Building heart tissue that beats: Engineered tissue closely mimics natural heart muscle

They presented their latest results at the 247^th National Meeting & Exposition of the American Chemical Society (ACS) in Dallas this week.

"Repairing damaged hearts could help millions of people around the world live longer, healthier lives," said Nasim Annabi, Ph.D. Right now, the best treatment option for patients with major heart damage -- which can be caused by severe heart failure, for example -- is an organ transplant. But there are far more patients on waitlists for a transplant than there are donated hearts. Even if a patient receives a new heart, complications can arise.

The ideal solution would be to somehow repair the tissue, which can get damaged over time when arteries are clogged and starve a part of the heart of oxygen. Scientists have been searching for years for the best fix. The quest has been confounded by a number of factors that come into play when designing a complex organ or tissue.

Simple applications, such as engineered skin, are already in use or in clinical trials. But building tissue for an organ as complicated as the heart requires a lot more research. To address this challenge and engineer complex 3-D tissues, researchers at the Brigham and Women's Hospital and Harvard Medical School in Boston and the University of Sydney in Australia were able to combine a novel elastic hydrogel with microscale technologies to create an artificial cardiac tissue that mimics the mechanical and biological properties of the native heart.

"Our hearts are more than just a pile of cells," said Ali Khademhosseini, Ph.D., who is at Harvard Medical School. "They're very organized in their architecture."

To tackle the challenge of engineering heart muscle, Khademhosseini and Annabi have been working with natural proteins that form gelatin-like materials called hydrogels.

"The reason we like these materials is because in many ways they mimic aspects of our own body's matrix," Khademhosseini said. They're soft and contain a lot of water, like many human tissues.

His group has found that they can tune these hydrogels to have the chemical, biological, mechanical and electrical properties they want for the regeneration of various tissues in the body. But there was one way in which the materials didn't resemble human tissue. Like gelatin, early versions of the hydrogels would fall apart, whereas human hearts are elastic. The elasticity of the heart tissue plays a key role for the proper function of heart muscles such as contractile activity during beating. So, the researchers developed a new family of gels using a stretchy human protein aptly called tropoelastin. That did the trick, giving the materials much needed resilience and strength.

But building tissue is not just about developing the right materials. Making the right hydrogels is only the first step. They serve as the tissue scaffold. On it, the researchers grow actual heart cells. To make sure the cells form the right structure, Khademhosseini's lab uses 3-D printing and microengineering techniques to create patterns in the gels. These patterns coax the cells to grow the way the researchers want them to. The result: small patches of heart muscle cells neatly lined up that beat in synchrony within the grooves formed on these elastic substrates. These micropatterned elastic hydrogels can one day be used as cardiac patches. Khademhosseini's group is now moving into tests with large animals. They are also using these elastic natural hydrogels for the regeneration of other tissues such as blood vessels, skeletal muscle, heart valves and vascularized skin.