Engineering tissue-mimetic hydrogels with continuous viscoelastic gradient for programmed cell migration

The dynamic, viscoelastic nature of the extracellular matrix (ECM), with variations in stiffness and viscosity, plays a key role in cellular behaviors like mechano-sensing, migration, and force generation. Viscoelastic hydrogels are important for mimicking the ECM to study cell migration and tissue engineering. However, creating hydrogels with continuous viscoelastic gradients is challenging due to issues with spatial resolution, reproducibility, and accurately replicating native tissue properties. Here we present a novel approach to generate hydrogels with precisely controllable viscoelastic gradients using drop-by-drop condensation. This approach allows fine-tuned replication of the tissue-specific local mechanical properties, resulting in hydrogels of heterogeneous viscoelasticity. Directed migration and separation of multiple cell lines are thus driven by local viscosity and elasticity rather than solely stiffness. By incorporating non-linear mechanical gradients, this technique provides insights into ECM viscoelasticity’s role in cellular behavior and offers a versatile platform for advanced tissue engineering and regenerative medicine applications.