Cardiac tissue cellular alignment programmed via bioprinting

SOPHIA CHEN: Welcome to MRS Bulletin’s Materials News Podcast, providing breakthrough news & interviews with researchers on the hot topics in materials research. My name is Sophia Chen. The most common birth defects occur in the heart. One common problem is a hole between chambers of the heart, which causes oxygenated blood from the lungs to mix with deoxygenated blood from the body. The heart pumps oxygen-rich blood back into the lungs instead of the body, which makes the heart work harder. John Ahrens, a bioengineering graduate student at Harvard University, is working to make biomaterials to cure these problems. In his research, he devises methods to make heart tissue. 

JOHN AHRENS: What would be a dream would be to create a tissue that matches the cellular architecture of that patient, wherever that hole is. And then ideally, it could even grow with the patient. 

SOPHIA CHEN: Ahrens says they’re still a long way from this type of cure, but recently his lab made a significant advance to address a particular design challenge of making heart tissue. That challenge is creating tissue with the correct alignment. You can think of alignment this way: Heart cells are narrow and rectangular in shape. In a natural heart, they line up in parallel to form aligned filaments. Then those aligned filaments are built up into a larger tissue with more complex alignment. 

JOHN AHRENS: If you want to fix a hole in someone's heart, then that tissue would have pretty complex alignment. 

SOPHIA CHEN: The alignment of the tissue is crucial for the heart to function. 

JOHN AHRENS: It actually twists to pump blood effectively out of the body. And that twisting motion come from this really complex alignment, where it changes through the thickness of the myocardial wall, or the thickness of your heart. 

SOPHIA CHEN: To create the alignment, Ahrens’s team uses a method known as bioprinting, which is a fancy term for squeezing material out of a syringe in a highly controlled manner.

JOHN AHRENS: What we attach it to is really complex, what we call a gantry, a really complex machine that is able to very finely move up and down and side to side. And it can speed up and slow down. And we can program all of that. But at the end of the day, all we’re doing is squeezing things out of a nozzle. 

SOPHIA CHEN: Previously, researchers had been able to align small units of tissue in one direction. Ahrens’s group took tens of thousands of these little tissues to create larger tissues that they aligned in complex ways. Ahrens describes their method to create alignment using an analogy. Imagine several logs aligned in all different directions flowing down a river. Over time, those logs will align parallel to the direction of flow. In a similar way, the material that comes out of the machine is aligned with the direction that the nozzle moves. 

JOHN AHRENS: By changing the speed, and the direction, and the print path, we're able to get different tissues with different orientations and different functions. And so in that sense, we're programming that function. 

SOPHIA CHEN: Their tissue samples were about a centimeter in size, about the thickness of a human heart. The material’s density was roughly between 100 and 300 million cells per milliliter, very similar to a natural heart. They demonstrated a few different alignments. They could make tissues that were aligned vertically, in a circular pattern, or even in the shape of a chevron.

JOHN AHRENS: We just wanted to demonstrate some orientations that are more difficult, that you couldn't really do without just by relying purely on self-assembly. 

SOPHIA CHEN: They evaluated the samples by staining them to see their alignment. They also placed the tissues on a platform where they could measure the force of the cells as they contracted, as heart muscles do. In future work, they will need to figure out to make bigger tissues and how to incorporate blood vessels to provide oxygen and nutrients to all the tissue. This research took four years of work, says Ahrens. He’s been motivated by the real-world application of this technology. During the first part of his graduate studies, he spent time at Boston Children’s Hospital, learning from doctors about real patients with congenital heart defects.  

JOHN AHRENS: It’s important to remember that it’s not just for a paper. Ultimately what we’re all trying to do in this bioengineering space and in cardiac tissue engineering is really change how we approach to try and treat disease. 

SOPHIA CHEN: This work was published in a recent issue of Advanced Materials. My name is Sophia Chen from the Materials Research Society. For more news, log onto the MRS Bulletin website at mrsbulletin.org and follow us on twitter, @MRSBulletin. Don’t miss the next episode of MRS Bulletin Materials News – subscribe now. Thank you for listening.