Nanomedicine boosts neurogenesis: new strategies for brain repair.

The subventricular zone (SVZ) and the hippocampal subgranular zone (SGZ) comprise two main germinal niches in the adult mammalian brain. Within these regions there are self-renewing and multipotent neural stem cells (NSCs) which can ultimately give rise to new neurons, astrocytes and oligodendrocytes. Understanding how to efficiently trigger NSCs differentiation is crucial to devise new cellular therapies aimed to repair the damaged brain. A large amount of data ranging from epigenetic alterations, chromatin remodelling and signalling pathways involved in NSCs differentiation are now within reach. Furthermore, a vast array of proteins and molecules have been described to modulate NSCs fate and tested in innovative therapeutic applications, however with little success so far. Nowadays, the main focus is on how to manipulate these factors to our full advantage. Unfortunately, concerns related to solubility, stability, concentration or spatial and temporal positioning can hinder their desirable effects. Biomaterials emerge as the ideal support to overcome these limitations and consequently boost NSCs differentiation towards desired phenotypes. However, the balance between biomaterials and differentiating factors must be well established, since the bioaccumulation and concomitant toxicity can be an undesired side-effect. Currently, innovative materials and formulations including more degradable carriers allow a controlled and efficient release of bioactive factors with minimal side-effects. Recently, micro- and nanoparticles have been successfully used to deliver molecules able to induce neurogenesis. This review presents recent research that highlights the role of both extracellular environmental factors as well as molecular remodelling mechanisms in the control of NSCs differentiation processes. Appropriate biomaterials that may trigger an efficient delivery of therapeutic molecules will be also discussed. Therefore, the interface between NSCs biology and tissue engineering may offer great potential in future therapeutics for treatment or amelioration of neurodegenerative diseases or brain injury.