Harnessing the dental cells derived from human induced pluripotent stem cells for hard tissue engineering

•Tooth is an organ developed by the interaction between the epithelium derived from the ectoderm and the mesenchyme derived from neural crest cells. For tooth regeneration, hiPSCs should be needed to differentiate two kinds of cell type, including dental epithelial cells (DECs) and dental mesenchymal cells (DMCs).Additionally, the characteristics of dental cells differentiated from hiPSCs were identified by RNA sequencing analysis.•To determine the lineage of differentiated dental cells, including hDECs andh DMCs, the hiPSC-derived dental cells were encapsulated in GelMA with a photoinitiator, and crosslinked. Bioengineered mineralized bilayers mainly induced bone-like tissue formation in the hDEC layer, and cartilage-like and bone-like tissues formation in the hDMC layer.•Differentiated dental cells were resuspended in collagen gel, and the mineralization was induced. A bioengineered mineralization construct was formed in the collagen gel in which hDEC and hDMC were surrounded by cartilage and bone.•When hDEC and hDMCs were recombined in agar gel, these bioengineered constructs induced the odontogenic lineage and formed bioengineered tooth-like constructs regenerating bone-enclosed odontoblasts, dentin, nerve, and ameloblasts.