Assembly of PEG Microgels into Porous Cell‐Instructive 3D Scaffolds via Thiol‐Ene Click Chemistry

The assembly of microgel building blocks into 3D scaffolds is an emerging strategy for tissue engineering. A key advantage is that the inherent microporosity of these scaffolds provides cells with a more permissive environment than conventional nanoporous hydrogels. Here, norbornene-bearing poly(ethylene glycol) (PEG) based microgels are assembled into 3D cell-instructive scaffolds using a PEG-dithiol linker and thiol-ene click photopolymerization. The bulk modulus of these materials depends primarily on the crosslink density of the microgel building blocks. However, the linker and initiator concentrations used during assembly have significant effects on cell spreading and proliferation when human mesenchymal stem cells (hMSCs) are incorporated in the scaffolds. The cell response is also affected by the properties of the modular microgel building blocks, as hMSCs growing in scaffolds assembled from stiff but not soft microgels activate Yes-associated protein signaling. These results indicate that PEG microgel scaffolds assembled via thiol-ene click chemistry can be engineered to provide a cell-instructive 3D milieu, making them a promising 3D platform for tissue engineering.