Reversible crosslinked assembly of a trimeric coiled‐coil peptide into a three‐dimensional matrix for cell encapsulation and release

Mimicking the extracellular matrix (ECM) continues to be a goal in the field of regenerative medicine. Herein, we report a modified trimeric GCN4 coiled‐coil sequence containing three ligands for metal ions specifically positioned for crosslinked assembly (TriCross). In the presence of metal ions, TriCross assembles into a three‐dimensional (3D) matrix with significant cavities to accommodate cells. The matrix was found to be stable in media with serum, and mild removal of the metal leads to disassembly. By assembling TriCross with a suspension of cells in media, the matrix encapsulates cells during the assembly process leading to high cell viability. Further disassembly under mild conditions allows for the release of cells from the scaffold. As such, this peptide‐based material displays many of the characteristics necessary for successful 3D cell culture. A trimeric GCN4 coiled‐coil peptide modified with ligands for metals (TriCross) assembles in the presence of metal ions into a stable 3D matrix that can encapsulate cells with high viability. Mild treatment with ethylenediaminetetraacetic acid (EDTA) releases the cells from the peptide scaffold, providing a material with promise for 3D cell culture.