In the latest effort to build an artificial laboratory model of the brain, Australian researchers have developed a novel method for constructing layered biological structures that looks just like cerebral cortex tissue using a handheld 3D printer.

Neuroscientists rarely get the opportunity to study the human brain directly, and so work on cells or tissue slices that have been dissected from animals and grown in Petri dishes. These in vitro methods are useful for studying development and processes such as neurodegeneration and cell-to-cell signalling, but are severely limited in that they do not resemble the complex three-dimensional structure of the brain.

To overcome these obstacles, Rodrigo Lozano of the University of Wollongong in Australia and his colleagues used 3D printing, a manufacturing process that involves creating three-dimensional objects by laying down successive layers of material one on top of the other.

The man who grew eyes | Mo Costandi Read more

The researchers harvested immature cortical neurons from embryonic mice and encapsulated them within a natural gellan gum polymer hydrogel to create a ‘bio-ink’ cell suspension. As well as being cheap and biocampatible, gellan gum protects the cells it encapsulates, is porous enough for them to exchange nutrients and waste materials with the surrounding growth medium, and solidifies effectively at room temperature.

Lozano and his colleagues fabricated the brain tissue with a simple handheld 3D printer, then used scanning electron microscopy to probe the internal structure of the printed structures, and fluorescent antibody staining combined with confocal microscopy to examine the cells within them.

This revealed that the hydrogel supported the survival and attachment of the neurons, allowing them to grow and extend their fibres over distances of several hundred microns, so that five days later they had an appearance characteristic of mature cortical cells and had formed layered structures resembling the cerebral cortex.

Recently, several groups have succeeded in growing artificial miniature models of the brain called cerebral organoids, but these can only grow to about 4mm in diameter because they lack an organized blood supply and, because they self-assemble from stem cells, do not lend themselves to being examined in any detail.

The new method is, therefore, something of an advance on this, but Lozano and his colleagues emphasise that it was not developed in order to grow replacement brain parts in the lab. Rather, it could offer researchers a cheap new method for testing drugs and studying nerve cell behaviour, injury, and disease.

Reference

Lozano, R., et al. (2015). 3D printing of layered brain-like structures using peptide modified gellan gum substrates. Biomaterials, 67: 264-273. [Abstract]