3D-Printed Cerebral Cortex Tissues to Enable Personalized Implantation for Repairing Brain Injuries

Brain injuries often lead to severe damage to the cerebral cortex, the brain's outer layer, which impairs cognition, movement, and communication. For instance, around 70 million people worldwide are affected by traumatic brain injury (TBI) each year, with 5 million of those cases being severe or life-threatening. Up until now, there have been no reliable treatments for such severe brain injuries which have a profound impact on quality of life. One possible future treatment could be tissue regenerative therapies using stem cell implants, but ensuring these cells mimic the brain's architecture remains a hurdle. Researchers have now made a breakthrough by successfully 3D printing neural cells that replicate the cerebral cortex's structure - a breakthrough that could soon enable tailored repairs for individuals with brain injuries.

Scientists at the University of Oxford (Oxford, UK) have created a two-layered brain tissue by 3D printing human neural stem cells. These printed cells showed promising integration when implanted into slices of mouse brain, both structurally and functionally. The artificial cortical structure was derived from human induced pluripotent stem cells (hiPSCs), which have the capability to produce the cell types found in the majority of human tissues. A major advantage of using hiPSCs is that they can be derived from cells harvested from the patients themselves, minimizing the risk of immune response. Researchers used specific combinations of growth factors and chemicals to differentiate these hiPSCs into neural progenitor cells for the two different layers of the cerebral cortex. The cells were then put into a solution to create two separate 'bioinks,' which were used to 3D print the layered structure. The printed tissues managed to maintain their layered cellular architecture for several weeks, as confirmed by the expression of layer-specific biomarkers.

Image: The 3D-printed 2-layer cerebral cortical tissue was implanted into a mouse brain slice (Photo courtesy of University of Oxford)

The 3D printed tissues, when implanted into slices of mouse brain, showed a high degree of integration. There was a significant projection of neural processes and movement of neurons across the boundary between the implant and host tissue. The implanted cells also demonstrated signaling activities that aligned with the host cells, indicating functional as well as structural integration between human and mouse cells. The scientists plan to further fine-tune this droplet printing technique to produce even more complex multi-layered structures that closely resemble the human brain's architecture. Beyond their potential for treating brain injuries, these engineered tissues could be valuable for drug testing, understanding brain development, and shedding light on the foundations of cognitive processes.

“Our droplet printing technique provides a means to engineer living 3D tissues with desired architectures, which brings us closer to the creation of personalized implantation treatments for brain injury,” said senior author Dr. Linna Zhou from the Department of Chemistry, University of Oxford.

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