[LAB Exploration] KAIST Develops Human Brain-Mimicking Platform Using Hydrogel

A new integrated platform has been developed that can use 3D printing to recreate the layered structure of neural cells found in the brain and precisely measure cellular activity.

Professor Jekyun Park (left) of the Department of Bio and Brain Engineering at KAIST and Dongjo Yoon, PhD of the Department of Bio and Brain Engineering. Korea Advanced Institute of Science and Technology (KAIST)

On July 25, the Korea Advanced Institute of Science and Technology (KAIST) announced that a joint research team led by Professors Jekyun Park and Yoonki Nam from the Department of Bio and Brain Engineering has developed a neural cell network platform that can analyze both the structural and functional connectivity of the brain by using a natural hydrogel similar to brain tissue.

Conventional bioprinting technology uses high-viscosity bioink to ensure structural stability, but this limits the proliferation of neural cells and the growth of neurites. Hydrogels, on the other hand, make it difficult to form precise patterns, resulting in a fundamental trade-off between structural stability and biological function.

To address this, the research team utilized a "capillary pinning effect" technology, which keeps the dilute hydrogel from flowing by adhering it tightly to a stainless steel micro-mesh. With this method, they succeeded in replicating brain structures with a resolution six times more precise than before. They also used a "3D printing aligner," a cylindrical design that ensures the printed layers are stacked accurately without misalignment, to assemble multi-layered structures with high precision. Furthermore, they applied a "dual-mode analysis system" technology, which allows for simultaneous observation of cellular activity by measuring electrical signals from the lower layer and performing calcium imaging on the upper layer.

The research team used fibrin hydrogel, which has elasticity similar to that of the brain, to 3D print a mini-brain structure composed of three layers and experimentally demonstrated that actual neural cells exchange signals within it. They placed cerebral neurons in the upper and lower layers, leaving the middle layer empty but designed so that neurons could connect by extending through the middle. The lower layer was equipped with an electrode chip to measure electrical signals, while the upper layer was observed for cellular activity via calcium imaging. When electrical stimulation was applied, neurons in both the upper and lower layers responded simultaneously. In addition, when a drug that blocks neural connections was introduced, the response decreased, demonstrating that the neurons were indeed connected and exchanging signals.

This research is expected to be applicable in various brain research fields, including neurological disease modeling, brain function analysis, and neurotoxicity assessment. Professor Jekyun Park stated, "Whereas previous technologies could not measure signals for more than 14 days, our system maintains a stable microelectrode chip interface for over 27 days, enabling real-time analysis of structure-function relationships. In the future, it can be utilized in a wide range of brain research areas, such as neurological disease modeling, brain function studies, neurotoxicity assessment, and neuroprotective drug screening."

The results of this study were published online in the June 11 issue of the international journal Biosensors and Bioelectronics.

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