Researchers at Tel Aviv University relied on principles of origami—the Japanese art of paper-folding—to develop an innovative solution for a problem that has proved troubling worldwide: positioning sensors inside 3D-bioprinted tissue models. Instead of bioprinting tissue over the sensors (found to be impracticable), they designed and produced an origami-inspired structure that folds around the fabricated tissue, allowing the insertion of sensors into precisely pre-defined locations.
The researchers are Noam Rahav, Adi Soffer, professor Ben Maoz, professor Uri Ashery, Denise Marrero, Emma Glickman, Megane Beldjilali-Labro, Yakey Yaffe, Keshet Tadmor and Yael Leichtmann-Bardoogo. The paper was published in the journal Advanced Science.
Maoz notes that “the use of 3D-bioprinters to print biological tissue models for research is already widespread. In existing technologies, the printer head moves back and forth, printing layer upon layer of the required tissue.”
However, the method has a significant drawback, he says, explaining that “the tissue cannot be bioprinted over a set of sensors needed to provide information about its inner cells, because in the process of printing the printer head breaks the sensors. We propose a new approach to the complex problem: origami.”
Using CAD (Computer Aided Design) software, the researchers designed a multi-sensing structure customized for a specific tissue model inspired by origami paper-folding. This structure incorporates various sensors for monitoring the electrical activity or resistance of cells in precisely chosen locations within the tissue. The computer model is used to manufacture a physical structure which is then folded around the bioprinted tissue so that each sensor is inserted into its predefined position inside the tissue.
The TAU team has named their novel platform MSOP: Multi-Sensor Origami Platform. The new method’s effectiveness was demonstrated on 3D-bioprinted brain tissues with the inserted sensors recording neuronal electrical activity.
The researchers emphasize, however, that the system is both modular and versatile. It can place any number and any type of sensors in any chosen position within any type of 3D-bioprinted tissue model, as well as in tissues grown artificially in the lab, such as brain organoids—small spheres of neurons simulating the human brain.
“For experiments with bioprinted brain tissue, we demonstrated an additional advantage of our platform: the option for adding a layer that simulates the natural blood-brain barrier (BBB)—a cell layer protecting the brain from undesirable substances carried in the blood, which unfortunately also blocks certain medications intended for brain diseases,” says Maoz. “The layer we add consists of human BBB cells, enabling us to measure their electrical resistance which indicates their permeability to various medications.”
The study was a joint effort of researchers from several units at TAU, including the School of Neurobiology, Biochemistry and Biophysics; Koum Center for Nanoscience and Nanotechnology; Department of Biomedical Engineering; Sagol Center for Regenerative Medicine; Sagol School of Neuroscience; and Drimmer-Fischler Family Stem Cell Core Laboratory for Regenerative Medicine.
“In this study, we created an ‘out-of-the-box’ synergy between scientific research and art,” the researchers summarize. “We developed a novel method inspired by origami paper-folding—enabling the insertion of sensors into precisely predefined locations within 3D-bioprinted tissue models—to detect and record cell activity and communication between cells. This new technology is an important step forward for biological research.”