Enzyme-Regulated Peptide-Liquid Metal Hybrid Hydrogels as Cell Amber for Single-Cell Manipulation

Current strategies to construct cell-based bioartificial tissues largely remain on a multicell level. Taking cell diversity into account, single-cell manipulation is urgently needed for delicate bioartificial tissue construction. Current single-cell isolation and profiling techniques involve invasive processes and thus are not applicable for single-cell manipulation. Here, we managed to fabricate peptide-liquid metal hybrid hydrogels as "cell ambers" which were suitable for single-cell isolation as well as further handling. The successful preparation of uniform liquid metal nanoparticles allowed the fabrication of peptide-liquid metal hydrogel with excellent recovery property upon mechanical destruction. The alkaline phosphatase-instructed supramolecular self-assembly process allowed the formation of microhydrogel post-filling in the PDMS template. The co-culture of the hydrogel precursor and mammalian cells realized the embedding of cells into elastic hydrogels which were the so-called cell ambers. The cell ambers turned out to be biocompatible and capable of supporting cell survival. Aided with the micro-operating system and a laser scanning confocal microscope, we could arrange these as-prepared 3D single-cell ambers into various patterns as desired. Our strategy provided the possibility to manipulate a single cell, which served as a prototype of cell architecture toward cell-based bioartificial tissue construction.