Self-Organization of Fibroblast-Laden 3D Collagen Microstructures from Inkjet-Printed Cell Patterns

One of the major challenges encountered in engineering complex tissues in vitro is to increase levels of complexity at the micron scale in 3D structures. Here, a strategy to create self-organized 3D collagen microstructures by 2D micropatterning of fibroblasts is developed. Drop-on-demand inkjet printing is used to pattern fibroblast cells on a collagen substrate in pre-designed patterns and with controlled density. It is found that cell-to-ECM interaction promotes cellular self-organization of 3D microstructures on collagen hydrogel, whereas the formation of 3D microstructure is inhibited by disruption of actin polymerization. Using this phenomena, the controlled sizes and morphologies of the 3D collagen microstructures is demonstrated by manipulating the designs of cell patterns and the density of cells. Finally, this technique is applied to build a human skin model with papillary microstructures at the dermo-epidermal junction. This approach to create 3D cell-laden collagen microstructures by cell patterning provides a simple and powerful way to mimic the structures and functions of complex tissues and organs, and can make a contribution to reduce the gap between the human body and in vitro tissue models.