Extracellular vesicles (EVs) originate from membranes of all cell types and can be found in all tissues and biological fluids.^{1 – 4} They are $\sim 30$ to 1000 nm in diameter and play a crucial role in intercellular communication by delivering a variety of cargo, including nucleic acids, proteins, glycans, and lipids to local and distant cells where they influence cellular phenotype.^2,3,5,6 EV-mediated intercellular signaling contributes to the regulation of a wide range of biological functions in target cells including immunological processes (e.g., antigen presentation), communication between components of the neurovascular unit, glial and neuronal function, development and differentiation of stem cells, and tissue regeneration. Additionally, in aberrant conditions, EVs have been associated with the pathophysiology of stroke, Alzheimer’s disease, Parkinson’s disease, cancer, obesity, cardiovascular disease, and rheumatoid arthritis.^{2,5,7 – 11} Therefore, there is a rapidly increasing scientific interest in EVs including their detection and imaging in tissue or biological fluids.

The potential of stem cells to differentiate into a variety of subgroups of neural cells makes stem cell differentiation and transplantation a promising candidate for neurodegenerative disorder therapies. However, selective differentiation of stem cells to neurons while preventing glial scar formation is a complex process. Mimicking the natural environment of neural tissue is pivotal, thus various synthetic materials have been developed for this purpose. The synthetic scaffolds can direct stem cells into a neural lineage by including extracellular factors that act on cell fate, which are mainly soluble signals, extracellular matrix proteins and physical factors (e.g. elasticity and topography). This article reviews synthetic materials developed for neural regeneration in terms of their extracellular matrix mimicking properties. Functionalization of synthetic materials by addition of bioactive chemical groups and adjustment of physical properties such as topography, electroactivity and elasticity are discussed.

The development of new biomaterials mimicking the neuronal extracellular matrix (ECM) requires signals for the induction of neuronal differentiation and regeneration.