In vitro microglia models: the era of engineered cell microenvironments

The most widely employed approach by cell biologists to performing in vitro cell culture assays is the one using 2D plastic culture ware systems, which allows reproducibility and ease of use. Moreover, this method is cost-effective. However, in most cases, these flat surfaces lead to the formation of unrealistic 2D cell monolayers, which do not reproduce the complex configuration characteristics of native tissues in terms of dimensionality, rigidity, and topography. For this reason, a new generation of interdisciplinary scientists, working across microengineering and cell biology has started to develop engineered cell microenvironments (Huang et al., 2017) by employing advanced materials and fabrication approaches (Fan et al., 2019) over the last two decades. Depending on the level of resolution of the adopted manufacturing technique, the geometrical features of these structures can reach micrometric or even sub-micrometric dimensions comparable to the ones of cellular somas or cellular filopodia, therefore fostering cell-biomaterial interactions. The developed structures are pivotal for a better investigation of fundamental mechanobiology (Lemma et al., 2019), the optimization of in vitro disease modeling, drug/treatment screening (Gao et al., 2021), and tissue engineering (Mani et al., 2022).