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Scientists at Delft University of Technology in the Netherlands have developed a 3D-printed brain model that allows neurons to grow and form networks, similar to how they do in the real brain. The development uses tiny nanopillars to mimic the soft nerve tissue and fibers of the brain's extracellular matrix.
Traditional Petri dishes used to grow cells are flat and rigid, a poor match for the soft, fibrous environment of the brain. The team created arrays of nanopillars using two-photon polymerization, a nano-precision 3D printing technique. These pillars, each a thousand times thinner than a human hair, are arranged like tiny forests on the surface.
By varying the width and height of the columns, the researchers tuned their effective shear modulus, a mechanical property that cells experience when moving across the surface of micro- or nanostructures. "This tricks the neurons into thinking they are in a soft, brain-like environment, even though the nanocolumn material itself is stiff," explains study leader Associate Professor Angelo Accardo.
To test the model, the scientists grew three different types of neuronal cells on the nanopillars. Unlike traditional flat Petri dishes, where neurons grew in random directions, on the 3D-printed nanopillar arrays, all three cell types grew in a more organized way, forming networks at specific angles. The study also revealed new information about neuronal growth cones—structures that guide growing neurons as they seek out new connections. On the nanopillars, the growth cones sent long processes out in all directions, more closely resembling the processes in the real brain.
George Flamourakis, first author of the study, notes that the created environment promoted the maturation of neurons. Neural progenitor cells grown on columns showed higher levels of a marker of mature neurons compared to cells on flat surfaces. The developed model may offer new opportunities to study the differences between healthy neural networks and those associated with neurological disorders such as Alzheimer's, Parkinson's and autism spectrum disorders.
