3D Organ Printing: Life in a Lab

When I tell friends that I think their grandchildren might live for hundreds of years, they usually think I’m kidding around. While I spend a fair amount of my life doing exactly that, in this case I’m not.

Advances in medical science are progressing at an exponential rate. While regulation and testing add delays of years before new medical advances can actually reach patients, the projected pace of progress in many areas is mind-boggling. That includes progress on longevity and on replacing the parts whose failure tends to kill us.

The idea of growing replacement organs has transitioned from speculative fiction (thanks for a rollicking start, Mary Shelley), to realistic science fiction. The next step, a transition to reality, is well on its way. The first human heart replacement was in 1967 (the patient died 18 days later) – and 50 years later the idea of having pork parts make your ticker work is old news.

The ability to grow replacement organs and parts in a lab is being actively researched around the world. Some of that research is happening right here in Rhode Island. Brown University has developed “P3” technology – short for pick, place and perfuse – that could be used to create custom tissue, grown from your own cells (and therefore much less likely to be rejected by your immune system than donated transplants). We had a chance to talk with Brown Professor of Medical Science and Engineering Jeffrey Morgan about the advances in technology that are making these pursuits possible, their current status and where they might be heading.

Motif: Tell us about the advances in your field of study over the last few years.

Jeffrey Morgan: It starts with stem cells, the versatile cells that can divide, multiply and differentiate. The advances have been so fast that we know someday in the not too distant future, we’re going to need to figure out and devise technologies to assemble these cells into tissues and organs.

There’s been great success growing them in thin, flat layers in petri dishes. What we need are three-dimensional constructs.
There’s been a lot of excitement around bio-printing, which has been going on for a while now and is essentially hacking an ink-jet printer to print living cells and the bio-glue that holds them together, instead of ink. Of course, with living tissues rather than ink, there are a lot more challenges in doing that successfully … We looked at that work and identified two fundamental challenges.

First, the cell density isn’t high enough. Actual liver and kidney tissue is much more densely packed than anyone’s been able to achieve with bioprinting so far.

The second limitation is that printed cells don’t have a pump. There’s no heart connected and no blood system. For an organ, the nutritional demands are very high – blood flow brings cells the nutrients and oxygen they need in high density, and flushes away the waste products.

Motif: Creating a vascular system is what a lot of attempts to artificially grow organs are having trouble with.

JM: Right. So we looked at other technologies. Much as the bioprinters looked at printing, we looked at the electronics industry. They have a very developed technology called Pick and Place. There is a small vacuum nozzle that picks up a tiny component and places it on a circuit board. A little robotic arm can pick it up and put it in place at lightning speed [wicked fast]. We saw a way to adapt that process to what we needed.

We set the cells into “micro molds.” Because they are living cells, they will grow together and basically grow into the shapes of these micro molds. So we can make donuts, microscopic honeycombs and other shapes … Using these parts, we can use the Pick and Place technology to stack them in combinations.

Motif: Like cellular Lincoln Logs or Legos?

JM: Somewhat. But here’s the difference – if you take living tissue parts, because they’re alive, they’ll actually fuse with one another. You stack a bunch of donuts and you get a tube. The cells are “sticky,” and then the parts are sticky.

Motif: And all this is microscopic?

JM: It’s on the scale of a small vein or artery. We’ve done stacks of 20 donuts, of 20 honeycombs. And the holes are important, because we have a nutritional soup, or broth, which serves as a stand in for the vascular system – it allows the needed nutrients to reach a thick layer of cells and keep them alive and healthy. That’s the profusion. It’s our fancy name for pumping.
We got a huge grant – over a million dollars – from the National Science Foundation, to develop this system further. We’re automating it, we have a lot more data measurement, cameras, and the chance to reexamine the machinery and the system.

Motif: What will that lead to?

JM: We’re aiming for a piece of tissue that’s 2 centimeters in every direction. That will be a major milestone, and we seem to be approaching it very rapidly. We’re really not thinking about millions of cells. We’re thinking forward to constructs with billions and trillions of cells.

Motif: What does that mean for the industry?

JM: There are tissue-engineered products being sold as we speak. There’s already living skin that you can buy from a company in Massachusetts called OrganoGenesis, for example.

Our immediate focus is on this instrument – an instrument that can achieve that two centimeter milestone. Then the instrument can be put in the hands of additional doctors and researchers. That’s the way that science works – we publish our findings or develop tools and inspire others to build on that. Looking beyond that, I can see an application would be with respect to small parts of tissues – a patch for a heart, a small piece of liver. Those would be the next target. And we think this will move forward quickly.

Another method that relies on an Extracellular matrix – basically, an animal organ that is flushed of all cells, then used as a sort of cast, around which a new organ is built using a person’s own cells – has been successful in the lab at producing beating hearts.

Motif: So when can a person get his or her liver replaced? We have a beer section to maintain.

JM: There are four organs that we have a serious need for. The pancreas (because of diabetes) – that’s being worked on by a number of firms, including CytoSolv here in Rhode Island, who were just acquired by Semma Therapeutics in Cambridge. Then the heart, kidney and liver. The largest number of cells is the liver. The kidneys are challenging because the plumbing is very complicated, and the heart and liver both consume a lot of oxygen – so the metabolic demands are very challenging.

How long until somebody can treat a patient? I think you’ll see significant progress on the pancreas in five years. For the others we’re probably looking at a 10-year span. I’m thinking of a patch or part, not an entire organ. There are some in the field who get excited and tend to overpromise on that point. I’ve given talks on this all over the world, and I always start out encouraging everyone to sign up to be organ donors, and to take care of their own organs as best they can. There’s a very real shortage right now. And there’s excitement in this industry. But we’re not building organs yet.