Scientists have created a three-dimensional (3D) organ-on-a-chip that can mimic the heart’s amazing biomechanical properties and could help in studying cardiac diseases, screening and development of drugs.
“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 Professor John Wikswo, from Vanderbilt University in the US.
“We believe it could prove invaluable in studying cardiac diseases, drug screening and drug development, and, in the future, in personalised medicine by identifying the cells taken from patients that can be used to patch damaged hearts effectively,” said Wikswo. The device faithfully reproduces the response of cardiac cells to two different drugs that affect heart function in humans, initial experiments have demonstrated.
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, which is continually stretching and contracting, in addition to its electrical and biochemical environment.
“Heart tissue, along with muscle, skeletal and vascular tissue, represents a special class of mechanically active biomaterials,” said Wikswo. “Mechanical activity is an intrinsic property of these tissues so you can’t fully understand how they function and how they fail without taking this factor into account,” he said.
The I-Wire device consists of a thin thread of human cardiac cells 0.014 inches thick stretched between two perpendicular wire anchors. The amount of tension on the fibre can be varied by moving the anchors in and out, and the tension is measured with a flexible probe that pushes against the side. The fibre is supported by wires and a frame in an optically clear well that is filled with 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 fibre. A floating microelectrode also measures the cells’ electrical activity. According to the researchers, the I-Wire system can be used to characterise 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.
Unlike other designs, I-Wire allows the researchers to grow cardiac cells under controlled, time-varying tension similar to what they experience in living hearts. The heart cells in the fibre align themselves in alternating dark and light bands, called sarcomeres, which are characteristic of human muscle tissue.
The research was published in the journal Acta Biomaterialia.
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