Bioengineers create 3D 'brain tissue'

Bioengineers at the Tissue Engineering Resource Center (TERC) at Tufts University, Boston have developed a three-dimensional (3D) ’brain-like’ tissue that closely mimic the functionality and structural features similar to that of a rat’s brain.

The researchers claim the synthetic tissue can be kept alive in the lab for more than two months, allowing them to study chemical and electrical changes that occur in the instances that immediately follow traumatic brain injury.

To recreate brain trauma, the researchers dropped a weight onto the brain tissue to study whether or not chemicals and electrical charges dramatically increased within the blood concentration.

According to research, the chemical and electrical changes were practically the same as that of someone who has suffered traumatic brain injury.

“This work is an exceptional feat

NIBIB program director Rosemarie Hunziker

As part of a separate experiment, the bioengineers also studied changes that occurred in the brain in response to certain drugs.

“In this case, the researchers used a neurotoxin, and wanted show the electrical signalling that happens as result of exposure to this toxin,” said Rosemarie Hunziker, program director of tissue engineering at the National Institute of Biomedical Imaging and Bioengineering (NIBIB), who helped fund the research.

The scientists suggest this research could be used to provide a superior model for studying normal brain function as well as injury and disease, and could assist in the development of new treatments for brain dysfunction.

“With the system we have, you can essentially track the tissue response to traumatic brain injury in real time,” said David Kaplan who led the research efforts to develop the tissue.

“Most importantly, you can also start to track repair and what happens over longer periods of time.”

In similar studies, tissues engineers have attempted to grow neurons in 3D gel environments, where they can freely establish connections in all directions.

However, this type of tissue modelling struggles to survive long enough for accurate study, and often fails to yield robust, tissue-level function.

To combat this, the TERC team created a functional 3D brain-like tissue that exhibits grey-white brain matter compartmentalisation, which is vital in the study of brain injury and disease.

“This work is an exceptional feat,” Hunziker said.

“It combines a deep understand of brain physiology with a large and growing suite of bioengineering tools to create an environment that is both necessary and sufficient to mimic brain function.”

In order to generate the brain-like tissue, the TERC engineers created a composite structure that consisted of two biomaterials with different physical properties: a spongy scaffold composed of silk protein, and a softer, collagen-based gel.

“With the system we have, you can essentially track the tissue response to traumatic brain injury in real time

Lead researcher David Kaplan

To do this, the researchers took a ’hole-puncher’, punching out the middle of the ’scaffold doughnut’ structure (see image) and filled it with collagen - creating the central area in which the neurons could extend and connect with other neurons, Hunziker told LaboratoryTalk.

According to the researchers, the scaffold served as a structure onto which neurons could anchor, while the gel encouraged axons - slender nerve cells - to grow through it.

Once the researchers had compartmentalised grey-white matter using rat neurons, functional networks were formed around the pores of the scaffold in a matter of days.

After several weeks’ research, the bioengineers found that the neurons in the tissues had a higher expression of genes involved in neuron growth and function. In addition, the neurons grown in the tissue maintained stable metabolic activity for up to five weeks, while the health of neurons grown in the gel-only environment began to deteriorate within 24 hours, the researchers said.

The research team has emphasised the fact that, because these tissue samples can stay alive for over two months, this technique should allow for greater in-depth research of neurological diseases.

“Good models enable solid hypotheses that can be thoroughly tested. The hope is that use of this model could lead to an acceleration of therapies for brain dysfunction as well as offer a better way to study normal brain physiology,” Hunziker said.

TERC will now look to form collaborations with tissue model laboratories, as per its funding agreement regulations.

Though it is as yet unclear exactly how Kaplan intends to pursue this research, the next steps will involve perfecting the technology for use with human brain cells, Hunziker said.