Bioprinting dynamic hydrazone hydrogels via light-mediated crosslinking

Viscoelastic hydrogels crosslinked by dynamic bonds hold great promise for mimicking the matrix dynamics of native tissues in cell culture and tissue engineering. Yet, their application in light-based crosslinking and bioprinting remains largely unexplored due to the incompatibility between reversible bond formation and photocrosslinking. This study addresses this key challenge by presenting a new class of photocrosslinkable, hydrazone-based bioinks developed from two modified polymers (Gelatin-adipic-diacetone acrylamide (DAAM) and gelatin-carbo-DAAM). These polymers are designed to enable reversible bond formation within hydrogel networks by attaching polymerizable groups to the polymer backbone via modular hydrazone conjugation chemistry. The resulting materials exhibit distinct mechanical properties depending on their hydrazide substituent, swelling medium, incubation temperature, and incubation time. Storage moduli of produced hydrogels vary between 0.08-1.2 kPa, which spans multiple scales of physiologically relevant tissue environments. The novel bioinks are suitable for droplet-based bioprinting followed by light-based crosslinking, and support cell spreading of human fibroblasts. Notably, the morphology of embedded cells varies with different hydrazide substituents, highlighting the potential of the developed bioink system to systematically investigate cell-matrix interactions. The combination of biological tunability and printability positions this system as a promising platform for fabricating next-generation tissue-mimetic constructs using advanced bioprinting technologies.