In vitro regulation of collective cell migration: Understanding the role of physical and chemical microenvironments

Collective cell migration is the primary mode of cellular movement during embryonic morphogenesis, tissue repair and regeneration, and cancer invasion. Distinct from single-cell migration, collective cell migration involves complex intercellular signaling cascades and force transmission. Consequently, cell collectives exhibit intricate and diverse migration patterns under the influence of the microenvironment in vivo. Investigating the patterns and mechanisms of collective cell migration within complex environmental factors in vitro is essential for elucidating collective cell migration in vivo. This review elucidates the influence of physical and chemical factors in vitro microenvironment on the migration patterns and efficiency of cell collectives, thereby enhancing our comprehension of the phenomenon. Furthermore, we concisely present the effects of characteristic properties of common biomaterials on collective cell migration during tissue repair and regeneration, as well as the features and applications of tumor models of different dimensions (2D substrate or 3D substrate) in vitro. Finally, we highlight the challenges facing the research of collective cell migration behaviors in vitro microenvironment and propose that modulating collective cell migration may represent a potential strategy to promote tissue repair and regeneration and to control tumor invasion and metastasis.