The brain is astonishingly complex, containing roughly 86 billion nerve cells. Reproducing lab-grown brain tissue that faithfully reflects this complexity remains a major scientific challenge.
Researchers at the ARC Centre of Excellence for Electromaterials Science (ACES) have moved closer to that goal by creating a 3D-printed, layered structure that integrates neural cells and replicates key aspects of brain tissue architecture. This development represents an important advance in building bench-top models that researchers can use to study how the brain works and to evaluate potential therapies.
The value of accurate bench-top brain tissue is substantial. Pharmaceutical development currently relies heavily on animal testing, which often fails to predict how drugs will behave in humans. A laboratory model that more closely mirrors human brain tissue could reduce costly late-stage failures and accelerate the development of treatments. Beyond drug testing, such models could provide new experimental platforms to investigate psychiatric and neurodegenerative disorders—including schizophrenia and conditions that cause progressive loss of neural function.
ACES Director and co-author Professor Gordon Wallace emphasized the significance of the work: the ability to position cells so they form neuronal networks within a layered structure is a notable step toward realistic in vitro brain models. “We are still a long way from printing a full brain, but arranging cells into networks that occupy discrete layers marks meaningful progress,” Professor Wallace said.
To fabricate the six-layered construct, the team developed a custom bio-ink formulated from naturally occurring carbohydrate-based materials. These tailored biopolymers enable precise cell dispersion through the printed structure while offering enhanced protection to the embedded cells. The researchers optimized the bio-ink for 3D printing and adapted the method so it can be implemented in standard cell culture facilities without requiring highly specialized bioprinting equipment. That accessibility is important for adoption across many research laboratories.
The resulting construct reproduces a layered arrangement akin to brain tissue, with neural cells placed precisely and retained within their intended layers. This fidelity is essential for studying how cells interact within a three-dimensional context and for observing network formation and cell behavior in conditions that resemble the in vivo environment more closely than traditional two-dimensional cultures.
Professor Wallace noted the importance of combining progress in 3D printing technology with advances in materials science to achieve biological outcomes. He added that this approach opens the door to using more advanced printers to generate structures with finer resolution and greater structural complexity.
Funding: The study received support through Professor Gordon Wallace’s Australian Laureate Fellowship.
Source: Natalie Foxon – ARC Centre of Excellence for Electromaterials Science
Image Credit: The image is in the public domain
Original Research: Abstract for “3D printing of layered brain-like structures using peptide modified gellan gum substrates” by Rodrigo Lozano, Leo Stevens, Brianna C. Thompson, Kerry J. Gilmore, Robert Gorkin III, Elise M. Stewart, Marc in het Panhuis, Mario Romero-Ortega, Gordon G. Wallace in Biomaterials. Published online July 14, 2015. doi:10.1016/j.biomaterials.2015.07.022
Abstract
3D printing of layered brain-like structures using peptide-modified gellan gum substrates
The brain is an enormously complex organ organized into regions composed of layered tissue. Traditional two-dimensional in vitro culture methods attempt to mimic elements of the in vivo environment, but they do not replicate the three-dimensional microstructure of neuronal tissue. This limitation has constrained our ability to study brain function at the tissue or organ level. To overcome these challenges, the authors present a method to bioprint three-dimensional brain-like structures made from discrete layers of primary neural cells embedded in hydrogel matrices.
These brain-like constructs were created using a bio-ink formulated from a peptide-modified biopolymer, gellan gum-RGD (RGD-GG), combined with primary cortical neurons. The ink was optimized for a modified reactive printing process and designed to be compatible with conventional cell culture facilities rather than requiring specialized bioprinting infrastructure. The peptide modification of the gellan gum hydrogel enhanced primary cell proliferation and supported the formation of neuronal networks, demonstrating the matrix’s cell-supportive properties. The ability to fabricate distinct cell-containing layers confirms the feasibility of this printing technique for constructing complex, layered, and viable three-dimensional cell structures.
These brain-like structures provide an opportunity to reproduce more accurate three-dimensional in vitro microenvironments, with potential applications ranging from fundamental studies of cell behavior and network formation to improved models for brain injury and neurodegenerative disease research.
“3D printing of layered brain-like structures using peptide modified gellan gum substrates” by Rodrigo Lozano, Leo Stevens, Brianna C. Thompson, Kerry J. Gilmore, Robert Gorkin III, Elise M. Stewart, Marc in het Panhuis, Mario Romero-Ortega, Gordon G. Wallace in Biomaterials. Published online July 14, 2015. doi:10.1016/j.biomaterials.2015.07.022