Welcome back to my corner of the dementia researcher blogs. Today I want to talk about a technique that I care a lot about. It has been a cornerstone of my research career so far; 3D bioprinting. It can be simply defined as “a form of additive manufacturing that uses cells and other biocompatible materials as inks, also known as bioinks, to print living structures layer-by-layer which mimic the behaviour of natural living systems.” Essentially, it is the process of trying to print human tissue-like structures in the lab.
3D bioprinting has multiple proposed applications. A big one is the effort to replace the need for organ transplantation (you could instead have a new organ 3D printed from your own biological materials). In the context of dementia research, however, 3D bioprinting has the potential to help revolutionise the way we “model” disease in the lab and screen new therapies.
For years dementia research has relied upon techniques like studying post-mortem tissue, ‘traditional’ cell culture (where cells are grown in plastic dishes) or animal studies to try and reach for breakthroughs. Progress has been made but we have been missing a key piece of the puzzle; being able to study human brain tissues in real time. With 3D printing, we can potentially get a lot closer to that goal.
I have been championing 3D bioprinting for around 6 years now but the response has often been mixed. Some see it as unfeasible, some love the idea and some say “why don’t you just use a mouse model?” Before I go into a bit more detail about why 3D bioprinting excites me as a revolutionary tool, let me set something straight to the animal specialists who ask me that question. I am not trying to steal your job. I do not like animal testing. I do not want to do it myself, but I recognise it has had an important role to play in the push for breakthroughs. Having said that, we still don’t have any clinically approved therapies and patients still deteriorate with dementia. Our society is changing ethically as more and more people stand staunchly against animal testing. In addition, the animals we test on don’t get dementia. We have to artificially induce it in a very “gung ho” approach, giving animals more mutations than we would ever see in a patient. It is no surprise, therefore, that we see therapies that look promising in mice repeatedly fail to show the same efficacy in clinical trials. We need to be prepared to embrace new approaches if we truly want to progress.
So why bioprinting? The brain is a very complex tissue. It is highly organised down to the micro scale. Different regions of the brain are structured differently to other regions and populated with specific cell populations.
Even within one region of the brain you can find hierarchies in structural and biological content. It is impossible to replicate this complexity by simply growing cells on a plastic surface and this is a big issue.
That complex, structural environment isn’t just there to support the cells of our brain. It actively partakes in controlling their behaviour. It could be as critical to the progression of disease as the cells themselves with many studies reporting structural changes that correlate to disease pathways.
What 3D bioprinting can do is give us the tools to replicate more of that complexity. It allows the user to pattern different cells and “tissue-like” materials in specific locations to generate highly organised structures. More importantly, the user can incorporate stem cells from patients with diseases like Alzheimer’s disease to give us a more “human” representation of the disease. In essence, it could allow researchers to print mini brains and study changes in cell behaviour and tissue structure as the disease progresses. Additionally, these mini brains may be a useful platform for early drug screening. A chance to test the efficacy of a therapy on something that arguably looks more like a human brain than a mouse does.
The technology is still in its infancy but progress is occurring at an impressive rate. Companies like L’Oreal are now entering the space by testing cosmetics on 3D printed skin rather than animals and multiple industrial and academic institutes across the globe are pursuing the technology as a means for tissue regeneration. It’s time we threw our name in the hat!
Dr Sam Moxon is a biomaterials scientist at the University of Manchester. His expertise falls on the interface between biology and engineering. His PhD focussed on regenerative medicine and he now works on trying to develop 3D bioprinting techniques with human stem cells, so that we better understand and treat degenerative diseases. Outside of the lab he hikes through the Lake District and is an expert on all things Disney.