Skip to 0 minutes and 14 secondsIn one of our most challenging programmes, we engage with Professor Mark Cook, a neurologist at St. Vincent's Hospital in Melbourne. OK, so epilepsy is really common. I guess most people don't realise it's the second most common serious neurological disease. Stroke's the most important. But epilepsy is really common, and no one knows it because of the stigma around and the fact that people don't discuss it openly. But 1% of the world's population have epilepsy chronically, so they're having recurrent seizures, and 5%, maybe as many as 8% have seizures during their life. So it's a really common problem.
Skip to 0 minutes and 46 secondsOf that 1% of the whole world's population, though, that have epilepsy, about 60% are controlled with medications that we have available currently, but the rest aren't properly controlled, and so they're still having active seizures. Even the people who are controlled are often putting up with a lot of bad side effects from the medications that are controlling their seizures. So there's plenty of opportunities to improve the situation, and we're not talking about some rare and uncommon problem, we're talking about what's a really serious disease burden for the whole of mankind. Our goal is to develop an implantable system for epilepsy detection and control. Electrical signals arising from the brain can be used to warn of an impending seizure.
Skip to 1 minute and 28 secondsWe will couple this warning system to a nanostructured reservoir containing anti-epileptic drugs. All components integrated into a fully implantable device. Upon detection of an emerging seizure, drug is released when and where it is needed and can act quickly to prevent a seizure occurring. Success in this area is dependent on the effective integration of advances in a number of somewhat disparate technological areas. It will be challenging, but success is possible. We're realising that a lot of problems associated with the brain malfunctions are concerned with this network properties, and at the moment we don't have good methods of studying how these networks function in using a real system.
Skip to 2 minutes and 14 secondsMaking these three-dimensional systems with stem cells or other living cells gives us a good way of looking how simple but realistic networks of neurons function, how to disturb it, how to fix it. At the moment we work with these 2D arrays, where we can study the connections between cells and their response to various stimuli, including drugs and chemicals that produce seizures, for instance. And we've got a lot of experience studying that in 2D. But the behaviour of these systems alters considerably when you move into the 3D world, and of course that's the real world.
Skip to 2 minutes and 45 secondsSo being able to create synthetic structures out of real cells that are connected in three dimensions might give us new ways to, for instance, test drugs, or to test other therapies. So it's really exciting. So how many layers of different types of cells do you think we would need to print to start to get meaningful information? Well, I think we'll get meaningful information just through having neurons connected. So just one type of cell, provided they're connected well and they're interacting, and we've seen that that happens in these 3D structures.
Skip to 3 minutes and 14 secondsWe could certainly make it more complex, introducing other cells that are present in the brain, the supporting cells, the glia of the brain, which have also turned out to be quite important in the way the brain works, rather than just providing mechanical support. Being able to include them in the system as well, that would also make for much more sophisticated environments where we might get a much better idea not only of how the brain works in these artificial structures but how it works in real life. The cortex, for instance, is about two to three millimetres thick in humans. Getting those sorts of thicknesses, I think, is achievable with these artificial structures at the moment.
Skip to 3 minutes and 51 secondsSo I see that building artificial structures that are broadly similar to the pattern of normal cortex as possible, of course, is very sophisticated, and the interconnections are far more elaborate than we could possibly hope to imitate now, but we've seen in other situations that simple models of living systems can give us great insights into how the normal systems function and more importantly how abnormal systems function. So we could do that with these systems, potentially. And again, might lead to revolutionary different therapies and different ways of intervening in the disease development?
Skip to 4 minutes and 25 secondsAbsolutely, and I guess the real blue sky thing is, could we create a 3D object that we could use to transplant directly into a brain to replace damaged or missing parts? That would be really exciting. I mean, that's obviously some way off yet.
Brain on the bench – testing other therapies
In 2012 Shimna Yamanaka and Sir John Gurdon received the Nobel Prize in physiology/medicine for an important discovery that shook the world of medicine.
The discovery was that through a specific chain of biochemical treatment, adult cells which had already differentiated could be remodeled or reprogrammed back to a primitive stage of development. In fact, it turns out that cells can even be reprogrammed back to the stem cell state, enabling them to differentiate into any kind of cell in the human body.
Such cells which have been treated are termed induced pluripotent stem cells or iPSCs and unlike previously explored fetal stem cells, many of the ethical issues traditionally encountered are moot.
So what does this mean for medical 3D printing? The short answer is everything. Because these pluripotent cells can be generated from a variety of accessible tissues in the body, which are often byproducts of routine surgery - such as their isolation from adipose (fat) tissue in the knee, a material which is usually discarded following a knee reconstruction. We now have a stable supply of iPSCs for tissue construction.
Not only that, but the cells can be multiplied in number through our proficiency in cell culture, allowing us to amplify their effect. This means that by the time the patient reaches the operating table, their implant is ready to go, and the cells are autologous (sourced from the patient), which is significant because it eliminates or at least drastically reduces the occurrence of immune response and rejection following implantation.
The ability of these cells to transform into any other cell type, gives us the opportunity to guide them into all of the essential cell types for a fully integrated tissue which encompasses the complex formations seen in the human physique.
University of Wollongong, 3D Bioprinting: Printing parts for bodies, 2014, Wallace, G.G., Cornock, R.C., O’Connell, C.D., Beirne, S., Dodds, S., Gilbert, F.
- Stem cells have been referred to throughout this course and Professor Mark Cook refers to them in the current research into the treatment of epilepsy. What do you think about the use of stem cells in 3D bioprinting?