Neurodegenerative diseases like Parkinson's and Alzheimer's are characterized by irreversible neuron damage and limited natural repair mechanisms. While stem cell therapy holds great promise for regenerating neural tissue, it has long been hindered by inefficiencies in cell delivery and low differentiation rates. Current methods, including surgical implantation or magnetic actuation, often fail to ensure precise cell placement and controlled differentiation. Ultrasound stimulation, known for its deep tissue penetration and safety, has emerged as a potential solution, but conventional transducers lack the necessary precision. Magnetic cell-based microrobots (Cellbots) offer targeted delivery, but integrating them with differentiation techniques has remained largely unexplored. The pressing need to develop integrated systems for precise cell delivery and localized differentiation has thus become a focal point in advancing neural regeneration therapies.
Published (DOI: 10.1038/s41378-025-00900-y) on March 20, 2025, in Microsystems & Nanoengineering, a study led by researchers at Daegu Gyeongbuk Institute of Science and Technology (DGIST) introduces a groundbreaking approach to neural stem cell therapy. The team combined magnetic Cellbots with a piezoelectric micromachined ultrasound transducer (pMUT) array to achieve targeted cell delivery and localized differentiation. By applying ultrasound stimulation to magnetically guided cells, they observed a remarkable 90% increase in neurite length, a key indicator of neuronal maturation. This hybrid technology has the potential to transform treatments for neurodegenerative diseases by enhancing the precision and efficacy of stem cell-based therapies.
The study's core innovation lies in the seamless integration of two cutting-edge technologies: magnetic Cellbots for precise stem cell delivery and a pMUT array for localized ultrasound stimulation. The Cellbots, loaded with superparamagnetic iron oxide nanoparticles (SPIONs), were guided to target regions using an electromagnetic system. Once positioned, the pMUT array delivered focused ultrasound pulses, significantly enhancing neurite outgrowth—119.9 µm in stimulated cells versus 63.2 µm in controls. The pMUT's miniaturized design, with 60 µm elements, enabled high spatial resolution, ensuring that stimulation was confined to desired areas without off-target effects.
Key highlights of the study include the pMUT's impressive acoustic performance, generating pressures up to 566 kPa, and its biocompatibility, validated through rigorous cell viability tests. The sequential activation of pMUT channels minimized overlap, optimizing stimulation efficiency. Moreover, the Cellbots exhibited excellent magnetic responsiveness, achieving speeds of 36.9 µm/s under a 20 mT rotating magnetic field, with no adverse effects on cell health. This dual-system approach overcomes longstanding hurdles in stem cell therapy, such as poor differentiation and uncontrolled cell placement, paving the way for reconstructing functional neural networks in damaged brains.
Dr. Hongsoo Choi, the study's corresponding author, emphasized the transformative potential of this work: "Our technology merges the precision of magnetic actuation with the non-invasive power of ultrasound to create a scalable platform for neural regeneration. By achieving localized differentiation, we can now envision therapies where stem cells not only reach their target but also mature into functional neurons on demand." The team plans to explore clinical applications, including adapting the system for minimally invasive procedures in human patients.
This research opens new avenues for treating neurodegenerative diseases and neural injuries. The ability to precisely deliver and differentiate stem cells could significantly improve outcomes in Parkinson's, Alzheimer's, and stroke recovery, where neural connectivity is critical. Beyond therapy, the technology may also aid drug testing by creating accurate neural models in labs. Future work could refine ultrasound parameters for optimal differentiation and scale the system for human use. Challenges remain, including ensuring long-term cell survival and integration in vivo. However, if successful, this approach could reduce reliance on invasive surgeries and offer safer, more effective regenerative treatments, marking a significant leap forward in bioengineering and personalized medicine.
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References
DOI
10.1038/s41378-025-00900-y
Original Source URL
https://doi.org/10.1038/s41378-025-00900-y
Funding information
This work was financially supported by the National Convergence Research of Scientific Challenges through the National Research Foundation of Korea (NRF) (no. 2021M3F7A1082275) funded by the Ministry of Science and ICT.
About Microsystems & Nanoengineering
Microsystems & Nanoengineering is an online-only, open access international journal devoted to publishing original research results and reviews on all aspects of Micro and Nano Electro Mechanical Systems from fundamental to applied research. The journal is published by Springer Nature in partnership with the Aerospace Information Research Institute, Chinese Academy of Sciences, supported by the State Key Laboratory of Transducer Technology.