A Brief Overview of Bioprinting

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Two hundred years ago, when young Mary Shelley gave the world a glimpse of scientist Victor Frankenstein and his monster, the idea of synthetically creating a human in a lab was mere fiction. Nevertheless, the tale never failed to send shivers down readers’ spines and warn Shelley’s audience of the dangers of “messing” with nature. But here we are, two centuries later, having turned fiction into reality. Yet, if we are careful with it, could this technology bring possibilities that not only won’t murder our families, but are capable of saving millions of lives?

Whether you work in an office or are still exploring the confines of a classroom, you’ve probably used a printer before. An inkjet printer basically works like this: lots of tiny guns shoot dots of ink at a piece of paper to make up your picture or text.

In my previous article, I covered 3D printing, which is essentially the same thing, except you replace the ink with materials such as plastic and metal, then layer them on top of each other to create a three dimensional object.

Bioprinting is built from the same idea. However, instead of just the x and y axes in inkjet printers, 3D printing and bioprinting adds a third dimension: the z axis. The x and y act as the base, and the z basically moves up and down, creating each layer of your object as it goes. So essentially, bioprinting is patient-specific prototyping and printing tissues by working with living cells. But here, bioprinting really takes regular old 3D printing to the next level by replacing the cartridge; not just with any ink or plastic, but with bioink.

Bioink

Bioinks are a hydrogel made up of two things: the actual living cells that we’ll use to fabricate our tissue, as well as biomaterials, which are basically just substances that we use to interact with biological systems.

The biomaterials are there to mimic the natural extracellular matrix in order for the cells to carry out their natural processes. Biomaterials can be split into two categories: hard and soft. Hard biomaterials such as titanium and glass are used in conditions where durability and strength is key, such as a bone transplant. On the other hand, soft biomaterials such as alginate and collagen are favourable for mimicking the elasticity of soft tissues such as skin.

It’s super important that the properties of the materials meet the necessary requirements for the cells to not only survive and grow, but also develop according to the researchers’ needs — or else things could really get out of control. The ink has to satisfy both the biological needs of the cell as well as the physical needs of the printer. For example, if it’s not the right viscosity and strength, the ink will either not hold its shape, or will require so much force to actually print out that you could potentially kill the cell. It can’t be cytotoxic (toxic to the cells), but should, if necessary, be able to dissolve the biomaterials that only serve as a temporary scaffolding for the cells to grow on.

The process

Just like with normal 3D printing, there are loads of methods in bioprinting, so there isn’t necessarily one way to do this. However, most methods generally follow something along the lines of this:

Let’s say you want to print a picture of an organ. First, you need to actually take the picture. Since one of the huge benefits of bioprinting is that it can be custom made for each patient, we need to actually know what the patient’s tissue/organ looks like. And what better way to do that than getting a good old CT/MRI scan? Doing so, we can get a pretty accurate picture of what we’re trying to achieve.

The next step would be uploading the picture you took to your computer, so that you can then send it to a printer. With bioprinting, what we do is we generate a blueprint using autoCAD software. are step by step instructions if you’re wondering exactly how. If you recall how 3D printing works, you’ll think of one word: layers. 3D printing is done layer by layer, printing each separate cross section and putting them together. With bioprinting, it’s not just any blueprint, but a highly detailed one that shows each layer of the tissue with specific instructions for the printer to follow. The blueprint should show the cells, the extracellular matrix (enzymes and proteins around the cell that help support it), as well as how they would fit together. So, if you’re replacing the tissue because there was something wrong with the old one, now would be a good time to make adjustments to your new one.

Next up, preparing the bioink. The first part: the biomaterials. Often, many different materials are combined in order to change the physical properties and enhance printability and cell viability. The key here is to find materials that almost fit the requirements, then slightly tweak its properties through cross linking (bonding one polymer chain to another). Like I mentioned, this will serve as an artificial scaffolding for the cells to grow on. And the second part: the actual cells. What generally tends to happen is that doctors take a blood sample from the patient that needs the organ/tissue. Since every cell in the body has the same genes, you could potentially take any cell, reprogram it, and send it out as a cell with whatever functions you want .Different chemicals are added to somatic stem cells in order for them to adhere and mature without scaffolding, as well as according to the needs of the patient.

After an experiment conducted by Dr. Shinya Yamanaka, he found that by introducing genes that help cells resume characteristics of embryonic stem cells, even fully developed adult cells can be changed back to induced pluripotent stem cells. This literally means that you could take blood cells from a patient, tweak it a bit, and then use those cells to grow potentially anything they would need to be repaired. With the recent advances in stem cell technology, they can then reprogram the blood cell to be used to repair or even regrow various tissues.

The blueprint has been sent to the printer, and the ink is ready to go. Now all that’s left to do is print! Even though preparing the bioink is probably the most complicated part of this process, it’s important to pay attention to the smaller details during the printing process. For example, each layer can’t be more than half a millimetre in width, and you need to make sure the nozzles and print heads used are suitable.

Ta da! Congratulations, you’ve now printed your tissue. But now is definitely not the time to let down your guard. The tissue comes out as a sort of gel, and only some help from UV light or specialized chemicals is your tissue really fully complete. Like a newborn baby, your bioprinted tissue needs a certain environment to survive. Since many newborns aren’t able to regulate their own temperature, it’s usually placed in an incubator. Similarly, the tissue is placed in an incubator to maintain a comfortable temperature, as well as a pollutant-free environment. If you’ve done everything up until now correctly, the cells should have enough instructions to develop, work with each other, and regulate nutrients and waste, just like any other adult cells.

It’s definitely a tricky process, but done correctly, this technology has the ability to save millions of people.

Applications

An annual 200,000 deaths are the results of burns, many of which are due to the fact that not enough healthy donor skin was available to perform a skin graft. Bioprinting offered a solution.

Just last year, University of Toronto researchers were able to develop a handheld bioprinter. All in under two minutes, this device is able to evenly print layers of skin tissue ranging from light scrapes to deep wounds. Current treatments rely on the basis that the healthy donor skin is healthy and plentiful enough to recover wounds that may affect deeper layers of skin. But the development of this handheld bioprinter, lead by PhD student David Hakimi along with Dr. Marc Jeschke, director of the Ross Tilley Burn Centre at Sunnybrook Hospital, changed the game completely.

Not only is the device able to directly print the skin tissue onto the patient, but also works at a better speed and efficiency than the standard, more bulky bioprinter. Currently, the device is still in its experimental stages, but the possibilities that a development like this could bring are phenomenal.

As you can imagine, the vast possibilities of creating artificial organs is one of the main incentives behind this technology. Ears, skin, bones — even heart tissue can be replaced.

Apart from actually creating tissue/organs, bioprinting is great for pharmaceutical testing. Once the technology is more developed, we won’t have to do tests on rats, or even humans anymore! New drugs, procedures, and materials can be tested on printed tissue. Not only is it much more ethnical, it’s super cost-effective too.

Currently, the main thing constricting this evolutionary technology to take larger leaps forward is technical issues. Larger, more complicated bioprinted systems aren’t able to survive for long and still maintain its usual functions. However, with the rate at which new discoveries and improvements are being made, there’s full reason to believe that within the next few decades, it may even be possible to bioprint entire organ systems.

Thanks for reading! As usual, feel free to leave any constructive feedback, and let me know what you think!

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