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During, development and regeneration cells are subject to dynamic topographic changes as the surrounding tissues shift and grow. Yet, in vitro experiments have shown that cell scale curvatures influence cell migration, whereby, cells tend to avoid convex peaks and are more likely to settle in concave areas. This behavior was demonstrated on static surfaces with a fixed sinusoidal landscape composed of curved hills-and-valleys. Based on these findings, we later proposed a computer model to theoretically explain the underlying physical mechanism. Nonetheless, how dynamic curvature impacts cell motion remains unknown. In this study, we extend our previous model to explore what would happen if substrate curvature were to change over time. Using travelling wave patterns, we simulate a dynamic surface curvature. We investigate the influence of wave height and wave propagation speed and we find that long-distance cell migration can be achieved. Our results open a new area of study to understand cell mobility in dynamic environments, from single cell in vitro experiments to multi cellular in vivo mechanisms involving embryogenesis and regeneration.

A lot of evidence has shown the importance of stimulating cell mechanically during bone repair. In this study, we modeled the challenging fracture healing of a large bone defect in tibial diaphysis. To fill the fracture gap, we considered the implantation of a porous osteoconductive biomaterial made of poly-lactic acid wrapped by a hydrogel membrane mimicking osteogenic properties of the periosteum. We identified the optimal loading case that best promotes the formation and differentiation into bone tissue. Our results support the idea that a patient's rehabilitation program should be adapted to reproduce optimal mechanical stimulations.

There is compelling evidence that substrate stiffness affects cell adhesion as well as cytoskeleton organization and contractile activity. This work was designed to study the cytoskeletal contractile activity of single cells plated on micropost substrates of different stiffness using a numerical model simulating the intracellular tension of individual cells. We allowed cells to adhere onto micropost substrates of various rigidities and used experimental traction force data to infer cell contractility using a numerical model. The model shows that higher substrate stiffness leads to an increase in intracellular tension. The strength of this model is its ability to calculate the mechanical state of each cell in accordance to its individual cytoskeletal structure. This is achieved by regenerating a numerical cytoskeleton based on microscope images of the actin network of each cell. The resulting numerical structure consequently represents pulling characteristics on its environment similar to those generated by the cell in-vivo. From actin imaging we can calculate and better understand how forces are transmitted throughout the cell.

International audience; This study aims at suggesting a new approach to peri-implant healing models, providing a set of taxis-diffusion-reaction equations under the combined influence of mechanical and biochemical factors. Early events of osseointegration were simulated for titanium screw implants inserted into a pre-drilled trabecular bone environment, up to twelve weeks of peri-implant bone healing. Simulations showed the ability of the model to reproduce biological events occurring at the implant interface through osteogenesis. Implants with shallow healing chamber showed higher proportions of lamellar bone, enhanced by the increase of mechanical stimulation. Osteoconduction was observed through the surface treatment model and similar bone healing patterns compared to in vivo studies.

Objective: The aim of this study was to assess, through biological analysis, the local effects and osseointegration of dental implants incorporating surface micro/nanofeatures compared to implants of identical design without surface treatment. Background: Known to impact bone cell behavior, surface chemical and topography modifications target improved osseointegration and long-term success of dental implants. Very few studies assess the performance of implants presenting both micro-and nanofeatures in vivo on the animal models used in preclinical studies for medical device certification. Methods: Implant surfaces were characterized in terms of topography and surface chemical composition. After 4 weeks and 13 weeks of implantation in sheep femoral condyles, forty implants were evaluated through micro-computed tomography, histopathologic, and histomorphometric analyses. Results: No local adverse effects were observed around implants. Histomorphometric analyses showed significantly higher bone-to-implant contact in the coronal region of the surface treated implant at week 4 and week 13, respectively 79.3$\pm$11.2% and 86.4$\pm$6.7%, compared to the untreated implant's 68.3$\pm$8.8% and 74.8$\pm$13%. Micro-computed tomography analyses revealed that healing patterns differed between coronal and apical regions, with higher coronal boneto-implant contact at week 13. Histopathologic results showed, at week 13, bone healing around the surface treated implant with undistinguishable defect margins while the untreated implant still presented bone condensation and traces of the initial drill defect. Conclusion: Our results suggest that the surface treated implant not only shows no deleterious effects on local tissues but also promotes faster bone healing around the implant. (word count: 241, Journal of Periodontal Research, Wiley, 2021

International audience; Background: Four-corner arthrodesis, which involves fusing four carpal bones while removing the scaphoid bone, is a standard surgery for the treatment of advanced stages of wrist arthritis. Nowadays, it can be performed using a dorsal approach by fixing a plate to the bones and a new radial approach is in development. To date, there is no consensus on the biomechanically optimal and most reliable surgical construct for four-corner arthrodesis. Methods: To evaluate them biomechanically and thus assist the surgeon in choosing the best implant orientation, radial or dorsal, the two different four-corner arthrodesis surgical constructs were virtually simulated on a 3D finite element model representing all major structures of the wrist. Two different realistic load sets were applied to the model, representing common tasks for the elderly. Findings: Results consistency was assessed by comparing with the literature the force magnitude computed on the carpal bones. The Von Mises stress distribution in the radial and dorsal plates were calculated. Stress concentration was located at the plate-screw interface for both surgical constructs, with a maximum stress value of 413 MPa for the dorsal plate compared to 326 MPa for the radial plate, meaning that the stress levels are more unfavourable in the dorsal approach. Interpretation: Although some bending stress was found in one load case, the radial plate was mechanically more robust in the other load case. Despite some limitations, this study provides, for the first time, quantified evidence that the newly developed radial surgical construct is mechanically as efficient as the dorsal surgical construct.

International audience; Pharmaceutical treatments can slow bone degradation, thus reducing the fracture risk inherent in osteoporosis. Antiresorptive treatments block the over-activation of osteoclasts vs osteoblasts, but the resulting decrease in bone remodeling frequency may weaken bone structure over time, with no gain in bone volume. Anabolic treatments, however, induce gain in bone volume. The quantitative results from existing studies on the effects of treatments over time are general and nonpatient-specific, while numerical models simulating evolution of patient-specific bone microarchitecture consider a spatially random distribution of the remodeling process. Here, we propose a new approach to simulate the remodeling over decades of an individual patient's bone microarchitecture, based on the hypothesis that the oldest sites, which are hypermineralized and more brittle, are remodeled first. Taking these older sites as prime targets of remodeling, simulations show that severe osteoporosis profoundly degrades the mechanical properties of the bone structure, which can be restored and even improved by anabolic, more than by antiresorptive, therapies.

International audience; The knowledge of local stress distribution in hand joints is crucial to understand injuries and osteoarthritis occurrence. However, determining cartilage contact stresses remains a challenge, requiring numerical models including both accurate anatomical components and realistic tendon force actuation. Contact forces in finger joints have frequently been calculated but little data is available on joint contact pressures. This study aimed to develop and assess a hybrid biomechanical model of the index finger to estimate in-vivo joint contact pressure during a static maximal strength pinch grip task. A finite element model including bones, cartilage, tendons, and ligaments was developed, with tendon force transmission based on a tendon-pulley system. This model was driven by realistic tendon forces estimated from a musculoskeletal model and motion capture data for six subjects. The hybrid model outputs agreed well with the experimental measurement of fingertip forces and literature data on the physiological distribution of tendon forces through the index finger. Mean contact pressures were 6.9 ± 2.7MPa, 6.2 ± 1.0 MPa and 7.2 ± 1.3MPa for distal, proximal interphalangeal and metacarpophalangeal joints, respectively. Two subjects had higher mean contact pressure in the distal joint than in the other two joints, suggesting a mechanical cause for the prevalence of osteoarthritis in the index distal joint. The inter-subject variability in joint contact pressure could be explained by different neuromuscular strategies employed for the task. This first application of an effective hybrid model to the index finger is promising for estimating hand joint stresses under daily grip tasks and simulating surgical procedures.

International audience; Computational models have become an essential part of exploratory protocols in cell biology, as a complement to in vivo or in vitro experiments. These virtual models have the twofold advantage of enabling access to new types of data and validate complex theories. The design of mechanically functionalized biomaterials or scaffolds, to promote cell proliferation and invasion in the absence or in the complement of synthetic chemical coatings, can certainly benefit from these hybrid testing approaches. The underlying fundamental process of cell migration and in particular its dependence on the cell mechanical/geometrical environment remains crudely understood. Currently at least two theories explain the migration patterns observed by cells on curved topographies, involving either polymerization dynamics of actin or assembly dynamics of focal adhesions. We recently proposed a third mechanism relying on nucleus mechanosensitivity, which has been tested extensively experimentally and computationally. We now explore the hypothesis that nucleosensitivity could be a mechanism for cells to optimally find microenvironments suited for mitosis, providing mechanical stability and relaxation. By means of a computational mechanical model with intracellular structure detail, we investigate how the complex interplay between this new migration mechanism and the microenvironment topography can lead to more relaxed cells and organelles. To go further, we simulated in this study cell migration via a novel protocol in silico which generates dynamical ripple wave on a deformable substrate and changes topography over time. This kind of in silico protocols based on a new understanding of cell migration and nucleosensitivity could, therefore, inform the design of optimized scaffold topographies for cell invasion and proliferation.

International audience; Introduction: Endodontic treatment success is achieved not only when the cement provides a hermetic seal but also when the injured periapical tissue is regenerated. However, an exaggerated inflammatory reaction hinders tissue regeneration and it has been shown that dental materials affect the inflammatory response through modulation of cytokine secretion. This work was set to investigate the effects of the presence of hydrocortisone in zinc oxide eugenol sealers (Endomethasone N) on modulating the initial steps of inflammation in vitro.Material and methods: Hydrocortisone and eugenol leaching from Endomethasone N and Pulp Canal Sealer (PCS) were quantified by ELISA and spectrofluorometry, respectively. The effects of Endomethasone N and Pulp Canal Sealer were studied on lipopolysaccharides (LPS)-stimulated human periodontal ligament (hPDL) cells. Cytokine (IL-6, TNF-α) secretion from cells was quantified by ELISA. Inflammatory cell (THP-1) adhesion to activated endothelial cells, their migration and activation were studied in vitro.Results: Endomethasone N decreased secretion of IL-6 and TNF-α from hPDL cells. THP-1 adhesion to activated endothelial cells (HUVECs) and migration significantly decreased with Endomethasone N while no effect was observed with PCS. Activation of THP-1 decreased with both materials’ extracts but was significantly lower with Endomethasone N than with PCS.Conclusion: These results performed in vitro show that Endomethasone N anti-inflammatory effects are due to the presence of hydrocortisone.Clinical relevance: Endomethasone N has potential local anti-inflammatory effects which appear to be due to its hydrocortisone rather than eugenol content. Decreasing the inflammatory response is a pre-requisite to initiate the periapical healing.

International audience; Recent experiments hint that adherent cells are sensitive to their substrate curvature. It is already well known that cells behaviour can be regulated by the mechanical properties of their environment. However, no mechanisms have been established regarding the influence of cell-scale curvature of the substrate. Using a numerical cell model, based on tensegrity structures theory and the non-smooth contact dynamics method, we propose to investigate the mechanical state of adherent cells on concave and convex hemispheres. Our mechanical cell model features a geometrical description of intracellular components, including the cell membrane, the focal adhesions, the cytoskeleton filament networks, the stress fibres, the microtubules, the nucleus membrane and the nucleoskeleton. The cell model has enabled us to analyse the evolution of the mechanical behaviour of intracellular components with varying curvature radii and with the removal of part of these components. We have observed the influence of the convexity of the substrate on the cell shape, the cytoskeletal force networks as well as on the nucleus strains. The more convex the substrate, the more tensed the stress fibres and the cell membrane, the more compressed the cytosol and the microtubules, leading to a stiffer cell. Furthermore, the more concave the substrate, the more stable and rounder the nucleus. These findings achieved using a verified virtual testing methodology, in particular regarding the nucleus stability, might be of significant importance with respect to the division and differentiation of mesenchymal stem cells. These results can also bring some hindsights on cell migration on curved substrates.

Cell deformation occurs in many critical biological processes, including cell extravasation during immune response and cancer metastasis. These cells deform the nucleus, its largest and stiffest organelle, while passing through narrow constrictions in vivo and the underlying mechanisms still remain elusive. It is unclear which biochemical actors are responsible and whether the nucleus is pushed or pulled (or both) during deformation. Herein we use an easily-tunable poly-L-lactic acid micropillar topography, mimicking in vivo constrictions to determine the mechanisms responsible for nucleus deformation. Using biochemical tools, we determine that actomyosin contractility, vimentin and nucleo-cytoskeletal connections play essential roles in nuclear deformation, but not A-type lamins. We chemically tune the adhesiveness of the micropillars to show that pulling forces are predominantly responsible for the deformation of the nucleus. We confirm these results using an in silico cell model and propose a comprehensive mechanism for cellular and nuclear deformation during confinement. These results indicate that microstructured biomaterials are extremely versatile tools to understand how forces are exerted in biological systems and can be useful to dissect and mimic complex in vivo behaviour.

International audience; Latest experiments have shown that adherent cells can migrate according to cell-scale curvature variations via a process called curvotaxis. Despite identification of key cellular factors, a clear understanding of the mechanism is lacking. We employ a mechanical model featuring a detailed description of the cytoskeleton filament networks, the viscous cytosol, the cell adhesion dynamics and the nucleus. We simulate cell adhesion and migration on sinusoidal substrates. We show that cell adhesion on three-dimensional curvatures induces a gradient of pressure inside the cell that triggers the internal motion of the nucleus. We propose that the resulting out-of-equilibrium position of the nucleus alters cell migration directionality, leading to cell motility toward concave regions of the substrate, resulting in lower potential energy states. Altogether, we propose a simple mechanism explaining how intracellular mechanics enable the cells to react to substratum curvature, induce a deterministic cell polarization and breakdown cells basic persistent random walk, which correlates with latest experimental evidences.

Introduction: A large body of studies have highlighted that cells are sensitive to nanotopographies or geometrical cell-scale structures. However, natural biotopes also exhibit much larger topographical cues that are often curved and smooth, such as walls of blood vessels, bone cell cavities, or other cell bodies. Very little is known about how isolated cells and tissues read and integrate cell-scale curvatures, and the mechanisms leading to the integration of such physical cues. Objective: Herein, our aim was to develop new model surfaces with controlled edge-free cell-scale anisotropic and isotropic sinusoidal patterns to investigate the mesenchymal stem cell and epithelial cell layers" response to cell-scale curvature variations. Materials and methods: Herein we develop a two-step fabrication method to produce a series of sinusoidal landscapes with very low micro roughness. We combine live imaging, biochemistry and modeling approaches to decipher integration mechanisms at the cellular and tissue levels using respectively human mesenchymal stem cells (hMSCs) and MDCK epithelial cells. Results: First, we report a new cellular sense which we term "curvotaxis" that enables the isolated hMSCs to react to cell-scale curvature variations, a ubiquitous trait of cellular biotopes. We show that hMSCs avoid convex regions during their migration and position themselves in concave valleys. Computational modeling, pharmacological assays and live imaging show that curvotaxis relies on a dynamic interplay between the nucleus and the cytoskeleton - the nucleus acting as a curvature sensor that guides cell migration towards concave curvatures (1). Further, we report the curvature-modulated anisotropic growth of unconfined epithelia over cell-scale grooves and ridges of various transversal curvature. Curved regions of the substrate work as "topographical barriers", causing heterogeneity and reorientation of the nuclei and F-actin position. As a result, the epithelium displays a spatial bias in various morphogenetic processes such as migration or mitosis (2). Conclusion: Altogether, this work establishes cell-scale curvature as a major tuning parameter to regulate the growth of cells and epithelia and opens new possibilities for tissue engineering research.

19-23 novembre 2018; In vivo les cellules sont en contact avec diverses caractéristiques topographiques qui couvrent plusieurs ordres de taille et d'organisation. L'intégration cellulaire de ces caractéristiques topographiques affecte de multiples aspects de la physiologie de la cellule. Un grand nombre d'études ont mis en évidence que les cellules sont sensibles aux nanotopographies ou aux structures géométriques à l'échelle des cellules. Les biotopes naturels présentent également des caractéristiques topographiques beaucoup plus grandes qui sont souvent courbées et lisses, tels que les parois des vaisseaux sanguins, les cavités des cellules osseuses, les acini ou d'autres corps cellulaires. On sait très peu de choses sur la façon dont les cellules lisent et intègrent les courbures à leur propre échelle et sur les mécanismes menant à l'intégration de tels signaux physiques. Nous rapportons ici un nouveau sens cellulaire que nous appelons «curvotaxie» qui permet aux cellules de réagir aux variations de courbure à l'échelle cellulaire, un trait omniprésent des biotopes cellulaires. Nous développons des surfaces 3D sinusoïdales ultra-lisses présentant des modulations de courbure dans toutes les directions, et contrôlons le comportement des cellules sur ces paysages topographiques simplifiés. Nous montrons que les cellules évitent les régions convexes pendant leur migration et se positionnent dans des vallées concaves. La modélisation computationnelle combinée à l'analyse fonctionnelle et à l'imagerie en direct montre que la curvotaxie repose sur une interaction dynamique entre le noyau et le cytosquelette de la cellule. D'autres analyses montrent que la courbure du substrat affecte la forme du noyau cellulaire, les tensions intracellulaires, l'organisation et la dynamique des adhésions focales et l'expression des gènes. Au total, ce travail identifie la curvotaxie comme un nouveau mécanisme de guidage et qui favorise la courbure à l'échelle de la cellule comme un signal physique essentiel entièrement intégré par les cellules. Mots clés : biomatériau, cellules, topographie

International audience; The mechanical behavior of the cortical bone in nanoindentation is a complicated mechanical problem. The finite element analysis has commonly been assumed to be the most appropriate approach to this issue. One significant problem in nanoindentation modeling of the elastic-plastic materials is pileup deformation, which is not observed in cortical bone nanoindentation testing. This phenomenon depends on the work-hardening of materials; it doesn't occur for work-hardening materials, which suggests that the cor-tical bone could be considered as a work-hardening material. Furthermore, in a recent study [59], a plastic hardening until failure was observed on the micro-scale of a dry ovine osteonal bone samples subjected to micropillar compression. The purpose of the current study was to apply an isotropic hardening model in the finite element simulations of the nanoindentation of the cortical bone to predict its mechanical behavior. The Johnson-Cook (JC) model was chosen as the constitutive model. The finite element modeling in combination with numerical optimization was used to identify the unknown material constants and then the finite element solutions were compared to the experimental results. A good agreement of the numerical curves with the target loading curves was found and no pileup was predicted. A Design Of Experiments (DOE) approach was performed to evaluate the linear effects of the material constants on the mechanical response of the material. The strain hardening modulus and the strain hardening exponent were the most influential parameters. While a positive effect was noticed with the Young's modulus, the initial yield stress and the strain hardening modulus, an opposite 1 effect was found with the Poisson's ratio and the strain hardening exponent. Finally, the JC model showed a good capability to describe the elastoplastic behavior of the cortical bone.

International audience; Additive manufacturing methods provide an increasingly popular industrial means of producing complex mechanical parts when classical methods are not suitable. The main advantage of these methods is the great freedom they give designers. At the same time, theoretical and numerical topology optimization tools can be used to simulate structures with complex shapes which exactly meet the mechanical constraints while requiring as little material as possible. Combining topology optimization and additive production procedures therefore seems to be a promising approach for obtaining optimized mechanical parts. Nonetheless structures obtained via topology optimization are composed of parts of composite densities which can not produced via additive manufacturing. Only numerical structures made of full or empty spaces only can be produced by additive methods. This can be obtained at the end of computational optimization through a penalization step which gives the composite densities from 0 to 1 the values 0 or 1. This means that the final part is different from the best solution predicted by topology optimization calculations. It therefore seemed to be worth checking the validity of an engineering approach in which additive methods are used to manufacture structures based on the use of industrial topology optimization codes. Here the authors propose to study, in the case of a simple mechanical problem, that of a metal cube subjected to a given pressure, three procedures, which differed in terms of the code and type of topology optimization calculations performed and the level of penalization applied. The three structures thus obtained were then produced using additive methods. Since all three structures proved to be mechanically resistant, the three procedures used can be said to be valid. However, one of them yielded better compromise between the mechanical strength and the amount of material saved. (C) 2017 The Society of Manufacturing Engineers. Published by Elsevier Ltd. All rights reserved.

Cette présentation a également été faite dans le cadre des colloques suivants : - Gordon Conference on Biointerfaces 2016 - 12-17 juin 2016 - Workshop Matériaux pour la Santé - 16 janvier 2018 - International Materials Research Congress (IMRC XXVI) (Cancun, Mexico) - 21-25 août 2017 - BIOMAT 2017 (Ambleteuse, France) - 12-16 juin 2017 - GDR Mecabio 2017 - 5-6 janvier 2017; Cells have evolved specific sensing mechanisms to recognize and integrate a diverse set of environmental cues. It is now well established that cells can detect sub-cellular topographical features, and these physical cues are sufficient to direct cell migration and trigger stem cell commitment to specific lineage. Nevertheless, most efforts in this field are focused on the impact of unnatural or geometric structures (e.g.: arrays of dots, microgrooves, micro pillars) and very little is known about natural and smooth cell-scale topographies, a ubiquitous trait of natural environments. Through this talk, recent findings that demonstrate that adherent cells can read and integrate cell-scale curvature variations will be presented. This new cellular sense was termed “curvotaxis”. We developed sinusoidal 3D surfaces presenting continuous variations of cell-scale curvature, and monitored cell behavior on these simplified biomimetic landscapes. We found that cells avoid convex regions during their migration and position themselves in concave valleys. Computational modeling, small-scale functional screen and live imaging suggest that curvotaxis relies on a dynamic interplay between the nucleus and the actin network - the nucleus acting as a mechano-sensing organelle that drives cell migration. Further analysis show that substratum concavity increases nuclear sphericity, lowers stress fiber tension and down-regulates a subset of genes involved in stem cell differentiation. Taken together, these data identify curvotaxis as a new guiding mechanism and suggest that cell-scale topography might be a true component of the stem cell niche. Keywords: surface topography, cell/surface interactions, curvature

International audience; Cell adhesion is crucial for many types of cell, conditioning differentiation, proliferation, and protein synthesis. As a mechanical process, cell adhesion involves forces exerted by the cytoskeleton and transmitted by focal adhesions to extracellular matrix. These forces constitute signals that infer specific biological responses. Therefore, analyzing mechanotransduction during cell adhesion could lead to a better understanding of the mechanobiology of adherent cells. For instance this may explain how, the shape of adherent stem cells influences their differentiation or how the stiffness of the extracellular matrix affects adhesion strength. To assess the mechanical signals involved in cell adhesion, we computed intracellular forces using the Cytoskeleton Divided Medium model in endothelial cells adherent on micropost arrays of different stiffnesses. For each cell, focal adhesion location and forces measured by micropost deflection were used as an input for the model. The cytoskeleton and the nucleoskeleton were computed as systems of multiple tensile and compressive interactions. At the end of computation, the systems respected mechanical equilibrium while exerting the exact same traction force intensities on focal adhesions as the observed cell. The results indicate that not only the level of adhesion forces, but also the shape of the cell has an influence on intracellular tension and on nucleus strain. The combination of experimental micropost technology with the present CDM model constitutes a tool able to estimate the intracellular forces. (C) 2016 Published by Elsevier Ltd.

Cet article presente un etat des connaissances en biomecanique et mecanobiologie du systeme osteoarticulaire. La premiere section de cet article porte sur les analyses du comportement et de la qualite osseuse d'un os en croissance et celles opposees d'un os degrade par le vieillissement. La deuxieme section concerne la restauration articulaire du membre inferieur par des implants. La derniere section analyse le role de la mecanotransduction cellulaire sur la formation de la matrice osseuse.

The shape that stem cells reach at the end of adhesion\ud process influences their differentiation. Rearrangement of\ud cytoskeleton and modification of intracellular tension may\ud activate mechanotransduction pathways controlling cell\ud commitment. In the present study, the mechanical signals\ud involved in cell adhesion were computed in in vitro stem\ud cells of different shapes using a single cell model, the\ud so-called Cytoskeleton Divided Medium (CDM) model.\ud In the CDM model, the filamentous cytoskeleton and\ud nucleoskeleton networks were represented as a mechanical\ud system of multiple tensile and compressive interactions\ud between the nodes of a divided medium. The results showed\ud that intracellular tonus, focal adhesion forces as well as\ud nuclear deformation increased with cell spreading. The\ud cell model was also implemented to simulate the adhesion\ud process of a cell that spreads on protein-coated substrate by\ud emitting filopodia and creating new distant focal adhesion\ud points. As a result, the cell model predicted cytoskeleton\ud reorganisation and reinforcement during cell spreading.\ud The present model quantitatively computed the evolution\ud of certain elements of mechanotransduction and may be a\ud powerful tool for understanding cell mechanobiology and\ud designing biomaterials with specific surface properties to\ud control cell adhesion and differentiation.\ud

International audience

International audience; A computational model based on finite element method (FEM) and computational fluid dynamics (CFD) is developed to analyse the mechanical stimuli in a composite scaffold made of polylactic acid (PLA) matrix with calcium phosphate glass (Glass) particles. Different bioreactor loading conditions were simulated within the scaffold. In vitro perfusion conditions were reproduced in the model. Dynamic compression was also reproduced in an uncoupled fluid-structure scheme: deformation level was studied analyzing the mechanical response of scaffold alone under static compression while strain rate was studied considering the fluid flow induced by compression through fixed scaffold. Results of the model show that during perfusion test an inlet velocity of 25 mm/s generates on scaffold surface a fluid flow shear stress which may stimulate osteogenesis. Dynamic compression of 5% applied on the PLA– Glass scaffold with a strain rate of 0.005 s À1 has the benefit to generate mechanical stimuli based on both solid shear strain and fluid flow shear stress on large scaffold surface area. Values of perfusion inlet velocity or compression strain rate one order of magnitude lower may promote cell proliferation while values one order of magnitude higher may be detrimental for cells. FEM–CFD scaffold models may help to determine loading conditions promoting bone formation and to interpret experimental results from a mechanical point of view.

International audience; Cell deformability and mechanical responses of living cells depend closely on the dynamic changes in the structural architecture of the cytoskeleton (CSK). To describe the dynamic reorganization and the heterogeneity of the prestressed multi-modular CSK, we developed a two-dimensional model for the CSK which was taken to be a system of tension and compression interactions between the nodes in a divided medium. The model gives the dynamic reorganization of the CSK consisting of fast changes in connectivity between nodes during medium deformation and the resulting mechanical behavior is consistent with the strain-hardening and prestress-induced stiffening observed in cells in vitro. In addition, the interaction force networks which occur and balance to each other in the model can serve to identify the main CSK substructures: cortex, stress fibers, intermediate filaments, microfilaments, microtubules and focal adhesions. Removing any of these substructures results in a loss of integrity in the model and a decrease in the prestress and stiffness, and suggests that the CSK substructures are highly interdependent. The present model may therefore provide a useful tool for understanding the cellular processes involving CSK reorganization, such as mechanotransduction, migration and adhesion processes.

Fractures in trabecular bone are due to degradations: bone density decreases and microarchitecture is altered with respect to aging. Many authors aimed modelling degradation of trabecular bone architecture due to aging or disease ([Adachi, 2001], [Muller, 2005], [Liu, 2008]). The precited models were only based on biological kinetics and parameters: lengths of apposition and resorption phase, depth of resorption lacunae, frequency activation... However, models considered millions of elements and did not integrate mechanical stimulus as a precursor of bone remodelling adaptation. As a result, they have simulated the micro-structure degradation and not the influence of mechanical stimulus on bone stiffness.