麻豆传媒

THE 3D-printing revolution is here. From guns and houses to prosthetic limbs and vehicle parts, if you can think it, you can print it. Or you can as long as it is inanimate matter.

But imagine being able to print a kidney, or a brand new beating heart. of Harvard University, who runs a team working at the living edge of 3D bioprinting, is aiming to do just that.

What do you see as being the long-term goal of bioprinting?

The ability to print and implant vital organs. Perhaps the first step will be an implanted tissue patch that would augment or repair a damaged organ. But clearly the holy grail would be to engineer vital organs, such as the kidney, the heart, the liver. To do so for those three organs would be of tremendous value. That鈥檚 what people are chasing, and what the research group I鈥檓 part of is focused on.

How close would you say we are to printing an organ?

We鈥檙e still decades away. It鈥檚 not enough to just print liver cells or cardiac cells or kidney cells. These cells have to function, they have to mimic the high densities of the living tissue. An organ performs many functions in the body, so we have to be able to replicate all of that and also put it into the body without the body rejecting it. There are so many challenges.

So we are also pursuing goals with immediate impact. As an example, the pharmaceutical industry spends about $1 billion bringing a single drug to the market, yet 20 per cent of all drugs fail clinical trials because they are toxic to the kidney. What the industry lacks is physiologically authentic models of human tissue to test drugs on. So we see the ability to print kidney tissue as an important focus.

What progress have you made on kidney tissue?

We鈥檝e been working with collaborators at Brigham and Women鈥檚 Hospital in Boston to create mini-kidney building blocks, which have many of the key features of kidneys.

We want to try to use those to build up a volume of tissue that is big enough to essentially function like your kidney. Using this approach, we ultimately want to create three-dimensional organs with their own blood vessels.

Will these organs look like normal human organs?

I think from the perspective of capturing imaginations, it鈥檚 very important for people to see this tissue printed in a shape that they鈥檙e already familiar with, otherwise it might freak them out. But there are a lot of interesting shapes you could print that don鈥檛 correspond to the actual shapes of human organs.

What brought you to the idea of bioprinting organs in the first place?

Colleagues at the University of Illinois wanted to make self-healing materials. The idea was to emulate the body: if you cut yourself, blood flows from the blood vessels of your vascular network and forms clots, so your skin heals. Together, we figured out how to 3D print a network of channels 鈥� microvasculature 鈥� inside a synthetic material. This advance enabled a new class of self-healing polymers.

It was also a light-bulb moment. I had never tried printing live cells before, but I had been watching the tissue-engineering field closely, and realised that we had overcome the obstacle that had been holding it back. So I decided to translate this approach to living materials. That was around 2010.

So what was that breakthrough?

You can鈥檛 print living cells in 3D if there鈥檚 no vasculature to carry nutrients or blood to those cells. They will simply die. So we used a 鈥渇ugitive ink鈥� to create patterns of tiny cylinders within a 3D-printed tissue. The crucial thing is that this ink is erasable 鈥� after you鈥檝e printed your tissue, you can remove that part, leaving behind open channels akin to vasculature.

What is fugitive ink and how does it work?

It is a substance designed to be a gel at room temperature. It comes out of the printer nozzle in a cylindrical shape and it keeps that shape within a printed structure. However, if you cool it down to 4掳C, the gel goes from being a solid to being a liquid, which is the opposite of how materials normally behave.

That was the secret sauce in a way, because if you鈥檙e printing a structure with living cells at room temperature and you have to heat that structure up to liquefy the fugitive ink, then all the cells would die. But, crucially, cells stay alive when you cool them down. It鈥檚 a very simple idea, yet it also gave us the ability to vascularise 3D-printed human tissues, overcoming a huge challenge for the field.

鈥淲hen the tissue fuses together, it starts beating as a collective unit鈥�

It seems like things are progressing fast.

Think of Moore鈥檚 law, which predicts exponential gains in computing power. The number of transistors on a computer chip has been roughly doubling every two years or so since the 1970s. The question is, does bioprinting follow its own version of Moore鈥檚 law? Without vascular networks, researchers could only really print tissues that were less than 1-millimetre thick. We have shown that you can print vascularised tissue that is around 1-centimetre thick. That means bioprinting is starting to scale exponentially.

When you print heart tissue, does it just start beating by itself?

Heart cells within the printed tissue do start beating synchronously. But it doesn鈥檛 happen immediately. First they beat asynchronously, until the tissue fuses together and beats as a collective unit, which is what your heart does. It takes several days or so for this process to happen. Then the tissue starts beating more strongly and the synchrony increases.

So you sort of set the scene for a living tissue, giving it what it needs to get going and then step back and let nature take over?

That鈥檚 right. We believe that to create these organ-specific tissues means printing some minimalist architecture that contains the appropriate cells, their vasculature and a support scaffold. But you let biology do as much of the building and assembly as possible, because we鈥檙e already programmed to create our own tissues. If you give these cells the right cues, they can do a lot on their own.

Could your technology displace animal testing by letting us check out drugs on printed organs?

Yes. But you don鈥檛 need a full organ to test drugs. We are currently focused on creating three-dimensional human tissue models that could be used for both drug toxicity testing and disease modelling. Specifically, we are creating 3D kidney tissues housed within chips in collaboration with a major pharmaceutical company.

This article appeared in print under the headline 鈥淗ow to print a heart鈥�