Probing stiffness anisotropies in three-dimensional materials non-destructively is a major challenge in disciplines as diverse as aeronautics and medicine. While the former typically relies on various mechanical tests—such as tensile, compression, bending, and shear—performed on sample parts, the latter often employs acoustic techniques or wave propagation through matter. The choice of techniques depends on the size of the sample of interest and the desired resolution. In our case, to probe the mechanical properties of sub-millimetre micro-tissues, it is necessary to use methods with high resolution and as furtive as possible. We present a method based, 1/ on imaging the displacement of microbeads within a hydrogel resulting from the growth of a three-dimensional micro-tissue and, 2/ on finite element modelling of the deformations underlying bead displacements. This approach allows us to determine the elastic properties of the hydrogel and, in particular, to show that beyond a certain thickness, incomplete cross-linking of the hydrogel results in a stiffness gradient. We show that when the micro-tissue contacts with an immediately rigid alginate wall, the pressure exerted over time increases very rapidly, whereas when the micro-tissue encounters a substrate with a stiffness gradient, the pressure increase is more gradual. Uncovering this could provide a better understanding of the role of tumour microenvironment stiffness in metastatic escape processes. Statement of Significance Understanding factors modulating tumours growth is crucial for developing better cancer treatments. This study introduces a non-destructive method to assess the stiffness of subcomponents of a tissue avatar, a question unwieldly to tackle. The authors show that small changes in stiffness of the tumour-mimic surrounding tissue can strongly affects how the tumour cell aggregate grows. This is an outreach in cancer biology because it connects the mechanical environment of tissues to cancer behaviour in a original way. It provides a powerful tool for studying 3D biological systems and could help design more suited materials for biomedical research and therapy. This work is relevant for the fields of cancer biology, biomaterials, and tissue engineering.

Understanding the interplay between biology and mechanics in tissue architecture is challenging, particularly in terms of 3D tissue organization. Addressing this challenge requires a biological model enabling observations at multiple levels from cell to tissue, as well as theoretical and computational approaches enabling the generation of a synthetic model that is relevant to the biological model and allowing for investigation of the mechanical stresses experienced by the tissue. Using a monolayer human colon epithelium organoid as a biological model, freely available tools (Fiji, Cellpose, Napari, Morphonet, or Tyssue library), and the commercially available Abaqus FEM solver, we combined vertex and FEM approaches to generate a comprehensive viscoelastic finite element model of the human colon organoid and demonstrated its flexibility. We imaged human colon organoid development for 120 hours, following the evolution of the organoids from an immature to a mature morphology. According to the extracted architectural/geometric parameters of human colon organoids at various stages of tissue architecture establishment, we generated organoid active vertex models. However, this approach did not consider the mechanical aspects involved in the organoids’ morphological evolution. Therefore, we applied a finite element method considering mechanical loads mimicking osmotic pressure, external solicitation, or active contraction in the vertex model by using the Abaqus FEM solver. Integration of finite element analysis (FEA) into the vertex model achieved a better fit with the biological model. Therefore, the FEM model provides a basis for depicting cell shape, tissue deformation, and cellular-level strain due to imposed stresses. In conclusion, we demonstrated that a combination of vertex and FEM approaches, combining geometrical and mechanical parameters, improves modeling of alterations in organoid morphology over time and enables better assessment of the mechanical cues involved in establishing the architecture of the human colon epithelium.

Cell division is a major event in tissue homeostasis, enabling renewal and regeneration. Stem cells, in particular, play an important role in this homeostasis, thanks to their ability to perform symmetric or asymmetric cell divisions. To study cell division, the human colon epithelium represents a model of choice due to its rapid renewal and therefore high proliferative potential. Currently, studying the live mechanical interactions between the epithelium and its matrix in vivo is challenging due to the lack of suitable methods. 3D human colon organoids seeded in Matrigel are good models for this purpose as, from isolated stem cells, they recapitulate the tissue architecture organization and properties. This culture set-up also allows to study the matrix displacements around the organoid. Here, we studied the impact of cell division within the colonic epithelium on the extracellular matrix. We performed and validated an original experimental and analytical process with a 3D time-lapse confocal microscopy to follow cell mitosis and matrix movements on which we performed Digital Volume Correlation. We showed that these two different types of cell division impact the matrix differently with the asymmetric divisions causing a mainly uniaxial displacement, whereas symmetric ones involved a multiaxial and more important one. ### Competing Interest Statement The authors have declared no competing interest.

Purpose The purpose of this paper is to optimize and improve a bipolar charge transport (BCT) model used to simulate charge dynamics in insulating polymer materials, specifically low-density polyethylene (LDPE). Design/methodology/approach An optimization algorithm is applied to optimize the BCT model by comparing the model outputs with experimental data obtained using two kinds of measurements: space charge distribution using the pulsed electroacoustic (PEA) method and current measurements in nonstationary conditions. Findings The study provides an optimal set of parameters that offers a good correlation between model outputs and several experiments conducted under varying applied fields. The study evaluates the quantity of charges remaining inside the dielectric even after 24 h of short circuit. Moreover, the effects of increasing the electric field on charge trapping and detrapping rates are addressed. Research limitations/implications This study only examined experiments with different applied electric fields, and thus the obtained parameters may not suit the experimental outputs if the experimental temperature varies. Further improvement may be achieved by introducing additional experiments or another source of measurements. Originality/value This work provides a unique set of optimal parameters that best match both current and charge density measurements for a BCT model in LDPE and demonstrates the use of trust region reflective algorithm for parameter optimization. The study also attempts to evaluate the equations used to describe charge trapping and detrapping phenomena, providing a deeper understanding of the physics behind the model.

Understanding the intertwining of biology and mechanics in tissue architecture is a challenging issue, especially when it comes to the 3D tissue organization. Addressing this challenge requires both a biological model allowing multiscale observations from the cell to the tissue, and theoretical and computational approaches allowing the generation of a synthetic model, relevant to the biological model, and allowing access to the mechanical constraints experienced by the tissue. Here, using human colon epithelium monolayer organoid as biological model, and combining vertex and FEM approaches, we generated a comprehensive elastic finite element model of the human colon organoid and demonstrated its flexibility. This FEM model provides a basis for relating cell shape, tissue deformation, and strain at the cellular level due to imposed stresses. In conclusion, we demonstrated that the combination of vertex and FEM approaches allows for better modeling of the alteration of organoid morphology over time and better assessment of the mechanical cues involved in establishing the architecture of the human colon epithelium.

Wire Arc Additive Manufacturing (WAAM) is revolutionizing the field of Additive Manufacturing (AM) by being the technological solution to manufacture thin-walled structures of large dimensions and medium geometric complexity at reduced cost with an excellent buy-to-fly ratio. Manufacturing parts with this technology is nowadays done through 2.5D strategies. This type of strategy consists in cutting a 3D model using planar layers parallel to each other. This 2.5D technique limits the complexity of the geometries that can be produced in WAAM without taking advantage of height deposit modulation. It also requires several start/stop phases of the arc during the transition from one layer to another, which leads to poor quality. This paper presents a new fast and efficient path planning strategy aiming at creating a continuous manufacturing path, thus increasing poor part quality. This strategy so called "Scalar Thermal Field for Continuous Toolpath"is generating a continuous spiral manufacturing toolpath for thin shaped parts. The modulation of deposition, by controlling the welding torch travel speed at constant wire feed rate, allows continuous deposition of material throughout the manufacturing process. The keypoint of the method is the use of a thermal scalar field associated with a 6-axis robotic arm kinematics which allows the manufacturing of closed parts after optimal closure point determination or direct manufacturing of opened parts with non-planar free edges. Validation of the presented method is performed by manufacturing three distinct parts : an opened, a closed part and a multi-branch part. The fabrication of these parts and their precise measurement have shown the reliability and the restitution capacity of our method which is clearly superior to 2.5D strategies nowadays commonly used in WAAM technology.

An optimization method known as Trust Region Reflective Algorithm has been employed to optimize the parameters of a bipolar charge transport (BCT) model. This model was developed to describe the dynamic behavior of the space charge in Low-Density Polyethylene (LDPE). Results obtained by the BCT model with the optimized parameters well described the behavior of charge distribution observed in a range of electric field. Furthermore, the effects of the variation of electric fields on trapping and detrapping rates are also addressed. Moreover, the model limitations and possible improvements are discussed.

Organoids, established from stem cells owing to their self-renewal and differentiation capacities, are self-organised three-dimensional tissue culture recapitulating the original cell populations and their associated functions, as well as tissue architecture. The intestinal organoids established from adult stem cells isolated from the intestinal crypts, recreate 3D epithelial mini-intestines. They represent an excellent tool to study intestinal stem cell capacities and their ability to reconstitute a fully polarised and functional epithelium. These 3D cultures recapitulate \textit{in vitro} the tissue characteristics, including architecture, either in physiological or disease conditions whether they are established from healthy or pathological tissue samples respectively. In this regard, their use for potential treatments screening carries the hopes for a future personalized medicine for which image-analysis such as HCS are increasingly being developed. Numerous numerical models have been developed to study the effects of organoid development on their shape. Most of them remain mainly restricted in their physical description due to the complex inter-relationship between cell physics, phenotypes and behaviors, exploding the number of variables in modeling formulation. Finite Element Method (FEM) is a numerical analysis method employed in mechanics to model deformation and evaluate residual stress of complex structures making it difficult to obtain analytical solutions. Considering epithelial architecture as a homogeneous material where each cell is an elemental equivalent part of the problem, FEM allows a direct link between tissue architecture deformations and local mechanical constraints. Here we formalise a new organoid cell centred FEM with a physical description borrowed from the engineering world. This model can allow a better understanding of the individual contribution of physical/mechanical properties of individual cells on general tissue architecture.

A bipolar charge transport model with two levels of traps (shallow and deep traps) is employed to describe and investigate the dynamic behavior of the space charge in low-density polyethylene (LDPE). This kind of model requires some initial experimental conditions alongside a set of parameters. An optimization method is used in order to provide the best precision for model parameters. Furthermore, the sensitivity of these parameters has been analyzed using an approach based on Sobol's method. In essence, this paper proposes a specific protocol that contributes to producing a global set of parameters able to provide the best approximate fit between experimental and simulated results. Net charge density is measured by the pulse electro-acoustic method (PEA) along with what is known as external charging current measurements. The simulated data are obtained by a bipolar charge transport model, which is developed for low-sensity polyethylene.

Structural topology optimization aims to design mechanical structures by seeking the optimal material layout within a given design space. Within this framework, this paper addresses the minimization of the structural mass under stress and buckling constraints, formulated as a nonlinear combinatorial optimization problem. An algorithm is proposed for such a problem, that follows a topological gradient-based approach. The adjoint method is applied to efficiently compute the constraint gradients. An iterative algorithm for buckling analysis, featuring low memory requirements, is also proposed. Numerical results, including a real application arising in the aeronautical field, illustrate the efficiency of the two proposed algorithms. (C) 2021 Elsevier Inc. All rights reserved.

Wire arc additive manufacturing (WAAM) is emerging as the main additive manufacturing (AM) technology used to produce medium-to-large-sized thin-walled parts (order of magnitude: 1 m) at lower cost. To manufacture a part with this technology, the path planning strategy used is the 2.5D. This strategy consists in slicing a 3D model into different planar layers parallel to each other. The use of this strategy limits the complexity of the topologies achievable in WAAM, especially those with large variations in curvature. It also involves several start/stops of the arc as it passes from one layer to another, which induces transient phenomena in which the control of the supply of energy and matter is complex. In this article, a new manufacturing strategy to minimize the start/stop phases of the arc to one unique cycle is presented. The goal of this strategy, called “Continuous Three-dimensional Path Planning” (CTPP) is to generate a continuous trajectory in spiral form for closed-loop thin parts. An adaptive wire speed coupled with a constant travel speed allows a modulation of the deposition geometry that ensures a continuous supply of energy and material throughout the manufacturing process. Using the 5-axis strategy coupled with CTPP allows the manufacture of closed parts with a procedure to determine the optimum closing area and parts on non-planar substrates useful for adding functionalities to an existing structure. Two geometries based on continuous manufacturing with WAAM technology are presented to validate this approach. The manufacturing of these parts with CTPP and several numerical evaluations have shown the reliability of this strategy and its capacity to produce complex new shapes with a good geometrical restitution, difficult or impossible to reach today using 2.5D with WAAM technology.

This article discusses an optimization method which is substantially based on the Trust-Region algorithm. At the same time, it attempts to configure the physical parameters pertaining to charge transport model for dielectrics. It is worth mentioning that the experimental data used are inherent to net density charge where the data are measured by Pulse Electro Acoustic method (PEA) in company with what is known by external charging current measurements. The simulated data are obtained by a bipolar charge transport model which is developed for Low Density Polyethylene (LDPE). This paper proposes a protocol that can contribute in figuring out a unique set of parameters for the model. Moreover, the effects of electrode materials on space charge formation in Low-Density Polyethylene have been investigated and discussed.

Recently, a numerical model has been developed for describing bipolar charge transport with two levels of traps (shallow and deep traps) in low density polyethylene (LDPE). This paper presents an optimization method, which is based on trust region algorithm. However, the enterprise has to be done with laying out the determination of physical parameters pertaining to bipolar charge transport model. Experimental data that have been used are net density charge measured by the pulse electro acoustic method (PEA) along with what is known as external charging current measurements. Simulated data are computed by the bipolar charge transport model, which is developed for LDPE. In essence, this paper sheds the light on the advanced algorithm that can give rise to a unique set of parameters for the model. Parameters will be reckoned using two different cost functions depending on current density and charge density data's. Conclusions on the best-to-use cost function are presented.

Recent experimental studies have demonstrated that the Electrostatic Force Distance Curve (EFDC) can be used for space charge probing in thin dielectric layers. Experiments highlight that this method seems to be sensitive to charge localization. However, the relative contributions of charge distribution parameters (density, lateral/in-depth spreading) remain unknown. The aim of this paper is to determine the contribution of each charge distribution parameters to EFDC. To reach this aim, we have developed an electrostatic and an electromechanical model to simulate EFDC over a charge cloud trapped in a thin dielectric layer. Hence, the EFDC sensitivity to charge localization could be investigated through the shape parameters of the charge cloud and by extracting the respective contributions from the atomic force microscopy tip and the cantilever.

This article reports on a parameter sensitivity analysis on a mathematical model for the charge transport in dielectrics, using the Sobol sensitivity method. The main point of the work is to perform a sensitivity analysis under the variation of the impacting experimental factors such as the temperature, the applied electric field, and the charging time. Useful indications were obtained on which variables contribute the most to the variability of the output and which variables can be neglected. A quantitative assistance is derived from these results. Indeed, this study helps in revealing the experimental conditions where the model becomes sensitive to particular variables. Then, the sensitivity analysis results are used to determine the best starting points for optimization process in order to precisely and rapidly estimate each model parameter.

This article addresses the problem of measuring an accurate temperature field on a multi-material part which exhibits spatial, temporal, spectral and thermal emissivity variations. The article analyses the contribution of trichromatic thermoreflectometry method compared to bichromatic thermoreflectometry method. Thermoreflectometry, an active thermography method, measures in-situ the emissivity, together with the temperature. The emissivity is measured indirectly by measuring the bidirectional reflectivity of the sample and by estimating its diffusion function. The bichromatic thermoreflectometry assumes an independent diffusion function with wavelength. For trichromatic thermoreflectometry, the diffusion function varies linearly with the wavelength. This article demonstrates the benefit of trichromatic thermoreflectometry on both simulated and experimental data. The simulated data come from measurements of emissivity and diffusion function of six different materials (metallic and dielectric) performed with a FTIR (Fourier Transform InfraRed) spectrometer. The addition of noise on these estimated values enables the propagation of uncertainties, which shows that the bias on temperature estimation is lower with trichromatic thermoreflectometry. Finally, an experimental demonstration on three of the six materials confirms a lower temperature measurement error (difference between the measured temperature and a reference temperature) with trichromatic thermoreflectometry.

Feed rate effect on scallop height in complex surface milling by torus-end mill is rarely studied. In a previous paper, an analytical predictive model of scallop height based on transverse step over distance has been established. However, this model doesn't take feed rate effect into consideration. In the present work an analytical expression of scallop height, including feed rate effect, is detailed in order to quantify feed rate effect and thus to estimate more precisely the surface quality. Then, an experimental validation is conducted, comparing the presented model predictions with experimental results. Actually, the share of the scallop height due to feed effect is highly dependent on the machining configuration. However, most of time, the feed effect on total scallop height values is far from being negligible.

Structural optimization is of increasing interest in a wide variety of application fields. In this article, structural optimization under stress and buckling constraints is investigated. A structure comprised of a set of frame elements is considered. The aim is to obtain the minimal mass structure, by optimizing the number of frame elements and their cross sectional dimensions. A formulation as a mixed-integer nonlinear optimization problem with a tailored objective function is introduced. This cost function is a combination of the structural mass and the sum of the second moments of inertia of each structural element. Moreover, a new algorithm, tailored to the considered problem, is proposed. Numerical results show that the proposed approach provides interesting structural mass savings.