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.