Engineering Organoid Development in 3D Artificial Microenvironments

The earliest steps of development are characterized by cellular reorganization and differentiation within a three-dimensional (3D) microenvironment. This 3D context allows for a complex spatial interplay between biochemical and physical signals, and governs important cellular rearrangements leading to morphogenesis. In vitro approaches have attempted to recapitulate key features of these processes, and it has now become possible to generate an increasing variety of self-organizing multicellular tissue constructs termed ‘organoids’. While important aspects of the 3D in vivo organization have been recreated in these organoid systems, such studies have been exclusively performed in Matrigel^TM, a poorly defined 3D microenvironment whose properties cannot be readily modulated. As such, the uncharacterized interactions between cells and this extracellular matrix (ECM) have proven to be a major challenge to understanding the underlying regulatory mechanisms governing morphogenesis. In this talk, I will highlight recent efforts in my lab to employ tunable synthetic hydrogels in order to disentangle the contributions of biochemical and physical components of the microenvironment in the specification of stem cell fate and morphogenesis.