Bio‐Metamaterials for Mechano‐Regulation of Mesenchymal Stem Cells

Abstract Cell behaviors significantly depend on the elastic properties of the microenvironments, which are distinct from commonly used polymer‐based substrates. Artificial elastic materials called metamaterials offer large freedom to adjust their effective elastic properties as experienced by cells, provided (i) the metamaterial unit cell is sufficiently small compared to the biological cell size and (ii) the metamaterial is sufficiently soft to deform by the active cell contraction. Thus, metamaterials targeting bio‐applications (bio‐metamaterials) appear as a promising path toward the mechanical control of stem cells. Herein, human mesenchymal stem cells (hMSCs) are cultured on three different types of planar periodic elastic metamaterials. To fulfill the above two key requirements, microstructured bio‐metamaterials have been designed and manufactured based on a silicon elastomer‐like photoresist and two‐photon laser printing. In addition to the conventional morphometric and immunocytochemical analysis, the traction force that hMSCs exert on metamaterials are inferred by converting the measured displacement‐vector fields into force‐vector fields. The differential responses of hMSCs, both on the cellular level and the sub‐cellular level, correlate with the calculated effective elastic properties of the bio‐metamaterials, suggesting the potential of bio‐metamaterials toward mechanical regulation of cell behaviors by the arrangement of unit cells.