Neurons kind networks by exchanging indicators, enabling studying and adaptation. Researchers at Delft College of Expertise (TU Delft) have developed a 3D-printed neuronal tradition platform that carefully replicates mind tissue structure. The examine was revealed in Superior Useful Supplies and featured on its cowl.
The researchers fabricated nanoscale pillar arrays to simulate the mechanical properties of neural tissue and the extracellular matrix. This mannequin offers insights into neuronal community formation and will function a instrument for finding out alterations related to neurological issues comparable to Alzheimer’s, Parkinson’s, and autism spectrum issues.
Neurons, like different cells, reply to the stiffness and construction of their surroundings. Conventional Petri dishes, being flat and inflexible, don’t replicate the mushy, fibrous extracellular matrix of mind tissue. To handle this, Affiliate Professor Angelo Accardo’s staff designed nanopillar arrays utilizing two-photon polymerization, a 3D laser-assisted printing approach with nanoscale precision.
The nanopillars, every hundreds of occasions thinner than a human hair, are organized in dense, forest-like patterns. By adjusting their side ratio (width-to-height ratio), the researchers managed the efficient shear modulus, a key mechanical property that influences mobile interactions inside micro- and nano-structured environments.
This methods the neurons into “considering” that they’re in a mushy, brain-like surroundings, though the nanopillars’ materials itself is stiff. Whereas bending below the crawling of neurons, the nanopillars not solely simulate the softness of mind tissue but in addition present a 3D nanometric construction that neurons can seize onto, very like the extra-cellular matrix nano-fibers in actual mind tissue.
Angelo Accardo, Affiliate Professor, Delft College of Expertise
This immediately impacts how neurons develop and set up connections with each other.
From Random Progress to Ordered Networks
To judge the mannequin, researchers cultured three kinds of neuronal cells, derived from mouse mind tissue or human stem cells, on the nanopillar arrays. Not like the random development noticed on typical flat Petri dishes and 2D biomaterials, neurons on the 3D-printed nanopillar buildings exhibited organized development, forming networks at particular angles.
The examine additionally offered new insights into neuronal development cone dynamics.
These hand-like buildings information the ideas of rising neurons as they seek for new connections. On flat surfaces, the expansion cones unfold out and stay comparatively flat. However on the nanopillar arrays, the expansion cones despatched out lengthy, finger-like projections, exploring their environment in all instructions — not simply alongside a flat aircraft but in addition within the 3D area, resembling what occurs in an actual mind surroundings.
Angelo Accardo, Affiliate Professor, Delft College of Expertise
“As well as, we discovered that the surroundings created by the nanopillars additionally appeared to encourage neurons to mature,” highlights George Flamourakis, first creator of the examine. Neural progenitor cells cultured on the nanopillars exhibited elevated ranges of a marker related to mature neurons in comparison with these grown on flat surfaces. “This reveals that the system not solely influences the course of development but in addition promotes neuronal maturation.”
A Software for Learning Mind Problems
If softness is so essential, why not merely develop neurons on mushy supplies like gels?
The issue is that gel matrices, like collagen or Matrigel, sometimes endure from batch-to-batch variability and don’t function rationally designed geometric options. The nanopillar arrays mannequin presents one of the best of each worlds: it behaves like a mushy surroundings with nanometric options, and holds extraordinarily excessive reproducibility because of the decision of two-photon polymerization.
Angelo Accardo, Affiliate Professor, Delft College of Expertise
The analysis is a collaborative effort throughout three departments within the School of Mechanical Engineering (PME, BmechE & DCSC), the School of Utilized Physics (ImPhys), and ErasmusMC, with assist from the Mechanical Engineering Cohesion and NWO XS grants.
Journal Reference:
Flamourakis, G., et al. (2024). Deciphering the Affect of Efficient Shear Modulus on Neuronal Community Directionality and Progress Cones’ Morphology through Laser‐Assisted 3D‐Printed Nanostructured Arrays. Superior Useful Supplies. doi.org/10.1002/adfm.202409451.
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