Magnetic graphene oxide functionalized composite nanofibrous stem cell-based neural scaffolds

Conductive nerve scaffolds have emerged as a promising alternative to autologous grafts for promoting nerve regeneration. However, optimizing the electroactive properties of scaffold materials and elucidating their regulatory mechanisms on neural stem cell (NSC) differentiation remain critical challenges. Magnetic graphene oxide (MGO), an innovative nanomaterial integrating magnetic responsiveness with two-dimensional carbon-based conductivity, exhibits potential for modulating neural regeneration. Nevertheless, its application in guiding NSC fate within nanofibrous scaffolds is still limited. In this study, a multifunctional MGO-gelatin-polycaprolactone (PCL) composite nanofibrous scaffold-termed the MGO Functionalized Nanofibrous Neural Scaffold-was developed via electrospinning technology, functionalized with superparamagnetic Fe₃O₄ nanoparticles and graphene oxide nanosheets. This design enhanced the scaffold's mechanical properties, electroactivity, biocompatibility, and structural stability. In vitro experiments demonstrated that the MGO Nanofibrous Scaffold not only supported NSC adhesion and proliferation but also significantly promoted differentiation toward excitatory neuronal phenotypes, suppressed excessive astrocyte activation, and maintained synaptic plasticity and functional maturity. RNA-Seq analysis revealed that the scaffold was associated with the enrichment of key neurogenesis-related pathways, including neurotrophic factor and Wnt-related pathways, which correlated with directed neuronal differentiation and functional maturation of NSCs. Further validation using dorsal root ganglion (DRG) models confirmed its efficacy in accelerating axonal regeneration. Collectively, the MGO Nanofibrous Neural Scaffold constructs an optimized electrophysiological microenvironment conducive to neuronal commitment and nerve fiber regeneration. These findings underscore its significant potential in regulating NSC differentiation and neuronal growth, highlighting the value of multifunctional graphene-based composites in neural tissue engineering.