Orthogonally crosslinked gelatin methacryloyl microgels for in situ assembly of granular hydrogel scaffolds

Abstract Gelatin methacryloyl (GelMA) microgels formed via physical crosslinking dissolve at the physiological temperature, hindering their translational use for the in situ fabrication of granular hydrogel scaffolds (GHS). To overcome this challenge, we present a dual crosslinking strategy that combines Schiff base chemistry for GelMA microgel stabilization with subsequent free‐radical photocrosslinking to form inter‐microgel covalent bonds. This technology yields stable microgels (SμG) that may be packed and photochemically interlinked in situ to form robust granular hydrogel scaffolds (GHS SμG ) under physiological conditions. The resulting GHS SμG support high cell viability and proliferation and have pore architecture and interconnectivity, as well as mechanical properties comparable to scaffolds fabricated using physically crosslinked GelMA microgels. This work is a step forward in developing translational granular biomaterials for the in situ tissue regeneration.