In article number 2002436, Tae-Hyung Kim and co-workers demonstrate a novel multifunctional hybrid platform that enables spontaneous cancer spheroids formation on the surface and real-time non-destructive electrochemical monitoring of spheroid viability simultaneously. The platform allows for mimicking the complex three-dimensional cellular networks and multicellular characteristics of real solid tumors in vitro, which will be highly useful for high-throughput anticancer drug screening.

In article number 2003765, Carmine Gentile and co-workers describe the major pathophysiological features required for the bioengineering of a heart attack in a Petri dish. The article presents a thorough comparison of current in vitro, ex vivo, and in vivo models. It also explores the potential use of latest technologies for advanced cardiac models, such as 3D bioprinting, microfluidic devices and patient-derived stem cell, with the potential to develop personalized novel therapies for heart attack patients.

Oxygen tension and extracellular matrix compositions play important roles in network formation of endothelial cells. In article number 2006091, Yi-Chung Tung and co-workers develop an in vitro model using an upside-down microfluidic device capable of generating oxygen gradients for three-dimensional cell culture within hydrogels under controlled oxygen microenvironments.

In article number 2004258, Ali Khademhosseini, Su Ryon Shin, and co-workers develop a model for investigating chemotherapy-induced cardiotoxicity where induced pluripotent stem cell-derived cardiac tissues are interacted with breast cancer tissues on a dual-organ platform. Using electrochemical immuno-aptasensors to monitor cell-secreted multiple biomarkers, the proposed platform could be potentially suitable for early detection and prediction of cardiotoxicity in individual patients.

Although animal experiments are still required to validate preliminary data on safety and efficacy of new compounds, high costs and ethical issues related to animal welfare are usually associated. Here, the main problems and challenges related to the use of animals in research are addressed, along with a variety of possible alternatives to animal testing.

Nanomaterials have unique properties that may alter the toxicity profile when compared to larger forms of the same material. There are opportunities to integrate in vitro methodologies into the hazard testing and risk assessment process although there are challenges in ensuring they are as robust and reliable as in vivo approaches and ensuring the protection goals are met.

There is a need for hazard testing in regulatory toxicology and biomedical research in the context of the 3Rs concept. From a researcher's perspective, insight is provided into the development process of alternative methods with a focus on in vitro cell culture methods through validation to regulatory acceptance.

AOPs enable the systematic organisation of the existing in silico, in vivo and in vitro toxicology data (specific to NM or non-NM data) and serve as mechanistic backbones for the establishment of potential animal reduction or replacement strategies and toxicity testing tools. Together with the information on material characterisation and exposure, they enable derivation of risk indicators.

A significant challenge facing engineered nanomaterial hazard assessment is the application of physiologically relevant in vitro models for evaluating genotoxicity. This review considers the benefits, limitations, and adaptations of 3D in vitro liver culture systems to assess DNA damage. Important advances that facilitate the evaluation of a range of genotoxicity endpoints are discussed.

Major molecular, cellular, and extracellular features typical of a heart attack in humans together with a direct comparison of currently available in vivo, ex vivo, and in vitro models are summarized in this review article with the goal to generate advanced bioengineered in vitro models better recapitulating the complex in vivo microenvironment typical of an infarcted heart.

A paradigm change in toxicology encourages the development of human-relevant in vitro models for hazard assessment. Functional units of organs with highest toxicological relevance are discussed and currently used in vitro models and ongoing developments in toxicity testing are highlighted. Especially stem cell-based models and the integration of innovative technologies like organs-on-a-chip and genome editing will revolutionize toxicity testing.

This article investigates the physicochemical changes exhibited by engineered nanomaterials (ENMs) treated with presimulants representing inhalation and oral exposure routes, and the subsequent effects of such ENM biotransformation upon primary and secondary organ systems. To evaluate this, ENM characterization is undertaken whilst cytotoxicity, (pro-)inflammatory response, and genotoxicity are assessed using in vitro models.

Using nanomaterial in vivo organ burden data for in vitro dose setting: 1) determine in vivo exposure to be reflected in vitro; 2) identify in vivo organ burden at LOAEC; 3) extrapolate to in vitro effective dose; 4) extrapolate to in vitro nominal concentration; 5) set in vitro concentration range; 6) consider uncertainties and specificities of in vitro test system.

In intestinal in vitro research, the choice of model impacts the outcomes. Strongest effects of silver and titanium dioxide particles are observed in proliferating monocultures. Negligible responses are quantified in complex multicell systems in healthy or inflamed state, which align with the outcomes of feeding studies in mice using the same nanomaterials.

This work investigates the genotoxicity of industrially relevant few-layered graphene upon human lung epithelial (16HBE14o^-) cells. The study reports the evaluation of the toxicity and genotoxicity of these materials. Oxidative stress, (pro)-inflammatory chemokine release, and mitochondrial function are all demonstrated as key mechanisms underlying the damage detected.

Fluorescent silica nanoparticles (SNPs) are introduced as a robust labeling strategy to visualize tumor cells within mineralized bone from in vitro and in vivo studies. SNP labeling efficiency of MDA-MB-231 breast cancer cells is characterized using a broad range of bone processing and imaging techniques. SNPs are tools with the potential to increase the understanding of mineral contributions to bone metastasis.

The delivered adverse outcome pathway (AOP) anchored structure-activity relationships model (Nano-QSAR) provides insights into predicting the pulmonary pathology induced by carbon nanotubes. A grouping strategy based on nanotubes’ aspect ratio and transcriptomic pathway associated genes is proposed. It shows how AOP framework can help guide Nano-QSAR modelling efforts; conversely, outcome of QSAR can aid in refining certain aspects of AOP.

Using a biomimetic microengineering approach, the interface between the vascular wall and flowing blood is reconstructed to model hemostasis from injury to wound closure. The vascular injury-on-a-chip system replicates i) multiscale structure, ii) biochemical and biomechanical function, and iii) the dynamic microenvironment that helps to determine the structure of the hemostatic plug as it forms in vivo after injury.

Microfluidic technology is a valuable tool for realizing in vitro models capturing cellular/organ level responses for rapid, animal-free risk assessment of chemicals and drugs. A microfluidic platform equipped with a silicon chip and integrated electrodes is developed for in vivo-like in vitro cell cultivation. A proof-of-concept using different cell models shows the suitability of this platform for label-free hazard assessment.

In this paper, a cardiotoxicity-on-a-chip platform containing induced pluripotent stem cell-derived cardiac tissue communicating with breast cancer tissue is presented with electrochemical immuno-aptasensors for non-invasively monitoring cell secreted biomarkers. The suggested platform is capable of differentiating functionality and toxicity in healthy/fibrotic cardiac tissues after treatment with chemotherapy to step toward early detection and prediction of cardiotoxicity in individual patients.

Biomimetic triregional glioblastoma multiforme (GBM) models are bioprinted with tumor regions, acellular extracellular matrix regions, and an endothelial region with regional stiffnesses patterned corresponding to the GBM stroma, pathological or normal brain parenchyma, and brain capillaries. Results show that biophysical cues are involved in various tumor cell behaviors and angiogenic potentials and promote different molecular subtypes of GBM.

A multifunctional conductive platform that allows for highly efficient multicellular cancer spheroid formation and real-time non-destructive electrochemical monitoring of spheroid viability under various drug treatment conditions. The platform is useful for high throughput drug screening based on 3D multicellular culture models.

An upside-down microfluidic device capable of generating oxygen gradients for cell culture within hydrogels is developed to study 3D network formation of endothelial cells under various combinations of oxygen microenvironments and extra cellular matrix compositions. The device provides a powerful and straightforward platform to perform 3D cell culture under controlled microenvironments for various biomedical researches in vitro.