The Tell-tale Heart: Researchers 3D Print Organ-on-a-Chip

Programmable 3D organ-on-a-chip printing system fabricates a heart-on-a-chip

2 min read
3D-printed organ-on-a-chip with integrated sensors
Eight cells comprise each 3D-printed organ-on-a-chip with integrated sensors.
Photo: Johan U. Lind/Harvard University

Researchers have used a 3D printer and six novel bioinks to build a “heart-on-a-chip” that can serve as a living organ for drug testing. The device, developed by a team of bioengineers out of Harvard’s Wyss Institute, was described this week in Nature Materials.

The Wyss team’s heart is the first organ-on-a-chip to be built with a 3D printer. The system can be programmed to print different types of organ-chips, and allows for automated production. “The whole field has been building one-offs [of organ-chips] that aren’t amenable to mass manufacturing,” says Kit Parker, a bioengineer at Wyss and an author of the paper. “We solved that.”

That may be enticing to pharmaceutical companies and academic labs that want to speed up the drug screening process. With mass produced organ-chips, those groups can test how living tissue might respond to a new drug without using animals or humans as test subjects.

The Wyss team’s device also automates the process of collecting data from the organ. By building sensors into the chip, the team enabled the device to spit out data on how it’s doing. That takes away the laborious process of optically measuring an organ-chip’s response, says Jennifer Lewis, a materials scientist at Wyss and an author of the paper. In the past, we “were literally sitting over a microscope taking video...and then going back in to do image analysis to try to measure” the organ’s response, she says. “It’s very difficult and imprecise,” she says.

The Wyss heart-on-a-chip is printed in one shot. After it’s completed, heart muscle cells, called cardiomyocytes, are added and grown in the chip’s eight wells. Scientists can then expose the cells to drugs or stressful environmental conditions and measure them to see how they perform.

The key indicator is the strength of the beat of the cells—like the strength of a beating heart. To measure this, each well contains a hairpin-shaped cantilevered flap made out of a piezo-resistive, biocompatible ink. Heart cells are added to the wells, and when they beat, they cause the cantilevered flap to elongate. That change in resistance creates a measurable change in electrical response.

“The resistance varies depending on how well the cells are beating,” says Lewis. A drug that’s bad for the cells diminishes the strength of the beat.

The Wyss team programmed the system to print a heart, but any muscular organ can be replicated using this chip design, says Parker. The gut, airways, vascular system, tongue, and skeletal muscle are all candidates for this type of mass manufactured organ-chip, he says.

The 3D-printed heart-on-a-chip is the most recent in a slew of organ-chips developed by the Wyss group. Previously developed chips, including a lunggut, kidney, tongue, and heart, were built as one-offs using multi-step microfluidic processes. The projects are part of a larger effort at Wyss to develop 10 organ-chips and link them together to mimic the human body. The work is supported by a US $37 million grant from DARPA, the U.S. military’s research arm.

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This CAD Program Can Design New Organisms

Genetic engineers have a powerful new tool to write and edit DNA code

11 min read
A photo showing machinery in a lab

Foundries such as the Edinburgh Genome Foundry assemble fragments of synthetic DNA and send them to labs for testing in cells.

Edinburgh Genome Foundry, University of Edinburgh

In the next decade, medical science may finally advance cures for some of the most complex diseases that plague humanity. Many diseases are caused by mutations in the human genome, which can either be inherited from our parents (such as in cystic fibrosis), or acquired during life, such as most types of cancer. For some of these conditions, medical researchers have identified the exact mutations that lead to disease; but in many more, they're still seeking answers. And without understanding the cause of a problem, it's pretty tough to find a cure.

We believe that a key enabling technology in this quest is a computer-aided design (CAD) program for genome editing, which our organization is launching this week at the Genome Project-write (GP-write) conference.

With this CAD program, medical researchers will be able to quickly design hundreds of different genomes with any combination of mutations and send the genetic code to a company that manufactures strings of DNA. Those fragments of synthesized DNA can then be sent to a foundry for assembly, and finally to a lab where the designed genomes can be tested in cells. Based on how the cells grow, researchers can use the CAD program to iterate with a new batch of redesigned genomes, sharing data for collaborative efforts. Enabling fast redesign of thousands of variants can only be achieved through automation; at that scale, researchers just might identify the combinations of mutations that are causing genetic diseases. This is the first critical R&D step toward finding cures.

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