Control the Neural Stem Cell Fate with Biohybrid Piezoelectrical Magnetite Micromotors

Inducing neural stem cells to differentiate and replace degenerated functional neurons represents the most promising approach for neural degenerative diseases including Parkinson’s disease, Alzheimer’s disease, etc. While diverse strategies have been proposed in recent years, most of these are hindered due to uncontrollable cell fate and device invasiveness. Here, we report a minimally invasive micromotor platform with biodegradable helical Spirulina plantensis (S. platensis) as the framework and superparamagnetic Fe3O4 nanoparticles/piezoelectric BaTiO3 nanoparticles as the built-in function units. With a low-strength rotational magnetic field, this integrated micromotor system can perform precise navigation in biofluid and achieve single-neural stem cell targeting. Remarkably, by tuning ultrasound intensity, thus the local electrical output by the motor, directed differentiation of the neural stem cell into astrocytes, functional neurons (dopamine neurons, cholinergic neurons), and oligodendrocytes, can be achieved. This micromotor platform can serve as a highly controllable wireless tool for bioelectronics and neuronal regenerative therapy.

诱导神经干细胞分化并替代退行性功能神经元，是治疗帕金森病（Parkinson’s disease）、阿尔茨海默病（Alzheimer’s disease）等神经退行性疾病的极具前景的策略。尽管近年来已提出多种相关策略，但绝大多数均因细胞命运不可控以及装置侵入性较强的问题而难以推进。本研究报道了一种微创微马达平台，以可生物降解的螺旋形钝顶螺旋藻（Spirulina plantensis，简称S. platensis）作为骨架，以超顺磁性Fe₃O₄纳米颗粒与压电BaTiO₃纳米颗粒作为内置功能单元。借助低强度旋转磁场，该集成微马达系统可在生物流体中实现精准导航，并完成单个神经干细胞的靶向定位。值得注意的是，通过调节超声强度进而调控微马达的局部电输出，可实现神经干细胞向星形胶质细胞、功能性神经元（多巴胺能神经元、胆碱能神经元）以及少突胶质细胞的定向分化。该微马达平台可作为一种高度可控的无线工具，应用于生物电子学领域以及神经元再生治疗。