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Heart Components Produced with 3-D Printing

Bioprinted heart valve

Trileaflet heart valve bioprinted in collagen (Carnegie Mellon University)

2 Aug. 2019. Researchers developed techniques for accurate three-dimensional printing of human heart elements with bio-inks containing the cellular framework on which tissue can grow. A bioengineering team from Carnegie Mellon University in Pittsburgh describes its process in today’s issue of the journal Science.

The techniques are protected by a U.S. patent assigned to Carnegie Mellon University. Two of the authors also formed the company FluidForm in Acton, Massachusetts to commercialize the technology.

Researchers led by biomedical engineering and materials science professor Adam Feinberg are seeking advances in 3-D printing to alleviate the shortage of human organs available for transplant at any one time, as well as provide better treatment options for people with organ failure. As of now, 3-D printing can produce patterned tissues and implantable scaffolds for regenerative medicine, but up to recently, could not produce soft biomaterials with the precision and resolution needed to function in vital organs like the heart.

A team in Israel, as reported by Science & Enterprise in April, demonstrated 3-D printing of human heart tissue, including blood vessels, from cells donated by living person. Feinberg and colleagues aim to extend that technology into a more scalable and reproducible process, using collagen, the material in extracellular matrix making up the structural framework of cells. But in its natural form, extracellular matrix is difficult to 3-D print with accuracy and consistency.

“Collagen is an extremely desirable biomaterial to 3-D print with because it makes up literally every single tissue in your body,” says co-lead author Andrew Hudson in a university statement. “What makes it so hard to 3-D print, however, is that it starts out as a fluid. So if you try to print this in air, it just forms a puddle on your build platform.”

The researchers developed a process they call Fresh, short for freeform reversible embedding of suspended hydrogels, to overcome this obstacle. With Fresh, collagen is printed layer-by-layer in a salt-based gelatin bath. The gel then melts away at room or body temperature leaving the 3-D printed structure intact. The process also allows for adding in other biomaterials, including alginate, fibrinogen, and hyaluronic acid with collagen in a single printing process.

With Fresh, the Carnegie Mellon team 3-D printed the frameworks for arteries with a resolution of 20 micrometers, where 1 micrometer equals 1 millionth of a meter, allowing for cells to quickly populate and grow. The researchers also printed a heart ventricle or chamber model with Fresh containing cardiomyocytes or heart tissue cells that showed synchronized contractions similar to human hearts. The team then printed a full-size tri-leaflet heart valve, a component of the heart that fails in many people, and a full-scale neonatal heart model, based on MRI scans, to prove the concept.

The researchers believe the Fresh method can be applied to other human organs as well as tissue for healing wounds. “It is important to understand,” notes Feinberg, “that there are many years of research yet to be done, but … we’re making real progress towards engineering functional human tissues and organs, and this paper is one step along that path.”

Feinberg and Hudson co-founded FluidForm in 2018. FluidForm is developing Fresh into a commercial process, as well as marketing the supporting gel bath for Fresh it calls LifeSupport. Feinberg is the company’s chief technology officer, while Hudson is its chief operations officer.

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