Selective Neural Differentiation Enhanced by Localized Ultrasound Stimulation

Localized ultrasonic stimulation using a piezoelectric micromachined ultrasound transducer array for selective neural differentiation of magnetic cell-based robots has emerged as a promising technique in stem cell engineering. The integration of precise magnetic control systems with selective neural differentiation presents a novel approach for establishing functional neural networks. Challenges in creating targeted functional neuronal networks have been attributed to difficulties in controlling the positions of stem cells and stimulating their differentiation simultaneously. These challenges often lead to suboptimal differentiation rates and abnormalities in transplanted neural stem cells.

Ultrasound stimulation has shown superior tissue penetration and focusing capability, offering a noninvasive method for modulating neural activity and promoting selective differentiation into neuronal stem cells. In a recent study, a method for targeted neural differentiation using localized ultrasonic stimulation with a piezoelectric micromachined ultrasound transducer (pMUT) array was introduced. The differentiation was quantitatively assessed by monitoring neurite outgrowth as the ultrasound intensity was increased. Results indicated that cells stimulated for 40 minutes displayed increased neurite length compared to the non-stimulated group.

The study further confirmed targeted differentiation by measuring neurite lengths, demonstrating that selective ultrasound stimulation induced differentiation in cells that were precisely delivered via an electromagnetic system. Magnetic cell-based robots reaching the area of localized ultrasound stimulation exhibited enhanced differentiation, showcasing the potential of combining precise stem cell delivery with selective neural differentiation to establish functional neural networks.

Neurodegenerative diseases such as Parkinson’s and Alzheimer’s pose challenges due to irreversible damage to neurons, limiting the brain’s regenerative capability. Stem cell therapy has emerged as a potential solution for regenerating and recovering the nervous system. Conventional surgical transplantation of stem cells carries risks, and current delivery methods face challenges in achieving high delivery efficiency and selective targeting. The use of magnetically actuated delivery systems offers a promising approach to precisely position cells at specific sites, enabling the delivery of stem cells to the central nervous system successfully.

Various strategies for promoting neuronal cell differentiation through neural cell stimulation using electrical, mechanical, and acoustic energy sources have been explored. Electrical stimulation, while effective, often requires surgical implantation of electrodes into the brain. In contrast, noninvasive interventions using electrical fields induced by magnetoelectricity or piezoelectricity offer low spatial resolution and may transfer energy to off-targeted sites.

Mechanical stimulation approaches involving the activation of mechanosensitive pathways through contact and vibrational forces have shown promise in inducing differentiation. Physical stimulation using repeated vibrational motion induced by a magnetic field has been efficient in enhancing neuronal differentiation in the brain’s deep tissue. However, challenges remain in localizing stimuli to the target area using these methods.

Ultrasound emerges as a suitable energy source for targeted brain stimulation due to its ability to penetrate deeply into tissues with good spatial resolution. The safety and established applications of ultrasound stimulation in diagnostic imaging and deep brain stimulation highlight its potential for precise and safe modulation of neuronal activity. Commercial ultrasound transducers, while effective, often face constraints in size and lack flexibility in adjusting the physical distance from the target area to target neuronal cells.

To address these challenges, the study introduced a method for targeted cell delivery and selective differentiation by combining an electromagnetic actuation system with selective ultrasound simulation using a miniaturized pMUT array. The pMUT array enabled localized stimulation and reduced size constraints for stimulation through a small, flexible array design. The study validated the effects of ultrasound on cell differentiation by assessing neurite outgrowth, indicating the potential of combining magnetic stem cell delivery with selective ultrasound stimulation using a pMUT array to establish functional neural networks.