What Should We Print? Emerging Principles to Rationally Design Tissues Prone to Self-Organization

In vitro-generated tissues hold significant promise to mimic healthy and diseased tissues and impact both regenerative medicine and fundamental science. Current technologies allow for the formation of precise multicellular assemblies using, for instance, cell patterning approaches. These approaches lead to the formation of systems that are not necessarily stable and will remodel and reorganize over time, based on physical and/or biological principles (i.e. migration of the cells, shrinkage of the hydrogel). Shapes and patterns are thus not inevitably translated to the final tissue. Besides the technical issues of tissue assembly, there is a need for understanding collective cellular behaviors so as to design tissues prone to predictable and adequate self-deformation, self-remodeling and self-organization. Microfabricated tissues are powerful tools to study, in vitro, these processes. They will help to set the basic principles to rationally design tissues prone to further development and subsequently improve approaches to engineer more complex tissue architectures and functionalities. In this chapter, we will first briefly define and discuss the principles and mechanisms of self-organization during natural tissue development. We will then depict current attempts in studying these principles in in vitro microfabricated tissue models. We will specifically focus on current models using hydrogel templates or supports to assemble cells into primitive patterns. Finally, we will discuss the role of geometries in promoting heterogeneity of biological and physical cues leading to the emergence of self-organized forms.