Scientists at Vanderbilt University have created a 3D organ-on-a-chip that can mimic the biomechanical properties of the heart. The device and the results of initial experiments are reported in the journal Acta Biomaterialia (for links see below).
|View of the cardiac fiber in the I-Wire device at two levels of magnification.
Credit: VIIBRE Vanderbilt University
The unique aspect of the new device, which represents about two-millionths of a human heart, is that it controls the mechanical force applied to cardiac cells. This allows the researchers to reproduce the mechanical conditions of the living heart in addition to its electrical and biochemical environment.
“We created the I-Wire Heart-on-a-Chip so that we can understand why cardiac cells behave the way they do by asking the cells questions, instead of just watching them,” said Gordon A. Cain University Professor John Wikswo, who heads up the project. “We believe it could prove invaluable in studying cardiac diseases, drug screening and drug development, and, in the future, in personalized medicine by identifying the cells taken from patients that can be used to patch damaged hearts effectively.”
The I-Wire device consists of a thin thread of human cardiac cells 0.014 inches thick (about the size of 20-pound monofilament fishing line) stretched between two perpendicular wire anchors. The amount of tension on the fiber can be varied by moving the anchors in and out, and the tension is measured with a flexible probe that pushes against the side of the fiber. The fiber is supported by wires and a frame in an optically clear well that is filled with a liquid medium like that which surrounds cardiac cells in the body. The apparatus is mounted on the stage of a powerful optical microscope that records the fiber’s physical changes. The microscope also acts as a spectroscope that can provide information about the chemical changes taking place in the fiber. A floating microelectrode also measures the cells’ electrical activity.
According to the researchers, the I-Wire system can be used to characterize how cardiac cells respond to electrical stimulation and mechanical loads and can be implemented at low cost, small size and low fluid volumes, which make it suitable for screening drugs and toxins. Because of its potential applications, Vanderbilt University has patented the device. Unlike other heart-on-a-chip designs, I-Wire allows the researchers to grow cardiac cells under controlled, time-varying tension similar to what they experience in living hearts.
To demonstrate the I-Wire’s value in determining the effects that different drugs have on the heart, the scientists tested its response with two drugs known to affect heart function in humans: isoproterenol and blebbistatin. Isoproterenol is a medication used to treat bradycardia (slow heart rate) and heart block (obstruction of the heart’s natural pacemaker). Blebbistatin inhibits contractions in all types of muscle tissue, including the heart.
According to Veniamin Sidorov, the research assistant professor at the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) who led its development, the device faithfully reproduces the response of cardiac cells in a living heart.
1. Sidorov, Veniamin Y., Philip C. Samson, Tatiana N. Sidorova, Jeffrey M. Davidson, Chee C. Lim, and John P. Wikswo. “I-Wire Heart-on-a-Chip I: Three-dimensional cardiac tissue constructs for physiology and pharmacology.” Acta Biomaterialia 48 (2017): 68-78. doi:10.1016/j.actbio.2016.11.009.
2. Schroer, Alison K., Matthew S. Shotwell, Veniamin Y. Sidorov, John P. Wikswo, and W. David Merryman. “I-Wire Heart-on-a-Chip II: Biomechanical analysis of contractile, three-dimensional cardiomyocyte tissue constructs.” Acta Biomaterialia 48 (2017): 79-87. doi:10.1016/j.actbio.2016.11.010.
Research funding: National Institutes of Health, National Science Foundation, Defense Threat Reduction Agency, American Heart Association, Department of Veterans Affairs.
Adapted from press release by Vanderbilt University.