Replication of natural surface topographies to generate advanced cell culture substrates

Surface topographies of cell culture substrates can be used to generate <i>in vitro</i> cell culture environments similar to the <i>in vivo</i> cell niches. <i>In vivo,</i> the physical properties of the extracellular matrix (ECM), such as its topography, provide physical cues that play an important role in modulating cell function. Mimicking these properties remains a challenge to provide <i>in vitro</i> realistic environments for cells. Artificially generated substrates' topographies were used extensively to explore this important surface cue. More recently, the replication of natural surface topographies has been enabling to exploration of characteristics such as hierarchy and size scales relevant for cells as advanced biomimetic substrates. These substrates offer more realistic and mimetic environments regarding the topographies found <i>in vivo</i>. This review will highlight the use of natural surface topographies as a template to generate substrates for <i>in-vitro</i> cell culture. This review starts with an analysis of the main cell functions that can be regulated by the substrate's surface topography through cell-substrate interactions. Then, we will discuss research works wherein substrates for cell biology decorated with natural surface topographies were used and investigated regarding their influence on cellular performance. At the end of this review, we will highlight the advantages and challenges of the use of natural surface topographies as a template for the generation of advanced substrates for cell culture.