3D-Printing Brain Model Unlocks Neuron Growth Secrets

Scientists at Delft University of Technology (TU Delft) have developed a groundbreaking 3D-printing brain-like model that allows neurons to grow and connect similarly to those in a real brain. By using tiny nanopillars, this model mimics brain tissue and the extracellular matrix, providing new insights into how neurons form networks—a discovery that could advance research on Alzheimer’s, Parkinson’s, and autism spectrum disorders.

How 3D Printing Mimics Brain Tissue

Traditional laboratory models use flat petri dishes, which do not accurately replicate the soft, three-dimensional structure of brain tissue. Neurons interact with their environment based on its stiffness and geometry, so creating a realistic brain-like setting is essential for understanding their behavior.

To overcome this challenge, Associate Professor Angelo Accardo’s team designed nanopillar arrays using two-photon polymerization, an advanced 3D laser-assisted printing technique. These nanopillars—thousands of times thinner than a human hair—form a microscopic “forest” that mimics the extracellular matrix. Although the nanopillars are made of stiff material, their ability to bend under neuron movement tricks the cells into behaving as if they were in a soft brain environment. This enables neurons to anchor themselves and grow in structured patterns, much like in a real brain.

From Random Growth to Ordered Neuronal Networks

The team tested their model by growing three types of neurons, derived from mouse brain tissue and human stem cells. On traditional flat surfaces, neurons grew in random directions, forming disorganized patterns. However, on the 3D-printed nanopillar arrays, neurons aligned in ordered networks, growing at specific angles.

The study, published in Advanced Functional Materials, also revealed new insights into neuronal growth cones—the hand-like structures that guide neurons as they form connections. On flat surfaces, these cones remained spread out and flat. But on the nanopillar arrays, they developed long, finger-like projections, actively exploring their surroundings in three dimensions, just as they would in a real brain.

A New Tool for Brain Disorder Research

An exciting discovery was that neurons growing on nanopillars matured more effectively than those on flat surfaces. Neural progenitor cells in the model showed higher levels of mature neuron markers, indicating that this environment supports both growth and maturation.

This breakthrough could provide crucial insights into neurological disorders such as Alzheimer’s, Parkinson’s, and autism spectrum disorders. Since many brain diseases involve abnormal neuronal connections, studying how neurons grow in this model may help researchers understand how these conditions develop.

Why Not Use Soft Gels Instead?

Soft materials like collagen or Matrigel have been used to culture neurons, but they suffer from batch-to-batch variability and lack precisely controlled geometric features. The nanopillar model offers a reproducible alternative, combining a soft-like response with engineered nanoscale structures that closely resemble the real brain environment.

“Our model provides the best of both worlds,” explains Accardo. “It behaves like a soft environment but with precisely designed nanoscale features that support neuron growth in a reproducible way.”

Shaping the Future of Neuroscience

This high-precision, 3D-printed brain model is a major step forward in neurobiology and regenerative medicine. By allowing neurons to grow and connect just like in a living brain, this innovation opens doors to new treatments, better drug testing models, and deeper insights into brain development.

As research advances, this technique could revolutionize how we study brain disorders, potentially leading to earlier diagnoses and more effective therapies for millions of people worldwide.

More Information: Flamourakis, G., et al. (2024). Deciphering the Influence of Effective Shear Modulus on Neuronal Network Directionality and Growth Cones’ Morphology via Laser‐Assisted 3D‐Printed Nanostructured Arrays. Advanced Functional Materials. doi.org/10.1002/adfm.202409451.