No abstract

The development of tissue‐like structures such as cell sheets, spheroids, and organoids has contributed to progress in regenerative medicine. Simultaneous achievement of scale up and high cell density of these tissues is challenging because sufficient oxygen cannot be supplied to the inside of large, high cell density tissues. Here, in vitro fabrication of vessels to supply oxygen to the inside of millimeter‐sized scaffold‐free tissues whose cell density is ≈200 million cells mL−1, corresponding to those of native tissues, is shown. Hierarchical vascular networks by anastomosis of capillaries and a large vessel are essential for oxygen supply, whereas a large vessel or capillary networks alone make negligible contributions to the supply. The hierarchical vascular networks are formed by a top‐down approach, which offers a new option for ex vivo whole organs without decellularization and 3D‐bioprinting.

Mechanical stimulation such as flood flow often plays a vital role in the growth and maintenance of a living body, and it is important to investigate cell responses to mechanical stimulation. To date, cell responses to mechanical stimulation have been investigated in detail. However, the cell responses have been little known in a cell sheet. In the present study, a small cyclic strain (CS) of ~0.5% generated by a nanoporous gold actuator was loaded on a cell sheet of fibroblasts, and the effects of the CS on cell orientation were investigated. Individual cells were randomly distributed after the CS application, whereas cells were oriented in a specific direction after the CS application for the cell sheet. Thus, the CS had a different effect on the cell sheet from that on the individual cells. It is suggested that the cadherin/p-120 catenin complex played an important role in the cell response to mechanical stimulation in a cell sheet.