three specimens per assembly were placed on a specific test bench. Lateromedial bone-block compression was exerted at 0.1 mm/sec at 3 points: superior, central, inferior. The resultant force and bone-block displacement were recorded. Results: Mean fixation rigidity with 1 screw, 2 screws, 1 Endobutton and 2 Endobuttons was respectively 158 N/mm (range, 133-179), 249 N/mm (241-259), 10 N/mm (5-13) and 14 N/mm (13-15), with significant difference between the screw and Endobutton groups (p < 0.001). Displacement was greater with 1 than 2 Endobuttons under superior or inferior force, while the difference was non-significant under central force (7.45 vs 6.93 mm; p = 0.53) Conclusions: Screw fixation showed greater rigidity, while the Endobutton assembly showed less tension, leading to greater bone-block mobilization. The interest of using two Endobuttons is to reduce displacement under polar pressure. the present biomechanical study confirmed the mechanical vulnerability of bone-blocks fixed by endobutton until consolidation is achieved. (C) 2020 Elsevier Masson SAS. All rights reserved.

Frailty is known to predict dementia. However, its link with neurodegenerative alterations of the central nervous system (CNS) is not well understood at present. We investigated the association between the biomechanical response of the CNS and frailty in older adults suspected of normal pressure hydrocephalus (NPH) presenting with markers of multiple co-existing pathologies. The biomechanical response of the CNS was characterized by the CNS elastance coefficient inferred from phase contrast magnetic resonance imaging and intracranial pressure monitoring during a lumbar infusion test. Frailty was assessed with an index of health deficit accumulation. We found a significant association between the CNS elastance coefficient and frailty, with an effect size comparable to that between frailty and age, the latter being the strongest known risk factor for frailty. Results were independent of CSF dynamics, showing that they are not specific to the NPH neuropathological condition. The CNS biomechanical characterization may help to understand how frailty is related to neurodegeneration and detect the shift from normal to pathological brain ageing.

Mechanical properties of cancellous bone is of increasing interest due to its involvement in aging pathologies and oncology. Characterization of fragile bone tissue is challenging and available methodologies include quasi-static compressive tests of small size specimens, ultrasound and indentation techniques. We hypothesized that modal analysis of flexure beams could be a complementary methodology to obtain Young modulus. The sampling methodology was adapted such that the uniqueness of the linear dynamic response was available to determine the elastic modulus from natural frequencies and mode shapes. In a first step, the methodology was validated using a synthetic bone model as control. Then, water-jet cutting allowed collecting fourteen small beam-like specimens in canine distal femurs. X-ray microtomography confirmed the microarchitecture preservation, the homogeneity and the isotropy at the specimen scale to derive effective properties. The first natural frequency in clamped-free boundary conditions was used to obtain mean values of Young modulus, which ranged from 210 MPa to 280 MPa depending on the specimen collection site. Experimental tests were rapid and reproducible and our preliminary results were in good agreement with literature data. In conclusion, beam modal analysis could be considered for exploring mechanical properties of fragile and scarce biological tissues. (c) 2020 Elsevier Ltd. All rights reserved.