Directing neural stem cell fate with biomaterial parameters for injured brain regeneration

The discovery of neural stem cells (NSCs), which have the ability to self-renew and differentiate into all types of neural lineages, offers promising prospect for the treatment of brain neurological disorders such as stroke/cerebral ischemia, traumatic brain injury and neurodegenerative disorders. However, only limited number of NSCs could survive or propagate due to tissue inflammation or blood-brain barrier. Therefore, it is necessary to develop an appropriate culture system that highly mimics the natural NSCs niche to direct stem cell fate and behavior for nerve regeneration. Both biophysical and biochemical properties of the NSC niche, including topology, mechanical properties, bioactive molecules, and their spatial and temporal presentations should be considered for the design of functionalized scaffolds, which could not only serve as the delivery vehicles of NSCs but also stimulate specific cellular responses at the molecular level, such as support endogenous or exogenous cells proliferation, migration and homing, even promote the growth of axon at the injured brain site. This review attempts to outline the varieties of biomaterial parameters that are applied as biophysical and biochemical signals to direct neural stem cell fate and behavior. The understanding on the interaction of NSCs decision and biomaterial parameters is helping to advance NSCs-based clinical approaches for nerve tissue regeneration and repair.