Directed neural stem cell differentiation on polyaniline-coated high strength hydrogels

Stem-cell-based neural regeneration has received significant attention, as it has potential to restore functionality to diseased or damaged neural tissues that have a limited ability to self-repair or regenerate. Culturing neural stem cells (NSCs) on hydrogel substrates has been shown to facilitate differentiation to neural progenitors, but this has only been achieved on very soft hydrogels, greatly increasing the difficulty of manufacture and limiting their wide applications. Here, we realized the differentiation of NSCs to neural and glial progenitors on high-strength hydrogels. Hydrogen-bonding-strengthened conductive hydrogels (PVV-PANI) were synthesized through one-pot copolymerization of 2-vinyl-4,6-diamino-1,3,5-triazine, 1-vinylimidazole and polyethylene glycol diacrylate, followed by post-coating with polyaniline (PANI). Diaminotriazine-diaminotriazine hydrogen bonding dramatically increases their mechanical strength, while copolymerization with VI pronouncedly promotes the adsorption of PANI particles, endowing the hydrogels with electrical conductivity. These hydrogels exhibit tensile strengths up to 1.16 MPa, a 559% breaking strain, a 9.9 MPa compressive strength and up to 16.7 mS/cm conductivity. Importantly, PVV-PANI hydrogels support the attachment, proliferation, and differentiation of NSCs, and allow the efficient induction of neural and glial differentiation via electrical stimulation. This work demonstrates high-strength conductive hydrogels can serve as an electroactive soft-wet platform for modulating the specific differentiation of NSCs, a significant step towards cell-based therapies for neurological diseases.