To recreate that scaffold, the researchers used a nanofiber production platform known as pull spinning, developed in Parker's Disease Biophysics Group. Pull spinning uses a high-speed rotating bristle that dips into a polymer reservoir and pulls a droplet from the solution into a jet. The fiber travels in a spiral trajectory and solidifies before detaching from the bristle and moving toward a collector.

To make the ventricle, the researchers used a combination of biodegradable polyester and gelatin fibers that were collected on a rotating collector shaped like a bullet. Because the collector is spinning, all of the fibers align in the same direction.


"It is important to recapitulate the structure of the natural muscle to obtain ventricles that function like their natural counterparts," said MacQueen. "When the fibers are aligned, the cells will be aligned, which means they will conduct and contract the way that native cells do."

After building the scaffold, the researchers cultured the ventricle with either rat myocytes or human cardiomyocytes from induced stem cells. Within three to five days, a thin wall of tissue covered the scaffold and cells were beating in synch. From there, researchers could control and monitor the calcium propagation and insert a catheter to study the pressure and volume of the beating ventricle.

The researchers exposed the tissue to isoproterenol, a drug similar to adrenaline, and measured as the beat-rate increased just as it would in human and rat hearts. The researchers also poked holes in the ventricle to mimic a myocardial infarction, and studied the effect of the heart attack in a petri dish that resulted.

To better study the ventricle over long periods of time, the researchers built a self-contained bioreactor with separate chambers for optional valve inserts, additional access ports for catheters and optional ventricular assist capabilities.

Using human cardiomyocytes from induced stem cells, the researchers were able to culture the ventricles for 6 months and measure stable pressure-volume loops. "The fact that we can study this ventricle over long periods of time is really good news for studying the progression of diseases in patients as well as drug therapies that take a while to act," said MacQueen.

Next, the researchers aim to use patient-derived, pre-differentiated stem cells to seed the ventricles, which would allow for more high-throughput production of the tissue.

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