In an innovative marriage of living cells and a synthetic substrate, bioengineers at Harvard University have found that a rubberlike, elastic film coated with a single layer of cardiac muscle cells can semi-autonomously engage in lifelike gripping, pumping, walking, and swimming. The tissue engineering feat was reported in the Sept. 7 issue of the journal Science.
The researchers, led by Kevin Kit Parker and Adam W. Feinberg, report that the exact movement undertaken by these hybrid muscular thin films (MTFs) can be tailored by controlling muscle alignment relative to the shape of the flexible film. Some of the MTFs even contract spontaneously, an intrinsic property of cardiac muscle that allows the devices to move around without user intervention.
“These MTFs can be thought of as soft robotic devices, or interchangeable machine parts made of cardiac muscle cells,” says Parker, assistant professor of biomedical engineering in Harvard’s School of Engineering and Applied Sciences. “With their thin polymer backing, they are uniquely durable and provide high specific force with good power and excellent spatial and temporal control.”
Parker and Feinberg engineered the adhesion and alignment of rat heart muscle cells onto thin films of a polymer called polydimethylsiloxane. Key to the MTFs’ high contractile forces was the alignment of all the muscle cells in a single direction, allowing the billions of molecular motors inside the cells, organized into structures called sarcomeres, to simultaneously fire and produce one big contraction.
“By carefully engineering the interface between the polymer film and the muscle cells,” says Feinberg, a postdoctoral researcher in Harvard’s School of Engineering and Applied Sciences, “we can combine the incredible properties of biological systems with manmade materials.”
The thin films can be sliced into any shape with an ordinary scalpel, hinting at the way these biohybrid materials may one day be used in the operating room. Both the shape of the MTF and the orientation of the sarcomeres on it affect the type of action performed. For example, rectangular MTFs with sarcomeres arrayed lengthwise roll up into tubes upon muscular contraction, resulting in a pumping action. A narrower, stiffer rectangular film contracts in a pinching motion, while a triangular MTF engages in a kind of walking.
Parker says there’s no reason to think such films couldn’t be made of other types of cells. While myocardial MTFs might eventually be useful as patches implanted in the heart to give a bit more oomph to a weakened location, thin films made with skin cells could be fashioned into wound dressings that are durable and protective like adhesive bandages, but with the added healing powers of actual skin cells.
The cell-polymer hybrids could also be very useful to scientists as models of cellular behavior.
“Because we know the stiffness of the polymer film, we can watch the MTF bend during contraction and calculate the exact force being generated by the muscle tissue,” says Feinberg.
“It’s often difficult for researchers to scale up studies from the level of single cells to the level of tissues,” Parker says. “Scientists could plate a polymer film with airway smooth muscle cells to simulate an asthma attack, with uterine cells to mimic the contractions of childbirth, or with cells from the gastrointestinal system to test new drugs for acid reflux or irritable bowel syndrome.”
While scientists have worked for years to develop artificial muscle, none of these efforts have succeeded in replicating natural muscle’s strength, rapid firing, or spatial capabilities. Parker’s group, which specializes in how cardiac muscle develops and how the heart’s function follows from its form, has perfected the engineering of two-dimensional structures requiring precise sarcomere placement, but such precision has proved elusive in attempts to build three-dimensional structures.
“This new approach sidesteps that limitation,” Feinberg says. “The three-dimensional shape is achieved by the spontaneous folding of a two-dimensional sheet.”
Parker and Feinberg’s co-authors on the Science paper are Alex Feigel, Sergey S. Shevkoplyas, and George M. Whitesides of Harvard’s Department of Chemistry and Chemical Biology, and Sean Sheehy of Harvard’s School of Engineering and Applied Sciences. The work was funded by the Defense Advance Research Projects Agency’s Biomolecular Motors Program, the Air Force Office of Sponsored Research, the Harvard Materials Research Science and Engineering Center, and the U.S. Army Research Office.