Carbon Nanotubes Help Grow Beating Heart Tissue

Heart attacks kill muscle cells called cardiomyocytes, leaving behind tissue damage. If scientists could grow cardiac tissue in the lab, they could perhaps graft patches of healthy tissue onto a patient’s damaged heart. A new carbon nanotube-studded hydrogel acts as a scaffold for growing cardiac tissue that beats spontaneously (ACS Nano, DOI: 10.1021/nn305559j).

One challenge for growing heart tissue in the lab is finding a material that simulates the environment of the heart, says Ali Khademhosseini, a bioengineer at Harvard Medical School. For the tissue to function properly, it needs a scaffold that is electrically conductive to transmit the cell-to-cell signals that regulate muscle contractions. The material also must be mechanically strong to withstand repeated contractions.

Previous studies have shown that cardiomyocytes can grow on porous scaffolds such as gels made from alginate or gelatin. However, these materials are poor conductors. To make a conductive scaffold, Khademhosseini and his colleagues, including Xiaowu (Shirley) Tang of the University of Waterloo, in Ontario, enveloped carbon nanotubes in a crosslinked gelatin film.

The team coated the nanotubes with gelatin modified with methacrylate monomers. They then shone light on the nanotubes to crosslink the methacrylate, producing a hydrogel. The nanotubes formed a fibrous network that connected pores of the gel. These nanotube strands mimic conductive fibers in heart muscle called Purkinje fibers, Khademhosseini says.

To grow tissue on the scaffolds, the researchers pipetted newborn rat cardiomyocytes on the gel. After a day, the cells spread out across the surface, aligning with each other and forming connections like cells in natural heart tissue. In contrast, cardiomyocytes seeded on a gel lacking carbon nanotubes grew only in patches of randomly arranged cells. The researchers think that the nanotube network may help the growing cardiomyocytes to organize properly, mimicking the role of collagen fibers in natural tissues.

The cultured cardiomyocytes contracted spontaneously, a property of normal cardiac tissues. The researchers could make the beating more regular by applying an electric pulse.

The nanotube-grown cells had spontaneous beating rates that were three times faster—and more similar to those of natural tissue—than the gelatin-only cells. Also, the nanotube material produced cells that required an 85% weaker electric field to stimulate contractions than that needed by cells grown on only gelatin. The mechanical integrity of the nanotube scaffold was also stronger, allowing it to withstand repeated cardiomyocyte contractions, whereas the gel lacking nanotubes ruptured quickly.

In addition to medical applications, the cardiac patches may prove useful as actuators—devices that convert energy into motion in mechanical devices. Scientists have already incorporated actuating tissues into tiny robots to produce rudimentary cyborgs. Khademhosseini and his colleagues showed that 1-cm² patches of lab-grown heart tissue rolled up into tubes or folded into triangles or other shapes, some of which could swim around a petri dish.

The new scaffold material is a “clever application that utilizes the main properties of carbon nanotubes—their fiber-like morphology, high electrical conductivity, and high mechanical strength,” says Hongjie Dai, a physical chemist at Stanford University. However, Dai notes that the work is still in its early stages and that the researchers must show that the lab-grown cardiac tissue is functional when transplanted into animals.

Khademhosseini agrees that medical applications of the scaffold still have a long way to go. The scaffold’s actuator applications may be closer to realization, he adds.