Fabrication of centimeter-sized 3D constructs with patterned endothelial cells through assembly of cell-laden microbeads as a potential bone graft.

Modular tissue engineering is a promising biofabrication strategy to create engineered bone grafts in a bottom-up manner, in which cell-laden micro-modules are prepared as basic building blocks to assemble macroscopic tissues via different integrating mechanisms. In this study, we prepared collagen microbeads loaded with human bone marrow derived mesenchymal stem cells (BMSCs) using a microfluidic approach. The cell-laden microbeads were characterized for size change, cell activity, osteogenesis, as well as their self-assembly properties to generate centimeter-sized constructs. Moreover, using the cell-laden beads as a supporting medium, induced pluripotent stem cell-derived endothelial cells (iPSC-EC) were patterned inside bead aggregates through extrusion-based 3D printing. This fabrication approach that combines modular tissue engineering and supports 3D printing has the potential to create 3D engineered bone grafts with a pre-existing, customized vasculature.