Researchers at the Korean Institute of Advanced Science and Technology (KAIST) have developed a complex 3D brain simulation platform that can maintain neural activity for 27 days, almost twice as many as previous systems. The platform is six times more accurate than traditional methods, while successfully replicating the brain’s complex hierarchical structure.
The research team, led by Professor Je-Kyun Park and Yoonkey Nam of Kaist’s Department of Biological and Brain Engineering, combines three key technologies to overcome the fundamental challenges of neuroscience: creating brain shaped structures that are both structurally stable and biologically functional.
Solve structural and functional problems
Traditional 3D brain models face key trade-offs. High viscosity materials provide structural stability but limit nerve growth, while low viscosity gels that support neuronal development are difficult to accurately classify. The KAIST team solved this problem by using the “capillary fixation effect” technology.
By printing the dilute hydrogel onto a stainless steel web, the researchers reached the structure with a resolution of 500 microns or less, which is more accurate than the traditional method. The mesh acts like a molecular scaffold, which fixes low viscosity gels in place while allowing the natural growth of neurons.
The second innovation of the platform is a cylindrical 3D printing aligner that ensures that the printed layers are stacked without misunderstanding. This ensures accurate assembly of the multilayer structure and stable integration with the microelectrode chip that monitors neural activity.
Dual-mode analysis reveals neural dialogue
Perhaps most striking is that the system can simultaneously measure electrical signals from below and observe cellular activity through the light above. This dual-mode analysis allows researchers to verify that neurons in different layers are actually communicating, not just adjacent to each other.
In the experiment, the team created a three-layer minibrain at the upper and lower levels, with cortical neurons, and an empty intermediate layer for the air layers that allow neural connections. When they apply electrical stimulation, neurons in both layers react simultaneously. When they use drugs to stop synaptic transmission, the response is reduced, demonstrating true neural communication.
“This study is a common development achievement of a comprehensive platform that can simultaneously reproduce complex multi-layer structures and functions of brain tissue,” explains Professor Je-Kyun Park. “The platform maintains a stable microelectrode chip interface for more than 27 days compared to existing technology for signal measurements over 14 days.”
Key technical achievements
The platform shows several notable features:
- Maintain 80% cell viability during the three-week culture period
- Achieving a signal propagation speed of 78-111 mm/s, consistent with brain tissue
- Real-time analysis of structural and functional relationships
- Supports complex multi-layered brain architectures
The fibrin hydrogel used by the research team has elastic properties similar to brain tissue to create its structure. Neurons show typical developmental patterns and gradually grow throughout the culture period, forming a dense network before day 23.
Future applications
The platform opens new possibilities for neurological disease modeling, brain function research, neurotoxicity assessment and drug screening. The ability to maintain a stable neural network for a long time while monitoring its activity can accelerate the treatment of diseases such as Alzheimer’s disease, epilepsy, and brain damage.
The study also addresses the key need of neuroscience: understanding the relationship between the brain’s structural organization and its function. By creating controllable 3D models that mimic the modular tissue of the brain, researchers can study how neural circuits process information and how it causes disease.
The study, published in biosensors and bioelectronics, is an important step in creating more innately relevant brain models for research and drug development. The platform’s combination of accuracy, stability and analytical capabilities can help bridge the gap between simple cell cultures and complex living brain tissue.
The study was conducted by Dr. Soo Jee Kim and Dr. Dongjo Yoon as co-authors, and the results were published online on June 11, 2025.
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