GSNO-Loaded Mesoporous Silica/Ti3C2Tx Nanosheet Composites as Magnetic Field-Responsive Scaffolds for Nerve Differentiation via Synergistic Electrostimulation and Nitric Oxide Release

Nitric oxide (NO) is a small, gaseous, and highly diffusible signaling molecule that plays a pivotal role in numerous physiological and pathological processes. Its therapeutic application, however, presents two major challenges: the cytotoxicity arising from high concentrations of NO that generate reactive nitrogen species and the difficulty in controlling its release due to an extremely short half-life (seconds to minutes). Herein, a GSNO-loaded mesoporous silica/Ti3C2Tx nanosheet composite was constructed by combining mesoporous SiO2 loaded with the NO donor GSNO and Ti3C2Tx nanosheet. Then, silica/Ti3C2Tx nanosheet composites were introduced into poly-l-lactide to fabricate a magnetic field-responsive electrostimulation/NO codelivery scaffold. This system achieves spatiotemporally coupled wireless electrical stimulation and NO delivery, significantly enhancing the regenerative capacity of damaged nerves. The results demonstrated that the scaffold exhibited synergistic wireless electrostimulation/NO codelivery. Under a rotating magnetic field, the current intensity was positively correlated to the magnetic field speed. Meanwhile, the stent achieves precise spatiotemporal control of the NO release. The mechanism of NO release is induced by the pulse effect of the rotating magnetic field, which acts on the S-NO chemical bond of GSNO. This process significantly promotes the neural differentiation and proliferation of mesenchymal stem cells. Through PCR and immunofluorescence analysis, the expression of MAP2 and Tuj was upregulated, while Nestin expression was downregulated. Summarily, the scaffold with electrical stimulation and NO release can further enhance nerve differentiation.