Hybrid cell constructs consisting of bioprinted cell-spheroids

Bioprinted cell constructs have been investigated for regeneration of various tissues. However, poor cell–cell interactions have limited their utility. Although cell-spheroids offer an alternative for efficient cell–cell interactions, they complicate bioprinting. Here, we introduce a new cell-printing process, fabricating cell-spheroids and cell-loaded constructs together without preparation of cell-spheroids in advance. Cells in mineral oil droplets self-assembled to form cell-spheroids due to the oil-aqueous interaction, exhibiting similar biological functions to the conventionally prepared cell-spheroids. By controlling printing parameters, spheroid diameter and location could be manipulated. To demonstrate the feasibility of this process, we fabricated hybrid cell constructs, consisting of endothelial cell-spheroids and stem cells loaded decellularized extracellular matrix/β-tricalcium phosphate struts for regenerating vascularized bone. The hybrid cell constructs exhibited strong angiogenic/osteogenic activities as a result of increased secretion of signaling molecules and synergistic crosstalk between the cells.