Scientists Develop 3D Aerohydrogel to Study Brain Cell Communication

Electron microscope image of tetrapodal zinc oxide. The four-armed crystals form the initial scaffold for the aerohydrogels, which is later transformed into an ultralight hydrogel network. Credit: AG Funktionale Nanomaterialien, Kiel University

Researchers Develop Advanced 3D Scaffold for Brain Cell Studies

Researchers at Kiel University have developed a novel three-dimensional material that allows human brain cells to grow and communicate under laboratory conditions that closely resemble the natural brain environment. The innovation could significantly improve scientists’ ability to study neuronal activity and cellular communication.

Until now, conventional 3D cell culture systems have faced major limitations. Many existing models are either too rigid or too unstable to replicate the complex interactions between brain cells accurately. The newly developed material addresses these challenges and enables researchers to examine neuronal processes in conditions that more closely mimic real physiology.

Ultralight Aerohydrogels Create a Realistic Cellular Environment

An interdisciplinary team led by materials scientist Stefan Schröder designed the new material, known as aerohydrogels. These ultralight, hollow-fiber scaffolds provide brain cells—particularly astrocytes and microglia—with a supportive three-dimensional structure that resembles the natural environment of brain tissue.

The team published its findings in the journal Chem & Bio Engineering, working in collaboration with scientists from Harvard Medical School in the United States and University of Oxford in the United Kingdom.

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Innovative Fabrication Process Behind the Scaffold

To create the aerohydrogels, the researchers first used tetrapodal zinc oxide crystals (t-ZnO) to build an interconnected three-dimensional skeleton. Next, they coated this structure with an ultrathin hydrogel layer using a specialised technique called initiated chemical vapor deposition (iCVD).

After completing the coating process, the team removed the zinc oxide framework. This step left behind a lightweight hydrogel scaffold that provides structural stability while still allowing nutrients and signalling molecules to move freely through the material.

Greater Stability and Customisation Than Traditional Models

Compared with conventional 3D cell scaffolds, the aerohydrogels offer several important advantages. Many traditional scaffolds dissolve after a few days or allow only limited control over their structural properties.

In contrast, the aerohydrogels remain stable for longer periods and allow researchers to independently adjust pore size, mechanical strength, and surface chemistry. In most other scaffolds, these properties are interconnected and cannot be modified separately, which limits their adaptability for different cell types.

Mimicking the Brain’s Extracellular Environment

According to Rainer Adelung, a co-author of the study and an expert in tetrapodal zinc oxide materials, the aerohydrogels closely replicate the brain’s extracellular environment.

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“Our aerohydrogels imitate the extracellular space in the brain,” Adelung explained. “We can precisely control mechanical properties such as stiffness and pore size. In the future, this will allow us to adapt the scaffolds for different tissues. For example, heart tissue is much stiffer than brain tissue, and the aerohydrogels can be adjusted accordingly.”

Meanwhile, the same iCVD coating technology is already being used commercially by a startup founded by Schröder and study co-author Torge Hartig at Kiel University. The company may eventually offer these advanced scaffolds for wider research and medical applications.

Brain Cells Form Functional Networks in the Scaffold

To evaluate the new system, the researchers grew two key types of human brain cells within the aerohydrogels:

  • Astrocytes, which support and maintain healthy nervous tissue
  • Microglia, which act as immune cells in the brain and detect potential threats

These cells formed networks within the ultralight scaffold, enabling researchers to observe how they communicate and respond to external stimuli.

Experiments Reveal Cell Communication Without Direct Contact

For the experimental analysis, Luise Schlotterose from the University of Oxford exposed the cells to Lipopolysaccharide (LPS)—a bacterial compound commonly used to trigger inflammatory responses.

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Working with colleagues at the Anatomical Institute, the team then examined how the cells reacted at the molecular level. They analysed the activity of genes responsible for producing inflammatory signalling molecules.

As reported by medicalxpress, the results revealed an important finding: microglia behaved differently when grown alone compared with when they were cultured alongside astrocytes. When astrocytes were present, certain inflammatory responses were reduced.

This observation suggests that the two cell types communicate through chemical signals within the three-dimensional scaffold—even without direct physical contact.

Potential Applications in Neuroscience and Tissue Engineering

Overall, the aerohydrogels enabled scientists to study neuronal processes, cell communication, and responses to external stimuli much more realistically than conventional two-dimensional or standard 3D culture systems.

In the long term, this technology could help researchers recreate damaged or lost tissue in the laboratory. Additionally, by enabling complex cellular interactions to be studied directly in vitro, the system may reduce the need for animal experiments in neuroscience research.