![]() The lack of this environmental context and structural architecture excludes physical cues for cell-cell and cell-matrix communication, critical for several cellular processes (e.g., mitosis, self-renewal, and differentiation). ![]() Firstly, they are simplistic imitations of the in vivo situation, where cells grow within a complex three-dimensional (3D) microenvironment. Although easy and convenient, 2D cultures exhibit numerous disadvantages. These cell systems rely mainly on adherent cultures, where cells grow as a monolayer attached to a plastic or glass substrate. In such studies, two-dimensional (2D) cell culture systems dominate, continuing to improve our perception and understanding of cell biology. Cell culture has come a long way since then and is now a vital and invaluable tool for a vast array of applications, both in academic and industrial settings, including drug development, cancer research and tissue engineering ( Przyborski, 2017 Kapałczyńska et al., 2018). Harrison's first experiments, early in the twentieth century, on development of frog nerve fibers in a dish, the establishment of aseptic technique and subculture methods by Carrell and Ebeling in 1920s and the successful isolation and maintenance of the first immortalized human cell line (HeLa cells) by Gey in the 1950s, made it possible to grow cells in artificial environments, laying the foundation for cell and molecular biology ( Taylor and Taylor, 2014 Jedrzejczak-Silicka, 2017 Simian and Bissell, 2017). By highlighting applications and examples of several physiological and disease models, we identify the limitations and challenges which the field needs to address in order to more effectively incorporate synthetic biomimetic culture platforms into biomedical research.Ĭell culture systems represent an indispensable tool for a wide range of biomedical studies. Here, we review recent advances in 3D biomimetic cultures, focusing on the technological bricks available to develop more physiologically relevant in vitro models of human tissues. Even though such systems are necessarily simplified to capture a particular range of physiology, their ability to model specific processes of human biology is greatly valued for their potential to close the gap between conventional animal studies and human (patho-) physiology. Modern biomedical research has at its disposal novel technological approaches that promote development of more sophisticated and robust tissue engineering in vitro models, including scaffold- or hydrogel-based formats, organotypic cultures, and organs-on-chips. ![]() Advances in 3D cell biology and engineering have led to the development of a new generation of cell culture formats that can better recapitulate the in vivo microenvironment, allowing us to examine cells and their interactions in a more biomimetic context. Despite the amazing progress and discoveries achieved with flat biology models, our ability to translate biological insights has been limited, since the 2D environment does not reflect the physiological behavior of cells in real tissues. Conventionally, in vitro models are based on experimental manipulation of mammalian cells, grown as monolayers on flat, two-dimensional (2D) substrates. The quality of such experimental models and particularly the level at which they represent cell behavior in the native tissue, is of critical importance for our understanding of cell interactions within tissues and organs. Research in cell biology greatly relies on cell-based in vitro assays and models that facilitate the investigation and understanding of specific biological events and processes under different conditions.
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