From breath-powered neurostimulation implants to arm cuffs that can head off migraines, the world of bioelectronic devices has come a long way from the early days of the humble pacemaker. But the future of electronic medicine may look less like implanted devices and more like gels injected directly into tissues.
That’s the vision of a team of Swedish researchers that has developed the first gel capable of harnessing the body’s own endogenous molecules to form electrodes. In a study published Feb. 23 in Science, scientists from Linköping, Lund and Gothenburg universities described how they designed and tested the gel in live zebrafish and leeches, where they were able to grow electrodes in nerve cells.
“For several decades, we have tried to create electronics that mimic biology,” corresponding author Magnus Berggren, Ph.D., a professor at Linköping University’s Laboratory for Organic Electronics, said in a press release. “Now we let biology create the electronics for us.”
Implanted bioelectronics like the neurostimulation devices used in stroke patients work by sending electrical signals to nearby cells. But the devices aren’t fully integrated with the tissue. Instead, they send impulses via conducting films on hard, solid electrodes.
This “rigidity can damage soft tissues and reduce an implant’s long-term performance,” Sahika Inal, Ph.D., chair of the Organic Bioelectronics Laboratory at the King Abdullah University of Science and Technology, wrote in a perspective article accompanying the study. The solid implant can trigger the development of an inflammatory microenvironment that causes scar tissue to build up while also degrading the device.
But what if the body could build its own electrode internally? Inspired by a bionic rose built in 2015 by another team of researchers from Linköping University, the scientists set out to develop a material that would match the electrical and physical characteristics of the neural environment. They had some qualifications in mind: The material would need to be dispensed as a fluid that could mesh with local tissues and diffuse within a certain distance of the injection site, must be made of and generate only nontoxic components and must form a highly conductive electrode that was soft, stable and could send signals to neural structures of different lengths.
To that end, they came up with a cocktail of monomers, enzymes and other materials that, when injected, would react with metabolites in the target tissue and form an electricity-conducting gel. They were careful to optimize it to avoid the buildup of toxic hydrogen peroxide, testing different gel formulations in cells and adjusting the ratios of the chemicals accordingly.
They then tested the gels in live anesthetized zebrafish, starting with injecting it into the fishes’ tailfins. The gel formed a dark color along the length of the fin cavities, creating the electrode as it reacted with the glucose and lactate in their tissues.
In another set of zebrafish, they injected it directly into their brains. After letting the fish swim for three hours, they harvested and thinly sliced brain tissue from three of them, then placed it upon a microelectrode array to study the electrical currents that had formed. Applying a voltage between -0.5 and 0.5 volts started a current. Studies on zebrafish brains that were dissected into two halves showed similar results, as did a set of experiments on zebrafish hearts. None of the fish appeared to experience pain, toxicity or behavior changes on account of the gels, including those in a group that was left to swim for 72 hours after the gel was injected into their brains. Their brain tissue showed no signs of structural damage, either.
To understand how the presence of glucose and lactate was driving the electrode formation, the scientists also injected the gel into tenderized beef, pork, muscle from freshly killed chicken and tofu. While the gel formed an electrode in all the meat, it wasn’t able to do so in the tofu because it lacked the necessary metabolites.
In the last set of experiments, the scientists attempted to use the gel to stimulate and record impulses from nerves in medicinal leeches. They used a similar setup as in neuroscience experiments but replaced the conducting polymers that typically coat implantable metal electrodes with the gels. While the gel was able to conduct electricity and improve the performance of the electrodes, it couldn’t stimulate nerves. The scientists will need to optimize the gel for such applications, they wrote in the paper.
There is much more work to do before the gel could come close to being used in humans, and the study has several limitations. Injecting a gel into a zebrafish brain is one thing, but getting to relevant human tissues with a syringe is another matter, as Inal pointed out in the perspective article. That will require more invasive strategies, which could cause implantation damage. Plus, the body is chemically dynamic and could alter the nature of the gel over the long term, potentially creating toxic byproducts, she added.
Limitations aside, however, the scientists have shown that it’s possible to get tissue to conduct electricity. That alone is a step forward for bioelectronic medicine, according to Inal.“The strategy … suggests that any living tissue can be turned into electronic matter and brings the field closer to generating seamless biotic-abiotic interfaces with a potentially long lifetime and minimum harm to tissues,” she wrote.