Self-Assembling Peptide Nanofiber Scaffolds for 3‐D Reprogramming and Transplantation of Human Pluripotent Stem Cell-Derived Neurons

While cell transplantation presents a potential strategy to treat the functional deficits of neurodegenerative diseases or central nervous system injuries, the poor survival rate of grafted cells in vivo is a major barrier to effective therapeutic treatment. In this study, we investigated the role of a peptide-based nanofibrous scaffold composed of the selfassembling peptide RADA16-I to support the reprogramming and maturation of human neurons in vitro and to transplant these neurons in vivo. The induced human neurons were generated via the single transcriptional factor transduction of induced pluripotent stem cells (iPSCs), which are a promising cell source for regenerative therapies. These neurons encapsulated within RADA16-I scaffolds displayed robust neurite outgrowth and demonstrated high levels of functional activity in vitro compared to that of 2-D controls, as determined by live cell calcium imaging. When evaluated in vivo as a transplantation vehicle for adherent, functional networks of neurons, monodisperse RADA16-I microspheres significantly increased survival (over 100-fold greater) compared to the conventional transplantation of unsupported neurons in suspension. The scaffold-encapsulated neurons integrated well in vivo within the injection site, extending neurites several hundred microns long into the host brain tissue. Overall, these results suggest that this biomaterial platform can be used to successfully improve the outcome of cell transplantation and neuro-regenerative therapies.