Cellular Array Research Articles

Amniotic Membrane-Derived Multichannel Hydrogels for Neural Tissue Repair.

In the pursuit of advancing neural tissue regeneration, biomaterial scaffolds have emerged as promising candidates, offering potential solutions for nerve disruptions. Among these scaffolds, multichannel hydrogels, characterized by meticulously designed micrometer-scale channels, stand out as instrumental tools for guiding axonal growth and facilitating cellular interactions. This study explores the innovative application of human amniotic membranes modified with methacryloyl domains (AMMA) in neural stem cell (NSC) culture. AMMA hydrogels, possessing a tailored softness resembling the physiological environment, are prepared in the format of multichannel scaffolds to simulate native-like microarchitecture of nerve tracts. Preliminary experiments on AMMA hydrogel films showcase their potential for neural applications, demonstrating robust adhesion, proliferation, and differentiation of NSCs without the need for additional coatings. Transitioning into the 3D realm, the multichannel architecture fosters intricate neuronal networks guiding neurite extension longitudinally. Furthermore, the presence of synaptic vesicles within the cellular arrays suggests the establishment of functional synaptic connections, underscoring the physiological relevance of the developed neuronal networks. This work contributes to the ongoing efforts to find ethical, clinically translatable, and functionally relevant approaches for regenerative neuroscience.

Abstract 6087: Cytomics-on-chip and AI-driven predictive analysis platform for early detection of epithelial cancers

Abstract Cancer is the 2nd leading cause of death (over 605,000 people) in the US, at an expense of over $200B, with 1 in 3 people projected to have cancer during their lifetime per CDC. Despite the significant impact of early detection and screening on prognosis, only some cancers are diagnosed at an early stage. Carcinomas, comprising >80% of cancer incidence, allow ease in cytology sample access chairside, due to the lesions’ epithelial presentation. This presents a unique opportunity for early detection and screening in epithelial cancers. In low-resource healthcare settings, from clinical examination to the long, tedious and expensive diagnostic journey for cancers & pre-cancerous lesions, can lead to missed, delayed or over diagnosis scenarios. This affects treatment initiation and potentially outcome. To facilitate early intervention, there is compelling need to develop accurate and effective minimally invasive screening platforms. Recent advances in the -omics disciplines, microfluidics and AI tools are starting to reveal promising signatures of early disease detection, with potential to drastically improve screening and diagnostic systems. We are developing a novel application of the cytomics-on-chip platform, for enabling chairside, quantitative screening of suspicious epithelial lesions. The biosensor module involves 1. a single use, cytomics platform employing a cartridge with cellular array and high specificity biomarker reagents, that allows single cell molecular imaging to be completed in a portable analyzer. 2. a microfluidics module that allows cytomorphometric measurements to be completed. 3. The results generated are utilized to train machine learning algorithms to detect cyto-signatures and provide an intuitive result that may be utilized by health care practitioners in clinical-decision making. The first cell-based point-of-care oncology tool has recently been validated with high accuracy (99.3%), sensitivity and specificity, in a multi-site prospective clinical study. Here we demonstrate a pilot study towards development of a smart single cell cytomics-on-chip platform for prompt cytomorphometric and biomarker characterization towards diagnosis of urothelial, anal and cervical cancers, and dysplasia lesions, utilizing brush/pap and fresh urine samples. This has potential for continuous quantitative indexing, for disease categorization. As cancers become more pervasive, improved early detection/screening methods that are accurate, cost effective, easy to implement during routine clinical practice, and providing minimal discomfort to the patient, are urgently needed, improving confidence in clinicians’ decisions. Citation Format: Kritika Srinivasan Rajsri, Michael P. McRae, Nicolaos J. Christodoulides, Khaled Algashaamy, Monica T. Garcia-Buitrago, Fei Chen, Fang-Ming Deng, Jennifer S. Smith, John T. McDevitt. Cytomics-on-chip and AI-driven predictive analysis platform for early detection of epithelial cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6087.

Staircase resiliency in a fluctuating cellular array.

Inhomogeneous mixing by stationary convective cells set in a fixed array is a particularly simple route to layering. Layered profile structures, or staircases, have been observed in many systems, including drift-wave turbulence in magnetic confinement devices. The simplest type of staircase occurs in passive-scalar advection, due to the existence and interplay of two disparate timescales, the cell turn-over (τ_{H}), and the cell diffusion (τ_{D}) time. In this simple system, we study the resiliency of the staircase structure in the presence of global transverse shear and weak vortex scattering. The fixed cellular array is then generalized to a fluctuating vortex array in a series of numerical experiments. The focus is on regimes of low-modest effective Reynolds numbers, as found in magnetic fusion devices. By systematically perturbing the elements of the vortex array, we learn that staircases form and are resilient (although steps become less regular, due to cell mergers) over a broad range of Reynolds numbers. The criteria for resiliency are (a) τ_{D}≫τ_{H} and (b) a sufficiently high profile curvature (κ≥1.5). We learn that scalar concentration travels along regions of shear, thus staircase barriers form first, and scalar concentration "homogenizes" in vortices later. The scattering of vortices induces a lower effective speed of scalar concentration front propagation. The paths are those of the least time. We observe that if background diffusion is kept fixed, the cell geometric properties can be used to derive an approximation for the effective diffusivity of the scalar. The effective diffusivity of the fluctuating vortex array does not deviate significantly from that of the fixed cellular array.

Viscoelastic circular cell honeycomb helmet liners for reducing head rotation and brain strain in oblique impacts

Rotational head motion is one of the major contributors to brain tissue strain during head impacts, which damages axons and vessels and leads to traumatic brain injury. Helmet technologies have come to market promising enhanced protection against such rotational head motion. We recently introduced novel air-filled viscoelastic cell arrays and showed that their shear response under oblique impacts can be tailored through altering the cell wall curvature. We found that concave cells provide shear stiffness that is a few folds larger than that of convex cells. Here we test whether altering the cell curvature can reduce head rotational kinematics and brain strain and whether the viscoelastic cell arrays outperform the reference EPS foam-based liner. To test these hypotheses, we incorporate the viscoelastic cell arrays in a bicycle helmet liner. We use validated finite element models of the helmet and replace the liner with validated finite element models of the cellular cell arrays. We simulate oblique impacts at different locations to represent a wide range of real-world bicycle head impacts. In all cases, the head kinematics and brain deformation metrics indicate significant improvements with the novel cell arrays over the conventional EPS liner. We show that the shear-compliant cell arrays can reduce head rotational acceleration by as much as 64 % and brain strain by 69 %, but not in all impact locations. Cell arrays with similar axial stiffness yet lower shear stiffness often bottomed out, indicating that a considerable amount of energy is dissipated via cell shearing around the impact zone. Our results show that placement of cells with varying amounts of shear stiffness should be optimised, with the most shear-compliant cells near the crown and the least near the temples. This study shows the promising performance of viscoelastic cell arrays in protecting the head and brain under oblique impacts and provides avenues for optimising the distribution of their compressive-shear properties.

RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding

BackgroundCeramide metabolism is crucial in the progress of brain metastasis (BM). However, it remains unexplored whether targeting ceramide metabolism may arrest BM.MethodsRNA sequencing was applied to screen different genes in primary and metastatic foci and whole-exome sequencing (WES) to seek crucial abnormal pathway in BM + and BM-patients. Cellular arrays were applied to analyze the permeability of blood–brain barrier (BBB) and the activation or inhibition of pathway. Database and Co-Immunoprecipitation (Co-IP) assay were adopted to verify the protein–protein interaction. Xenograft and zebrafish model were further employed to verify the cellular results.ResultsRNA sequencing and WES reported the involvement of RPTOR and ceramide metabolism in BM progress. RPTOR was significantly upregulated in BM foci and increased the permeability of BBB, while RPTOR deficiency attenuated the cell invasiveness and protected extracellular matrix. Exogenous RPTOR boosted the SPHK2/S1P/STAT3 cascades by binding YY1, in which YY1 bound to the regions of SPHK2 promoter (at -353 ~ -365 nt), further promoting the expression of SPHK2. The latter was rescued by YY1 RNAi. Xenograft and zebrafish model showed that RPTOR blockade suppressed BM of non-small cell lung cancer (NSCLC) and impaired the SPHK2/S1P/STAT3 pathway.ConclusionRPTOR is a key driver gene in the brain metastasis of lung cancer, which signifies that RPTOR blockade may serve as a promising therapeutic candidate for clinical application.

The Tubulin Code, from Molecules to Health and Disease.

Microtubules are essential dynamic polymers composed of α/β-tubulin heterodimers. They support intracellular trafficking, cell division, cellular motility, and other essential cellular processes. In many species, both α-tubulin and β-tubulin are encoded by multiple genes with distinct expression profiles and functionality. Microtubules are further diversified through abundant posttranslational modifications, which are added and removed by a suite of enzymes to form complex, stereotyped cellular arrays. The genetic and chemical diversity of tubulin constitute a tubulin code that regulates intrinsic microtubule properties and is read by cellular effectors, such as molecular motors and microtubule-associated proteins, to provide spatial and temporal specificity to microtubules in cells. In this review, we synthesize the rapidly expanding tubulin code literature and highlight limitations and opportunities for the field. As complex microtubule arrays underlie essential physiological processes, a better understanding of how cells employ the tubulin code has important implications for human disease ranging from cancer to neurological disorders.

Extending Conway’s Game of Life

We introduce an n-state Game of Life (GoL) on a cellular array (cells indexed by (i, j)), where each state σ = 0, ..., n − 1 has a nominal values vσ ≥ 0. The game involves computing the sum of the state values of the eight cells that surround cell (i, j) and using this sum to determine whether cell (i, j) stays in state σ, progress to state σ + 1, or reverts at state 0. We illustrate examples of this game, identifying still-life, oscillator, glider, and replicator patterns, as well as the long term behavior arising from random and regular starting configurations. Importantly, we provide two freely downloadable application programs that can be used to explore the behavior of the three and four state GoLs discussed in this paper

Cell invasion during competitive growth of polycrystalline solidification patterns

Spatially extended cellular and dendritic array structures forming during solidification processes such as casting, welding, or additive manufacturing are generally polycrystalline. Both the array structure within each grain and the larger scale grain structure determine the performance of many structural alloys. How those two structures coevolve during solidification remains poorly understood. By in situ observations of microgravity alloy solidification experiments onboard the International Space Station, we have discovered that individual cells from one grain can unexpectedly invade a nearby grain of different misorientation, either as a solitary cell or as rows of cells. This invasion process causes grains to interpenetrate each other and hence grain boundaries to adopt highly convoluted shapes. Those observations are reproduced by phase-field simulations further demonstrating that invasion occurs for a wide range of misorientations. Those results fundamentally change the traditional conceptualization of grains as distinct regions embedded in three-dimensional space.

Attempt to correlate dislocations network and distribution to macroscale plane rotations in <001> cast-mono ingots

This work aims to contribute to the understanding of the mechanisms behind electrically active crystalline defect formation in cast-mono (cm) ingots grown along the <001> axis. Both the spatial distributions of background dislocations in the cellular dislocation array and the driving force for dislocation multiplication in the sub-grains are not perfectly understood. Macroscale length crystal rotations are here characterized by the (θ/2θ) X-ray diffraction (XRD) method at different ingot heights and along two perpendicular sample axes. XRD measurements show the presence of crystal rotations in the large single grain domain. Two orthogonal misorientations components are found to evolve linearly along each sample axis forming plane orientation gradients up to (0.05 ± 0.02) degree/cm extending over 12 cm inside the cast-mono grain. (001) crystal structure deformation are also analysed by rocking curve imaging (RCI) using synchrotron radiation on wafers of a neighboring brick. First, results confirm the presence of the plane orientation gradient measured by XRD and its order of magnitude. Second, RCI results demonstrate that the plane orientation gradient is associated to the cellular dislocation network. Therefore, these results strongly suggest that background dislocations network of a cellular form can create an organized orientation gradient at large distance within the ingot. The involvement of the characterized orientation gradients in the formation and extension of electrically active SGBs in cast-mono ingots is discussed. • Crystal structure deformation measurements of cm-Si ingots. • Evidence of the presence of {001} planes orientation gradients. • Plane orientation gradients almost constant along the sample axes. • Orientation gradients increase with the ingot height. • Orientation gradients associated to the cellular network of dislocations.

Spatio-temporal pattern formation due to host-circuit interplay in gene expression dynamics

Biological systems are majorly dependent on their property of bistability in order to exhibit nongenetic heterogeneity in terms of cellular morphology and physiology. Spatial patterns of phenotypically heterogeneous cells, arising due to underlying bistability, may play significant role in phenomena like biofilm development, adaptation, cell motility etc. While nonlinear positive feedback regulation, like cooperative heterodimer formation are the usual reason behind bistability, similar dynamics can also occur as a consequence of host-circuit interaction. In this paper, we have investigated the pattern formation by a motif with non-cooperative positive feedback, that imposes a metabolic burden on its host due to its expression. In a cellular array set inside diffusible environment, we investigate in-silico spatio-temporal diffusion in one dimension as well as in two dimension in the context of various initial conditions respectively. Moreover, the number of cells exhibiting the same steady state, as well as their spatial distribution has been quantified in terms of connected component analysis. The effect of diffusion coefficient variation has been studied in terms of stability of related states and time evolution of patterns.

Edge of Chaos Explains Prigogine’s Instability of the Homogeneous

One of the complex phenomena, which most attracted the attention of the scientific community over the past few decades, is the emergence of diffusion-driven instabilities in homogeneous cellular media. Explaining this symmetry-breaking process, which the Russian luminary Ilya Prigogine referred to as the Instability of the Homogeneous, is only possible upon invoking the Physics Law of the Edge of Chaos. While the emergence of inhomogeneous static or dynamic periodic solutions in biological reaction-diffusion systems was recently reproduced in two-cell networks, leveraging the Negative Differential Resistance of certain volatile memristors, so far, to the best of our knowledge, no cellular array was ever found to undergo dissipation-induced dynamical phenomena of higher complexity, including a route to chaos, or an uncontrollable upsurge in the respective physical variables. This manuscript determines all the possible sets of conditions on the parameters of a one-port, extracted from the classical Chua circuit, enabling to poise it on some stable and locally-active operating point, employing a deep mathematical analysis, focusing on the properties of its local impedance. The polarisation of the one-port on some Edge of Chaos operating point is the Conditio Sine Qua Non for the Destabilisation of the Homogeneous Solution, resulting in the steady-state appearance of high-order dynamical phenomena, as outlined above, in a simple Reaction-Diffusion Cellular Nonlinear Network, where a linear and passive resistor, interposed between two identical copies of the one-port, lets them interact by means of a diffusion process. Notably, as demonstrated here, whether or not the dissipative coupling path may truly succeed in moving each of the two one-ports of the two-cell array, under study, away from the respective common Edge of Chaos operating point, depends critically upon the satisfaction of the logical disjunction between three inequalities, which enforces the instability of the denominator polynomial of the rational function associated to the local input impedance of the cellular array, as seen across either of the two one-ports.

A Multimodal and Multifunctional CMOS Cellular Interfacing Array for Digital Physiology and Pathology Featuring an Ultra Dense Pixel Array and Reconfigurable Sampling Rate.

The article presents a fully integrated multimodal and multifunctional CMOS biosensing/actuating array chip and system for multi-dimensional cellular/tissue characterization. The CMOS chip supports up to 1,568 simultaneous parallel readout channels across 21,952 individually addressable multimodal pixels with 13 μm × 13 μm 2-D pixel pitch along with 1,568 Pt reference electrodes. These features allow the CMOS array chip to perform multimodal physiological measurements on living cell/tissue samples with both high throughput and single-cell resolution. Each pixel supports three sensing and one actuating modalities, each reconfigurable for different functionalities, in the form of full array (FA) or fast scan (FS) voltage recording schemes, bright/dim optical detection, 2-/4-point impedance sensing (ZS), and biphasic current stimulation (BCS) with adjustable stimulation area for single-cell or tissue-level stimulation. Each multi-modal pixel contains an 8.84 μm × 11 μm Pt electrode, 4.16 μm × 7.2 μm photodiode (PD), and in-pixel circuits for PD measurements and pixel selection. The chip is fabricated in a standard 130nm BiCMOS process as a proof of concept. The on-chip electrodes are constructed by unique design and in-house post-CMOS fabrication processes, including a critical Al shorting of all pixels during fabrication and Al etching after fabrication that ensures a high-yield planar electrode array on CMOS with high biocompatibility and long-term measurement reliability. For demonstration, extensive biological testing is performed with human and mouse progenitor cells, in which multidimensional biophysiological data are acquired for comprehensive cellular characterization.

Successive cytotoxicity control by evolutionary surface decorated electronic push-pull green ZnCr-LDH nanostructures: Drug delivery enlargement for targeted breast cancer chemotherapy

The reason for the increasing bioavailability and biocompatibility of the porous nanomaterials in the presence of different (bio)molecules is still unknown. The role of difference functional groups and their interactions with the potential bioavailability and biocompatibility is of great importance. To investigate the potential contribution of the electronic effects (especially on the surface of the porous nanomaterials) on their biomedical behavior, a series of surface-decorated green ZnCr-layered double hydroxide (LDH) porous nanocarriers is developed as a non-viral vector. Different conjugations investigated these porous LDHs for optimizing and minimizing the cytotoxicity for targeted breast cancer therapy. Quick low-temperature synthesized ZnCr-LDH nanocarriers method with enlarged drug delivery windows decorated with leaf extracts and benzamide-like molecules revealed a push-pull electronic synergistic effect on cytotoxicity and enhanced cell viability, biocompatibility, aggregations, and interactions with the cell membranes. The pre-defined model drug, doxorubicin (DOX), unraveled chemotherapy performance in response to MCF-7 cell lines, with ≈ 60% drug payload contributed from functional groups of leaf extracts. Moreover, electron-poor and electron-rich benzamide-like molecules attached to the ZnCr-LDH surface enhanced the relative cell viability up to 29% and 32%, respectively. The in vivo experiments on breast cancer of treated mice (H&E) revealed unaggregated cellular arrays and antibacterial activity against E. coli (gram-negative) and S. aureus (gram-positive) bacteria. Benzamide-like ZnCr-LDH nanocarriers showed a suitable zone of inhibition beyond 10 mm, compared to the standard. Cytotoxicity control achieved herein seems promising for the future ahead of nanomedicine.

Convolutional kernel function algebra

Many systems for image manipulation, signal analysis, machine learning, and scientific computing make use of discrete convolutional filters that are known before computation begins. These contexts benefit from common sub-expression elimination to reduce the number of calculations required, both multiplications and additions. We present an algebra for describing convolutional kernels and filters at a sufficient level of abstraction to enable intuitive common sub-expression based optimizations through decomposing filters into smaller, repeated, kernels. This enables the creation of an enormous search space of potential implementations of filters via algebraic manipulation. We demonstrate how integral image and sliding window optimizations can be expressed in the context of common sub-expression elimination as well as show the direct use case for this algebra in massively SIMD multiply-free contexts such as in cellular processor arrays. We then show that this algebra is general enough to express and optimize kernels that use non-standard semi-rings to enable shortest path algorithms.

Dynamic behaviour of low- to high-density anisotropic cellular materials

The dynamic behaviour of a novel anisotropic cellular micro-structural geometry derived from the basic symmetric Kelvin cell is discussed for varying relative density. The cells are arranged in a cubic array and the dynamic response is studied in a classical seismic mass setup using beam elements to represent the ligaments of the cell. The eigenfrequencies and the eigenmodes of the cellular array are computed together with forced response simulations where a proportional damping model of the Young’s modulus for the cell ligaments is assumed. The frequency dependence of the damping is based on a fractional derivative representation. Using a recently developed inversion method, equivalent, homogenised solid material models of the cellular array are discussed with the associated equivalent elastic properties given in terms of the 21 elastic constants of the Hooke’s tensor. For the equivalent solid material models, the eigenfrequencies and eigenmodes are computed, and forced response simulations are performed assuming the same type of proportionality in the damping as the cellular array, for the same seismic mass setup. The correlation, between the eigenfrequencies and the eigenmodes, shows an overall interesting agreement between the cellular and the equivalent solid model for the quite complex deformation shapes observed. The forced response results indicate that the equivalent solid modelling accurately represents the global dynamics of the anisotropic cellular array, but needs to be further refined when local shearing deformation within the individual cells starts to be dominating.

Efficient 3D AlexNet Architecture for Object Recognition Using Syntactic Patterns from Medical Images.

In computer vision and medical image processing, object recognition is the primary concern today. Humans require only a few milliseconds for object recognition and visual stimulation. This led to the development of a computer-specific pattern recognition method in this study for identifying objects in medical images such as brain tumors. Initially, an adaptive median filter is used to remove the noise from MRI images. Thereafter, the contrast image enhancement technique is used to improve the quality of the image. To evaluate the wireframe model, the cellular logic array processing (CLAP)-based algorithm is then applied to images. The basic patterns of three-dimensional (3D) images are then identified from the input image by scanning the whole image. The frequency of these patterns is also used for object classification. A deep neural network is then utilized for the classification of brain tumor. In the proposed model, the syntactic pattern recognition technique is used to find the feature vector and 3D AlexNet is used for brain tumor classification. To evaluate the performance of the proposed work, three benchmark brain tumor datasets are used, i.e., Figshare, Brain MRI Kaggle, and Medical MRI datasets and BraTS 2019 dataset. The comparative analyses reveal that the proposed brain tumor classification model achieves significantly better performance than the existing models.

Shape evolution of long flexible fibers in viscous flows

The present work studies numerically the dynamics and shape evolution of long flexible fibers suspended in a Newtonian viscous cellular flow using a particle-level fiber simulation technique. The fiber is modeled as a chain of massless rigid cylindrical segments connected by ball and socket joints; one-way coupling between the fibers and the flow is considered while Brownian motion is neglected. The effect of stiffness, equilibrium shape, and aspect ratio of the fibers on the shape evolution of the fibers are analyzed. Moreover, the influence of fiber stiffness and their initial positions and orientations on fiber transport is investigated. For the conditions considered, the results show that the fiber curvature field resembles that of the flow streamline. It is found that the stiffer fibers experience not only a quicker relaxation phase, in which they transient from their initial shape to their “steady-state shape,” but they also regain their equilibrium shape to a larger extent. The findings also demonstrate that even a small deviation of fiber shape from perfectly straight impacts significantly the early-stage evolution of the fiber shape and their bending behavior. Increasing the fiber aspect ratio, when other parameters are kept fixed, leads the fiber to behave more flexible, and it consequently deforms to a larger extent to adjust to the shape of the flow streamlines. In agreement with the available experimental results, the fiber transport studies show that either the fiber becomes trapped within the vortices of the cellular array or it moves across the vortical arrays while exhibiting various complex shapes.

Kirigami-inspired foldable 3D cellular structures with a single degree of freedom

It is common to fold a hollow 3D Archimedean solid flat using paper folding. However, little has been done to create 3D cellular assemblies of polyhedrons consisting of rigid facets that can be folded flat with a single degree of freedom. Inspired by both origami and kirigami, we present two groups of foldable truncated octahedrons composed of rigidly thin and thick facets, respectively. Starting by identifying seven possible connection types between a pair of foldable truncated octahedrons, we use these connection types to construct various foldable 3D cellular arrays. Kinematically, these arrays contain spherical 4R linkages or a mixture of spherical 4R linkages and Bennett 4R linkages if facets of uniform and finite thickness are used. Through a thorough kinematic analysis, we are able to obtain the relationships amongst all dihedral angles along each folding crease. We demonstrate that the foldable cellular assembly has a single degree of freedom. Moreover, the arrays made from thin and thick facets are kinematically equivalent. Physical models were made, which have successfully validated our findings. The proposed foldable cellular structures can be used to construct space habitats or create robot arms.

Development of bone cell microarrays in microfluidic chips for studying osteocyte–osteoblast communication under fluid flow mechanical loading

Bone tissue remodels throughout life in response to mechanical loads. Impaired activities of bone cells (osteocytes, osteoblasts and osteoclasts) result in a disruption of the bone remodelling cycle, which eventually leads to bone disorders such as osteoporosis. To develop efficient therapeutic strategies against bone disorders, new tools are needed to unravel the bone remodelling cycle at the molecular level. Here, we developed a microfluidic platform, which should allow understanding the bone remodelling cycle in much more detail and ultimately be used to discover new therapeutic compounds. We focused specifically on studying cell–cell communication between osteocytes and osteoblasts cells via connexin 43-gap junctions. Therefore, a new cell printing method was developed to create living cellular bone cell arrays in a microfluidic channel. Several cell printing designs where osteocytes and osteoblasts heterotypically interacted at localized interfaces were evaluated. Physical contacts between the bone cells were characterized at high resolution by correlative atomic force microscopy (AFM)—fluorescence microscopy. We demonstrated that the platform is compatible with single-cell mechanostimulation by AFM nanoindentation and subsequent fluorescent analysis of the mechanoresponse. As a proof of concept, we showed the functionality of the platform by analysing the induced in vivo-like Ca++ wave in the printed osteocyte–osteoblast network upon mechanical stimulation by fluid flow shear stress.

Cellular growth during rapid directional solidification: Insights from quantitative phase field simulations

In this paper, columnar cellular growth with kinetic effects including kinetic undercooling and solute trapping in rapid directional solidification of alloys was investigated by using a recent quantitative phase-field model for rapid solidification. Morphological transition and primary spacing selection with and without kinetic effects were numerically investigated. Numerical results show that doublon structure is an intermediate state in the primary spacing adjustment of cellular arrays. It was found that the inclusions of kinetic effects result in the increase of the solute in the solid phase and the solute enrichment in the interdendritic liquid channel. Moreover, predicted results indicate that the growth directions of the cellular arrays in rapid directional solidification with and without kinetic effects are independent of the Péclet number. Therefore, the kinetic effects play important roles in numerical simulations of the growth pattern selection and solute distribution during rapid solidification. Neglecting them will result in the inaccurately predicted results.