Electrotherapy Using Wireless, Body-Integrated Devices With an Advanced Bioresorbable Pacemaker

Podcast Discussion With Igor Efimov, PhD, Anna Pfenniger, MD, PhD, and John Rogers, PhD

In this episode of The EP Edit podcast, we are highlighting a discussion with researchers from Northwestern University about the concept of a bioresorbable pacemaker. Igor Efimov, PhD, is a professor of biomedical engineering and professor of medicine at Northwestern University. Anna Pfenniger, MD, PhD, is physician scientist in cardiac electrophysiology at Northwestern Medicine. John Rogers, PhD, is a physical chemist and materials scientist, the Louis Simpson and Kimberly Querrey professor of materials science and engineering, biomedical engineering, and neurological surgery at Northwestern University, and director of the Querrey Simpson Institute for Bioelectronics.

This episode is also available on Spotify and Apple Podcasts!

John Rogers: Hi, my name is John Rogers, and I am on the faculty at Northwestern University. I have appointments in materials science and engineering, biomedical engineering, neurological surgery, and dermatology. I run a fairly large, broad research program at Northwestern in the context of an institute set up for the development of bioelectronics technologies. These are advanced semiconductor devices designed to be biocompatible so they can serve as unique tools for facilitating biomedical research, but also ultimately as systems to address unmet needs in patient care.

So, this particular study¹ involves a type of technology that we have been interested in for the past 10 years or so, specifically, classes of electronic devices that are uniquely characterized by their ability to dissolve harmlessly over engineered time frames when exposed to biofluids. It opens up interesting opportunities and temporary implants of various sorts. You can think of them sort of like resorbable sutures in the sense that they exist for a finite time, aligned with a natural biological process, such as a recovery process following a surgical operation or wound healing process. But before they dissolve away, they offer full electronic functionality, digital capabilities and sensing, transmitting data, delivering therapeutic stimulation far beyond anything that is supported by a resorbable suture, but conceptually it is similar in the sense that it is there when you need it, and then it disappears afterward to eliminate any kind of need for a surgical extraction or removal process. We are very intimately engaged with various aspects of the medical community in Chicago, specifically, folks associated with the Feinberg School of Medicine. This particular project was brought to us by cardiac surgeons who identified a need for an alternative type of temporary pacemaker that is currently used during the recovery period after cardiac surgery that eliminates risks associated with the tethered interface that is required to allow external control electronics to deliver pacing signals to the heart and to eliminate the need for that surgical retrieval process.

So this is a great synergy between a unique engineering capability that we have been working on, resorbable electronics, and a specific clinical need. This publication represents the outcomes of that kind of collaborative interaction, bringing engineering science into interface with cardiac science, both through our collaborations with Anna and Igor as well.

Igor Efimov: My name is Igor Efimov and I am also at Northwestern. I am a professor of biomedical engineering and a professor of medicine in the division of cardiology. About 20 years ago, I was fortunate to deliver the C. Walton Lillehei lecture at the University of Minnesota. Dr Lillehei was the first cardiac surgeon. He did the first open-heart surgery in pediatric patients, and I was fascinated to learn during my visit how exactly it happened. They showed me his lab in which the first pacemaker was implanted—first in a dog and later in a patient.

Since that time, which was in the 1950s, the temporary pacemaker, which was required for open-heart surgery patients, was basically unchanged. It was a wire which is implanted on the surface of the heart and then connected to an external pacemaker. That allowed for infections and other complications. I was always interested in developing new technology, but there are 2 problems that have to be addressed in developing such a technology. First, it has to be a small, miniature pacemaker that can be implanted on the surface of the heart and occupy as little space as possible. Second, it has to have the ability to dissolve and disappear after it is no longer needed. We attempted it a number of years ago. We started 10 years ago with a design in which we had a battery and microprocessor, but at the time, I realized it was still too large. That is when we came across this technology of inductive power transfer, in which you can move energy into the pacemaker from an external electromagnetic field. This addressed all the problems with programming—a microprocessor or battery was not needed within the pacemaker, which allowed making it very small.

The second factor was how to make it bioresorbable. John’s laboratory developed a toolkit of different materials that were bioresorbable, but at the same time, can be designed to have various electromagnetic properties. They can be conductors, insulators, or semiconductors for rectifying the current. When this technology became available, we developed this pacemaker with John’s laboratory. In my lab, we tested about 130 implanted devices in rats. We developed a surgical procedure for making sure it was safe. I am very excited that this technology is currently very close to clinical practice.

Anna Pfenniger: I am Anna Pfenniger. I am an assistant professor at Northwestern in the Feinberg School of Medicine, but I am also a cardiac electrophysiologist and physician scientist. I was really excited to interact with this technology, seeing the unmet clinical needs in our patients. We talked about the postsurgical patients who require a temporary pacemaker. Those patients can need a pacemaker for several days, and it is a little bit of a guessing game at some point when they will no longer need a pacemaker or if they will need a permanent pacemaker. During that time, they are tethered to a cable, and they require an intensive care unit (ICU) bed, so that delays their recovery and ability to start physical therapy and leave the hospital. Having a technology that does not require wires that are attached to the heart is a big advantage for that set of patients.

Thinking further, there is a large population of patients who we are not sure whether they will need a pacemaker or not. These can be patients who have surgery or potentially transient heart block or other procedures such as transcatheter valve procedures, for instance. It would be great to have a tool to delay that decision so that we only implant permanent pacemakers in patients who need them long term. As we know, getting a permanent pacemaker is not trivial—it comes with lifelong potential consequences. So, even beyond the reduction in acute harm or risk of side effects from a procedure, this has the potential to reduce long-term risks associated with exposure to a permanent pacemaker. I was fortunate to be part of this study to show that this is actually feasible.

JR: We have emphasized in our discussion up to this point about the resorbable pacemaker itself. This is a wireless, battery-free device that is implanted in the body, sits on the surface of the heart, and delivers electrical stimulation. Physically, it is the thickness of maybe 2-3 sheets of paper, so it is very thin. By consequence, it is very bendable, and the kind of polymer materials that we use to encapsulate the electronics is also elastomeric. Think of it almost as a rubber band—it bends and also stretches. Those turn out to be very important mechanical characteristics to allow for robust adhesion to the outside curved surface of the beating heart, in a way that maintains contact without adverse effect on the soft, fragile tissues of the heart. So that is a core piece of the technology. The other component is another soft, flexible piece of electronics, but one that is not implanted inside the body—instead, it sits on the surface of the skin, just over the location where the pacemaker is implanted. That device is battery powered and serves 2 main functions. One is in delivering power wirelessly using this magnetic, inductive coupling scheme, with a physics similar to that used for wireless payments through your smartphone. This function relies on a coil antenna embedded in the device and powered by that battery. Oscillating current flowing through the coil electromagnetically couples to a corresponding coil that serves as the power-harvesting component of the pacemaker. This mechanism can not only deliver power wirelessly to the pacemaker, but it can be modulated in time to determine the rate of pacing. This modulation creates the pulsatile waveforms that pass from the pacemaker to stimulate the heart.

That is one core function of the skin-mounted device. The other function is in monitoring cardiac activity. It has capabilities in collecting single-lead electrocardiogram (ECG) data, at ICU-grade accuracy. Additional high-bandwidth motion sensors allow capture of cardiac sounds—the kind of data you would collect with a stethoscope, also built into the device. So, from measurements of cardiac activity, the device can autonomously determine whether pacing is needed or not. The simplest threshold for that determination is if the heart rate drops below a certain threshold value—the device can see when that happens. If it does happen, then the device automatically activates the wireless power transfer mechanism to start pacing the heart up to a normal, healthy rate. The complete operation occurs in a completely closed-loop manner, in a sense, without the tethered wires that reduce mobility of patients while they are in the hospital. It is also worth mentioning that an ability to release patients earlier than otherwise would be possible by providing them with an ability to walk, move, and operate the device without direct physician oversight, is an important part of our vision for the future.

AP: If we compare to current pacemakers, they sense from the electrode that they pace from, that obviously needed to be circumvented in this technology. That was done by this skin interface module that acts as a sensor, as the pacemaker itself does not have sensing capabilities. So with this addition, we went from an asynchronous pacing mode, which was the first generation, to effectively a VVI mode, which is comparable to current pacemakers, so that we can adapt the pacing rate and only pace as needed. This also allows us to record the underlying rhythm and how much we pace to determine the needs over time. So we have the potential to follow what is happening with the underlying rhythm, the pacing needs, and trajectory of heart block: is there any sense that there is recovery or not? With all of that together, it is really an elegant tool with which clinicians could be able to follow their patients, even potentially remotely, to see what is happening with their recovery and determine early whether they need to come back for a permanent pacemaker or if they are starting to do better. We can then wait for that temporary pacemaker to dissolve and let them go on with their recovery.

IE: I would like to also speculate about the future of this technology. Transient electronics offer truly unimaginable opportunities in the future. Currently, the low-hanging fruit is this pacemaker, which we have developed together, and we have also created a network of wearable devices that can wirelessly integrate with this device, but the reality is this platform can be extended well beyond just the pacemaker. We are thinking about applications to cardiovascular disease, cardiac arrhythmias, or neuromodulation. We would like to be able to control sympathetic and parasympathetic neurons. The technology is already available for both stimulating and inhibiting neurons. John’s lab just published a paper on cooling neurons, which inhibits propagation of impulses, which for example, would be used for inhibiting transmission of impulses through sympathetic neurons, essentially reducing sympathetic drive into the heart, which has been shown in many studies to contribute to development of heart failure (HF) or atrial fibrillation (AF).

Similarly, we are thinking about developing an implantable bioresorbable transient spinal cord stimulation device, which also can be used, for example, to prevent postoperative AF or development of HF. Also, devices are being developed for drug delivery. Again, they can be designed in a bioresorbable mode. They deliver their therapy and then resorb. In addition, devices can be developed for monitoring various parameters, not only for electrocardiographic purposes such as ECG or mechanics or heart movement, but also to monitor various biomarkers, and we are working on that. There are sensors for monitoring inflammatory markers or certain proteins or even certain cells with specific cell chemistry. All of these are currently being developed or in the portfolio of development, and can ultimately be put on the platform of transient electronics. This is a really exciting time to be in this field.

JR: I agree, Igor! I think it is useful to talk about what the translational pathway would look like and the regulatory hurdles. One of the things that we have here is a collaborative collection of experts touching on all of the key aspects associated not only with the technology, but the clinical use, biosafety, biocompatibility, capacity for doing animal model studies, and so on. It is a wonderful community of highly collaborative individuals and I am lucky to be part of that. As an engineer, you want to put out into the broader world and into the public domain the new ideas and schemes that you think could be valuable to patient outcomes, so that other people may build on those ideas and extend them.

Ultimately, you want to do more than publish papers—you would like to be involved in the actual translation and deployment at scale to impact patient care. How does that happen? There are a number of different pathways. We have fielded inbound interest from all of the large medical device companies in the United States, a number of investors have expressed interest in helping us with commercialization, and we are sorting out the best path given where we are right now. But I think the regulatory framework will probably represent a rate-limiting step, as in any kind of implanted device. It is interesting to think about, because to my knowledge, the U.S. Food and Drug Administration (FDA) has never looked at a bioresorbable electronic implant. This is a totally novel technology. It will be an interesting process in working together with the FDA to identify the risk factors and conduct the experiments and trials that would lend insights. We have 2 different perspectives. One revolves around the uncertainty of how the regulatory process will work, given that this type of device has never been looked at before, and the possible resulting extensions of the timeline to regulatory approval. The other perspective is that, in some ways, the device is a lot less risky than a permanent implant, because it is only there for a certain period and then it ultimately dissolves and disappears completely. At that point, there is no longer any risk to the patient. So, it is an interesting circumstance. Bioresorbable electronics is a powerful concept and we are eager to move down the path of translating it out of an academic setting into a form that can be impactful at scale.

IE: Yes, absolutely. This is an interesting translational pathway. Transient electronic devices have never been translated, as far as I know. Also, there was one experience, as I understand, with a bioabsorbable stent. However, this is a relatively simple device, as it does not have multiple components or electrical components, and it deals with a much more defined problem. Here, we have a lot of uncertainties, but at the same time, we can dwell on previous experience with other bioabsorbable materials, because some of the materials we are using are similar to previous materials. Even though there is some risk, in our initial experience with the FDA, they are very excited about this new field of transient medical devices, which clearly have applications beyond cardiology. But cardiology, and in particular, heart rhythm, is the first field in which we can develop sophisticated devices that will solve a meaningful clinical problem.

AP: That would also be an easy place to clinically test them, because we have a simple way to measure outcomes and a simple backup system. We can design a clinical trial in the postoperative setting where we could have a dual pacing system, adding a bioresorbable system to a currently used temporary pacemaker, with minimal risk of harm for the patients. That is clearly the first place to start.

JR: Yes. One final thought is, as academics, we try to put new ideas out into the world and other people can build on them. We are interested in translation, but we are also educators. That is the way I think about part of my job and my role in mentorship. I think this kind of activity, engineering science with medical science in a collaborative environment, is such a powerful experience for the students.

As an anecdote, I actually lost the materials scientist in my group who led this project to the cardiology department, because he decided he wanted to spend more time learning about cardiac science. He moved out of my lab and joined Rishi Arora’s lab, and has been working with Anna and learning how to do surgeries and all sorts of things about how the heart works. I think that is a great example of the kind of cross-fertilization in the deep and broad environment that this kind of work creates for the students.

IE: Thank you for this opportunity to discuss our recent paper. It is exciting technology. I would like to reiterate what John said about education. I am in the middle of putting together a proposal for the Heart Rhythm Society (HRS) for a session on bioresorbable electronics and its challenges, and how this is interesting for physicians, allied professionals, and scientists. It is a completely new field emerging from materials science and physiology that is now becoming more mature and applicable in heart rhythm disease.

AP: I am certainly looking forward to that session at the next HRS meeting!

JR: Yes, it is great to be part of this conversation, podcast, and wonderful collaboration. I think communicating these results to the broader community will create ideas for these types of technologies that we have not even contemplated yet. There are a lot of smart people in the community, and I look forward to hearing their feedback. 

Reference

1. Choi YS, Jeong H, Yin RT, et al. A transient, closed-loop network of wireless, body-integrated devices for autonomous electrotherapy. Science. 2022;376(6596):1006-1012. doi:10.1126/science.abm1703

Editor’s note: Transcripts were edited for length and clarity.