A scanning electron microscope (SEM) image of nanowire-alginate composite scaffolds. Star-shaped clusters of nanowires can be seen in these images. Image: The Disease Biophysics Group, Harvard University |
A
team of researchers at the Massachusetts Institute of Technology (MIT) and
Children’s Hospital Boston has built cardiac patches studded with tiny gold
wires that could be used to create pieces of tissue whose cells all beat in
time, mimicking the dynamics of natural heart muscle. The development could
someday help people who have suffered heart attacks.
The
study, reported in Nature Nanotechnology, promises to improve on
existing cardiac patches, which have difficulty achieving the level of
conductivity necessary to ensure a smooth, continuous “beat” throughout a large
piece of tissue.
“The
heart is an electrically quite sophisticated piece of machinery,” says Daniel
Kohane, a professor in the Harvard-MIT Division of Health Sciences and
Technology (HST) and senior author of the paper. “It is important that the
cells beat together, or the tissue won’t function properly.”
The
unique new approach uses gold nanowires scattered among cardiac cells as
they’re grown in vitro, a technique
that “markedly enhances the performance of the cardiac patch,” Kohane says. The
researchers believe the technology may eventually result in implantable patches
to replace tissue that’s been damaged in a heart attack.
Co-first
authors of the study are MIT postdoc Brian Timko and former MIT postdoc Tal
Dvir, now at Tel Aviv
University in Israel; other authors are their
colleagues from HST, Children’s Hospital Boston, and MIT’s Department of
Chemical Engineering, including Robert Langer, the David H. Koch Institute
Professor.
Ka-thump, ka-thump
To build new tissue, biological engineers typically use miniature scaffolds
resembling porous sponges to organize cells into functional shapes as they
grow. Traditionally, however, these scaffolds have been made from materials with
poor electrical conductivity—and for cardiac cells, which rely on electrical
signals to coordinate their contraction, that’s a big problem.
“In
the case of cardiac myocytes in particular, you need a good junction between
the cells to get signal conduction,” Timko says. But the scaffold acts as an
insulator, blocking signals from traveling much beyond a cell’s immediate
neighbors, and making it nearly impossible to get all the cells in the tissue
to beat together as a unit.
A wider SEM image of the nanowire-alginate composite scaffolds. Image: The Disease Biophysics Group, Harvard University |
To
solve the problem, Timko and Dvir took advantage of their complementary
backgrounds—Timko’s in semiconducting nanowires, Dvir’s in cardiac-tissue
engineering—to design a brand-new scaffold material that would allow electrical
signals to pass through.
“We
started brainstorming, and it occurred to me that it’s actually fairly easy to
grow gold nanoconductors, which of course are very conductive,” Timko says. “You can grow them to be a couple microns long, which is more than enough to
pass through the walls of the scaffold.”
From micrometers to millimeters
The team took as their base material alginate, an organic gum-like substance
that is often used for tissue scaffolds. They mixed the alginate with a
solution containing gold nanowires to create a composite scaffold with billions
of the tiny metal structures running through it.
Then,
they seeded cardiac cells onto the gold-alginate composite, testing the
conductivity of tissue grown on the composite compared to tissue grown on pure
alginate. Because signals are conducted by calcium ions in and among the cells,
the researchers could check how far signals travel by observing the amount of
calcium present in different areas of the tissue.
“Basically,
calcium is how cardiac cells talk to each other, so we labeled the cells with a
calcium indicator and put the scaffold under the microscope,” Timko says.
There, they observed a dramatic improvement among cells grown on the composite
scaffold: The range of signals conduction improved by about three orders of
magnitude.
“In
healthy, native heart tissue, you’re talking about conduction over
centimeters,” Timko says. Previously, tissue grown on pure alginate showed
conduction over only a few hundred micrometers, or thousandths of a millimeter.
But the combination of alginate and gold nanowires achieved signal conduction
over a scale of “many millimeters,” Timko says.
“It’s
really night and day. The performance that the scaffolds have with these
nanomaterials is just much, much better,” Kohane says.
The
researchers plan to pursue studies in
vivo to determine how the composite-grown tissue functions when implanted
into live hearts. Aside from implications for heart-attack patients, Kohane
adds that the successful experiment “opens up a bunch of doors” for engineering
other types of tissues.
