Implantable amyloid hydrogels for promoting stem cell differentiation to neurons

We report a new class of amyloid-inspired peptide hydrogels that was designed and based on a-synuclein protein for which hydrogel formation is triggered by various stimuli, such as heating/cooling or changes in pH. The peptides resemble a cross-beta-sheet-rich amyloid, and they assemble into a nanofibrous meshwork that mimics the natural extracellular matrix. Our design principle allows easy manipulation of the gelator sequence to exploit the desirable properties of amyloids for use in cell replacement therapies for neurodegenerative diseases. The amyloid hydrogels facilitate the attachment and neuronal differentiation of mesenchymal stem cells (MSCs) and assist in the delivery and engraftment of MSCs in the substantia nigra and caudate putamen of a Parkinsonian mouse model.