Kathy Werzer (3:11)

How much can you tell as a dermatologist about a person's overall health by looking at their skin?

Dr. Sarenya Wiles (3:16)

You can tell a lot by just looking at the skin. I mean, I consider the skin as a mirror to your systemic health. I often tell my patient to pay attention to your skin. It's more than vanity, it's more than cosmetic, because it is your external facing barrier barrier. And it can impact a lot of ways that our systemic aging is occurring. But also it can show signs. We can tell if there's something gone array. You can tell if somebody is very sick or sleep deprived. All of these signs show up on the skin.

Kathy Werzer (3:45)

So I can see where folks living with skin cancer, other skin diseases, those who've been badly burned, kind of bear an extra psychological burden in addition to a physical one.

Dr. Sarenya Wiles (3:55)

Right.

Kathy Werzer (3:55)

Is that part of the human story driving some of the research into 3D skin printing and skin regeneration? Dr. Feinberg?

Dr. Adam Feinberg (4:01)

Yeah, I mean, the. The idea of 3D, you know, bioprinting, which is really just 3D printing applied to biological materials and living cells and tissue, is to try to come up with just better ways of reconstructing these systems. A lot of time, you know, we're dealing with, like, liquids. You know, cells are in liquids. You know, we're dealing with these things like collagen and gels and even the lotions, right. We're used to applying to skin come in these liquid forms. But obviously the tissue itself is solid and physical, right? And so the printing is really kind of an advanced way of really trying to put the cells and the collagen and the different biological materials exactly where they need to be to reform the tissue structure. The human body is not necessarily great at rebuilding these things on its own. So we're using these advanced technologies to try to augment that. I think everyone has had a cut, right, that forms into a scar upon healing and not back into normal skin tissue. And that's partly because it's challenging for the biology entirely on its own to reconstruct those. Those architectures as we normally develop as we grow, you know, through early development in the womb into an adult. You know, all those tissues form, but once they're formed, our bodies are not great at recreating them. And so the 3D printing is really a technological solution to that problem.

Kathy Werzer (5:19)

So the cells and the tissues assemble themselves, right, in kind of this matrix of protein fibers. I know your lab has spent significant time trying to replicate that, Matri. And I'm curious as to what substances did you use to do that.

Dr. Adam Feinberg (5:32)

We came up with a complicated solution, I think, for a simple solution. And that simple solution is we just wanted to use the same materials as the human body, right? So we just wanted to use cells and collagen and hyaluronic acid and all the good stuff that's in tissue. And we didn't want to have to use synthetic materials, right? So things like plastics, ceramics and metals, those are great. And we're really good as society or from a technological standpoint, and using those materials to build, you know, automobiles and aircrafts and even a lot of medical devices. But that's so far different than living human tissue. And every, even every medical device we get implanted in our bodies today, they're still inferior to the original tissue, right? They're really just a stopgap, whether it's a hip implant, right, Or a stent or any other, any other device. So our system is really designed to work with entirely biologic materials. And therefore what we create is entirely biologic. The beauty of that is that hopefully it functions more similar to the native tissue to begin with. And then also, if we translate from in vitro models, which is kind of where we are today, ultimately, to tissues that we can implant for therapy, then because they are biologic, they should perform better and integrate better into the living body.

Kathy Werzer (6:50)

Now, Dr. Wiles, your lab is pretty cool. It's kind of very sci fi. I think you have huge 3D bioprinters. What are you doing?

Dr. Sarenya Wiles (6:59)

So we are trying to model the cake layers of the skin. So I call them cake layers because there's different layers. We have the epidermis, dermis, and the hypodermis. So these are structures that we can resemble to human skin. So we can try to print them. And as Dr. Feinberg was talking about, the idea is to use native human tissue as our bioprint, as essentially our model to say how do we reconstruct what is existing as natural skin tissue? And what we do is we work with different types of printing technologies. One technology is called extrusion bioprinting. And we essentially lay out the different cells that would go into each component of the cake layer. So you would have, in the dermis, fibroblasts, which are often the matrix producing cells. So they produce collagen, elastin, glycosaminoglycans, or other matrix proteins that really keep your scaffold together. You know, we lose about 1% of collagen per year starting in our early adulthood. So this is really important to try to emulate across time. So a 30 year old skin would look very different from a 50 year old skin or an 80 year old skin. So the idea is to recapitulate those collagen matrices. And then of course the epidermis, where we have cells called keratinocytes and melanocytes that live there. And they are essentially cells that can regenerate the top layer of the skin. This is a living epidermis. This, the skin regenerates naturally. Like every 30 days we have a new layer of skin that can pop up. So this is the idea that we can resemble the keratinocyte turnover and also melanocyte. So these pigment the skin layer. So across different cell types, across different people, we have different diversity of cells. So we are trying to put all these puzzles together to make the human skin model.

Kathy Werzer (8:44)

I'm curious then, what will these 3D bioprinted skin models allow you to do?

Dr. Sarenya Wiles (8:51)

At the moment, we're working on diagnostic testing. So we want to work closely with the US FDA and try to see if we can utilize these models as preclinical testing. So we want to create a system that is an alternate to animal testing. And actually there's a story behind this, Kathy, of why we started to work on 3D bioprinted system is we were initially doing testing for preclinical drugs. So we wanted to develop a topical biologic for atopic dermatitis or eczema. And there was a long wait for getting our pig models. So it was going to be about a year to get the right mini pigs to do these testing on them. So then we turned into an alternate source to see how can we start developing this in house. And sometimes I joke that we should have just waited for the mini pigs because it took about a year to get the model sorted out. And we're. It's still a work in progress.

Kathy Werzer (9:41)

Now, Dr. Feinberg, Dr. Wiles mentioned collagen, which is the key building block of skin. Your lab, which I thought was very interesting, has used bioprinting to build and help me out here, a tissue model of collagen. What does that look like. And what is its importance in your work?

Dr. Adam Feinberg (9:58)

Collagen is the most prominent material in the human body. We're actually mostly water, but the next thing we are is collagen. It's really the. This. The main structural material of the human body and really serves as the kind of the scaffolding for the skin, but really every. Every organ we have. So when we were working on technologies to rebuild human tissue, it's kind of like the. The ideal choice, right? If we could. If we could use collagen as our scaffolding, well, that's essentially what the human body's already doing with collagen. The problem was, how do you 3D bring collagen? Because it's a protein, it's assembles into these fibers that you can kind of create all these structures with. And so that's really why we focus on collagen. Before that, there was really no way to 3D print collagen in any way that looked even remotely like native collagen in the. In the human body. Now we can 3D print collagen that under the best electron microscopes down to kind of a nanometer scale, which is, you know, essentially like 1 10,000 the diameter of a human hair. It still looks like collagen should. Right. Which means then when we implant it in the body, the body actually recognizes it as normal collagen, which is always our goal. You know, all these synthetic materials, like, if you implant, you know, any metal or plastic you put in the body, ultimately the body responds to that the same way it responds to a splinter. Right. I think we've all had a splinter. And we know, like, the body kind of tries to wallow it off and get it out. That's what the body does to any synthetic material, really. And so that's the beauty of using things like collagen. We had a paper in Science back in 2019 where we applied that to building parts of the human heart. And now we've expanded that in a paper actually just this year to do more of these kind of in vitro model systems to make things like skin and microfluidics and vascularization as well. And that's like. The other piece we've used this for is when you build a tissue, getting the blood supply to it is absolutely fundamental to its ability to survive. Most blood vessels are built with linings of collagen to help reinforce the vessels. And so with our technology, we've actually been able to build vascular networks so that we can build larger tissues that we can actually Perfuse. And now we're even testing where we build a little tissue and we actually implant it and we directly connect it to the vasculature of the animal. We're testing it in just like the way you would do a transplant for an organ, where you would take the organ and you'd obviously connect it up to all the blood vessels. We're now starting to get to that point with the little tissues we're building. So still a long way before, you know, we're ready to treat human patients. But I think the real take home is by building with collagen we're able to build tissues that really do behave like real human tissue. And once you can do that, then you can do all the things you do with real human tissue, like have models or create organs potentially for transplant and so on. Really an unlock to all those capabilities.

Kathy Werzer (12:51)

Wow, Dr. Wiles, how can you use what Dr. Feinberg's developing in his lab for what you're doing? How does it dovetail?

Dr. Sarenya Wiles (12:58)

You know, just this morning in our lab meeting, we were talking about collagen cross linking. So this is so timely. We face these problems all the time in trying to make sure that the skin model recapitulate human tissue. And collagen is very unique because it's a helical model, a protein that basically needs to be cross linked a very specific way. And the cross linking in physiological systems. So what is happening endogenously may be different than what is happening outside the body. So we really try to learn from the lessons of the human body to then emulate it outside. So I think both from the level of vascularization, but also innervation. Remember, the skin is your largest sensing organ. So we have, it's an external facing organ that is constantly encountering what we call the exposome external stressors, whether it be UV radiation, whether it's pollution or other environmental toxins, it's our greatest barrier. And it is also an organ that senses whether it's love or touch or it is pain or pressure. And so with that sensation, we, we need to better learn about recreating these networks of nerves within the skin. Recreating the vascularization within the skin so that the blood flow can keep the nerves alive, keep the cells alive. So those are some important problems that we're working on as a next step.

Kathy Werzer (14:20)

Okay, wow, this is really exciting stuff. I can see why you both are really excited about this. And I'm wondering then in the future with some of this, this framework that you're both working on, how might it benefit, say, a patient who has had bad burns, perhaps.

Dr. Sarenya Wiles (14:36)

So with patients, you know, especially with bad burns, you're losing that top layer of the skin, the epidermis. Sometimes, if it's a full thickness injury, you're also losing the dermis and subcutaneous tissue. And depending on the age of the patient, their innate microenvironment may struggle to close that wound properly. You may not have the right tin cell strength to bring the skin tissue back together. You may not have the right cell types there. You may, it's a compromised barrier and you may need to rely on your own body's immune system, which plays a big role in wound healing. So bringing all these concepts together, I think thinking about burn victims and our patients that are in need for therapeutics, we want to develop wound patches as a way to help solve their acute need. Whether it's a patient that has a genetic condition where they have a compromised skin barrier, or a burn victim, or older adults that don't heal well just from getting small tears or other types of pressure injuries.

Dr. Adam Feinberg (15:31)

We've kind of done some work that's complementary to that, funded by the military, looking at, you know, blast injuries, right, which are basically obviously the skin, but also go deeper right into the fascia and the muscle and the adipose tissue as well. But it's really similar concepts, right? You know, the tissue types are different, but what we're really trying to do is that we have basically, you know, loss of tissue integrity. We can really recreate different types of cells for each layer. So obviously the muscle layer is going to be quite different than the skin, but all these layers are different. And so one thing that we've done is actually pretty cool. We've actually taken a CT scan of the injury. So that's like a three dimensional injury of the tissue that's missing. Say you have a leg blast injury, you can image the contralateral leg that's not injured. So now you know what it should look like. And so we've actually created three dimensional designs that fill that space where all the different tissue is supposed to be. And then we're able to reprint that. And so we're not yet testing that in humans, but we have tested that in animals and it's quite compelling. So in that case, we actually use more than just collagen. We use a technology called decellularized extracellular matrix, which is similar to collagen. But the idea is that we would take an existing tissue and then remove all the cells. Right. Which just leaves behind the collagen but other proteins that kind of make up the scaffolding, but includes a lot of things like growth factors and other things that are maybe specific to a muscle tissue or specific to a skin tissue, which is a little bit different than just pure collagen. But we're also able to use those as our bioinks to 3D, print the scaffold. And so by doing that we can add in kind of additional factors that really help those specific tissues regenerate. So it fits into this realm called regenerative medicine, which is kind of complementary or along those same lines of what we've already been discussing. We call that volumetric tissue regeneration.

Kathy Werzer (17:24)

The regenerative part of our conversation is going to be, I think, fascinating. And I'm curious here. Dr. Wiles, you deal with zombie cells, right? I'm just curious to know what they are, what they, how they play into aging and regeneration.

Dr. Sarenya Wiles (17:39)

Absolutely. So zombie cells, or senescent cells are cells that basically obtain a cell cycle arrest. They are no longer dividing, but they don't die off. So why does this happen? This actually is a good thing initially. It's a evolutionarily conserved mechanism for cancer prevention. So say a cell gets a mutation. Instead of getting rid of the cell because you may not have enough energy to do that, the cell undergoes house arrest. So that mutation is no longer propagated. So it's a good thing initially. But over time what happens is our immune system slows down, we have inflammation, immune aging, and we don't clear these cells as well. So these zombie cells or senescent cells can accumulate. And we're doing a lot of analysis on gene expression, spatial transcriptomics, proteomics, and really mapping out chronic wounds from patients. And we're able to understand at the cellular level of these senescent melanocytes and senescent fibroblasts and how these cell types are playing a role in healing chronic wounds like diabetic foot ulcers. And then we take what we know from patient stories and we translate them into our 3D bioprinted skin scaffold. So essentially we, we kind of understand if there's a certain types of senescent cells involved, we can use them, as Adam mentioned, as patient specific bio links. So we get a lot of patient samples and we're able to procure very specific melanocyte bioinks that is from a 35 year old female or from a chronic wound 57 year old male. You know, these patients are able to provide us sources that we can then recapitulate their skin model or a chronic wound model.

Dr. Adam Feinberg (19:21)

Busy healthcare professionals. This one's for you. Find Mayo Clinic talks on your favorite podcasting app or visit ce mayo.edu podcasts to learn more. Every week we share succinct, relevant and practical medical insights tailored for healthcare clinicians that you can immediately apply to your practice. Each episode covers common health issues seen in a primary care practice shared by Mayo Clinic experts. Hi, I'm Dr. Bill Maurice from Mayo Clinic Laboratories. Curious to learn more about healthcare innovation?

Dr. Sarenya Wiles (20:04)

I'm Dr. Bobbi Pritt, host of Answers from the Lab, a podcast that explores trends and innovations in laboratory testing and clinical diagnostics.

Dr. Adam Feinberg (20:13)

New episodes drop twice a month. You can subscribe on your favorite podcast app or visit mayocliniclabs.com to learn more.

Kathy Werzer (20:20)

So I'm wondering what you're learning about the aging process as you work with these undead cells.

Dr. Sarenya Wiles (20:25)

Yeah, so the aging process that we learn at the level of the skin is actually influences systemic health too. So what we've learned is that when you increase senescence at the level of the skin, these cells don't just sit there and influence their local environment, but they're secreting factors. This is known as a SAS or senescence associated secretory phenotype. These this noise that comes from that senescent or zombie cell. And this noise is pervasive, so it can actually affect other organ systems, other end organ damage, and even your cognitive function. We published a study that if you increase senescent cell burden on skin in certain animal models that actually affected their gait speed and their ability to navigate and cognitive decline was seen. So really important to know at the level of the skin how these senescent cells play a role and then perfusing into our systemic health.

Kathy Werzer (21:17)

And Dr. Feinberg, when you hear this, how does it again, this dovetail into your work?

Dr. Adam Feinberg (21:21)

Yeah, you know, so it actually parallels some of the work we've done. You know, we also build these in vitro models, you know, obviously in other areas than skin. And one of them we've done is in the heart. When you go for say like a chemotherapy treatment, say for breast cancer, there's a subset of chemotherapy recipients that actually get heart failure from the chemotherapy to treat the breast cancer. That's a really unfortunate outcome. But today we have no way to predict that. So we just monitor all the patients. There's no genetic test, but what we did was we actually made little engineered heart tissues from stem cells that we either took from the breast cancer patients that actually had heart failure from the chemo and those that didn't. So we compared the two. So we built little heart tissues. So either you got chemo induced heart failure or you didn't. We then gave the little heart tissues the chemo. Right? And of course, the ones that were from the patients that had heart failure, their little engineered heart tissues also underwent failure, but it turned out to be due to senescence. So the chemotherapy was inducing a much higher rate of senescence in the heart muscle cells. And that seems to be what was leading to the heart failure induced by chemo, which in some ways maybe just accelerated a normal aging process by the harsh treatment, because that chemotherapy actually also interferes with cell division and replication in certain ways. So while we still don't know why it's happening, we now have a model system though that can accurately demonstrate it. So a, we can use that as a scientific tool to just understand the Y, which is ongoing, but you could potentially use it as a patient specific model. So even if we never understand the why, there's still the possibility of just building each patient a little heart tissue ahead of time if the cost becomes low enough and just testing the chemo. So if a chemo is going to put you into heart failure, we probably want to choose a different chemo. And that's critical knowledge. And that's a story that is likely you can expand to a wide range of other disease states beyond just, you know, this one example.

Kathy Werzer (23:28)

Indeed. You know, I'm betting, listening to you both, that the validation process for some of these models, I'm betting, are pretty complex and probably expensive. Am I right about that?

Dr. Sarenya Wiles (23:38)

Yeah. So there's definitely a lot, you know, to do with replicative accuracy and making sure that every time we bioprint, how well is it reproducing to the same print of the skin tissue that we have and the human skin pathology. So we have dermatopathologists that help us review our printed skin tissue and to take a look in a blinded way to see if we are reproducing similar prints. The skin physiological model, once it's printed, is a living organ. It's still alive, so it's secreting different cytokines and other particles. So we measure what's being secreted out. We also add different topical drugs to it, whether it's Retin A to thicken the skin or topical steroids to reduce inflammation. And we watch the skin increase and decrease in thickness as we do these different topical treatments. So there's a lot of things that we can do for outcomes and readouts of these skin models, but it's definitely cumbersome in the sense we want to make sure that it is done well, that the measurements are accurate and have high sensitivity and specificity.

Kathy Werzer (24:43)

Any comment, Dr. Feinberg?

Dr. Adam Feinberg (24:44)

I would just add, you know, the FDA is really interested in moving away from animal models and moving to these engineered human tissue models. So there's a lot of support that continues to be moved into that space, but the problem is just the validation and also just humans have a wide range of variability already built into us because of, you know, genetic variability and age differences and lifestyle. So that makes it a little bit more challenging. And, you know, animal models have obviously, I think, brought us to this point of medical advance. Right. But at the end of the day, an animal has a different physiology than a human. Right. And so, you know, one of the issues we always face is there are drugs that we try to develop that fail in animals, but would probably work in humans, but we never find that out because they fail in animals. And then most of the drugs that fail in humans worked fine in animals, right? And then when you get to humans, that's when we find out they don't work well in humans. So that's the, the value and potential of the models, but really validating that they're predictive will be the challenge going forward, but it will, I think, without a doubt, end up being the standard process as we advance. I think it's also where things like some of the AI technologies and other things that can potentially augment the tissue models. And what I mean by that is the tissue may not actually have to be a perfect mimic of a human patient. It just needs to get close enough right. Where the readouts we're getting can be interpreted by the A model and mapped on to what would happen in a full patient.

Kathy Werzer (26:12)

I'm wondering what kinds of ethical and philosophical questions do you both need to wrestle with as this technology moves forward?

Dr. Sarenya Wiles (26:20)

I think thinking about the ethical considerations around moving away from animal testing and getting closer to a more human relevant platform is very important and it's exemplary because we actually can try to model the human tissue, whether it's diversity of skin and different types of pigmentation, so a lighter skin to a darker skin. A lot of times clinical trials are not as inclusive. So this is an opportunity to try to start inclusivity much earlier on and try to get different types of pigmented skills, skin models to test at the level of the preclinical diagnostic testing platform. And then I think, you know, accessibility. I mean, the, the cost of all of this is a lot more reasonable than what we were previously doing with animal models. And if we were to get closer to that reproducibility and making sure each of these models are aligned close to each other, and it can model diseases. Now we're opening up new ways to study rare diseases, patients that we wouldn't have been able to utilize or diagnose before. Now we can actually screen and test those. We're actually developing a graft versus host disease model, which is a rare disease condition, using the 3D bioprinted system. So I think creating access, creating more inclusivity, those are all really positive things that we can yield from this technology.

Dr. Adam Feinberg (27:40)

Maybe I'll add to that in a couple ways, right? So I think for most diseases, if you're like within the, say the 90% of the people, right, that like kind of have the most typical symptoms and root cause of a disease, then, you know, medical science typically is pretty good at addressing those. But when you're more on the fringe, right. Or you have a more of an atypical case, sometimes you can be kind of out in the wilderness, I think, trying to find a solution. By having these more patient specific models, it really allows us to really better understand the unique interplay between genetics and physiology for a specific disease. But if you start adding up all the rare diseases together, it's actually a massive number of people, right? And so rare diseases collectively are actually a major, major health problem. They're just diverse. And so these models, I think, also start to address that space as well. And then the FDA actually has some really, I think, valuable opportunities specifically for rare diseases, because, you know, there's less financial incentive for companies that develop therapies for a rare disease. So the FDA has tried to, I think, encourage innovation, right, by making it more straightforward, with less burden to get into clinical trials to treat those patients. But as I said, like, I think once you start to tackle one rare disease with this approach, it then does also open up the opportunity to treat a lot more. This idea that we can really address a much broader patient population with these technologies is really what's going to, I think, make, you know, these types of healthcare innovations far more equitable. Busy healthcare professionals, this one's for you. Find Mayo Clinic talks on your favorite podcasting app or visit CE Mayo Edu Podcasts to learn more. Every week we share succinct, relevant and practical medical insights tailored for healthcare clinicians that you can immediately apply to your practice. Each episode covers common health issues seen in a primary care practice shared by Mayo Clinic experts. Are you trying to become a better human? Well, the Human Optimization Project is an exciting new podcast offering for Mayo Clinic which aims to help you do exactly that. We're all struggling to balance the need to perform and do more while simultaneously maintaining our wellness. In the Human Optimization Project, we're focusing on 10 key domains of human performance to help people achieve more, improve well being, and become the best humans they can be. If that sounds like what you're looking for, search for for the Mayo Clinic Human Optimization Project on your favorite podcasting app.

Kathy Werzer (30:37)

Because you both are on the forefront of innovation. I'm wondering how the technology is being shared right now, and I ask that because I understand, Dr. Feinberg, you have workshops that you're holding for building and kind of democratizing bioprinter technology. Can you talk about that?

Dr. Adam Feinberg (30:53)

Yeah, sure. This is actually how Dr. Wiles and I met. So when I started my lab 15 years ago, and we really were at the forefront of this bioprinting work. A bioprinter costs a quarter million dollars, right? Which is a lot of money when you start a lab. So this is really at the same time that this maker movement started, which some folks may have heard of, but it was really a lot of 3D printer technology coming off patent and just getting very cheap where you could even build your own printer at home. So we actually bought those and started converting them into bioprinters. But these were all open source technologies and. Right. Open source just means that everything is shared freely. Right? So there are the hardware designs, the software, it's all just shared. So being at Carnegie Mellon University, where we're an engineering school, that's essentially a godsend. Right? Because my students see that, they're like, oh, yeah, no problem. I can, I can take that and start building stuff, which I don't think is a universal capability, but being at an engineering school, that is one of the advantages. So we started building our own bioprinters and over the years, we've just continued to evolve them. And then because we built it initially on open source, we've always contributed back to the community. So after doing that for, you know, about seven or eight years and publishing a number of papers, the feedback I got was like, this is really cool. It's great that you open source it. But we still can't figure out how to do it ourselves because they're not at Carnegie Mellon University. And so we decided, you know what, we know how to do this easily. Let's create a workshop where you can come to Carnegie Mellon, build your own 3D bioprinter and then take it back with you to your research lab. And now you built it, you understand how it works. And so we've removed or lowered that barrier to participation and using the technology, there are so many things that this can be applied to. We don't want the printer itself to be the barrier. Now you can still go out and buy a 3D bio printer for a quarter million dollars or less. And I think Dr. Wiles probably has a few of her own as well. They're pretty common nowadays, and they have come down in price, but they're still about usually somewhere around 40 or 50k for a decent one or higher. Ours cost $1000 at most, and I would argue they outperform all the others pretty substantially, if you know how to use it properly. And so, yeah, we've run this workshop now, I think, six times. We've trained, I think, 300 people and produced probably about 50 printers. And a lot of them have now started to publish their own papers. It's really a great experience, and you meet great people and make new connections. There's really nothing quite like building with your own hands as well. And so I found the workshop is really great. Once you build it, once the intimidation of the technology, I think, starts to melt away and you're really able to now focus on layering whatever innovation you want on top of it, such as improved skin models. Wow. For a thousand bucks or far less. So we've also got a version of this we use in K through 12, like, more STEM education. And, you know, that's actually, we have these for about, you know, two to $300. I mean, it literally is as simple as going onto Amazon, buying the cheapest normal 3D printer you can find, and then you convert it into a bio printer. But the 3D printer you buy will print all the parts you need to convert it into the bio printer. So, you know, we've been a little bit cute with it, but it really is designed for accessibility, and we have, like, a really cheap version for more K through 12 education and the ones where we're publishing in, like, Science, which is arguably the top journal, and we've been fortunate to publish there a few times with this technology. I mean, that printer is, like, slightly fancier. It's like a $2,000 version. Right. So innovation does not need to be expensive. I think innovation really comes actually from folks like my lab working with folks like Dr. Wiles lab, really combining the clinical problems with some of the most advanced engineering solutions and using that to kind of drive the process.

Dr. Sarenya Wiles (34:39)

I think there is something magical that happens when engineers and physicians meet in a room because we have a lot of the problems and unanswered questions that we want to ask for our patients. And you know, at the Mayo Clinic, we are always thinking about the needs of the patient and the unmet needs of the patient and how we can address those. And that's where when we partnered with Dr. Feinberg and took the course, I mean, we really learned from all different levels of teachers, including undergrads and, and other postdoctoral fellows who are incredible engineers that are thinking about solutions to problems. And when we start posing questions of how do we answer this specific need that a patient has or this specific problem in biology that we don't have a solution for, that's when I think these, these solutions are very targeted and to that point about creating innovation that is applicable really comes into fruition.

Kathy Werzer (35:31)

What do you think the biggest barriers are at this point facing patients and providers as bioprinting moves really closer to the clinic?

Dr. Sarenya Wiles (35:39)

I think the biggest barrier is to try to define the problem very, very closely and carefully because there's a lot of things and opportunities, as you can see, when you open the doors of possibilities, but really focusing on the need and focusing on things like organ replacement and transplant as well as need for burn victims and, and creating the right wound patches and creating the right solutions, they're trying to figure out what those problems are initially and defining them carefully. Working with our regulatory colleagues in FDA and working with our government colleagues at the NIH to try to figure out what are the right ways to fund these studies and take them to the next next level. I think that's where we need to focus more on with defining the right problem.

Dr. Adam Feinberg (36:22)

Yeah, I mean, I would largely agree. I think from my perspective, it's really getting wins on the board. Meaning we really need to demonstrate that this technology can change the practice of medicine for the better. Right. And really positively impact patients lives. And that really does come down to carefully identifying a problem that is large enough to have real impact in a wide swath of people's eyes, but where our technology is the unique solution to doing that. Right. And so that's really, I think that very much aligns with what Dr. Wallace was saying. That's, that's really the, the key point because once we prove that it does work, then I think that unlocks a lot more financial resources as well as regulatory pressure. Right. To expand this to more indications. Right. And that'll need to be done in a thoughtful way. But I think the example goes back to maybe like a gene therapy. We've known for a long time that many diseases are due to a mutation. We know that if we could fix that gene, we could probably cure the disease. But getting that technology to work in a human patient successfully has always been an issue. And there were gene therapy trials, you know, a few decades ago where there was a patient death, which can happen, and that kind of slowed the progress. Right. And so now we're seeing a reemergence of this same technology again with some newer capabilities. But I think, you know, it's selecting the disease and then making sure we do it in a rigorous, you know, high quality way. Right. So that we don't run into those issues that will really demonstrate the technology and then I think really unlock the financial resources from both government funding, but as well as venture capital for startup companies and ultimately getting the large strategic biopharmas that buy in. If we had billions of dollars in this industry, we would be getting these solutions much faster. But we have to really crank up that machine.

Kathy Werzer (38:13)

So it sounds as if, then if I'm listening to you carefully, both of you, it's going to take maybe a little while before we see bioprinted skin available for patient care.

Dr. Sarenya Wiles (38:21)

And I think part of that is also learning from the right sectors. We have an opportunity here to learn from our colleagues in the automotive industry and also from software engineering. So how do we, once we establish the 3D bioprinted protocol of this is what we would need for therapeutic or diagnostic diagnostic application, then we would need to think about scaling the manufacturing and where this is, where we can learn from building cars and airplanes and see how they have applied the scale to a very effective way and to work with colleagues in AI and others to bring this technology to the masses.

Kathy Werzer (38:56)

Both of your faces light up when you're talking about what you do. And I'm curious, Dr. Feinberg, what inspires you? What drives you forward?

Dr. Adam Feinberg (39:05)

Back when I was in school, I was toying with this MD, PhD kind of space. I'm sure I'm not the only one. Dr. Wiles, maybe you also had this conundrum at a time when I was an undergrad, I did a co op at a company called Abiomed, which is trying to develop a mechanical artificial heart. When I was just really inspired, that device largely failed because of the interface between blood and the materials lining the inside of the device. It was a material science problem and I'm a material science engineer by training. So I was really inspired that this was the critical problem. But I was really passionate about saving people's lives and really addressing that. And so as I kind of went through my career, I realized, you know, if. If we've been working on a mechanical heart since the 1960s with Jarvik, we've kind of started that and we still don't have one, maybe that's not the best approach. Maybe we could just actually make a new biologic heart. You know, at this point in time, like, the technology has advanced, and that's really kind of the premise I started my lab under was, can we just build the tissue itself? Because I do believe that's essentially how we almost reach the next stage of medicine. I think we're at a stage now where we can replace some body parts with mechanical devices. Right. A knee, a hip valve. Right. But we can't replace an organ if we can start to replace organs. You know, we've fundamentally shifted human lifespan, human quality of life. It's hard to have more impact than that on society. Right. And so while that's a high bar, and I'm not really sure at the end of the day how far we'll get, I think we'll get pretty far. I'm sure wherever we end up stopping, someone will pick it up obviously from there. And we will. We will get there. I have no doubt that this technology is coming. We already know that Transplanted organs work 100%. They work. They just have. The immune rejection issue is the primary challenge. So once we can start doing that and just build them on demand, like an aircraft part, there we go. We're off to the races. Really what motivated me, though, was we're fundamentally changing medicine and human longevity as we know it, if this becomes capable.

Dr. Sarenya Wiles (41:06)

So for me, I actually did take that MD, PhD, long path conundrum. I was an undergrad at Barnard College and all women's college in New York City. And really there I was inspired to try to go into the medical sector. And when I was learning more and getting into regenerative medicine, this area that seems like magic, that you can create and engineer new solutions to problems that hasn't existed, it was really a driving force. When I came to Mayo Clinic, I wanted to help patients and really thinking about how do we create new products for patients, how do we create accessibility? And especially within the field of dermatology, where patients have to wear their skin disease, it's hard to see the influence that these skin conditions have on patients mental health. And this is a really big driving factor for me to see how we can introduce new solutions for these patients. So here we are, working on creating some magic.

Kathy Werzer (41:57)

It was quite a conversation between you two. I really enjoyed this. I appreciate your time and your work, Dr. Wiles. Dr. Feinberg, thank you so very much.

Dr. Sarenya Wiles (42:07)

Thanks, Kathy.

Dr. Adam Feinberg (42:08)

Thank you.

Kathy Werzer (42:09)

Tomorrow's Cure is a production of Mayo Clinic with production help from the Podglomerate. Be sure to follow Tomorrow's Cure wherever you get your podcasts. I'm Kathy Warzer. Thank you so much for listening.