Vendors and Researchers Develop Flexible Brain Implants

by James Cavuoto, editor

March 2023 issue

One of the greatest challenges confronting vendors of brain implants such as DBS and BCI systems is developing devices that conform better with brain tissue. Almost all implanted neurostimulation devices on the market today are based on metal electrodes that come into contact with neural tissue. The better the contact, the more useful the device.

Metal electrodes are stiffer than surrounding brain tissue, and are prone to all the mechanical impacts the human body is exposed to. Implanted electrodes frequently produce inflammation and sheaths of glial tissue surrounding the foreign object, which can not only lead to tissue injury but also reduce the electrical effectiveness of the device. The increased biocompatibility and electrical signal transduction properties of conducting polymer electrodes address each of these issues and promise a new generation of implanted electrodes that will benefit patients and clinicians.

We reported 20 years ago on David Martin’s efforts at the University of Michigan to grow networks of PEDOT electrodes that are intimately intertwined with neural cells. They also produced hybrid electrodes that incorporate both conducting polymers and live neural cells. Their goal was to create a matrix that actually attracts neural cells to the biomimetic template. Martin’s efforts led to a spinoff coatings firm called Biotectix, which was later acquired by Haraeus.

More recently, commercial firms such as WISE and Blackrock Neurotech have developed more flexible electrode arrays that conform to the brain’s surface and could well become key products in cortical stimulation or BCI applications.

A newer approach, introduced by researchers in Sweden, involves growing electrodes in the brain. Investigators at Linköping, Lund, and Gothenburg universities have successfully grown electrodes in living tissue using the body’s molecules as triggers. The result, published in Science, paves the way for the formation of fully integrated electronic circuits in living organisms.

“For several decades, we have tried to create electronics that mimic biology. Now we let biology create the electronics for us,” said Magnus Berggren, professor at the Laboratory for Organic Electronics, at Linköping University.

The team developed a method for creating soft, substrate-free, electronically conductive materials in living tissue. By injecting a gel containing enzymes as the “assembly molecules,” the researchers were able to grow electrodes in the tissue of zebrafish and medicinal leeches.

“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,” said Xenofon Strakosas, researcher at LOE and Lund University and one of the study’s main authors.

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.

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 their study, the researchers show that the method can target the electronically conducting material to specific biological substructures and thereby create suitable interfaces for nerve stimulation. In the long term, the fabrication of fully integrated electronic circuits in living organisms may be possible.

In 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 in these trials was to take the animals’ immune system into account.

“By making smart changes to the chemistry, we were able to develop electrodes that were accepted by the brain tissue and immune system. The zebrafish is an excellent model for the study of organic electrodes in brains,” said Roger Olsson, professor at the medical faculty at Lund University, who also has a chemistry laboratory at the University of Gothenburg.

It was Olsson who took the initiative for the study, after he read 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.

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