Viscoelastic Alginate‐Based Hydrogels: Regulating Neural Stem Cell Behavior Through Viscosity

ABSTRACT The mechanical properties of the extracellular matrix (ECM) play a crucial role in cell adhesion, proliferation, and differentiation. In this study, a series of viscoelastic alginate‐based blend hydrogels with tunable viscosity were prepared to investigate the effects of their viscosity on the spreading and viability of NE‐4C neural stem cells. The hydrogels with the same initial modulus but different viscosities were obtained by adjusting the degree of crosslinking through covalently and ionically crosslinked techniques. The study results indicated that at a low initial modulus, an increase in the viscosity of the viscoelastic substrate could lead to a rise in the spreading area of NE‐4C neural stem cells, along with the formation of synapses, suggesting that an increase in substrate viscosity is beneficial for cell adhesion and spreading. Furthermore, the survival rate of NE‐4C neural stem cells on a high‐viscosity matrix is significantly higher than on a low‐viscosity matrix, as the high‐viscosity matrix provides a more stable microenvironment for the cells. These results can not only enhance the understanding of the effect of the viscoelasticity of biomaterials on neural stem cell behavior but also provide experimental data and theoretical support for designing new biomaterials suitable for neural tissue engineering.