It works like a layer cake—one that eventually becomes an organ.
It sounds like a sci-fi scenario: You're rushed to the hospital with a failing organ—a liver, let's say, or maybe even a heart. The only solution is a transplant, but instead of finding yourself on a waiting list hoping a donation comes through in time, you're whisked into the operating room to be prepped. While doctors scrub up, a machine whirring nearby assembles your new organ, specifically tailored for your body and printed on demand. Before the first incision is made, your doctors have a pristine organ, ready to go to work.
To be clear, this is a sci-fi scenario. Indeed, it's practically utopian—but to solve the ongoing shortage of transplantable organs, we may need some utopian thinking. Consider the status quo. According to the US Department of Health & Human Services, just about 33,500 transplants were performed in the United States in 2016. That's a record number, and up almost 20 percent from 2012. But there's still a waiting list for organs, which right now stands at a little more than 118,000, with one person being added to it every 10 minutes. On average, 22 people die every day waiting for a transplant.
Simply put, demand exceeds supply. Transplants have increased largely because donations have increased, coming mainly from the deceased, and clinicians have adapted their criteria for accepting organs. For some time, the largest source of transplantable organs has been traffic fatalities, which last year killed an estimated 40,200 people in the US. Of course, most of those killed were not donors, and depending on traffic deaths to save lives via transplantation has created an absurd imbalance. As Slate put it, in the most Slatest of headlines, "Self-Driving Cars Will Make Organ Shortages Even Worse."
That's the status quo: thousands of people desperately waiting for transplants, dropping off the lists as they become too sick to be helped by the trickling supply of viable organs provided by car crashes. With an aging population of both donors and recipients, and absent a new approach, things are likely to only get worse.
Proposed solutions include removing the prohibition on selling (rather than donating) one's organs, adopting an "opt-out" system that would assume the deceased is willing to donate unless otherwise specified, and providing some sort of compensation (monetary or otherwise) to those who donate. (Queue up your reference to Never Let Me Go, with its bucolic dystopia where people are farmed for their organs.)
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Or we could simply remove human donors from the process altogether. Instead of depending on them, we could print whatever organs we need, whenever we need them, thereby skirting the supply-and-demand problem.
That's the radical solution suggested by Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, and others currently working on bioprinting. While still experimental, it's not as radical is it might sound. Imagine 3D printing, but with living cells instead of plastic. To prevent rejection by the immune system, the new organ would be built with cells taken from the patient, preferably from the organ to be replaced; it's easier to grow a bladder starting with bladder cells, for example. Cells would be grown in large quantities outside the body, then forced through the nozzle of a printer. A scaffold made of biomaterial, designed to biodegrade once it's no longer needed, gives shape to the organ-in-progress; after each layer of cells is deposited, they grow together, developing into functional tissue. "It's like a layer cake, if you will," Atala says. A layer cake that becomes a bladder.
That's the vision, anyway. It's ambitious, but not impossible. In fact, many of the necessary components are already available. In fact, Atala has been engineering organs for decades. In 1999, he and his team provided the first lab-grown organ ever implanted in a patient. They made it using the layer-cake process described above, with one important difference: instead of being printed, it was layered by hand.
Getting to that point took hundreds of people and many years, as Atala acknowledges, it's difficult technology. It meant understanding cell biology, lots of experimentation, and then the laborious work of layering cells to build the organ.
Once you get a formula, though, you can replicate it. And that's where the true appeal of bioprinting lies: scaling up those formulas. Tissue engineering is like artisanal prototyping; bioprinting could be mass production. To have an impact on the organ shortage, it'll need to be. "The question now is how can we do these in large quantities. And that's where the printer comes in," Atala says.
The printer, custom-built over ten years, is called ITOP, the Integrated Tissue and Organ Printing System. Like a typical 3D printer, it can turn computer models into fully realized forms—in this case, made of human tissue. It can even use medical images of the patient to create customized models, to replace a damaged ear, for example. Rather than start with a scaffold that's then hand-layered with cells, the ITOP uses cells embedded within a hydrogel that holds them in place during the printing process.
To prove the system worked, Atala and his team printed a human ear—which they then implanted under the skin on a mouse's back. Several months later, they confirmed that blood vessels had attached to the ear and kept its cells alive. They found similar results using printed muscle tissue and fragments of a jawbone.
Atala describes the advantages of 3D bioprinting, and they're just what you'd expect in a move from hand-crafted, bespoke organs to those made by a machine. First, there's scalability: You can just make more, more quickly. But you also get precision; with the ITOP, you can more position the cells exactly where you need them. You get reproducibility, because the printer follows the same model every time. And finally, it reduces your cost: The machine does what you used to have to pay a human to do.
Unfortunately, that doesn't yet mean bioprinted organs is ready for the masses. "You still have to go through a whole new regulatory process, basically," Atala says, to proceed from engineered organs (which have already been implanted in humans) to their bioprinted counterparts. "We know they work," he adds, of the hand-made tissues that have been implanted. "The question is how do you transfer that technology."
In addition to the regulatory hurdles, there remain some technological challenges. Atala divides organs into four levels of complexity. The least complex are flat structures, such as skin, where a lot of progress has been made. Slightly more complex are tubular structures, including blood vessels. Beyond that are hollow, non-tubular organs such as the bladder. Finally, the solid organs such as the heart, kidney, and lungs are the most complex to create. "There are so many cells per centimeter in a solid organ like the heart or liver that keeping all the cells alive is much more complex, and is not yet doable," Atala says.
Which means 3D-printed are both very close and yet still just out of reach, likely decades away from mainstream use. But Atala is optimistic about the technology and its potential impact. After all, he's been working on it for a very long time.
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