Self-assembling hydrogel substrates for neural networks

Martin AD

University of New South Wales.

Primary neuronal cultures are a powerful tool to understand neuronal maturation, aging and neurodegeneration. They have been used to screen the effects of drugs and misfolded proteins on neural networks in vitro. However, culturing primary neurons in vitro is notoriously difficult, owing to their high sensitivity to their environment. Currently, primary neurons are cultured on glass coverslips coated with poly-D-lysine (PDL). However, it is well known that significant differences exist in cell behaviour in a 2D versus 3D environment, which more accurately mimics in vivo conditions. Hydrogels have significant potential biomedical applications, including in cell culture, owing to their similarity to the extracellular matrix. We have previously used short peptides capped at their N-terminus with an aromatic group to form biocompatible hydrogels with tuneable stiffnesses, pore sizes and chemical functionalities. Here, we present a collaborative, multidisciplinary effort where short peptide hydrogels which support the growth of primary neurons in a 2D and 3D environment have been developed. Neurons cultured atop these hydrogels display initial development and maturation comparable to that on PDL, complete with synapse formation and electrical activity. Neurons can also be cultured within the hydrogels, with these 3D neuronal cultures having potential in identifying neurodegenerative disease biomarkers, better screening of drug molecules, modelling CNS damage and insights into aging.