Conductive and bioactive supramolecular scaffolds promote neuronal maturation [Stupp06_RNA-seq]

Traumatic injury in the central nervous system (CNS) results in neuronal damage and death, with chronic symptoms such as damaged cognition and paralysis. While chemically engineered scaffolds can be delivered to provide a substrate to stimulate axon regrowth, many grafts lack efficacy due to inefficient electrical coupling between the material and the conductive in vivo environment. We have incorporated a conductive component, functionalized poly[3,4-(ethelynedioxythiophene)] (PEDOT), into a supramolecular biomaterial scaffold which facilitates neuronal differentiation and maturation. Peptide amphiphiles (PAs) can self-assemble into high-aspect ratio nanostructures that mimic native extracellular matrix and may be functionalized with bioactive epitopes such as (previously described) laminin mimetic (IKVAV). Interestingly, this synthesized PEDOT:PA enhanced neurite length and branching in murine primary cortical neurons. Furthermore, protein analysis clearly showed PEDOT:PA upregulated maturation and pre-/post-synaptic markers (Map2, PSD 95, Syn). Moreover, human induced pluripotent stem cell (iPSCs) derived spinal cord neuron models showed enhanced differentiation of iPSCs into human spinal cord progenitors through increased expression of TUJ-1. These results strongly suggest that PEDOT:PA promotes CNS maturation in mouse and human systems and shows its potential as a therapeutic in spinal cord injury.