Cellular Architects at Work: Cells Building their Own Microgel Houses.

Microporous annealed particle (MAP) scaffolds are investigated for their application as injectable 3D constructs in the field of regenerative medicine and tissue repair. While available MAP scaffolds provide a stable 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 interlinked spherical microgels, a cellularity gradient can be observed with the highest cell density on the scaffold surface. Additionally, the interlinked microgel network limits the ability of cells to remodel their environment, which contradicts 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 dextran-based microgels and function as a glue between the microgels, resulting in a more homogenous cell distribution throughout the scaffold with efficient cell-cell interactions.

Tuning the Porosity of Dextran Microgels with Supramacromolecular Nanogels as Soft Sacrificial Templates.

Hydrogels, as well as colloidal hydrogels (microgels), are important materials for a large variety of applications in the biomedical field. Microgels with a controlled pore size (meso- and macropores) are required for efficient nutrient support, modulation of cell adhesion, removal of metabolic products in cell cultures, and probiotic loading. Common microgel fabrication techniques do not provide sufficient control over pore sizes and geometry. In this work, the natural polysaccharide dextran modified with methacrylate groups is used to synthesize highly monodisperse meso- and macroporous microgels in a size range of 100-150 µm via photo cross-linking in microfluidic droplets. The size of mesopores is varied by the concentration of dextran methacrylate chains in the droplets (50-200 g L-1 ) and the size of macropores is regulated by the integration of pH-degradable supramacromolecular nanogels with diameters of 300 and 700 nm as sacrificial templates. Using permeability assays combined with confocal laser scanning microscopy, it is demonstrated that functional dextran-based microgels with uniform and defined pores could be obtained.