In vivomigration of endogenous brain progenitor cells guided by an injectable peptide amphiphile biomaterial

Biomaterials hold great promise in helping the adult brain regenerate and rebuild after trauma. Peptide amphiphiles (PA) are highly versatile biomaterials, gelling and forming macromolecular structures when exposed to physiological levels of electrolytes. We are here reporting on the first ever in vivo use of self-assembling peptide amphiphile carrying a Tenascin-C signal (E(2)Ten-C PA) for the re-direction of endogenous neuroblasts in the rodent brain. The PA forms highly aligned nanofibers, displaying the migratory sequence of Tenascin-C glycoprotein as epitope. In this in vivo work, we have formed in situ a gel of aligned peptide amphiphile nanofibers presenting a migratory Tenascin-C signal sequence in the ventral horn of the rostral migratory stream, creating a track reaching the neocortex. Seven days post-transplant, doublecortin positive cells were observed migrating inside and alongside the injected biomaterial, reaching the cortex. We observed a 24-fold increase in number of redirected neuroblasts for the E(2)Ten-C PA injected animals compared to control. We also found injecting the E(2)Ten-C PA to cause minimal neuroinflammatory response. Analyzing GFAP(+) astrocytes and Iba1(+) microglia activation, the PA does not elicit a stronger neuroinflammatory response than would be expected from a small needle stab wound. Re-directing endogenous neuroblasts and increasing the number of cells reaching a site of injury using peptide amphiphiles may open up new avenues for utilizing the pool of neuroblasts and neural stem cells within the adult brain for regenerating damaged brain tissue and replacing neurons lost to injury.