Bioadhesive anisotropic nanogrooved microfibers directing three-dimensional neurite extension

Neurodegenerative diseases and acute nerve injuries are becoming global clinical problems. Engineering three-dimensional (3D), anisotropic neural cellular structures in vitro is therefore desirable in the regenerative medicine research community. Here, we present, for the first time, a single-step, facile but delicate, fabrication of a 3D macroporous microfibrous scaffold with both anisotropic nanogrooved topography and in situ functionalization with a mussel inspired bioadhesive, poly(norepinephrine) (pNE). Specifically, immiscible blends of polycaprolactone (PCL) and polyethylene oxide (PEO) were electrospun into a grounded coagulation bath containing the precursor of pNE. Upon jet entrance in the bath, both phase-separation-driven longitudinal nanotopography and in situ pNE surface functionalization were introduced on individual microfibers that were packed into a 3D macroporous structure. The resulting scaffold significantly promoted 3D neurite extension capacity, 8-fold higher neurite extension over the isotropic counterpart, demonstrating that such a scaffold has great promise in 3D neural cell culture for nerve tissue modelling and engineering.