3D-printed microstructured alginate scaffolds for neural tissue engineering.

Alginate (Alg) is a versatile biopolymer for scaffold engineering and a bioink component widely used for direct cell printing. However, due to a lack of intrinsic cell-binding sites, Alg must be functionalized for cellular adhesion when used as a scaffold. Moreover, direct cell-laden ink 3D printing requires tedious disinfection procedures and cell viability is compromised by shear stress. Here, we demonstrate proof-of-concept, bioactive additive-free, microstructured Alg (M-Alg) scaffolds for neuron culture. The M-Alg scaffold was formed by introducing tetrapod-shaped ZnO (t-ZnO) microparticles into the ink as structural templates for interconnected channels and textured surfaces in the 3D-printed Alg scaffold, which were subsequently removed. Neurons exhibited significantly improved adhesion and growth on these M-Alg scaffolds compared with pristine Alg (P-Alg) scaffolds, with extensive neurite outgrowth and spontaneous neural activity, indicating the maturation of neuronal networks. These transparent, porous, additive-free Alg-based scaffolds with neuron affinity are promising for neuroregenerative and organoid-related research.