Scientists create 3D living brain sponges to study the effect of brain injuries on living brain tissue.
It is now possible to 3D print replacement body parts from a range of biomaterials. But the brain is difficult to engineer because neurons have to grow and form connections to make functional brain tissue. Previously people have tried to grow neurons in 2-dimensional gels made up of collagen or fibrin. Neurons initially like to grow in these gels, but they do not form into 3D networks like they do in the brain, and they die after 2 weeks.
So this time, scientists tried a different approach. They tried to grow neurons on a 3D scaffold made from silk proteins filled with tiny 500 micrometre pores. Axons grew out from the neurons on this scaffold but only 2-dimensionally. They didn’t branch out and make 3D connections. So the scientists decided to combine the stiff silk scaffold with the soft collagen gel to create a brain sponge. This allowed the neurons to anchor to the silk protein, and the axons to grow through the gel in the pores to connect with other neurons and form a 3D structure of living interconnected brain cells. Axons in the brain sponge grew on average over twice as long as axons in the collagen gel alone. The scientists had achieved a 3D structure that mimics the properties of the brain to maximise development of brain cells in vitro.
These sponges were then wrapped into donut shapes and stacked concentrically like Russian dolls. This copied the natural structure of the human brain.
The human brain is divided into grey matter and white matter. The grey matter is made up of bodies of neurons and the white matter comprises the axons that extend from the neurons. So the brain sponges had an inner donut with neurons and an outer donut with only axons.
The scientists manipulated the size of the pores and the size of the central holes of the donuts to end up with a sponge that mimicked the mechanics of the human brain. They settled on sponges that were 5 or 12 mm in diameter and 2mm high with 2mm centre holes and 500um pores. These sponges reacted like rat and mouse brain to compression and strain tests. They also showed similar electrical and chemical signals to a real brain.
So the scientists used the brain sponges to look at the effects of traumatic brain injury – a major problem amongst retired veterans and sports people. It is much easier to look at the real time cellular changes that occur after trauma in the sponges than in human or animal brains. Weights were dropped on the brain sponges. This caused damage to the neurons in the sponges. The amount of damage correlated with the force of injury. There was a surge of brain activity for up to two minutes after injury. This was, at least in part, due to increased levels of glutamate – a neurotransmitter molecule that excites neurons.
This is a really exciting tissue model. Of course there is a long way to go before these sponges are really like our brains. The cells in the sponges only live for a few weeks, so they can’t yet be used for any long term studies. Also the sponges in this study only had neurons, they didn’t have the other brain cells astrocytes and oligodendrocytes.
The Scientific Paper
Schomer et al. Bioengineered functional brain-like cortical tissue. PNAS. 2014.