The study asks how printed surface geometry can position human cortical organoids, strengthen their interface with a substrate, and guide neuronal outgrowth. Two-photon polymerization fabricated IP-Q cultivation platforms with funnels, slopes, rods, steps and walls. Experiments after 14 days of culture showed positioning, rod enclosure and biased neurite orientations; migrated neurons fired action potentials. A mirrored platform supported a two-organoid co-culture with neuronal outgrowth across a shared imaging window. The co-culture remains a proof of concept: the study did not establish func

BIOENGINEERING • SMALL, 2026

Can a printed landscape help position living tissue—and direct the networks growing from it?

Tiny funnels, rods and steps give human brain organoids a place to settle, attach and extend. Explore how three-dimensional design becomes a guide for living cells.

Based on research by Siegmund, Müller and colleagues

Print the environment. Then add the tissue. Human cortical organoids are self-organized, three-dimensional tissue models derived from induced pluripotent stem cells. Here, the researchers print the polymer scaffold first. The organoids grow on it afterward.

THE VIRTUAL SCAFFOLD LAB

Three shapes. Three biological jobs.

Start with an organoid on a flat platform. Add features, turn the scaffold, and reveal outgrowth. Discover what each piece of the landscape is designed to do.

Place an organoid. Give it a landscape.

Conceptual model · not to scale. Growth timing is illustrative; measurements were made after 14 days.

Add living tissue

A cortical organoid is a tissue model, grown before seeding.

Shape the environment

Each feature has a distinct role.

Reveal the outgrowth

The flat surface provides a place to grow. Seed an organoid, then add a feature to discover how the printed landscape changes its interface.

Position

Flared funnels leave room for a pipette tip. Slopes guide settling toward the channel entrance, while walls shelter the organoid from turbulence.

Anchor

The tissue can engulf rods, while migrated cells and neurites wrap around them. This strengthens the organoid–substrate interface.

Guide

Neurites—the extensions of neurons—encounter steps and walls. Their edges bias the direction of outgrowth across a population.

THE TWO-PHOTON CONNECTION

A laser writes the landscape.

Two-photon polymerization solidifies selected regions inside a photosensitive resin. The precision and design freedom make it possible to combine positioning, anchoring and guidance on one platform.

The study used IP-Q resin and a Nanoscribe Photonic Professional GT2 with a 10× objective. The scaffold was printed and developed before any organoid was seeded.

Laser power: 50.05 mW · Scan speed: 50,000 µm/s · Slicing: 5 µm · Hatching: 1 µm .

Structures were developed in PGMEA, washed with isopropanol, and dried. Cone supports were 400 µm high. Platforms fit approximately 12 × 12 mm substrates in standard 12-well plates.

Organoids were seeded at 50–60 days in vitro for interaction studies and at 150–160 days for the co-culture experiment, then cultured on the scaffold for 14 more days.

See Methods 5.1 and 5.5 for fabrication and seeding, and Figure S6 for support geometry.

The focused laser writes solid features inside IP-Q resin. Unpolymerized resin is then removed during development.

CONTACT GUIDANCE

Which way will a neurite turn?

A growing neuron encounters a landscape, not a command. Change the pattern to see how edges bias the population—and compare the conceptual paths with the paper’s measurements.

MEASURED IN THE PAPER

On Flat, neurites close to the organoid mainly extended radially. Further away, orientation varied across regions and samples.

Reported observations after 14 days. Figure 7 and Results 2.5.1.

Edges bias many neurites, without forcing every neurite to follow them. Their orientation relative to incoming outgrowth matters. The study connects microscale geometry with the direction of a larger neuronal network.

FROM ONE ORGANOID TO TWO

A shared window for growing networks.

Combining the fine structures created a platform for controlled co-culture. Two mature cortical organoids settled into opposing funnels, with a central window available for migration and neurite outgrowth.

Median positioning offset

The distance between the organoid center and the intended seeding position was measured for 9 organoids across 3 batches.

Observed neuronal migration

After 14 days, MAP2-positive neurons migrated into the shared window. TUBB3-positive neurites and SYP1-positive presynaptic terminals were detected there.

What the markers show. MAP2 and TUBB3 identify neuronal structures. Synaptophysin 1 (SYP1) labels presynaptic terminals. The co-culture is a proof of concept for positioning and network outgrowth; functional communication between the two organoids remains a future investigation.

A surface compatible with excitable neurons. Patch-clamp recordings of migrated neurons showed action potential trains on IP-Q. Compared with glass, the analyzed action potential characteristics did not differ significantly (6 IP-Q cells; 8 glass cells; p = 0.66).

THE POSSIBILITY

Design the interface. Expand the model.

A customizable landscape could help arrange several organoids into more deliberate brain models, or place growing tissue close to recording interfaces.

The authors propose future conductive or hollow rods for electrical readout, and platforms tailored to different organoid types. This work establishes the physical design vocabulary: position, anchor, guide.

THE SOURCE & VISUAL CREDITS

3D Nanoprinted Structures Promote Robust Integration of Brain Organoids into Topography-Guided Neuronal Networks

Malte Siegmund, Tobias Müller, Emma Wollesen, Kim Krieg, Jack Muse, Jan Hahn, Maya Luongo, Wolfgang J. Parak, Ole Pless, Robert Zierold and Robert H. Blick. Small, 2026, e75936. doi:10.1002/smll.75936 ↗

Figures 4, 5, 6, 7 and 8 © 2026 The Authors, published by Wiley-VCH GmbH. Reproduced under Creative Commons Attribution 4.0, unchanged apart from scaling. The graphical abstract is an AI-generated conceptual illustration adapted from Figures 5 and 8. Interactive geometry and growth paths are explanatory illustrations; all reported measurements are identified separately.

Fabrication detail also appears in the paper’s supporting figures, including cone supports (Figure S6) and image analysis (Figure S8). Supporting Information ↗

Original figure

From Siegmund, Müller et al., Small (2026). Source paper ↗ · CC BY 4.0 · Figure unchanged apart from scaling.