Bioprinting is the most radical forefront for medical 3D printing (also known as additive manufacturing).
Using similar technology to more standard printing techniques such as Selective Laser Sintering, bioprinting takes a digital file and prints it. By taking more complex digital models and layering them in bio-ink (living cells), it has become possible to print biological products for transplants and testing.
This leads to an adventurous question: can we print a brain?
The technology is new. The complexities are immense. The risks are uncountable. However, additive manufacturing has a track record with making revolutionary changes to the world; bioprinting has already improved lives.
The Process of Bioprinting
Due to the nature of bioprinting, the process is much slower than printing plastics or metals. It happens in three distinct stages.
The creation of the base digital model is much more complex than other types of 3D printing. An in-depth process has to take place, usually by scanning the brain or other part of the body using Magnetic Resonance Imaging (MRI), Computerised Tomography (CT), or Tomographic Reconstruction (TR). These scans are digitised into a printable model. For the brain, this can take up to and including two days.
Once the model is complete, the bio-ink needs to be prepared. This is done by taking natural biopolymers and mixing them with cells taken from the patient. Bio-ink needs to be physically, chemically, and biologically identical to the organ or tissue being replaced to reduce the risks of rejection.
The bio-ink is then placed into a cartridge and the model is used to print the replacement body part or organic matter. Bioprinting can use a variety of methods, such as stereolithography, photolithography, magnetic 3D bioprinting, or direct cell extrusion.
Current experimentation in the field of bioprinting is being undertaken on the ISS, as microgravity environments circumvent Earthbound limitations such as magnetic field disruption and retaining structure.
The printed tissue is checked for stability and functionality — suitable environmental conditions are replicated to ensure the cells are healthy and working. The transplant or application is then undertaken — much the same as a traditional medical procedure would be.
The Challenges of Bioprinting
As an emerging technology, the additive manufacture of living tissue has severe technical limitations, medical considerations, and ethical questions.
The nozzles used in bioprinters are only modified versions of those used in the manufacture of plastics and metals. Whilst these set-ups allow for certain uses and enable continuing research, achieving more consistent results will require specialised nozzles for material compatibility, as well as printing speed and accuracy.
Alongside living tissues, polymers are utilised in bioink to give support and structure. Synthetic polymers, whilst stronger than natural polymers, will not enable ideal levels of growth for the cells to become part of the patients bodily ecosystem. Natural polymers, though having the ability to adhere to the cells and holding a lesser chance of rejection, are not as resilient as synthetics throughout the printing process.
In addition, organs must be supplied with oxygen and cleansed of waste via blood vessels, incredibly small vasculature throughout the body through which materials can flow. These vessels are simply too small to be recreated with current printing technology, meaning many printed organs are unable to survive.
It goes without saying that this forefront of medical technology is expensive. Personalised organs entering the mainstream market could still be accessible only to the very rich, increasing the disparity between the rich and the poor. However, with the improvements to efficiency brought about by bioprinting, healthcare provision could become quicker and cheaper.
The Benefits of Bioprinting
Despite the setbacks that come with new technologies, bioprinting opens up a world of possibilities.
Drug Testing and Research
Cancer is a leading cause of death worldwide; as pollution increases, lifespans lengthen, and modern lifestyle and dietary trends continue, it is likely that a sharp increase in cancers is on the horizon. By printing human tissues and organs, research into predictive diagnoses and clinical trials of new treatments for cancers will become both more affordable and more accurate; with brain cancers being one of the most severe types to treat, could printed brain cells offer the solution?
Over 100,000 organ transplants occur worldwide each year, and the exact number increases every year. The commonality of these procedures is still unable to meet demand. With the coming advancements to bioprinting technology, organs including kidneys, livers, and hearts can be printed from stem cells. Will brains arrive soon after?
How to Print a Brain
Conducting a brain scan through Magnetic Resonance Imaging can cost up to and including £750. To print a model, it can cost almost £500 per full-scale hemisphere replica. That’s just an inert replica in plastic, and to print a brain in bio-ink is a very different story.
How to Print a Model of Your Brain
The process of using additive manufacturing to craft a plastic replica of your brain, whilst not the easiest thing in the world, is very much possible with existing technology.
- With an MRI scan completed, convert the raw data into a printable file. It will most likely be in the DICOM format.
- By using a brain imaging software, convert the DICOM file into NIFTI.
- Extract the brain tissue data, now stored as a NIFTI file, using the brain imaging software. Both hemispheres need to be extracted separately, as well as any other selected parts of the brain such as the cerebellum. This can take up to and including two days, depending on the power of the computer.
- Convert the extracted tissue data, stored in separate files according to region of the brain, into the .stl format.
- Using a 3D mesh processing software, import the .stl files to create a singular mesh of your brain.
- With the final .stl mesh of your brain, all that needs to be done is the physical production. Choose your material and printing process. Print your brain.
Can We Print a Real Brain?
Printing a plastic representation of your brain created via a medical scan is a fun use of additive manufacturing technology, and a showcase of the role these technologies can play for a greater case-by-case understanding of neurological ailments.
It’s still a far cry from creating a real brain through 3D printing. With an unfathomable number of neurons, a laundry list of specialised cells with unique functions, and the delicate environment required to print simple tissues, the recreation of a thinking brain remains a long way off.
That’s not to say there haven’t been promising breakthroughs in the meantime. In 2020, Tsinghua University in Beijing was able to inject bioprinted brain-like tissue into a rat, forming a stimuli-response circuit in the cortex.
Back in 2021, a team of researchers encompassing the Canadian universities of Montréal and Concordia, and Brazil's Federal University of Santa Catarina, were able to 3D print living brain cells from laboratory mice. This was done using a new bioprinting technology named LIST (Laser-Induced Side Transfer). Extracted from the rodents, these cells were held within bio-ink and then ejected onto a microbubble created by means of a low-energy laser. The majority of these dorsal root ganglion neurons, vital in the transmission of sensory and pain stimulation, survived at least two days of incubation.
2021 was a very good year for rodent brain cells, as additive manufacturing was used in Sweden to bioprint complex patterns of neurons taken from rats. Using a specialised printer allowing for manual control over where materials are deposited, this is likely one of the most promising early examples of brain printing.
In 2022, the Federal University of Sao Paulo in Brazil further developed work on 3D printed brain cells by creating a methodology allowing for tissue to survive up to two weeks. Astrocytes, the most common cell in the nervous system, were placed into bio-ink and printed to form a neural-like tissue structure. These cells are known to perform a number of vital brain functions, such as homeostasis, controlling metabolism, and the regulation of neurotransmitters. A member of the research team said, “The bio-ink we developed attempts to reproduce the relationship between the cell and the microenvironment”.
After a few days, these printed cells began to replicate, show variance, and generally act in similar ways to natural nerve tissue. The behaviour of the astrocytes indicated that 3D bioprinting enables the layering of cells into tissue, even complex tissues such as those in the brain and central nervous system.
Conclusion — The Future of Bioprinting
Great strides are being made into printing brains. As with other, more simple organs, it remains impossible to use additive manufacturing to print a stable, functioning brain. However, the production of printed neuron and cell patterns or networks has been proven successful in laboratory settings.
Ethical questions as to the printing of entire brains remain; is a printed brain a sentient, individual life form? Would functioning brain cells printed for the purpose of treating a neurological condition have rights? Once the realm of science fiction novels, these questions will soon require answers as additive manufacturing revolutionises the fundamental nature of the medical industry.