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.

Direct laser writing-enabled 3D printing strategies for microfluidic applications

“…Specifically, because the distance the laser passes through the photomaterial is relatively short compared to that of the immersion oil (and substrate), a wide range of photoresists and photocomposites can be printed via oil-immersion DLW. 196–200…”

Minimal-invasive 3D laser printing of microimplantsin organismo

“…Coating with extracellular matrix (ECM) proteins via physisorption is regularly used to increase cell attachment on PDMS surfaces 33,34 . Specifically for multi-photon printed IP-PDMS, it has recently been shown to be able to support cell attachment of human mesenchymal stem cells after fibronectin functionalization 9 . Given that our PDMS-like material microstructures reside outside bona fide epithelia of the Drosophila and medaka embryos, a natural coating with ECM or yolk resident proteins via physisorption after UV curation or 3D printing seems likely.…”

“…This technology has evolved originally from applications in mainly technical fields such as optics and photonics, but has also found its way into the life sciences thanks to the development of biocompatible materials. Today, this method is established in the life sciences for the precise fabrication of biocompatible scaffolds with subcellular resolution and applied in single cell, organoid, and cultured tissue research 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 . The biocompatible scaffolds can be prepared either by physically encapsulating cells in a photocurable hydrogel or by printing and successive development, i.e.…”

Printed Electronic Devices and Systems for Interfacing with Single Cells up to Organoids

“…These bio‐metamaterials can be used to mechanically regulate the morphology and active traction forces generated by mesenchymal stem cells. [ 170 ] Moreover, the integration of stimulus‐responsive polymers [ 171,172 ] into the printed 3D micro‐scaffolds offer the possibility to stimulate single cells mechanically. Whereas 3D microstructures printed by a photoresist doped with poly(N‐isopropylacrylamide) (pNIPAM) exhibit a substantial response to changes in temperature, [ 173 ] stimulus‐responsive, supramolecular hydrogels [ 174 ] enable the reversible actuation of cells under physiological conditions by non‐cytotoxic chemical stimuli.…”