This Device Could Tune Your HeartThen Dissolve Away
The heartâ€"that paragon of natural rhythmâ€"sometimes needs help to stay on beat. Permanent pacemakers, which supply jolts of muscle-contracting current to regulate each thump, can correct chronically irregular hearts, and temporary ones can resolve fleeting dysfunctions that follow open heart surgery. Doctors wire up the heart with electrical leads that pass through the skin, and the muscle tissue envelopes the intruding electrodes like quicksand.
But if the pacemaker is just a temporary precaution, it’s all got to come out. And that’s where it gets tricky.
Dislodging the wires might scar the heart permanently. And the surgery to pull them out could result in bleeding or infection. “Anytime we put sutured wires on the surface of the heart, there's a risk,†says Rishi Arora, a cardiologist and researcher at Northwestern University.
Writing in June in Nature Biotechnology, Arora’s team debuted a “transient†pacemaker that gets the job done, then dissolves away. The device weighs about a 10th as much as a dime, and it receives wireless power through a tiny metallic coil antenna, which funnels pacemaking zaps into even tinier electrodes. Then it performs its disappearing actâ€"all of its electrical components are biocompatible and bioresorbable within three months.
“This is a breakthrough,†says Subha Raman, a cardiologist and director of Indiana University’s Cardiovascular Institute who was not part of the team. Infections from pacemaker removals are common, Raman says, especially among patients with diabetes, which often coincides with heart disease. Plus, if residual wiring stays lodged in the heart, it can make it impossible to run an MRI, a critical diagnostic tool for people who have strokes. A transient device insulates against these consequences.
Illustration: Northwestern University/George Washington UniversityThe secret to making a pacemaker disappear comes down to chemistry. It has long been known that polymers and certain metals, such as iron, magnesium, and tungsten, can naturally dissolve into the body as nontoxic waste. But medical electronics need more than just metals and plastic; they need semiconductors that precisely manage programmed inputs and outputs. John Rogers, a biomedical engineer at Northwestern who co-led the project, remembers feeling stuck: “What are you going to use for the semiconductor?†Rogers recalls thinking. “We didn't really have an answer for that.â€
The breakthrough came in 2012: It turned out that silicon could be bioresorbable. “When you're playing around with super-thin silicon, then you notice funny things,†Rogers says. Researchers in his lab engineered the element into wires, membranes, and ribbons that were far thinner than the silicon chips you’d find in most electronics. “One of my postdocs noticed that if he left some of this silicon immersed in a water bath for a few days, he couldn't find the silicon anymore,†Rogers recalls. “So that tipped us off to the fact that there might be something interesting happening.â€
In water, silicon atoms flake off like dead skin, nanometer by nanometer, then vanish. “The fact that you can kind of use the workhorse material that serves as a foundation for all of consumer electronics gadgetry really opens up a wealth of opportunities,†Rogers says.
The first medical implant to come of that breakthrough was a thin sheet that electrically jolts injured tissue to kick-start nerve regeneration, which the team tested in rats. Rogers then teamed up with cardiologists, including Arora, who saw an opportunity to forgo traditional temporary pacemakers used to treat slow heart rhythms. Rogers likens this dissolvable device to an internal wound healer, an “electronic medicine†in which all the components are soluble.
At first glance, the half-inch-wide, half-inch-long device may seem like a flimsy plastic strip. But, in actuality, it’s a dynamic stack of surfaces and carefully selected elements. The electrical contacts are a mix of tungsten and magnesium. Wireless power feeds into those contacts though a flat coiled antenna made of the same materials. Energy arrives from a near-field communication, or NFC-enabled, antenna, which could sit on a hospital bed or wearable patch. (Sorry, your phone’s tap-to-pay NFC isn’t efficient enough to unbreak any hearts yet.)
Having a stable electrical contact is critical to any cardiac device, since each blood-pumping contraction depends on heart cells firing quick impulses. But a device also has to be dynamic. When a wet heart fills and empties, its curved surface stresses and strains. The challenge of making something that is both stable and flexible has been “kind of an open question for this field for a while,†Rogers says. “Bioelectronics are great, but then how do you maintain robust interfaces over time?â€
The team cracked this problem with an adhesive hydrogel, which doesn’t just stick to the heart mechanicallyâ€"it latches on chemically. The hydrogel forms covalent bonds with the tissue’s surface. Loose molecular threads on the hydrogel and heart weave together chemically. Nitrogen atoms in one fuse with carbon atoms in the other, and vice versa, to form strong, protein-like connections. “It provides a mechanically soft, intimate electrical coupling,†Rogers says.
Each layer can begin dissolving as soon as it gets wet, and it’s important that the device does not degrade too soon after it’s implanted. So the pacemaker sits inside a dissolvable polymer shell that acts as a buffer against timeâ€"the hardware has two weeks to do its work while its shell dissolves. The rest starts breaking down after that, but by then, the patient shouldn’t need the pacemaker anymore. In cases where a longer-lasting device is needed, the team could build a verison with a thicker capsule.
The team tested the device on animals with small hearts (rats and mice), medium hearts (rabbits), and ones with nearly human-size hearts (dogs). In all cases, their device could control the pace of an animal's heartbeat. (They also tested tissue isolated from human donors and found the same success.)
Rogers and Arora’s team also tested how the pacemakers faded away in rats. They showed that the devices stayed intact for one week, were mostly dissolved at three weeks, and stopped working at four weeks. By 12 weeks, they were entirely gone.
“Accomplishing that functionality, but also having the whole thing go away without having any potentially dangerous or toxic byproductsâ€"that's a huge challenge,†says Ellen Roche, a biomedical engineer at MIT who develops cardiac devices, who was not involved in this work. “Independently, either of those is doable,†Roche continues. “But to do them both together, I think, is a big accomplishment.â€
“It's really cool to see simple materials; we already know about their toxicity burden,†says Chris Bettinger, a biomedical engineer at Carnegie Mellon. “I think simplicity is often underappreciated.â€
But an invasive device like a pacemaker will require much more testing to prove safety and efficacy in humans. Another challenge could be the landscape of the heart’s surface, which would be much more damaged among cardiac patients than among lab animals. Raman, the cardiologist who is not part of Arora’s team, notes that some of the people who might need this sort of device already have tissue scarring caused by heart disease and blockages, which would make forming electrical connections harder. “But based on the design, one would guess it’s likely to work,†Raman says.
Arora’s hope is that the dissolving implants won’t just replace traditional temporary pacemakers, but expand the scenarios for when people get them, such as after heart attacks and drug overdoses. Electrolyte imbalances in these cases might cause slow heart rates, he says. “You could really help the patient basically get over that acute phase of that illness without having to put in external hardware that could potentially be damaging,†says Arora.
Clinical trials of resorbable pacemakers based on the team’s designs could begin in three years, according to Rogers.
The current demonstration also lays the groundwork for other kinds of electronic medicine. Rogers and Arora are developing transvenous pacemakers to correct rhythms from inside the heart without needing surgery. And showing that one can stick dissolvable implants to the slippery heart bodes well for developing vanishing biosensors for the kidneys and bladder, where it’s hard to attach sutures. (For the bladder, that’s because its wall is very thin. For the kidneys, it’s because of the risk of immune system rejection.)
Rogers’ experiments with transient bioelectronics flips a rubric of gear on its head. “If you think about the history of solid-state electronics, it's all been around the ability to build devices that last forever,†he says. But the environmentâ€"and our bodiesâ€"are proficient at busting chemical bonds and recycling atoms. There’s a value in embracing that finitude, of making things that aren’t built to last.
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