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The study asks how the shape and density of artificial dendritic spines influence early neuronal development. Two-photon polymerization produced thin, stubby and mushroom-shaped polymer arrays at three densities. Experiments with primary chicken-embryo cortical neurons measured growth dynamics, growth-cone morphology, adhesion-protein localization and neurite branching, showing that surface geometry and spacing alter these responses. The evidence concerns early in vitro development; applications to neural interfaces and tissue regeneration are proposed rather than demonstrated.
A growing neuron feels its way forward. This study asks how microscopic, spine-inspired shapes beneath it can guide that journey.
Print a physical cue
Two-photon polymerization turns a 3D design into polymer microstructures inspired by dendritic spines.
Let neurons explore
Primary cortical neurons from chicken embryos grow on coated arrays of three shapes and three densities.
Look where they touch
Live imaging and microscopy connect the landscape to growth, branching, and cell–surface contact.
Change the ground. Watch the neuron explore.
Choose a shape, change the density, and let growth unfold. The 3D scene makes the paper's physical idea tangible; the finding below it comes from the experiment.
Sprout, then extend.
At medium density, live imaging showed sprouting before further extension. At 4 days in vitro, mushroom arrays supported a higher proportion of secondary neurites.
An enlarged rounded head on a narrow neck.
Array spacing is illustrative.
Try this Make room with low density. Grow the neuron, then switch to a crowded landscape. What changes at the leading edge?
Biology inspires the shape. Light writes the structure.
Dendritic spines are small protrusions on living neurons. Here, their geometry inspired three artificial structures: a straight thin pillar, a stubby dome, and an enlarged mushroom head.
A focused pulsed laser polymerizes IP-Dip resin by two-photon polymerization. The printed arrays on fused silica were developed and coated with poly-L-lysine before the neurons were added.
Growth is a conversation with the ground.
At medium density, the live imaging showed neurites sprouting and then extending. Watch the cell develop branching processes across the printed landscape.
A growth cone is the exploring tip of a growing neurite. Its protrusions probe nearby physical and chemical cues.
More than a surface. A place to hold on.
The neuron does not simply sit on top. Electron microscopy reveals close contact and a membrane that adapts around the printed microstructures.
Slide the reveal to follow the membrane around an enlarged head and narrow neck.
Microscopy makes the hidden contact visible.
In the paper's 3D reconstruction, the membrane curves around the structures. The authors reconstructed approximately 300 successive FIB–SEM sections per cell, each 5 nm thick.
One landscape. Several scales of response.
The study combines live trajectories, growth-cone morphology, adhesion markers, and branching. Explore the measured evidence.
A changing leading edge.
Growth cones appeared as large, small bullet-like, or tree-like forms. Their morphology and area responded to the combination of microstructure shape and density.
Small growth cones were more prevalent on the arrays than in the controls across the conditions analyzed. The fixed-cell measurements add a second view to the live navigation movies.
Build the landscape. Shape the interaction.
Shape and density offer a way to tune the physical environment of a neuron. These early in vitro experiments connect microstructure design with navigation, anchoring, and branching—providing a foundation for future neuronal scaffolds and interfaces.
How Neuromorphic Microstructures Control In Vitro Early‐Stage Neuronal Outgrowth
Claudia Latte Bovio, Esther Matamoros, Valentina Mollo, Anna Mariano, Valeria Criscuolo, and Francesca Santoro
Advanced Science (2026), 13, e10822 · DOI: 10.1002/advs.202510822
Scientific content: Latte Bovio et al. (2026), main article and Supporting Information. This is an experimental study of early neuronal outgrowth on non-conductive polymer arrays. Proposed neural-interface applications extend beyond the measurements presented here.
Article figures, Supplementary Figure S18, and supplementary video: © 2026 The Authors. Published by Wiley-VCH GmbH. Used under Creative Commons Attribution 4.0. Figure reproductions are resized; video is resized and transcoded. Source credits accompany each reproduction.
The graphical abstract is an AI-generated conceptual illustration. Interactive scenes are qualitative illustrations based on the paper; displayed densities are those reported in Figure 1.
Topics in this paper
Biology
Primary cortical neurons were obtained from chicken embryo brains
Section 4.4, Cell Culture
Engineering
The fabrication was carried out with Nanoscribe Photonic Professional GT system
Section 4.1, Fabrication of Artificial Spines Arrays
two photon polymerization
High‐resolution fabrication was achieved via two‐photon polymerization (2PP)
Section 2, Results and Discussion
neuronal outgrowth
Frame‐to‐frame changes in length were used to identify growth and retraction events.
Section 4.8.2, Analysis of Neurites Outgrowth
biomimetic materials
we designed three corresponding artificial spine types
Section 2, Results and Discussion