Nanotubes improve paediatric heart-defect patches

Texas Children’s Hospital and Rice University have developed new patches infused with conductive single-walled carbon nanotubes that enhance electrical connections between cells.

The invention could serve as a full-thickness patch to repair defects due to tetralogy of fallot, atrial and ventricular septal defects and other defects without the risk of inducing abnormal cardiac rhythms.

A team led by bioengineer Jeffrey Jacot and chemical engineer and chemist Matteo Pasquali developed the patches, made of a sponge-like bioscaffold that contains microscopic pores and mimics the body’s extracellular matrix.

The nanotubes overcome a limitation of current patches in which pore walls hinder the transfer of electrical signals between cardiomyocytes, the heart muscle’s beating cells, which take up residence in the patch and eventually replace it with new muscle.

Researchers at Rice and elsewhere have found that once cells take their place in the patches, they have difficulty synchronising with the rest of the beating heart because the scaffold mutes electrical signals that pass from cell to cell. That temporary loss of signal transduction results in arrhythmias.

Nanotubes can fix that, and Jacot, who has a joint appointment at Texas Children’s and Rice, took advantage of the surrounding collaborative research environment.

Three otherwise identical patches darken with greater concentrations of carbon nanotubes, which improve electrical signalling between immature heart cells in patches invented at Rice University and Texas Children’s Hospital. (Credit: Jacot Lab/Rice University)

Nanotubes enhance the electrical coupling between cells that invade the patch, helping them keep up with the heart’s steady beat. “When cells first populate a patch, their connections are immature compared with native tissue,” Jacot said. The insulating scaffold can delay the cell-to-cell signal further, but the nanotubes forge a path around the obstacles.

Jacot said the relatively low concentration of nanotubes - 67 parts per million in the patches that tested best - is key. Earlier attempts to use nanotubes in heart patches employed much higher quantities and different methods of dispersing them. Jacot’s lab found a component they were already using in their patches - chitosan - keeps the nanotubes spread out. Because the toxicity of carbon nanotubes in biological applications remains an open question, Pasquali said, the fewer one uses, the better.

The patches start as a liquid. When nanotubes are added, the mixture is shaken through sonication to disperse the tubes, which would otherwise clump, due to van der Waals attraction. Clumping may have been an issue for experiments that used higher nanotube concentrations, Pasquali said.

The material is spun in a centrifuge to eliminate stray clumps and formed into thin, fingernail-sized discs with a biodegradable polycaprolactone backbone that allows the patch to be sutured into place. Freeze-drying sets the size of the discs’ pores, which are large enough for natural heart cells to infiltrate and for nutrients and waste to pass through.

As a side benefit, nanotubes also make the patches stronger and lower their tendency to swell while providing a handle to precisely tune their rate of degradation, giving hearts enough time to replace them with natural tissue, Jacot said.

“If there’s a hole in the heart, a patch has to take the full mechanical stress,” he said. “It can’t degrade too fast, but it also can’t degrade too slow, because it would end up becoming scar tissue. We want to avoid that.” Pasquali noted that Rice’s nanotechnology expertise and Texas Medical Center membership offers great synergy.