New Bioprinter Makes It Easier to Fabricate 3D Flesh and Bone

Photo: Danny Cabera

The ideal 3D bioprinter, says tissue engineering expert Y. Shrike Zhang, would resemble a breadmaker: “You’d have a few buttons on top, and you’d press a button to choose heart tissue or liver tissue.” Then Zhang would walk away from the machine while it laid down complex layers of cells and other materials. 

The technology isn’t quite there yet. But the new BioBot 2 printer seems a step in that direction. The tabletop device includes a suite of new features designed to give users easy control over a powerful device, including 

• automated calibration; 
• six print heads to extrude six different bioinks; 
• placement of materials with 1-micrometer precision on the x, y, and z axes; and 
• a user-friendly software interface that manages the printing process from beginning to end.

BioBots cofounder and CEO Danny Cabrera says the BioBot 2’s features are a result of collaboration with researchers who work in tissue engineering.“To push this work forward, we had to do more than just develop a new robot.”—Danny Cabrera, CEO of BioBots

“We’ve been working closely with scientists over the past year and a half to understand what they need to push this work forward,” he says. “What we found is that they needed more than just a bioprinter—and we had to do more than just develop a new robot.”

The company’s cloud-based software makes it easy for users to upload their printing parameters, which the system translates into protocols for the machine. After the tissue is printed, the system can use embedded cameras and computer-vision software to run basic analyses. For example, it can count the number of living versus dead cells in a printed tissue, or measure the length of axons in printed neurons. “This platform lets them measure how different printing parameters, like pressure or cellular resolution, affect the biology of the tissue,” Cabrera says.

The BioBot 1 hit the market in 2015 and sells for US $10,000. The company is now taking orders for the $40,000 BioBot 2, and plans to ship later this year. 

Photo: Danny Cabrera BioBots will soon begin selling a kit with all the materials necessary to print soft tissue, such as cartilage.

Each of the BioBot 2’s print heads can cool its bioink to 4 degrees Celsius or heat it to 200 degrees Celsius. The printbed is also temperature-controlled, and it’s equipped with visible and ultraviolet lights that trigger cross-linking in materials to give make printed forms more solid. 

Cabrera says the temperature controls make it easier to print collagen, a principal component of connective tissue and bone, because it cross-links at colder temperatures. “A lot of people were hacking their bioprinters to get collagen to print,” Cabrera says. “Some were printing in the refrigerator.”

While some researchers won’t be interested in using the six print heads to make tissue composed of six different materials, Cabrera says the design also allows researchers to multiplex experiments. For example, if researchers are experimenting with the concentration of cells in a bioink, this setup allows them to simultaneously test six different versions. “That can save weeks if you have to wait for your cells to grow after each experiment,” Cabrera says.

And the machine can deposit materials not only on a petri dish, but also into a cell-culture plate with many small wells. With a 96-well plate, “you could have 96 lilttle experiments,” says Cabrera. 

Photo: Danny Cabrera. Another kit will include the materials needed to print bone and other hard tissue.

One long-term goal of bioprinting is to give doctors the ability to press a button and print out a sheet of skin for a burn patient, or a precisely shaped bone graft for someone who’s had a disfiguring accident. Such things have been achieved in the lab, but they’re far from gaining regulatory approval. An even longer-term goal is to give doctors the power to print out entire replacement organs, thus ending the shortage of organs available for transplant, but that’s still in the realm of sci-fi. 

While we wait for those applications, however, 3D bioprinters are already finding plenty of uses in biomedical research. 

Zhang experimented with an early beta version of the BioBot 1 while working in the Harvard Medical School lab of Ali Khademhosseini. He used bioprinters to create organ-on-a-chip structures, which mimic the essential nature of organs like hearts, livers, and blood vessels with layers of the appropriate cell types laid down in careful patterns. These small chips can be used for drug screening and basic medical research. With the BioBot beta, Zhang made a “thrombosis-on-a-chip” where blood clots formed inside miniature blood vessels. 

Now an instructor of medicine and an associate bioengineer at Brigham and Women’s Hospital in Boston, Zhang says he’s intrigued by the BioBot 2. Its ability to print with multiple materials is enticing, he says, because he wants to reproduce complex tissues composed of different cell types. But he hasn’t decided yet whether he’ll order one. Like so much in science, “it depends on funding,” he says. 

Photo: EnvisionTec

The BioBot 2 is on the cheaper end of the bioprinter market.

The top-notch machines used by researchers who want nanometer-scale precision typically cost around $200,000—like the large 3D-Bioplotter from EnvisionTec. This machine was used in research announced just today, in which Northwestern University scientists 3D-printed a structure that resembled a mouse ovary. When they seeded it with immature egg cells and implanted it into a mouse, the animal gave birth to live pups. 

Photo: Cellink

But there are a few other bioprinters that compete with the BioBot machines on price. Most notably, a Swedish company called Cellink sells three desktop-sized bioprinters that range in price from $10,000 to $40,000. 

And a San Francisco startup called Aether just recently began sending beta units to researchers for testing and feedback; the company has promised to begin selling its Aether 1 this year for only $9000.

Photo: Aether

The biggest source of competition may not be other companies, but bioengineers’ innate propensity for tinkering. “We’ll often get some basic sort of printer and make our own print heads and bioinks,” Zhang says.

But for biology researchers who don’t have an engineering background, Zhang says, the BioBot 2 would provide a powerful boost in abilities. It would be almost like giving a kitchen-phobic individual the sudden capacity to bake a perfect loaf of whole wheat bread. 

Learn More 3D-Bioplotter Aether EnvisionTec 3D printer BioBot bioprinterCellink tissue engineering BioBot 2

ORIGINAL: IEEE Spectrum

By Eliza Strickland

Posted 16 May 2017