Researchers at Linköping, Lund, and Gothenburg Universities in Sweden have successfully grown gel-based electrodes in living tissue using the body’s molecules as triggers. By injecting a gel containing enzymes as the assembly molecules, the researchers were able to form the electrodes in the tissue of zebrafish and medicinal leeches.

The achievement, the team suggests, could lead to the development of techniques for generating fully integrated electronic circuits in living organisms. “For several decades, we have tried to create electronics that mimic biology,” said Magnus Berggren, PhD, at the Laboratory for Organic Electronics, LOE, at Linköping University. “Now we let biology create the electronics for us.”

The team reported on its development in Science, in a paper titled “Metabolite-induced in vivo fabrication of substrate-free organic bioelectronics.”

The boundaries between biology and technology are becoming blurred, and the ability to link electronics to biological tissue will be important to help understand complex biological functions, combat diseases in the brain, and develop future interfaces between man and machine, the authors suggested. However, conventional bioelectronics, developed in parallel with the semiconductor industry, have a fixed and static design that is difficult, if not impossible, to combine with living biological signal systems. “Interfacing electronics with neural tissue is crucial for understanding complex biological functions, but conventional bioelectronics consist of rigid electrodes fundamentally incompatible with living systems,” the team wrote. “The difference between static solid-state electronics and dynamic biological matter makes seamless integration of the two challenging.”

To bridge the gap between biology and technology, Berggren and colleagues developed a method for creating soft, substrate-free, electronically conductive polymer materials in living tissue. The multicomponent mixture is based on a derivative of a substance known as ETE, and uses endogenous metabolites to trigger enzymatic polymerization of the organic precursors within the injectable gel “thereby forming conducting polymer gels with long-range conductivity,” the investigators commented. “Gels containing enzymes and small electroactive monomers were injected into the biological tissue, and endogenous metabolites induced polymerization of the monomers. This resulted in organic electronic gels without the requirement of a rigid—and thus inherently biologically and rheologically incompatible—substrate material.”

As the body’s endogenous molecules are enough to trigger the formation of electrodes there is no need for genetic modification or external signals, such as light or electrical energy, which has been necessary in previous experiments. “… the endogenous compound–fueled polymerization method does not necessitate genetic manipulation of target cells or tissue, making it more easily translatable,” they continued. The Swedish researchers are the first in the world to succeed in this.

Xenofen Strakosas, PhD, a researcher at LOE and Lund University, who is one of the study’s lead authors, further explained, “Contact with the body’s substances changes the structure of the gel and makes it electrically conductive, which it isn’t before injection. Depending on the tissue, we can also adjust the composition of the gel to get the electrical process going.”

In their study, the researchers further show that the method can be used to target the electronically conducting material to specific biological substructures and thereby create suitable interfaces for nerve stimulation.

Through experiments conducted at Lund University the team successfully achieved electrode formation in the brain, heart, and tail fins of zebrafish and around the nervous tissue of medicinal leeches. The animals were not harmed by the injected gel and were otherwise not affected by the electrode formation.

One of the many challenges the team had to overcome was to circumvent possible immune system reactivity in the animals. “By making smart changes to the chemistry, we were able to develop electrodes that were accepted by the brain tissue and immune system,” said co-author Roger Olsson, at the Medical Faculty at Lund University, who also has a chemistry laboratory at the University of Gothenburg. “The zebrafish is an excellent model for the study of organic electrodes in brains.”

Professor Roger took the initiative for the study after reading about the electronic rose developed by researchers at Linköping University in 2015. One research problem, and an important difference between plants and animals, was the difference in cell structure. Whereas plants have rigid cell walls which allow for the formation of electrodes, animal cells are more like a soft mass. Creating a gel with enough structure and the right combination of substances to form electrodes in such surroundings was a challenge that took many years to solve. The new development, the investigators suggest, will be “…  applicable to a wide range of tissue and animal models … This approach can be used to target specific biological substructures and is suitable for nerve stimulation, paving the way for fully integrated, in vivo–fabricated electronics within the nervous system.”

Their study paves the way for a new paradigm in bioelectronics, where it previously took implanted physical objects to start electronic processes in the body, injection of a viscous gel will be enough in the future. In the long term, the fabrication of fully integrated electronic circuits in living organisms may be possible, the scientists suggested. “This approach can be used to target specific biological substructures and is suitable for nerve stimulation, paving the way for fully integrated, in vivo–fabricated electronics within the nervous system,” the team stated.

“Our results open up for completely new ways of thinking about biology and electronics,” said Hanne Biesmans, a PhD student at LOE and one of the study’s lead authors. We still have a range of problems to solve, but this study is a good starting point for future research.”

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