A comprehensive experimental analysis of the local passive response across the healthy porcine left ventricle.

This work provides a comprehensive characterization of porcine myocardial tissue, combining true biaxial (TBx), simple triaxial shear (STS) and confined compression (CC) tests to analyze its elastic behavior under cyclic loads. We expanded this study to different zones of the ventricular free wall, providing insights into the local behavior along the longitudinal and radial coordinates. The aging impact was also assessed by comparing two age groups (4 and 8 months).

Modelling glioblastoma resistance to temozolomide. A mathematical model to simulate cellular adaptation in vitro.

Drug resistance is one of the biggest challenges in the fight against cancer. In particular, in the case of glioblastoma, the most lethal brain tumour, resistance to temozolomide (the standard of care drug for chemotherapy in this tumour) is one of the main reasons behind treatment failure and hence responsible for the poor prognosis of patients diagnosed with this disease. In this work, we combine the power of three-dimensional in vitro experiments of treated glioblastoma spheroids with mathematical models of tumour evolution and adaptation.

Tuneable hydrogel patterns in pillarless microfluidic devices.

Organ-on-chip (OOC) technology has recently emerged as a powerful tool to mimic physiological or pathophysiological conditions through cell culture in microfluidic devices. One of its main goals is bypassing animal testing and encouraging more personalized medicine. The recent incorporation of hydrogels as 3D scaffolds into microfluidic devices has changed biomedical research since they provide a biomimetic extracellular matrix to recreate tissue architectures.

Experimentally-guided in silico design of engineered heart tissues to improve cardiac electrical function after myocardial infarction.

Engineered heart tissues (EHTs) built from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) showed promising results for cardiac function restoration following myocardial infarction. Nevertheless, human iPSC-CMs have longer action potential and lower cell-to-cell coupling than adult-like CMs. These immature electrophysiological properties favor arrhythmias due to the generation of electrophysiological gradients when hiPSC-CMs are injected in the cardiac tissue.

A Mathematical Modelling Study of Chemotactic Dynamics in Cell Cultures: The Impact of Spatio-temporal Heterogeneity.

As motivated by studies of cellular motility driven by spatiotemporal chemotactic gradients in microdevices, we develop a framework for constructing approximate analytical solutions for the location, speed and cellular densities for cell chemotaxis waves in heterogeneous fields of chemoattractant from the underlying partial differential equation models. In particular, such chemotactic waves are not in general translationally invariant travelling waves, but possess a spatial variation that evolves in time, and may even oscillate back and forth in time, according to the details of the chemotactic gradients. The analytical framework exploits the observation that unbiased cellular diffusive flux is typically small compared to chemotactic fluxes and is first developed and validated for a range of exemplar scenarios.

Modelling cell adaptation using internal variables: Accounting for cell plasticity in continuum mathematical biology.

Cellular adaptation is the ability of cells to change in response to different stimuli and environmental conditions. It occurs via phenotypic plasticity, that is, changes in gene expression derived from changes in the physiological environment. This phenomenon is important in many biological processes, in particular in cancer evolution and its treatment.

The Role of Mechanical Properties and Structure of Type I Collagen Hydrogels on Colorectal Cancer Cell Migration.

Mechanical interactions between cells and their microenvironment play an important role in determining cell fate, which is particularly relevant in metastasis, a process where cells invade tissue matrices with different mechanical properties. In vitro, type I collagen hydrogels have been commonly used for modeling the microenvironment due to its ubiquity in the human body. In this work, the combined influence of the stiffness of these hydrogels and their ultrastructure on the migration patterns of HCT-116 and HT-29 spheroids are analyzed.

A mechanobiological model for tumor spheroid evolution with application to glioblastoma: A continuum multiphysics approach.

Background: Spheroids are in vitro quasi-spherical structures of cell aggregates, eventually cultured within a hydrogel matrix, that are used, among other applications, as a technological platform to investigate tumor formation and evolution. Several interesting features can be replicated using this methodology, such as cell communication mechanisms, the effect of gradients of nutrients, or the creation of realistic 3D biological structures. The main objective of this work is to link the spheroid evolution with the mechanical activity of cells, coupled with nutrient consumption and the subsequent cell dynamics.

A comparison between the effect of systemic and coated drug delivery in osteoporotic bone after dental implantation.

The increased life expectancy has boomed the demand of dental implants in the elderly. As a consequence, considering the effect of poorer bone quality, due to aging or associated diseases such as osteoporosis, on the success of dental restoration is becoming increasingly important. Bisphosphonates are one of the most used drugs to overcome the effect of osteoporosis as they increase bone density.

Fabrication of human myocardium using multidimensional modelling of engineered tissues.

Biofabrication of human tissues has seen a meteoric growth triggered by recent technical advancements such as human induced pluripotent stem cells (hiPSCs) and additive manufacturing. However, generation of cardiac tissue is still hampered by lack of adequate mechanical properties and crucially by the often unpredictable post-fabrication evolution of biological components. In this study we employ melt electrowriting (MEW) and hiPSC-derived cardiac cells to generate fibre-reinforced human cardiac minitissues.

Understanding glioblastoma invasion using physically-guided neural networks with internal variables.

Microfluidic capacities for both recreating and monitoring cell cultures have opened the door to the use of Data Science and Machine Learning tools for understanding and simulating tumor evolution under controlled conditions. In this work, we show how these techniques could be applied to study Glioblastoma, the deadliest and most frequent primary brain tumor. In particular, we study Glioblastoma invasion using the recent concept of Physically-Guided Neural Networks with Internal Variables (PGNNIV), able to combine data obtained from microfluidic devices and some physical knowledge governing the tumor evolution.

Image-based Cardiac Electrophysiology Simulation through the Meshfree Mixed Collocation Method.

State-of-the-art solvers for in silico cardiac electro-physiology employ the Finite Element Method to solve complex anatomical models. While this is a robust and accurate tech-nique, it requires a high-quality mesh to prevent its accuracy from being severely deteriorated. The generation of a good quality mesh for realistic anatomical models can be very time-consuming, making the translation to the clinics challenging, especially if we try to use patient-specific geometries.

Evidence-Based Selection on the Appropriate FIT Cut-Off Point in CRC Screening Programs in the COVID Pandemic.

The COVID pandemic has forced the closure of many colorectal cancer (CRC) screening programs. Resuming these programs is a priority, but fewer colonoscopies may be available. We developed an evidence-based tool for decision-making in CRC screening programs, based on a fecal hemoglobin immunological test (FIT), to optimize the strategy for screening a population for CRC.

Predicting cell behaviour parameters from glioblastoma on a chip images. A deep learning approach.

The broad possibilities offered by microfluidic devices in relation to massive data monitoring and acquisition open the door to the use of deep learning technologies in a very promising field: cell culture monitoring. In this work, we develop a methodology for parameter identification in cell culture from fluorescence images using Convolutional Neural Networks (CNN). We apply this methodology to the in vitro study of glioblastoma (GBM), the most common, aggressive and lethal primary brain tumour.

On the effect of antiresorptive drugs on the bone remodeling of the mandible after dental implantation: a mathematical model.

Bone remodeling identifies the process of permanent bone change with new bone formation and old bone resorption. Understanding this process is essential in many applications, such as optimizing the treatment of diseases like osteoporosis, maintaining bone density in long-term periods of disuse, or assessing the long-term evolution of the bone surrounding prostheses after implantation. A particular case of study is the bone remodeling process after dental implantation.

Force Spectroscopy Imaging and Constriction Assays Reveal the Effects of Graphene Oxide on the Mechanical Properties of Alginate Microcapsules.

Microencapsulation of cells in hydrogel-based porous matrices is an approach that has demonstrated great success in regenerative cell therapy. These microcapsules work by concealing the exogenous cells and materials in a robust biomaterial that prevents their recognition by the immune system. A vast number of formulations and additives are continuously being tested to optimize cell viability and mechanical properties of the hydrogel.

Mathematical formulation and parametric analysis of in vitro cell models in microfluidic devices: application to different stages of glioblastoma evolution.

In silico models and computer simulation are invaluable tools to better understand complex biological processes such as cancer evolution. However, the complexity of the biological environment, with many cell mechanisms in response to changing physical and chemical external stimuli, makes the associated mathematical models highly non-linear and multiparametric. One of the main problems of these models is the determination of the parameters' values, which are usually fitted for specific conditions, making the conclusions drawn difficult to generalise.

Data-Driven Computational Simulation in Bone Mechanics.

The data-driven approach was formally introduced in the field of computational mechanics just a few years ago, but it has gained increasing interest and application as disruptive technology in many other fields of physics and engineering. Although the fundamental bases of the method have been already settled, there are still many challenges to solve, which are often inherently linked to the problem at hand. In this paper, the data-driven methodology is applied to a particular problem in tissue biomechanics, a context where this approach is particularly suitable due to the difficulty in establishing accurate and general constitutive models, due to the intrinsic intra and inter-individual variability of the microstructure and associated mechanical properties of biological tissues.

A mechano-chemo-biological model for bone remodeling with a new mechano-chemo-transduction approach.

Bone remodeling is a fundamental biological process that develops in bone tissue along its whole lifetime. It refers to a continuous bone transformation with new bone formation and old bone resorption that changes the internal microstructure and composition of the tissue. The main objectives of bone remodeling are: repair of the internal microcracks; adaptation of the macroscopic stiffness and strength to the actual changing mechanical demands; and control of the calcium homeostasis.

Author Correction: Enabling cell recovery from 3D cell culture microfluidic devices for tumour microenvironment biomarker profiling.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Force spectroscopy-based simultaneous topographical and mechanical characterization to study polymer-to-polymer interactions in coated alginate microspheres.

Cell-laden hydrogel microspheres have shown encouraging outcomes in the fields of drug delivery, tissue engineering or regenerative medicine. Beyond the classical single coating with polycations, many other different coating designs have been reported with the aim of improving mechanical properties and in vivo performance of the microspheres. Among the most common strategies are the inclusion of additional polycation coatings and the covalent bonding of the semi-permeable membranes with biocompatible crosslinkers such as genipin.

Finite element comparison of the effect of absorbers' design in the surrounding bone of dental implants.

Despite the high success rate achieved in current dental implantation, there are still important problems to solve like incomplete early osteointegration, bone damage, and long-term implant loosening. Highly compliant stress absorbers are a possible solution to these problems. Although several works examined the stress-strain distribution in bone without and with absorbers to show their favorable results, none of them analyzed their impact on long-term remodeling.

Enabling cell recovery from 3D cell culture microfluidic devices for tumour microenvironment biomarker profiling.

The tumour microenvironment (TME) has recently drawn much attention due to its profound impact on tumour development, drug resistance and patient outcome. There is an increasing interest in new therapies that target the TME. Nonetheless, most established in vitro models fail to include essential cues of the TME.

Computational Multiscale Solvers for Continuum Approaches.

Computational multiscale analyses are currently ubiquitous in science and technology. Different problems of interest-e.g.