Features & Columns

Bioprinters Revolutionize 3D Printing

New advances in bioengineering will one day give us 3D-printed livers, kidneys and hearts—with impacts on pharmaceuticals, surgery and more

The thing hasn't moved all night. Not an inch. Looped with coils of wire that wend their way down to a motherboard, the machine looks like it's coursing with energy, but it has sat perfectly, maddeningly still for the last two hours. The one sign of life in there is the brief alert beep, which is generated by a computer and not the machine itself, when someone plugs its USB cable into a laptop. For a bioprinter—an object meant to "print" living cells—so far, well, it's pretty lifeless.

Half a dozen volunteers have their backs to the printer, hunched around a laptop, patiently watching and making suggestions as a member of the group spins a rectangular object around on the screen, refining its angles. They're designing an object destined for the bioprinter, but it doesn't resemble the item they ultimately plan to make.

The goal: printing a fully functional artificial leaf, one actually capable of photosynthesis. For now, that's the objective of this bioprinting meetup, which takes place weekly at BioCurious labs in Sunnyvale.

The thing currently on the screen, a box with cutouts on each end, will be 3D-printed, all right, but in plastic. It's a new component for the bioprinter, a box to hold syringes of cell culture. It's another small step in the process of making a machine that will make a leaf.

A late arrival to the group, a first-timer, wants to see the bioprinter in action, too. He stares down at the inert machine, gives it a few tentative pokes and prods and eventually takes to reading the code on the laptop it's plugged into. The bioprinter will stay idle tonight as meetup members work on upgrading its components.

Fallen leaves litter the sidewalk outside, but in the lab, a leaf made from scratch is harder to come by.

Plants and Animals

"Animal cells are finicky," says meetup leader Patrik D'haeseleer, noting that high-maintenance animal cells would require more monitoring than is possible at a community co-op lab like BioCurious.

D'haeseleer, a researcher in bioinformatics at Lawrence Livermore Lab, takes on projects such as the bioprinting meetup at BioCurious as a hobby. He points out that in the realm of bioprinting, little research has been conducted with plant cells. The focus is on animal cells, with the aim of developing printing techniques with biomedical applications, such as printing a piece of tissue that could be used to test new drugs, printing new skin cells or eventually, entire organs.

"It's much easier to get stem cells from plants," he says. It's a concept that anyone who's tried to grow a plant from a cutting has employed, knowingly or not. Stem cells are present when cuttings can take root.

The trick for the meetup will be to identify both the distribution methods and materials that will allow the leaf cells to grow together correctly. One possibility is a technique used in molecular gastronomy that suspends a liquid within little spheres—in this case, thousands of tiny spheres. So far, the meetup's bioprinter has had success printing bacteria cells.

"We don't want to compete with the biomedical," D'haeseleer says. The meetup's work is purely for scientific fun.

Already, the group has made available a how-to for its bioprinter (instructables.com/id/DIY-BioPrinter/). Its original model is deliberately DIY, a Frankenstein's monster of parts gleaned from other machines, including the framework of an old inkjet printer and the motor from an old CD drive. Cable ties strap down a couple parts—and is that a block of wood down at the base? The printer doesn't cost much to make—D'haeseleer estimates about $150—and the group tried to use parts readily available so that others might build their own home bioprinters. The sleekest thing about the whole rig is its thick Plexiglas top, laser-etched with the logo "BioCurious." That was custom-made at The Tech Shop.

In its first incarnation, the printer employed a recycled inkjet cartridge to distribute cells. However, the parts for the bioprinter are evolving, thanks in part to the conventional 3D printer that the group won after achieving an initial success: printing fluorescent E. coli cells in the shape of the BioCurious logo. Now the meetup is making upgrades to some of the printer's parts. Fine needles have already replaced the inkjet printer head and the syringe-holder box that volunteers just designed will replace an unsteady arrangement of plastic plates and screws.

It has taken about two years to construct a bioprinter that prints bacteria cells—not that long, considering that the progress of the BioCurious project relies strictly on members' availability and whatever knowledge (whether it's biology, engineering, computer science or design) they bring to the lab. Plus, the weekly meetup is an all-volunteer endeavor.

Elsewhere, bioprinting has already become part of an industry: biomedical engineering.

How It Works

The idea of "printing" a vital organ is lifesaving. Over 120,000 people are on the Organ Procurement and Transplantation Network waiting list in the United States (98,142 need kidneys and 15,839 need livers), and many more who need transplants don't qualify because of health risks, such as the risk of bodily rejection. By printing a kidney from one's own cells, the organ is more likely to be accepted by the body and thus function normally.

As recently as five years ago, experts mused on the possibility of printing internal structures like heart valves or complex systems like the pancreas, or even a complete heart, on demand and with a patient's own cells. The technology has the potential to revolutionize the way we view not only organ transplants, but drug research, cosmetic surgery and even space travel.

Though similar in theory, 3D bioprinting is vastly different from the 3D printing which has exploded in popularity in the past few years. Standard 3D printing uses a variety of inorganic materials (mostly plastics) to print everything from bobbleheads to handguns. One cannot simply print out a living tissue structure at home with a downloaded CAD drawing and a MakerBot home 3D printer.

A modern 3D bioprinter looks somewhat similar to a conventional 3D printer except it's larger, has much more circuitry and uses multiple printing nozzles—one for modeling material, called "hydrogel," and others containing cells called "bioink." Much like BioCurious' printer, early versions cannibalized inkjet cartridges, which were cleaned and sterilized, because human cells happen to be roughly the same size as older ink droplets (new ink cartridges are too fine for this).

Since living tissue is composed of many cell types, the different print heads expel the correct amount of a specific cell type along with the biodegradable hydrogel to hold it in place. The biogel structure creates a skeleton of sorts, called a scaffold, which degrades once the cells grow into the right shape. The trick is to find the right scaffold material that will support each different organ, promote cell growth and degrade after the right amount of time.

Because its cells regenerate on their own, the liver is a likely candidate to become the first bioprinted complex organ to be transplanted into a human. But as Wake Forest University's Institute for Regenerative Medicine director Anthony Atala says, "It is really impossible to predict when this technology would be available to patients through clinical trials." He estimates it will take at least a decade, "and likely much longer."

One major hurdle scientists face is building the intricate blood vessel networks needed to keep an organ alive. "In efforts to engineer solid organs such as the kidney and liver," says Atala, "it is a challenge to incorporate the large number of cells required and to engineer a vascular system that can keep the structures alive until they integrate with the body after implantation...
Read more