Innovative MXene/SilMA-Based Conductive Bioink for Three Dimensional Bioprinting of Neural Stem Cell Spheroids in Neural Tissue Engineering

Conductive bioinks, integrated with 3D bioprinting and electrical stimulation, are essential for advancing neural tissue engineering. This study developed a SilMA/Pectin/MXene-soybean phospholipids (SP) bioink, where SilMA (silk fibroin modified with glycidyl methacrylate) provides a structural base, pectin enhances printability and shear-thinning properties, and MXene-SP improves conductivity through superior dispersibility. Increasing pectin and MXene-SP concentrations reduced the hydrogel's Young's modulus, promoting neural stem cell (NSC) differentiation into neurons. Electrochemical analyses revealed that higher MXene-SP levels decreased impedance and increased redox current, while conductivity measurements showed improved performance compared to unmodified MXene. NSCs encapsulated in the bioink achieved maximum proliferation under electrical stimulation at 300 μA for 10 min daily over 5 days. Neuronal differentiation positively correlated with MXene-SP concentration and stimulation intensity. Synaptic activity and vesicle recycling, assessed using FM1-43 dye, were significantly enhanced under electrical stimulation. This study successfully developed a biocompatible conductive bioink capable of inducing neuronal differentiation. Electrical stimulation further promoted cell proliferation, neuronal differentiation, and enhanced synaptic function. This bioink shows great potential for future applications in neural tissue engineering.