Cellular Architects at Work: Cells Building Their Own Microgel Houses

Microporous annealed particle (MAP) scaffolds are currently being investigated for their application as injectable 3D constructs in the field of regenerative medicine and tissue repair. While available MAP scaffolds provide a stable chemically interlinked matrix of microgels for cell culture, the infiltration depth and space for cells to grow inside the scaffolds is pre-determined by the void fraction during the assembly. In the case of MAP scaffolds fabricated from spherical microgels, a gradient of cellularity can be observed with the highest cell density on the scaffold surface. At the same time, the interlinked microgel network limits cells to remodel their environment and thereby does not fully allow for native tissue dynamics. In this work, a cell-induced interlinking method for MAP scaffold formation is established, which avoids the necessity of chemical crosslinkers and pre-engineered pores to achieve micro- or macropores in these 3D frameworks. This method enables cells to self-organize with microgels into dynamic tissue constructs, which can be further controlled by altering the microgel properties, the cell/microgel ratio, and well shape. To form a cell-induced interlinked scaffold, the cells are mixed with the support material, here dextran-based microgels, and function as glue between the microgels, resulting in a more homogenous cell distribution throughout the scaffold with efficient cell-cell interactions. This article is protected by copyright. All rights reserved.