Design of Neuronal Supramolecular Scaffolds Integrating Cell Signaling and Electrical Conductivity

Scaffolds with neuronal bioactivity are important to promote repair of the central and peripheral nervous systems, in vitro neuronal differentiation and maturation for transplantation, and the integration of electronic devices with neural tissues, among others. Previous work in this area includes the incorporation of growth factors, stem cells, or conducting polymers into scaffolds, but efficacy has been limited. We report here on an extrusion-printable bioactive scaffold that incorporates laminin-mimetic peptide amphiphile (PA) supramolecular filaments, a conducting polymer, and the anionic polysaccharide known as gellan gum. The conducting polymer used was poly(3,4-ethylenedioxythiophene) (PEDOT) with dual functionalization by design with alkoxysulfonates and hydroxyl groups. Hydroxyl groups hydrogen bonded with the polysaccharide, which enhanced both the conductivity and biocompatibility of the scaffolds by preventing the PEDOT from leaching out into cell media. When combined with PA filaments, the scaffold synergistically enhanced neuronal maturation and electrophysiological function in cultures of mouse and human cells. Interestingly, the conducting polymer was found to scavenge reactive oxygen species (ROS) and increase neuronal maturation potentially through cAMP response element-binding protein (CREB) pathways. Furthermore, extrusion printing the scaffold resulted in alignment of the bioactive supramolecular filaments and the cultured neurons, a key feature of natural neural tissues. Our findings suggest this biomaterial scaffold shows potential to promote neural bioactivity in a wide variety of regenerative medicine and bioelectronic applications.