'Cyborg organoids' built from scratch with integrated sensors

To get a peek into how cells combine to form tissues and how tissues lay the foundations of organs, you can check in at different times using a microscope as they grow—or, you can build the organ itself around a mesh of integrated, electric sensors.

The so-called “cyborg organoids” developed by researchers at Harvard University’s John A. Paulson School of Engineering and Applied Sciences aim to track the earliest stages of tissue development and differentiation.

Their work, published in the journal Nano Letters, followed stem cells as they morphed into beating heart cells while measuring electrophysiological activity for about three months. 

“I was so inspired by the natural organ development process in high school, in which 3D organs start from few cells in 2D structures,” said senior study author Jia Liu, an assistant professor of bioengineering at the school.

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“I think if we can develop nanoelectronics that are so flexible, stretchable and soft that they can grow together with developing tissue through their natural development process, the embedded sensors can measure the entire activity of this developmental process,” Liu said. “The end result is a piece of tissue with a nanoscale device completely distributed and integrated across the entire three-dimensional volume of the tissue.”

Liu’s work began with flexible, netlike nanoelectronics developed to be injected into specific areas of tissues. By altering the warp and weft of the mesh, making it more stretchable and transferring it to a flat sheet of stem cells, the researchers saw how the cells surrounded and took up the sensors as they grew to form a 3D shape.

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The team believes this could help answer fundamental questions in biology as well as be used to test cellular responses to different therapies.

“This method allows us to continuously monitor the developmental process and understand how the dynamics of individual cells start to interact and synchronize during the entire developmental process,” Liu said. “It could be used to turn any organoid into cyborg organoids, including brain and pancreas organoids.”

Video courtesy of Jia Liu and Harvard University's John A. Paulson School of Engineering and Applied Sciences.