Human Bones, Made In the Lab

innovations human body parts made in the lab. I'm Jacob Goldstein and this is What's Your Problem, the show where I talk to people who are trying to make technological progress. My guest today is Nina Tandon, co founder and CEO of EpiBone. Nina's problem is this, how do you grow human bone in a lab and do it at a price that makes economic sense. In our conversation we talked about how EpiBone is growing human bone that's being used even now to treat patients, but also we talked more

broadly about the field that EpiBone is part of. It's a field called tissue engineering. Maybe just to start, like, what is tissue engineering? Well, tissue engineering is a branch of engineering that's devoted to the creation of surrogate body parts. Okay, the future, Yeah, one stop body shop for human prepare to what extent is tissue engineering the present? What tissue

engineering is actually happening in mass production, normal medicine. Now, that is a good question, and I think you know an easy way to think about it is, you know, if you and I were to do a thought experiment of what would be an easy tissue to grow, what might you say? None? I would say it sounds crazy hard to grow tissue, all right, right, Well, maybe something flat, okay, maybe something with a single cell type. Maybe a tissue

then regenerates on its own. Skin okay, boom rites a skin is a flat tissue, single cell type, and regenerates on its own. Okay, has a lot of stem cells in it, and so regenerates on its own. Like you get a cut, you get a scrape, and magically a week later or whatever, you have new skin there. Yeah. And so in the early two thousands, we saw two products in the late nineties early two thousands be released to the market, I believe, for burns and diabetic foot

ulcers something like that. And so that's the first that's easy. So you have this moment twenty years ago, people are making skin graphs in the lab and there's sort of big dreams. So if we can do skin, maybe we can regrow everything in the lab. And so when do you get into the field, When do you walk into the story. I was an electrical engineer coming out of undergrad and I had worked as a software programmer for a telecom company. So this was not what I thought

I was going to be doing with my life. But nine to eleven happened. I was living in the suburbs for the first time in my life, and I got a little bored and started taking classes at the local community college in anatomy and physiology. And I think because I was so lonely, because I was so kind of starved for that type of engagement, I really got into this class and I decided I was gonna, you know,

I had to follow this. So I applied to the bioelectrical engineering track at MIT and got in for a PhD for a PhD program, And so it's at MT that you sort of discover this emerging field of tissue engineering. Yeah. Yeah, And when you discover it, like, what do you think, oh, my gosh, it's so cool this woman, Gordona, who was one of the professors, and I just connected with her

as a person. To discover that one of the nicest people that I knew at MIT also happened to be experimenting with using electrical signals to grow hearts, and that I was like, wow, I need to know if maybe she might want to work with someone who's an electrical engineer on that, and she did, And that was really felt like destiny to me because I thought to myself, I mean, I'd already fallen in love with the heart at that point through my studies, so it really spoke

to me. And the idea that we could copy those electrical signals to try and coax embryonic stem cells into becoming heart cells or you know, to essentially coax the tissue to form that to me was intoxicating. So how do you get from there? I mean, you fell in love with the heart, but you didn't end up starting EPI Heart, You started EPI bone, Right, how do you get from from there to starting your company? Cardiac tissue is on the end of the spectrum in terms of difficulty.

There's a lot of intermediate hard end of growing tissues mechanically at most metabolically active tissue in the body, multiple cell types arranged in a very specific manner. So really the most difficult you could possibly imagine, and bone is in the middle. It's a complex shape, but we could solve that using digital fabrication, and we could use a single cell type to engineer a pretty high quality bone.

So it was clear to me that if I wanted to be involved in translating that's the word we use in the field, translating science towards the clinic in my lifetime, I should probably you work on a tissue that's closer to the skin side of the spectrum than cardiac. Right, so you start epic bone, you decide to work on bone. That's like almost ten years ago now, and today you

do have this engineered bone. You're doing a clinical trial and as I understand it, right, this is bone that is going into people's jaws, where typically a surgeon would cut a piece of a patient's own bone out of some other part of their body. But you're growing the bone in a lab basically from scratch. So tell me about the clinical trial that's going on right now. Okay,

so patient I think I'm allowed to say this. Patient one suffered a traumatic injury due to a car accident, and so we provided bone to help reconstruct the jaw. Patient two had suffered from a degenerating jaw resulting in airway obstruction, so we provided bone to help elongate the

jaw and relieve that airway obstruction. Patient three, he was born with facial asymmetry that would only be correctable by taking bones out of some other part of his body to reposition his jaw, and we were just able to grow bones for him using a small sample of his fat tissue. So you know, whether it's for cancer, trauma, or congenital defects, people need bone. It's bone is the most transplanted team in material after blood. And so he is three. The number of patients in the trial, that's

the we've done six. Oh, he's done six, Okay, yeah, And what is the total number of patients you plan to enroll? That's the fully enrolled. So that was our phase one too. That was our phase one two, first in human, first in class. Basically safety and a little bit of efficacy. That's what phase one two, that's right, Yeah, yeah, in a little bit of efficacy, and hopefully we'll move forward with a phase three in the not too distant future where we'll be able to help a few more patients.

And so how does the process work. So we take two things from the patient. One, we take an image a CT scan, which is like a three dimensional X ray, so we can extract three dimensional data out of that and design a perfect puzzle piece shaped biomaterial that will

be the eventual shape of the bone. We also take a small sample of fat tissue from the patient so we can extract the stem cells out of it, so those cells can attach to the scaffold, proliferate, lay down new matrix, and essentially turn that biomaterial into living bone.

It takes about three weeks for bone. So you take a CT scan to get the image of the shape of the bone you need, and then from that you make when you say a puzzle piece, you make basically something that is the shape of the bone you need made of stick or something. What is it made of? So we take a cowbone, strip all the cellular material out of it, so we're left with essentially protein and

mineral and it's a very porous material. It looks like pumice stone and you can infuse cells onto that and the cells kind of recognize that matrix as being a place that gives them a cue towards differentiating them towards bone. It feels bony enough to these cells that they say, okay, let's let's make the rest of this bone. So right, so you have this puzzle piece made of cowbone essentially, right, that's in the right shape. So that's kind of one

one track. And then on the other track, you're taking fat from the patient. You're getting the stem cells out of that fat, and stem cells are cells that can become any kind of cell. Right, So, yeah, we've got the cowbone puzzle piece, we've got the stem cells from the patient. What exactly how happens next? Well, this is

our secret sauce. The bioreactor. So a bioreactor is just a fancy word for a cell culture system, like a place where you can culture cells in and so we get those cells to turn to grow up and turn into bone. So so just to be able to see it, like, is the bioreactor a metal box? What actually does it look like? You know, you imagine a little bone and

then you imagine the reverse image of that bone. So a little gasket that like covers that bone perfectly, and that gasket has holes in it so I can perfuse liquid food through it as it grows. And that gaskets contained in kind of like another canister where we can have fluid that comes in and fluid that comes out. It's about the size of a coke can, and the fluid input and output are attached to a pump, so

it's constantly pumping. And that whole contraption, which we've made quite efficient in terms of sizes about a shoe box in terms of size, and we can stack them up so that we can grow many at a time. Great, So you take the cowbone puzzle piece, how do you get the stem cells to like go on to the puzzle piece and grow. Yeah, we perfuse them very slowly

and the cells attach. And that's part of why the biomaterial is so important, because you know, a piece of decellularized bone has a lot of these nanostructure attachment sites that cells recognize and glom onto, and so there's a period of time where the cells attach. Most cells in our body are attached to some sort of three dimensional matrix and then they start to proliferate. And lay down even more matrix. So they proliferate around sevenfold and they

fill up that porous structure. So even though it was porous at the beginning, it looks like bone at the end of huh. So you take the puzzle piece, you put the puzzle piece into the reactor, and then you send the patient stem cells into the reactor and they attached to and grow over the puzzle piece in within as well, they're filling up the three dimensional YEA, yeah, it's not a pancake. It's not a pancake. It's it

it's like a honeycomb or something. It's really important to get the cells in three D. You know, a lot of people can grow cells on a Petrie dish, but grow cells in three D is a that's a big challenge. But we've seen that the bones perform their mechanical duties on day one. You know, patients are able to eat, speak, drink, all the things that you'd want to do after the break. The problems Nina and her teams still have to solve

to get lab grown bone approved and into widespread use. Also, how should we think about the pace of progress in tissue engineering and in biotech More broadly. Now back to the show. So I want to talk about sort of the future and what you're working on next in a minute. But before we do that, I mean, you've been in the field now for twenty years. Your company has been around for nine years, and so tell me about the progress of the field in the time you've been in it.

Tell me about the progress of the field in the twenty years. What has what has happened faster than you might have expected, what has happened slower? And like where are we now? What is happening in tissue engineering right now? There was a technology developed for cartilage, cartilage in a couple of generations of cartilage, so that's been established as like another tissue that can be engineered. There's another company called hum Site which makes tissue engineered vasculator. They are

very close to getting in approved for commercial use. They are hope within about a year or so. They're a publicly traded company. So so vasculature, Just to be clear, like blood vessels, they're making blood vessels. Blood vessels. That seems hard. It's hard. Yeah, it's hard. It seems hard. You gotta get the tube. It's a tube. I don't know why that seems harder to Me's a that. Yeah, hollow organs are a step above flat tissue for sure.

And UM and there's their founder, Laura Nicholson. What she learned in growing vasculature was that cells needed flow, not just flow of liquid, but pulsatile flow. Be interesting, you're moving like pulsatile, like like the way the heart beats. And it's not like a river. It's like, yeah, exactly, it's not a river. And so that's that was her genius discovery. And they are you know, they've treated UM soldiers and civilians in the Ukraine who need who need

blood vessels. UM. They are close to commercials. Has the progress of tissue engineering been slower than you would have thought twenty years ago? Yeah, I think my notion of time was very different following years ago. You know. Now I'm like, oh, twenty years okay, that's nothing. A human lifetime, that's nothing. You know, what can be done in a human lifetime? Not much? You know, that's like more my kind of gallows humor. Now, things move slowly, slash wisdom,

slash wisdom. Yeah, sure, but like yeah, things it's a glacial I like to tell people this is like a slow motion marathon in a way like this past twenty years have you know, blinked and been gone in a heartbeat. But yeah, it takes a long time to do things. I think I've gotten better at being more honest or realistic in terms of estimating how long something's going to take, because you can't rush the science. And it's really, you know, interesting,

you say, oh, it sounds so futuristic. I think a lot of people believe that this should happen, and there's very few people that have the skill set to make it happen. You know, because if you watch science fiction, and or if you watch I don't know, even Star Wars or the Marvel movies, there's always examples of people getting healed with technologies like tissue engineering, so people assume that that's going to happen. Like Luke Skywalker got a

new hand, So why can't I get a new hand totally? Totally? Or in Waconda, you know, they just regenerated, or you know, there's all these technologies in pop culture. Even in Grey's Anatomy they had episodes of tissue engineering. And yet it's very hard and it takes a long time. And so I'm glad that I've been working on this particular tissue because you know, it's been ten years as a company and we've brought it to where it's never been before. And now the challenges a lot more with a lot

of that technical de risking behind us. The challenges are more or less of will this work in a living system and more towards will this work in a clinical setting? Will this work in the economy? And I find that to be extremely exciting when you say will this work in the economy, that's a big interesting question that we really haven't talked about yet. So so how do you think about that? How how are you approaching that? You know,

unit cost economics need to work. That's where the biomanufacturing comes in. Automation of cell culture is a big driver. It's a very artisanal process, you know, using our hand pipets and expensive, right, artisanal and hand this that that that is expensive, right. I don't want an artisical bone. I want to mass producing bone, right yeah, right. Creating the infrastructure that allows for automated biomanufacturing is a big

piece of it. We're not the only ones that need to be working on that um But then also I think scientifically and clinically being very clever in terms of the end points you're measuring in your clinical trials so that you can make the economic case. For Look, if we're going to give you this piece of tissue, it's going to save you surgeries down the line. That is very interesting, And like, tell me specifically what that means in the case of the of the jawbone easy economic

cost of avoided. What is the economic cost avoided for evybone? Well, if you had evybone, you don't have to do an extra hour or half hour of surgical time, you don't have to put the patient in the ICU for as much time for recovery. What those all are very easily calculatable costs. So so that economic case is as important to me as as the clinical case. So if things go well, when do you think you might actually be

approved and out in the world twenty six, twenty seven? Okay, yeah, not crazy if you had at maut a future but a while yet. So for some people that's forever. For some people they're like, oh, that's pretty soon. I wonder if the sort of absurd rate of development of basically semiconductors right, basically if Moore's law, and the development of computer technology has messed up our sense of the rate

of technological development. Like if we have come to expect so funny that you brought up law, Well, you were an electrical engineer, so you know than I do. Yes. So in biotech there's a joke called e Room's law, which is if you spell more backwards, what do you get? Because we're sort of the opposite of that, it gets twice as expensive and twice as slow every year. Yeah, and the FDA is backlogged and there's just been so

few approvals over time, it's really gone down. So I think everyone understands that no one wants to hurt people from a regulatory standpoint, no one. They don't want to hurt people. Entrepreneurs and companies, we don't want to hurt people. But there's a risk benefit to you know, if you if you hold back innovation, sure fewer people will get hurt, but also a fewer people will will get these breakthrough treatments. There's regulation, and that's clearly important, but I feel like

also the body is just super complicated. Like I feel like, even independent of regulatory bottlenecks, it's just very hard problems it's hard, but it does feel like, well, I'm climbing a mountain that's worth climbing, and you know we'll get there. We'll be back in a minute with the lightning round, including a very compelling argument that ourselves are intelligent. Okay, that's the end of the ads. Now it's done for the Lightning round. What's one tip for finding a mentor?

M who's your professional crush finding? I'm run, sure, yeah, you're professional crush. That's that's how that's Identifying a mentor is like, who do you have a crush? How do you find a mentor? How do you find a mentor? Here's my answer. Good people lead you to good people. I like all of those answers. As a former McKinsey consultant, do you think McKinsey is overrated or underrated? I think

I think neither appropriately rated. They're appropriately powerful. I mean, they do good work and they're full of very earnest people, and my goodness, do they know how to make a two by two matrix out of any problem? Um? Good? I like broken down to do a two by matrix? Um. What's been the most surprising thing about running a company? I think, how much your psychology gets amplified. You know, just think how much of the company is a mirror, and if I'm having a bad day, it amplifies to

the team. It just makes me have to just really take my own mental health and really seriously. Downward dog or Warrior one, Oh, down dog? I think I love them? Well, yeah, Warrior one, I'd say Warrior two. Okay, good, I love yoga. I could talk about that for a long time. What do you understand about human body that most people don't That sells are intelligent all of our selves. Intelligence isn't only in the brain. Intelligence is everywhere in the body,

at the cellular level. What do you mean by that, Well, we tend to think of intelligence as being in our brain, and that places like our heart are dumb. It's a dumb pump that listens to the brain. But the heart is thinking on its own. It's making a lot of decisions about how much blood to pump and send signals up to the brain, but also does plenty of thinking

on its own. The eye isn't just a camera. The eye contains a lot of decision making processes about what we're seeing before even sending the image up to the brain. The optic nerve is the largest amount of data compression known in biology. So intelligence is distributed throughout the body. And I don't think a lot of people think that, but I know that, and I love that about the body. It makes me, It makes living in a body fun for me. Nina Tandon is the co founder and CEO

of EPIBOE. Today's show was produced by Edith Russolo, edited by Sarah Knicks, and engineered by Amanda kay Wong. I'm Jacob Boldstein and just one last quick note. We're going to be off for the next couple of weeks and we'll be back with a new episode on Thursday, April twentieth,