Ti₃C₂T_<i>x</i> Nanosheet/UIO-66 MOF Nanoparticle Composites as Piezoelectric Scaffolds for Promoting Nerve Regeneration

Following peripheral nerve injury, a large number of macrophages will be recruited to the nerve defect site to regulate the immune microenvironment and then initiate a series of inflammatory reactions, which is not conducive to nerve repair. Electrical stimulation can not only affect the polarity of macrophages by regulating the immune microenvironment but also promote nerve regeneration by modulating voltage-gated ion channels. However, traditional electrical stimulation relies on power sources, wires, and implanted electrodes, which may pose risks of infection and secondary surgery. Here piezoelectric materials Ti3C2Tx/UiO-66 are synthesized by a hydrothermal method and then blended into PLLA to prepare a self-power nerve scaffold using laser additive manufacturing technology. Under ultrasound stimulation, UiO-66 nanoparticles can generate localized piezoelectric potential, while Ti3C2Tx nanosheets accelerate the charge transfer. The results indicate that a nerve scaffold promotes the current generation, with a current of up to 0.036 μA. The results indicate that electrical stimulation can promote the transformation of macrophages into the M2 antiinflammatory phenotype by inhibiting the Ca2+-CaMKII-NF-κB signaling pathway. Furthermore, the scaffold can upregulate the expression of bone marrow mesenchymal stem cell neural markers Tuj and Map under ultrasound treatment. This work provides insights into wireless electrical stimulation regulating the immune microenvironment to promote nerve repair.