Synergistic effects of aligned PCL/rGO scaffolds and electrical stimulation on BMSC neuronal differentiation

Abstract

Directed differentiation of bone marrow mesenchymal stem cells (BMSCs) provides a promising route for neural trauma repair, yet faces challenges in establishing an optimal microenvironment for efficient neuronal maturation. In this work, a synergistic bio-electroactive platform was established to specifically induce neuronal differentiation from BMSCs by coupling spatially oriented, conductive polycaprolactone/reduced graphene oxide (PCL/rGO) nanofibrous scaffolds with exogenous electrical stimulation (ES). Through the integration of topological guidance and rGO-enhanced conductivity, significant cytoskeletal remodeling and cell proliferation were realized. Notably, the synergistic stimulation robustly drove the lineage commitment toward mature neurons, evidenced by the distinct neuron-like morphology (spherical-elliptical somas and elongated processes) and the marked upregulation of neural-specific markers (Tuj1 and MAP2) at both transcriptional and translational levels. The PCL/rGO + ES group achieved the highest differentiation efficiency, outperforming PCL/rGO group with an approximate 2.29-fold increase in MAP2 expression, confirming the superior synergy of the dual-signal stimulation. This bio-electroactive strategy effectively creates a conducive microenvironment for mature neuronal differentiation and offers a facile, promising perspective for the treatment of neural trauma.