Scientists have 3D-printed the world's first human brain replica that grows and behaves like natural brain tissue in what's seen as a potential game changer in diagnosing neurological disorders like Down Syndrome and even making neurosurgery safer.
Su-Chun Zhang, the lead researcher and a professor of neuroscience and neurology at the Waisman Centre at the University of Wisconsin Madison-Madison told Tech Times in an interview that the simulation model is "hugely powerful" and can help "understand how different brain tissues communicate and impact each other."
How Researchers Printed The First Human Brain
The UW-Madison researchers were off to a rocky start and initially relied on conventional 3D models that rely on vertical stacking to print simulation cells. The neurons and glia couldn't establish the crucial network connections needed for function.
This time, the team placed pluripotent stem cells horizontally in thin layers of a "bio-ink" gel, a combination of fibrin and hyaluronic gel, to bioprint the cerebral cortex and striatum, leading to greater control and precision over the formation and replication of cells. To maintain the integrity of individual printed bands, thrombin, a crosslinking agent, was applied without delay following deposition.
The technique also made it possible for scientists to maintain cell separation and thinness, both crucial to transporting oxygen and nutrients inside the brain. With time, these cells fuse to grow into tissues, replicate themselves, and build a network of neurotransmitters. The presence of a soft liquid gel medium ensures the tissues form, bond with each other, and establish communication without any external support.
While the technique was different, scientists leveraged a readily available benchtop bioprinter so their work was reproducible for other research groups. They are now looking to design cells with predefined orientations to improve the reliability of their model.
"Our lab stands out for its ability to generate a vast array of neurons on demand at any time. We can then assemble them freely, tailoring their arrangement to our requirements," says Zhang.
The mini-brain is also different from self-assembling cerebral miniature organoids. As Zhang explains, Unlike organoids, we have control over which cells will end up exactly where in the final simulation. Also, organoids usually take months to form neural connections; our printed tissues make it happen in five weeks.
"Printing by design allowed us to understand how nerve cells communicate with each other, so now we have the flexibility to construct personalized interactions between different cells."
While the achievement is rare, the model still has some weak spots. Soft ink gels have low reproducibility and can only print one layer at a time. These individual layers also restrict the tissue size and have to be fed nutrients layer by layer, or else they might collapse.
"A model is a model, not the real brain, and working to address these pitfalls," says Zhang.
Many Potential Applications
Each year, 22.6 million require surgery to address damage to their peripheral nervous system, often from traumatic events like motor vehicle accidents, violence, or workplace injuries. While existing surgical techniques can realign nerve ends and promote regrowth, regaining full function after nerve injury remains uncertain and incomplete. Studies on rats suggest that nerve gaps exceeding two centimeters can cause permanent muscle weakness or loss of sensation.
When the world is perennially dealing with organ shortages, and a rise in neurological disorders, a printed brain like the University of Wisconsin-Madison can be a lifesaver.
Moreover, a real-time brain replica can also help neurosurgeons by helping them practice on accurate models, and even personalize neurotherapy.
Senthilkumar Duraivel, a researcher at the University of Florida, highlighted the shortcomings of current pre-surgical training for neurosurgeons. He pointed out that existing methods heavily depend on static models, which often lack accuracy in representing crucial blood vessels, realistic tactile feedback, and important anatomical details. This limitation hampers the team's readiness for actual surgical procedures. Duraivel suggested that utilizing 3D-printed brain replicas could provide a more realistic and customizable alternative, enabling surgical teams to minimize errors during operations.
Even in drug discovery and targeting, a bioprinted brain appears to be the next frontier. Individualized brain models could be created to guide treatment plans and predict responses to therapies for neurological disorders like Parkinson's and Alzheimer's disease.
The discovery will also reduce the burden on animal testing as a 3D-printed brain, especially when derived from individual patients' cells, could offer more accurate and relevant models for drug testing compared to animals. Australia's Monash University is already designing brain cells for drug discovery and is looking to get FDA approval for the testing procedure in the coming years.
However, scientists still face challenges like inconsistent regulations and lack of standardization, limited accessibility, high-cost burden, and limited cell viability, discouraging the long-term survival and functionality of printed neurons. Despite these challenges, ongoing research and development hold promise for overcoming technical and regulatory hurdles and realizing the full potential of 3D-printed brain tissues.
Avya Chaudhary is a technology writer whose work has appeared in TechRepublic Premium, PageFly, TechnologyAdvice, and Hatica. Find her on LinkedIn at https://www.linkedin.com/in/avya-chaudhary.
