Granular hydrogels, or densely packed microgel fragments, are an emerging class of biomaterials with tunable, attractive properties that have mainly been applied to tissue engineering and bioprinting. Here, we demonstrate the advantages of forming granular hydrogels with secondary inter-particle crosslinking through reversible dynamic covalent interactions. Structural and chemical characterization was performed to assess the physiochemical changes imparted to granular hydrogels by secondary crosslinking. Mechanical and rheological analysis is used to quantify the improved strength and recovery of the dynamic covalent granular hydrogels. Injectability and self-healing assays highlight the benefits of reversible, spontaneous crosslinking between fragmented microgel particles. The strain-yielding and self-healing granular hydrogels were investigated for 3D printing applications, showing filament formation and printability of different shapes. The ability of granular hydrogels to load and release biomolecules was also assessed, in order to explore the injectable biomaterial for a more specific application. Overall, we show that the secondary crosslinking through dynamic covalent interactions is beneficial for biomedical applications, specifically injectable biomaterials for tissue engineering.
