In Vitro Models for Assessing Toxicity and Cellular Effects

Dear Colleagues,

Growing concern for animal welfare, together with the need for more human-relevant data, has intensified the demand for alternative testing strategies to animal use. Traditional in vivo models, despite their widespread adoption, are often associated with high costs, long experimental timelines, limited standardisation, and suboptimal predictive power for human responses. Moreover, they offer limited control over experimental variables, particularly when investigating complex cellular and molecular interactions. These limitations, combined with the ethical imperative of the 3Rs principles—replacement, reduction, and refinement—underscore the urgent need for advanced in vitro approaches.

Conventional two-dimensional (2D) cell cultures, while widely used, represent an oversimplified approximation of native tissue environments. The absence of three-dimensional architecture, extracellular matrix components, and biomechanical cues significantly affects cell behavior and functional responses, reducing the reliability of pharmacological and toxicological evaluations. This is especially relevant for the assessment of nanoparticles and advanced materials, whose cellular uptake, distribution, and biological effects are highly dependent on tissue structure and microenvironmental conditions.

To address these challenges, innovative in vitro models such as 3D cultures, organoids, millifluidic bioreactors, and organ-on-chip platforms provide enhanced physiological relevance by mimicking in vivo cell organization and the extracellular environment and enhanced experimental control by finely tuning and sensing culture conditions. These systems enable more predictive assessments of toxicity, disease mechanisms, and nanoparticle–cell interactions under dynamic and human-relevant conditions.

This Special Issue aims to collect recent advances, challenges, and future perspectives in the development and application of innovative in vitro models for toxicity testing and cellular effect assessment, including studies involving nanomaterials and nanoparticle-based systems. 

Dr. Anna Bassi
Dr. Sara Tirendi
Dr. Alice Zoso
Dr. Camilla Paoletti
Guest Editors

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