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.

Engineered Liver Tissue Culture in an In Vitro Tubular Perfusion System.

Liver disease and the subsequent loss of liver function is an enormous clinical challenge. A severe shortage of donor liver tissue greatly limits patients' options for a timely transplantation. Tissue engineering approaches offer a promising alternative to organ transplantation by engineering artificial implantable tissues. We have established a platform of cell-laden microbeads as basic building blocks to assemble macroscopic tissues via different mechanisms. This modular fabrication strategy possesses great potential for liver tissue engineering in a bottom-up manner. In this study, we encapsulated human hepatocytes into microbeads presenting a favorable microenvironment consisting of collagen and mesenchymal stem cells, and then we perfused the beads in a three-dimensional printed tubular perfusion bioreactor that promoted oxygen and medium diffusion to the impregnated cells. We noted high cell vitality and retention of parenchymal cell functionality for up to 30 days in this culture system. Our engineering-based approach led to the advancement in tissue size and long-term functionality of an artificial liver tissue in vitro.