Novel biomaterials to study neural stem cell mechanobiology and improve cell-replacement therapies

Neural stem cells (NSCs) are a valuable cell source for tissue engineering, regenerative medicine, disease modeling, and drug screening applications. Analogous to other stem cells, NSCs are tightly regulated by their microenvironmental niche, and prior work utilizing NSCs as a model system with engineered biomaterials has offered valuable insights into how biophysical inputs can regulate stem cell proliferation, differentiation, and maturation. In this review, we highlight recent exciting studies with innovative material platforms that enable narrow stiffness gradients, mechanical stretching, temporal stiffness switching, and three-dimensional culture to study NSCs. These studies have significantly advanced our knowledge of how stem cells respond to an array of different biophysical inputs and the underlying mechanosensitive mechanisms. In addition, we discuss efforts to utilize engineered material scaffolds to improve NSC-based translational efforts and the importance of mechanobiology in tissue engineering applications. [Display omitted] •Neural stem cells (NSCs) are a promising resource for tissue engineering and regenerative medicine.•Various mechanical cues can affect NSC differentiation, proliferation, and maturation.•Biomaterial advancements are driving new discoveries in NSC mechanotransduction.•Understanding biophysical regulation of NSCs is crucial for designing novel cell replacement strategies.