Paul Rand: What if the future of technology isn’t something you carry around in your pocket or strapped to your wrist, but something that lives under your skin? Not computers we plug into, but computers that plug into us?

Bozhi Tian: The line between biology and technology is already blurring, and the bioelectronics is at the forefront of this transformation.

Paul Rand: Bioelectronics, this emerging science isn’t about gadgets or wires, it’s about a seamless connection between biology and technology, erasing the boundary between you and it.

Bozhi Tian: Cyborgs actually may not be fictional as we once seemed.

Paul Rand: That’s Bozhi Tian, a professor of chemistry at the University of Chicago who leads a research group that develops a wide array of bioelectronics that are paving the way for our cyborg future.

Bozhi Tian: The cyborg term probably reminds us of the images of bulky, futuristic machines, but the reality could be far more elegant and the technologies may not look as bulky mechanical implants, but instead be seen flexible and seamlessly integrated into the body. And this really blurred the line between what is the human and what is electronic.

Paul Rand: Imagine electronics that don’t just heal your body, they upgrade it. Tiny devices that speak the language of your cells, enhance your senses, and fight disease. This isn’t the stuff of science fiction. It’s science, and it’s happening now.

Bozhi Tian: Imagine wearable patches that actively regulate our gut microbiomes or neural implants that can help us review the hidden cognitive potential or a skin-like devices that can monitor and optimize our health in real time. Those are all possible.

Paul Rand: Tian’s lab has been making breakthroughs in all sorts of bioelectronics devices.

Bozhi Tian: We are engineering silicon to interact directly with the biologic systems, making it not just as the passive materials, but also active participants in processes such as neural signaling or cardiac modulation. So the goal isn’t just to make the devices smaller or faster, like what we do in industry for making computer chip, it’s to make them smarter and more adaptive and also deeply integrated with the biology that they’re designed to support.

Paul Rand: This technology can even exist at the smallest scales. Picture tiny devices that could go into your cells and tune into your body’s electrical symphony.

Bozhi Tian: So I hope that one day this high-precision intracellular tools could become a game-changer for medicine and synthetic biology. And for example, they could potentially guide stem cells to regenerate tissues, and they can deliver drugs directly to the right parts of a single cell.

Paul Rand: But where things get really mind-blowing is when these tools could be used not just in your body, but in your brain.

Bozhi Tian: And this photo stimulation can also allow the modulation of the, let’s say, brain activities at high spatial and temporal resolution. So in enhancing the sensory perception is actually a very exciting frontier among those possibilities.

Paul Rand: Welcome to Big Brains, the podcast where we translate the biggest ideas and complex discoveries into brain food you could use. I’m your host Paul Rand. On today’s episode, Our Bioelectric Future.

Paul Rand: Big Brains is supported by UChicago’s Online Master of Liberal Arts program, which empowers working professionals to think deeply, communicate clearly, and act purposely to advance their careers, choose from optional concentrations in ethics and leadership, literary studies, and tech and society more at mla.uchicago.edu. So let’s talk about for a second, let’s break down some of these words. What does the word bioelectronics actually mean?

Bozhi Tian: Well, bioelectronics in general means that we have to use electronic systems to interact with cells and tissues, and we collect electrical signals from the cells and tissues, or we apply electrical signals to affect a cell’s response.

Paul Rand: And you start out having an interest of the looking at the intersection between material sciences and biology, which is a really interesting combination. How in the world did you come to deciding to marry the two of those?

Bozhi Tian: Growing up, I was fascinated by nature’s ability to self-heal and adapt. I was always amazed by the intricate structures of some naturally occurring biomaterials, such as bone or sea sponges.

Paul Rand: Sorry, bone or what was the other one?

Bozhi Tian: Sea sponges.

Paul Rand: OK, sea sponges. OK.

Bozhi Tian: Sea sponges. And in those structures, the inorganic materials they actually form the majority of the skeleton of those complex structures. At some point during my undergraduate studies, I found myself looking at those materials and then asking, what if this could become metals or semiconductors while still maintaining those intricate structures? And what if they could interact with cells and tissues in an even more seamless and dynamic way? And that question really stuck with me.

Paul Rand: Okay. It does come across if you think about it as science fiction in its own ways. And so is there a point where you said, this is actually a concept that seems far-fetched, but I think I can make it work?

Bozhi Tian: Well, actually, I haven’t watched that much science fiction, to be honest. Don’t get me wrong, so it is fascinating and I know how it inspires many people, but for me, the creative spark really comes from somewhere else. I love using my imagination, but it’s more rooted in art and also natural world. The way a spider spins its web or the structure of a sea sponge I just mentioned, it’s like a perfectly designed blueprint for engineering. And that’s where I see innovation, not in a galaxy far, far away, but actually right here in the details of our own world. And I also mentioned art. Art plays a big role as well, observing, for example, how light bounces across a sculpture or other patterns in abstract paintings often gives me some ideas for designing materials that could blend seamlessly with biology. So I would say that science fiction is great for some, but for me it is really the beauty in every day and the mysterious of the nature that really sparked my curiosity.

Paul Rand: So if you were designing a semiconductor to work in a machine or another piece of electronics, it has to be compatible, but not necessarily from a biological point of view. What things do you have to keep in mind about really the bridging biology and technology that may be different than if it was on an actual piece of hardware?

Bozhi Tian: Biocompatibility is probably one of the biggest challenges in creating these bioelectronics systems. So the materials we use must integrate seamlessly with the body’s tissues. This is no small feat. Biological systems are incredibly dynamic. They are constantly shifting, growing, and also responding to their environment. So a material such as silicon, they might work well in the short term, but it may trigger some inflammation or rejection or even immune response over time. So in our lab, for example, to address this challenge, biocompatibility challenge, we have to make the material very flexible, soft, almost match the mechanical properties of the naturally occurring tissue. But at the same time, we need to modify the surfaces, engineer the surfaces with some chemicals or some polymer coatings so that they can resist degradation and also minimize immune responses. There are two strategies that we currently are using. The first one is to make the material more flexible, almost like a thin sheet of the tissue. So that’s the first strategy, make them mechanically more compliant. And the second strategy is to change their surface chemistry so that they can interact with cells and tissues better.

Paul Rand: Designing materials that can seamlessly integrate with the body is an incredible challenge, but it’s only the beginning. Once you’ve built something the body can accept, the next question becomes, how do you make it solve problems the body can’t handle on its own? For example, what if the solution to a massive challenge like antibiotic resistance wasn’t a new drug at all, but something entirely different?

Bozhi Tian: Overusing antibiotics has created a global health crisis giving rise to resistant superbugs that are increasingly difficult, sometimes almost impossible to treat.

Tape: We are still losing the battle against so-called superbugs, bacteria that are resistant to nearly all the antibiotics.

Bozhi Tian: The more we rely on antibiotics indiscriminately, the more we actually push back to evolve defenses. And that’s a problem. And it also create a vicious cycle that we don’t want to see.

Tape: Antibiotic resistance contributes to the death of 700,000 people around the world each year. Experts have predicted it will eclipse the number of people affected by cancer by 2050. One of the biggest causes is the overuse of antibiotics.

Bozhi Tian: And our approach, the patch offers we believe, a game-changing solution.

Paul Rand: The patch Tian’s lab has developed is a revolutionary way to use bioelectronics to treat bacterial infections in an entirely new way.

Bozhi Tian: It actually uses precise and localized electrical signals to target bacteria right at the source of infection. And it’s a drug-free alternative that reduces the risk of resistance entirely, because it doesn’t involve any chemicals that bacteria can adapt to. So by disrupting their behavior without killing them outright, the patch avoids creating the evolutionary pressure for resistance. So how does it work? It works by delivering gentle electric signals, which can change the electrical potential across the bacterial membranes. And when the bacterial membrane potential changes, it actually shift the bacterial behavior, but result killing them. Here, the fascinating part, when the membrane potential changes, it reduces the bacterial ability to cause harm and essentially dialing down their virulence. But why not just kill them outright? So we totally think that we just kill the bacteria directly. That’s probably the easiest solution. The answer lies in understanding that bacteria aren’t just invaders, they’re actually a integral part of our body’s complex microbial ecosystem.

Paul Rand: So here’s the thing about bacteria, they’re not all bad. Some are troublemakers, sure, causing infections and making us sick, but others, well, they’re basically running vital systems in your body from digestion to immunity.

Bozhi Tian: Think about E. coli. So E. coli is one of the major bacterial species, and they can be good. They can be bad and cause infection, but they can also be really good.

Paul Rand: And here’s the problem with antibiotics. They don’t always care which is which. They just wipe them all out. But the patch, well, that’s much more targeted, much more precise.

Bozhi Tian: We just use gentle electrical stimulation to bacterial but not killing them, because I mentioned earlier that bacteria can be good, can be bad, and what we hope to achieve is to inhibit their harmful side, but leverage their beneficial side, for example, for therapeutics.

Paul Rand: So in the current case, if somebody had a cut that got infected, you would then put, instead of giving a penicillin or any number of other antibiotics to treat it, you would in turn use one of your patches?

Bozhi Tian: In the future, it is entirely possible that patients can use advanced versions of those patches to treat everyday scrapes or cuts. I think it’s totally possible. Imagine just a band-aid that not only protect wounds, but also accelerate wound healing and prevent infections with embedded bio-electronic technology.

Paul Rand: OK, wow. OK. And if you thought about treating of some infections, the thought is that 10 days or less, you’re treating an infection. How long would it take under this system to be able to treat?

Bozhi Tian: In our published work, we showed that just a few hours electric stimulation would be sufficient.

Paul Rand: My gosh.

Bozhi Tian: Yeah, as far as the biofilm goes.

Paul Rand: And if we thought a little bit further down the road and we’re taking this technology and we’re thinking about, well, where could this go? What other conditions i.e., cancer could be treated with such a process?

Bozhi Tian: Well, I believe so. The similar bioelectronic principles or bioelectrical device designs could disrupt the cancer cell goals or enhance the delivery of the therapies to the tumor sites. And besides this cancer therapy, I do believe that for some autoimmune disorders, this device can be used as well because the electric fuse could be adapted to modulate the overreactive immune responses. And this can potentially provide new treatments for autoimmune diseases such as lupus. And if I project what we could achieve like five years or 10 years from now, I would say that it might become a product at that time point, because the whole process does not involve chemicals, does not involve genetic modification in terms of FDA approval, it would be faster.

Paul Rand: Applying bioelectronics to our skin is one thing, but what if we could infuse those electronics with living materials so that they could be placed deeper into our bodies, even into our cells so that they could rewrite the code of how our bodies work? Living bioelectronics, well, that’s after the break.

Paul Rand: If you’re getting a lot out of the important research shared on Big Brains. There’s another University of Chicago podcast network show you should check out. It’s called Entitled, and it’s about human rights. Co-hosted by lawyers and new Chicago law school professors, Claudia Flores and Tom Ginsburg, Entitled explores the stories around why rights matter and what’s the matter with rights. One of the main focuses of Tian’s lab is developing what’s called living bioelectronics, devices that have had living cells integrated into the systems, allowing them to adapt and sync up with your body.

Bozhi Tian: So in my previous discussion I mentioned that electronics can actually inhibit bacteria. So we don’t want bacteria to grow, but in this case, we actually want to use the beneficial sides of the bacteria if we know how to inhibit the harmful sides. So basically living bioelectronics can integrate living bacteria or other mammalian cells into the bioelectronics devices. And this can create a fusion of the biology and technology that is both innovative and also functional. Imagine a symphony, each microorganism play a role in controlling the inflammation or healing wounds or even regulating the immune systems. And now we can incorporate all those biological functions in the electronic system as well.

Paul Rand: Can I maybe go a little further and say talk about a prototype and what it is and how it could actually work?

Bozhi Tian: Last year we published a work in science, and that work was led by my very talented former graduate student, Dr. Jiuyun Shi. He’s now a postdoc at Stanford. In that work, we showed that we can have a viable and flexible device, living bioelectronics that can be used for treating psoriasis.

Paul Rand: Psoriasis is a chronic autoimmune condition that primarily affects the skin, causing it to become inflamed and red and covered with silvery scales.

Bozhi Tian: And what we did in that work is that we incorporate the bacteria as epidermis into some hydrogels together with some electronic sensors and stimulators. So what happens with that? This bacteria is on just passive components. They actively interact with the skin’s immune system to modulate the inflammation and promote regeneration. So with this approach, the bacteria can sense and respond to local inflammation and then deliver the therapeutic effects precisely where they’re needed most. I think the truly exciting part of this device is that they’re not just used to treat symptoms, they actually work in harmony with the body’s natural systems to enhance their ability to heal and adapt. I think this is just the first step in our effort in this living bioelectronics, and we have some ongoing work in the lab as well.

Paul Rand: Living bioelectronics could go far beyond just healing wounds. These nanoscale tools can dive straight into your cells, delivering signals that could fine tune your body’s bioelectric code to regenerate tissue, catch early signs of disease, or even engineer cells to create entirely new therapies.

Bozhi Tian: We also designed some nanoscale tools, so they are so small that they can actually enter the cell. So target specific organelles or they’re small, that they can deliver signals only to a part of cell we call subcellular component. So those tools led us to watch and control what is happening inside cell or just the part of the cells with incredible precision. So our devices use living cells to directly engage with the body’s bioelectric signals, and this can amplify or modify these signals to guide processes such as the tissue regeneration or healing. So this bio-hybrid approach could introduce new regenerative capabilities by tapping into the inherent bioelectric language of the cells. And this could also allow us to leverage the body’s natural healing and ghost mechanisms and they can deliver drugs directly to the right parts of a single cell or catch early signs of the disease like cancer and even engineer cells to produce therapeutic molecules.

Paul Rand: And when it comes to chronic diseases like diabetes, this could be a game changer. Imagine a device powered by living cells that can sense your glucose levels and release insulin exactly when you need it, no needles and no constant monitoring.

Bozhi Tian: And the basic idea is that some living cells, they can actually sense glucose levels and release insulin in response. In our body that is the pancreatic beta cells. So what we hope to achieve is to incorporate those cells or engineered living cells into the bioelectronic device so that they can sense the glucose level in our body, release insulin response, and then can potentially give the diabetic patients a seamless and also biologically integrated solution. And this can also eliminate the need for constant monitoring or injections.

Paul Rand: I would imagine you’d have people lining up down the block for that one.

Bozhi Tian: Yeah. So this is something that we truly hope to achieve and probably we can accomplish this in a few years from now.

Paul Rand: There’s even to the point where you’ve thought about edible types of materials that could actually get involved in helping regulate the gut microbiome. Is that right?

Bozhi Tian: Yeah, exactly. What we did is that we create a synthetic materials that can help the gut microbiome, and this edible material contain nanoscale mineral particles as well. So when they are delivered into the GI tract and eventually go to intestine, they interact with the gut microbiome. And what we found is that they can restore the balance in the gut for conditions such as inflammatory bowel disease, and they can deliver biotics or other therapies exactly at where they’re needed.

Paul Rand: But it doesn’t stop there. These tiny bioelectronics are not just for your gut or your body, they’re even possible to use in your brain.

Bozhi Tian: Yes, absolutely. So we have been working on bioelectronics tailored for neural applications as well. For instance, we have developed technologies to deliver a precise photostimulation to certain neural tissues, and those neural tissues can be the brain tissues or some peripheral nerve tissues. Imagine devices that don’t just restore lost functions but actually enhance it. For example, bioelectronics systems that could improve memory by optimizing the neural communication or serve as external data storage system that integrates seamlessly with the brain. Let’s just picture a device that gives someone ability to see infrared light or hear frequencies beyond the range of human hearing. Those things are actually totally possible if we have some correct signal transducers. So we could unlock entirely new sensory experiences by doing so. But it goes further, bioelectronics system could also regulate emotions by gently modulating the neural circuits that govern mood or anxiety.

Paul Rand: But you may be wondering how would these electronics under our skin be powered? Tian’s lab came with something truly ingenious, photo-electroceuticals. It’s a fancy way of saying that they use light.

Bozhi Tian: By using specific wavelengths of light, we can develop a tools that is capable of precisely modulating neurons or even controlling the rhythm of a beating heart. And this approach doesn’t require very invasive surgical procedures or direct electrical contacts, and it also allows a very precise targeting of cells and tissues without affecting the surrounding areas. So we believe it’s a technology that opens exciting new doors for treating conditions like epilepsy where the precise neural control is actually critical, or for cardiac arrhythmia treatment where the fine-tuning of the heart rhythm can be lifesaving

Paul Rand: Like a pacemaker.

Bozhi Tian: Exactly. So pacemakers, traditionally, they are bulky and rigid and they can provide some electrical stimulation to the heart so that the heart can beat at the same frequency as the electric stimulation. This is a traditional design. And in our lab, I would say that we have designed a new type of pacemaker, which is not driven by direct electric stimulation, but actually by optical stimulation. And I’m actually incredibly-

Paul Rand: By optical stimulation?

Bozhi Tian: Yeah, optical pulses, optical stimulation, not electric one. But the mechanism is not that complicated to understand. Think about a solar cell panel. We shine light on the solar cell panel and the solar cell panel can convert energy from light into electricity, and we use that converted electricity to stimulate the heart tissues. So essentially we need to use a transducer, and in our case, it’s a very thin, silicon-based membrane that is the optical cardiac pacemaker. So we shine light to that flexible membrane and that can convert into some electrical process to stimulate the heart in a less invasive manner.

Paul Rand: Those have to be implanted but also removed when they’ve ended the end of their life cycle. But that would not be the case for some of the devices that you’re talking about.

Bozhi Tian: Yes, absolutely. So a key feature of this pacemaker is its ability to safely dissolve within the body over time. And unlike the traditional devices that require surgical removal, an [inaudible 00:25:00] electronic or optoelectronic pacemaker actually degrades naturally after completing its function. So this approach minimizes the risk of complications and also alleviates the burden on patients, particularly those with limited surgical options.

Paul Rand: Is this something that you see being commercially viable within our lifetime?

Bozhi Tian: Yes, absolutely. We are actually having a startup. We’re still in the process to make this happen, and our goal is in about five years to 10 years, this optical cardiac pacemaker can be used in the patient.

Paul Rand: Wow, my goodness. And I’m sure as people are listening to this more, I’m going to go back to the scientific or rather science fiction concept, because I think some of these things, if you think them far out, lead into this idea of almost enhanced human capabilities or what some people would thought. Even the concept of cyborgs, if you think back to Terminator or some of these other type things. That goes beyond treating medical conditions, but evolve into enhancing human capabilities. As you start going through all these things, this is about at the point where folks are listening and they’re saying, “Well, that’s interesting, but should we be doing these things?” Are there ethical considerations that come into play? And if so, where? I would bet folks are thinking, “Well, that’s pretty cool.” And to interfere and treat infections this way seems like a very compelling approach. But as you start talking about enhanced human capabilities, perhaps that starts raising a different set of questions. How do you and your folks in your lab think through issues like this?

Bozhi Tian: Yes, absolutely. I love this question. The ethics are certainly at the forefront of everything we do. When you are working on technologies that could fundamentally alter how we interact with biology, you have to ask tough questions about their impact. For us, it’s about ensuring those tools are used to improve health and the quality of life not to control or exploit. So the potential of the misuse is actually real, especially with technologies that can precisely control biological systems. For example, the neural devices can enhance cognitive performance, but they also raise questions about surveillance and coercion. So to address this, we should work closely with ethicists, policymakers and also some stakeholders to consider these risks and build safeguards into the design of our technologies.

Paul Rand: As you start sitting down and start thinking about what do you hope to accomplish during this period of work and where do you expect us to be in the next 10 years or further away, that is kind of shaping your vision?

Bozhi Tian: Bioelectronics have the potential to go far beyond the body. They could be woven into the fabric of art, architecture, and even environmental protection. That’s just a picture of beauty that breathes bioelectronics systems regulating its internal climate, using the principles inspired by human physiology. Or imagine bioelectronics art installations that interact dynamically with their environment, responding to light sound, or even the people viewing them. So those technologies could also play a vital role in sustainability. Think about bioelectronics devices that monitor ecosystems, mitigate pollution, or harness energy from biological processes to power the clean technology. So my lab has been working on bioelectronics for over 12 years since I joined UChicago. Now I actually exploring broader intersection of biology and material science. I believe the growth really happens outside of our comfortable zones, so I’m eager to leap into new areas that push the boundaries of what is possible.

Tape: Big Brains is a production of the University of Chicago Podcast Network. We’re sponsored by the Graham School. Are you a lifelong learner with an insatiable curiosity? Access more than 50 open enrollment courses every quarter. Learn more at graham.uchicago.edu/bigbrains. If you like what you heard on our podcast, please leave us a rating and review. The show is hosted by Paul M. Rand, and produced by Lea Ceasrine, and me, Matt Hodapp. Thanks for listening.