Advanced Multi-Dimensional Cellular Models as Emerging Reality to Reproduce <i>In Vitro</i> the Human Body Complexity

• Main Authors: Giada Bassi, Maria Aurora Grimaudo, Silvia Panseri, Monica Montesi
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: International Journal of Molecular Sciences
• Subjects: multicellular spheroids; organoids; organ-on-a-chip; nanostructured biomaterials; tissue engineering; 3D <i>in vitro</i> models
• Online Access: https://www.mdpi.com/1422-0067/22/3/1195

A hot topic in biomedical science is the implementation of more predictive <i>in vitro</i> models of human tissues to significantly improve the knowledge of physiological or pathological process, drugs discovery and screening. Bidimensional (2D) culture systems still represent good high-throughput options for basic research. Unfortunately, these systems are not able to recapitulate the <i>in vivo</i> three-dimensional (3D) environment of native tissues, resulting in a poor <i>in vitro–in vivo</i> translation. In addition, intra-species differences limited the use of animal data for predicting human responses, increasing <i>in vivo</i> preclinical failures and ethical concerns. Dealing with these challenges, <i>in vitro</i> 3D technological approaches were recently bioengineered as promising platforms able to closely capture the complexity of <i>in vivo</i> normal/pathological tissues. Potentially, such systems could resemble tissue-specific extracellular matrix (ECM), cell–cell and cell–ECM interactions and specific cell biological responses to mechanical and physical/chemical properties of the matrix. In this context, this review presents the state of the art of the most advanced progresses of the last years. A special attention to the emerging technologies for the development of human 3D disease-relevant and physiological models, varying from cell self-assembly (i.e., multicellular spheroids and organoids) to the use of biomaterials and microfluidic devices has been given.