Bioprinting 3D functional neural tissue using human neural and induced pluripotent stem cells

摘要

Printing stem cells with biomaterials is a promising strategy to engineer tissue for in vitro modelling and regenerative medicine. Here we report a simple and reproducible approach to constructing neural tissue by printing human neural or induced pluripotent stem cells that are differentiated in situ to functional neurons and supporting neuroglia. The supporting biomaterial incorporates a novel clinically relevant gel-based bioink comprising alginate, carboxymethyl-chitosan and agarose. The printed bioink rapidly gels by stable crosslinking to form a porous 3D scaffold encapsulating stem cells for subsequent expansion and differentiation. Differentiated neurons are spontaneously active, show a bicuculline-induced increased calcium response, and are predominantly gamma-aminobutyric acid expressing. The 3D tissues will enable interrogation of neural development, function and disease, and may be adaptable for generating other neuronal and non-neuronal tissue subtypes in vitro.