3D print technology for cell culturing

Cells can be grown under controlled conditions outside their natural environment. This process is called cell culture. Cell culture has been instrumental and indispensable down the centuries in enriching our treasure trove of knowledge related to various biological processes running inside our body. It is important to the extent that lots of effort is being put in to evolve cell culture into a system authentic enough to reproduce the in vivo conditions. Increasing dependence on authenticity of cell culture to reproduce in vivo is partly due to its ease of execution and partly, due to the limitations associated with the alternative technique involving animal models. However, before discussing this alternative technique that has been preferably used instead of cell culture so far, it is relevant that the limitations of existing cell culture are discussed. Cell culture originally is two-dimensional (2D); that is, cells, either primary or transformed, can be grown in petri dishes as adherent or suspension cultures depending on the cell type. With advent of polymer technology, cell culture plastic wares underwent revolutionization in terms of extracellular matrix (ECM) coating that now provides better growth conditions to adherent cells. However, this is barely enough to provide the in vivo microenvironment. It is where the three-dimensional (3D) cell culture establishes its need and dominance. The 3D cell culture involves growing cells in scaffolds that could be made of natural or biocompatible synthetic polymers. However, here also the cells are not provided with their natural niche in true sense. Scaffold-supported 3D cell culture, as the name indicates, is a supported growth, may be a little better supported than the 2D culture, but a supported system. It lacks the features of the in vivo microenvironment created because of the growth and behavior of the surrounding cells. The 3D cell culture is a relatively recent addition to the technique. Animal models were more trusted right from the beginning as the advent of cell culture. Understandably, an animal model is expected to be more relevant when in vivo validations are required. However, animal models are not quite apt to know human system. Here, the obvious species difference makes things less authentic. Therefore, with a situation where several human physiological processes await acute validation, there is, definitely, a need for a more authentic system. This is when the 3D bioprinting steals the spotlight with its associated feature of providing several degrees of freedom when it comes to engineering the microenvironment of the cell growth. It provides the option of carrying out cell culture in three dimensions with a precisely designed niche representing the microenvironment as required. The icing on the cake comes when 3D bioprinting facilitates 4D cell culture: cell culture with the option of changeable microenvironment with time, something, akin to what happens in vivo. Thus, 3D/4D bioprinting when used in cell culture is promising enough to help provide almost near in vivo conditions in our petri dishes. This chapter will be dedicated to discussing all these aspects in detail, beginning with a brief introduction of 3D bioprinting, followed by 3D bioprinting in cell culture, its applications, 3D bioprinting in stem cell culture, then shifting the focus to 4D cell culture, and finally, closing with a summary.