A team of bioengineers from Tufts University in Massachusetts have developed three-dimensional brain-like cortical tissue that is similar in structure and performance to tissues found in the brain of a rat, exhibits biochemical and electrophysiological responses, and can be kept alive in the laboratory for more than 8 weeks.
In research published within the August 11 early online edition from the journal Proceedings from the National Academy of Sciences (PNAS) and funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the research authors explain how these were in a position to create the tissue utilizing a silk protein-based scaffold and ECM composite and primary cortical neurons.
They used the tissue to research the chemical and electrical changes that occur within the brain rigtht after a traumatic injury, and conducted a separate experiment to see the way the tissue responded to a drug. They report that their creation could serve as a better model for the study of normal brain function, in addition to brain injuries and diseases, and could result in the development of new treating these problems.
“There are few good options for studying the physiology from the living brain, yet this is perhaps one of the biggest regions of unmet clinical need considering the requirement for new options to understand and treat an array of neurological disorders linked to the brain,” senior and corresponding author Dr. David Kaplan, chair of biomedical engineering at Tufts School of Engineering, said inside a statement.
“To generate this technique which has such great value is extremely exciting for the team,” he added.
Rather than recreating a whole-brain network from the ground up, Dr. Kaplan and colleagues from the Tufts biomedical engineering, physics and neuroscience departments opted instead to build up a modular design which replicated fundamental features which are best to the physiological functions at the tissue-level from the brain.
“Each module combined two materials with various properties: a stiffer porous scaffold made of cast silk protein which the cortical neurons, derived from rats, could anchor and a softer collagen gel matrix that allowed axons to enter and connect three dimensionally,” the university explained. “Circular modules of cast silk were punched into doughnuts, then assembled into concentric rings to simulate the laminal layers of the neocortex.”
Simultaneously layers was seeded with neurons independently before they were assembled C a procedure that didn’t require glue or adhesive. The doughnuts were then immersed in the collagen gel matrix, and also the mixture of silk and collagen gel turned out to be an optimum microenvironment for the formation and performance of neural networks.
“The stiffness from the silk biomaterial might be tuned to support the cortical neurons and the different types of gels, maintaining both stability in culture and brain-like tissue elasticity,” said first author Dr, Min D. Tang-Schomer, a post-doctoral scholar in biomedical engineering at Tufts. “The tissue maintained viability for at least nine weeks C significantly more than cultures made of collagen or hydrogel alone C as well as offered structural support for network connectivity that is crucial for brain activity.”
“This work is an exceptional feat,” added Dr. Rosemarie Hunziker, program director of Tissue Engineering at NIBIB. “It combines a deep understand of brain physiology with a large and growing suite of bioengineering tools to produce an environment that’s both necessary and sufficient to imitate brain function.”
Since the 3D brain-like tissue possessed physical properties similar to rodent brain tissue, the research team decided to test whether it could be accustomed to study traumatic brain injury. They dropped fat loss around the cortical tissue from various heights to be able to simulate this kind of injury, after which recorded changes in the electrical and chemical activity within the neurons. The outcomes were described as much like those typically present in animal brain injury studies.
However, Kaplan noticed that the brand new tissue model has advantages over animal studies, since the latter requires research to become delayed while scientists dissect the mind and make preparations it for experiments. The new system, he noted, allows them to “essentially track the tissue reaction to traumatic brain injury in real time. Most significantly, you may also start to track repair and what happens over for a longer time of time.”
He also said that the longevity of the brain-like tissue will be important in studying other brain disorders, because the proven fact that the tissue could be maintained within the laboratory not less than 8 weeks “means we are able to start looking at neurological diseases in ways that you can’t otherwise because you need long timeframes to study a few of the key brain diseases.”
Kaplan and his colleagues will also be searching for ways by which they are able to make their tissue model even more brain-like. As they reported within their new study, the cortical tissue can be modified so that the doughnut scaffold is comprised of six concentric rings, each capable of being populated with various types of neurons. This set-up would mimic the six layers of the human brain cortex, because both versions is home to various kinds of neurons, the study authors said.
