Duration: 31:01 | Published: October 26, 2020
Episode Summary
“Every time you take a step, your cartilage acts like a shock absorber so your body can have pain-free movement,” says Lesley Chow, former associate professor in the Department of Bioengineering and the Department of Materials Science and Engineering.
But once cartilage is damaged—whether by a sports injury, accident or aging—it has very little ability to repair itself.
“And while there are some surgical interventions,” says Lesley, “you eventually hit a point where you’re in so much pain and have such a loss of mobility that you need a total knee replacement.”
That’s because cartilage damage often progresses to osteoarthritis, the most common form of arthritis, eventually leaving many patients with chronic pain and joint replacements as their only treatment option.
In this episode, Lesley explains why cartilage is so difficult to regenerate and how advances in tissue engineering may one day change that reality.
Her research focuses on understanding how healthy cartilage develops naturally and how biomaterials can recreate the biochemical environment that encourages stem cells to rebuild cartilage with the proper structure.
Her lab combines 3D printing, biomaterials, and regenerative medicine to build implantable scaffolds that gradually dissolve inside the body while guiding stem cells to regenerate healthy cartilage and bone. By carefully controlling the placement of biochemical signals within these scaffolds, her team hopes to recreate the organized architecture that gives cartilage its unique ability to cushion joints and absorb impact. The approach could someday help patients recover from cartilage injuries before osteoarthritis develops, potentially delaying or even eliminating the need for joint replacement surgery.
For Lesley, the work is personal. She suffered a sports injury as a teenager, and now faces the possibility of a future knee replacement. Although she admits her own research is unlikely to benefit her in time, she hopes it will spare future generations—especially young athletes—from following the same path.
Key Moments
- 2:14 — What cartilage does in the body
- 5:20 — How cartilage damage leads to osteoarthritis
- 7:41 — Why knee replacements aren’t the ideal solution
- 11:04 — The problem Lesley’s research is solving
- 14:24 — Using 3D printing to regenerate cartilage
- 17:49 — How biochemical cues guide stem cells
- 21:37 — Surprising discoveries from the lab
- 24:55 — A future treatment for cartilage injuries
- 26:23 — Beyond cartilage: potential applications for skin regeneration
- 27:51 — Why this research is personal
Featured Quotes
"The dream would be that you could implant this material…and it would be as if you had never had the injury in the first place." — Lesley Chow
"Once you have damage, your path to osteoarthritis is inevitable." — Lesley Chow
Full Transcript
Transcript is auto-generated and lightly edited for clarity.
Host-Christine Fennessy (00:06):
Welcome to Rossin Connection, a podcast about all things Lehigh engineering. Coming to you from the P.C. Rossin College of Engineering and Applied Science at Lehigh University. It's a show for students, alumni, faculty and staff, current, former and future. And for anyone who's interested in the many creative ways, the engineers are solving the world's problems. I'm your host and producer, Christine Fennessy So I have to walk down two flights of stairs from my home office to get to this basement closet where I record this podcast. And I'm lucky none of those steps cause me any pain. But that is not the case for 31 million Americans who suffer from osteoarthritis. Osteoarthritis is the most common form of arthritis, and it occurs when the protective cartilage that cushions the ends of your bones wears down over time. Lesley Chow is really familiar with that breakdown. Lesley is the Frank Hook assistant professor in the Department of Bioengineering and the Department of Material Science and Engineering.
Welcome to Rossin Connection, a podcast about all things Lehigh engineering. Coming to you from the P.C. Rossin College of Engineering and Applied Science at Lehigh University. It's a show for students, alumni, faculty and staff, current, former and future. And for anyone who's interested in the many creative ways, the engineers are solving the world's problems. I'm your host and producer, Christine Fennessy So I have to walk down two flights of stairs from my home office to get to this basement closet where I record this podcast. And I'm lucky none of those steps cause me any pain. But that is not the case for 31 million Americans who suffer from osteoarthritis. Osteoarthritis is the most common form of arthritis, and it occurs when the protective cartilage that cushions the ends of your bones wears down over time. Lesley Chow is really familiar with that breakdown. Lesley is the Frank Hook assistant professor in the Department of Bioengineering and the Department of Material Science and Engineering.
Host-Christine Fennessy (01:11):
And earlier this year, she received a faculty early career development program award from the National Science Foundation. It's also called the Career Award. It supports the work that she and her team are doing to, in a nutshell, regenerate cartilage. I wrote a story about Lesley's research and her award for the fall issue of Resolve. The issue comes out this week, both in the mail and online. We wanted her to talk more about her research on the show because honestly what she's doing is very cool and it's super relatable because we've all got joints and a lot of us have pain. In this episode, Lesley talks about the role cartilage plays in the body, why injuries to it can be so devastating, and the novel approach that she and her team are taking that may someday help people avoid debilitating pain. Remind us what cartilage is exactly and why it's so important.
And earlier this year, she received a faculty early career development program award from the National Science Foundation. It's also called the Career Award. It supports the work that she and her team are doing to, in a nutshell, regenerate cartilage. I wrote a story about Lesley's research and her award for the fall issue of Resolve. The issue comes out this week, both in the mail and online. We wanted her to talk more about her research on the show because honestly what she's doing is very cool and it's super relatable because we've all got joints and a lot of us have pain. In this episode, Lesley talks about the role cartilage plays in the body, why injuries to it can be so devastating, and the novel approach that she and her team are taking that may someday help people avoid debilitating pain. Remind us what cartilage is exactly and why it's so important.
Lesley Chow (02:14):
Yeah. So cartilage is a tissue that exists in your joints, um, and it plays a really important role in you being able to transfer load. So every time you move your joints, every time you take a step, your cartilage acts like a shock absorber. So your body can, um, have pain-free movement.
Yeah. So cartilage is a tissue that exists in your joints, um, and it plays a really important role in you being able to transfer load. So every time you move your joints, every time you take a step, your cartilage acts like a shock absorber. So your body can, um, have pain-free movement.
Host-Christine Fennessy (02:35):
Okay, great. And so how does it get damaged?
Okay, great. And so how does it get damaged?
Lesley Chow (02:39):
So it, uh, it gets damaged rather easily, actually. So you can have damage due to, you know, an athletic injury. Um, you could, you know, slip and fall and it eventually gets damaged as you age as well. So it'll change over time. And the main issue is that it doesn't heal itself.
So it, uh, it gets damaged rather easily, actually. So you can have damage due to, you know, an athletic injury. Um, you could, you know, slip and fall and it eventually gets damaged as you age as well. So it'll change over time. And the main issue is that it doesn't heal itself.
Host-Christine Fennessy (03:00):
Ah, okay. Okay. Yeah, that was what I was gonna ask nex is, so why is the damaged cartilage a bad thing compared to say, like breaking a bone?
Ah, okay. Okay. Yeah, that was what I was gonna ask nex is, so why is the damaged cartilage a bad thing compared to say, like breaking a bone?
Lesley Chow (03:10):
Yeah, so your bones, um, have a capacity to heal. So they, they have a natural capacity to regenerate themselves, um, within reason, but they that you can have a broken bone and not have any procedure done, and your bone can heal itself in a cast cartilage, on the other hand, doesn't have the same propensity to heal, meaning that it, it doesn't have blood vessels, it doesn't have nerves, and those are parts of your tissues that are typically involved in the healing process. So your bone has nerves, it has blood vessels, um, and it can bring cells in to help clean up the damage. Unfortunately, in cartilage, you don't have that same sort of a setup to have the healing process occur. And so once you have damage, it can reform tissue, but it's just not really what your original tissue was like.
Yeah, so your bones, um, have a capacity to heal. So they, they have a natural capacity to regenerate themselves, um, within reason, but they that you can have a broken bone and not have any procedure done, and your bone can heal itself in a cast cartilage, on the other hand, doesn't have the same propensity to heal, meaning that it, it doesn't have blood vessels, it doesn't have nerves, and those are parts of your tissues that are typically involved in the healing process. So your bone has nerves, it has blood vessels, um, and it can bring cells in to help clean up the damage. Unfortunately, in cartilage, you don't have that same sort of a setup to have the healing process occur. And so once you have damage, it can reform tissue, but it's just not really what your original tissue was like.
Host-Christine Fennessy (04:04):
Got it. Okay. And so when you say it can reform tissue, but it's not the same, what does that mean? Like say for example, I've damaged the cartilage in my knee, what might that mean for me, say 10 or 20 years down the road?
Got it. Okay. And so when you say it can reform tissue, but it's not the same, what does that mean? Like say for example, I've damaged the cartilage in my knee, what might that mean for me, say 10 or 20 years down the road?
Lesley Chow (04:20):
Yeah, that's a great question. So the, so your tissue as all of your tissues are in your body, are very specifically organized so that the tissue can function the way that it needs to. So with cartilage, you have distinct zones within your tissue, and those zones are really important for you to be able to, what we talked about earlier, be able to take a step and have that load transfer to your bones without feeling pain. So your shock absorbers. So when you have damage occur, that tissue doesn't have the same organization. So typically your cartilage tissue that's in your joints is called articular cartilage. When that tissue becomes damaged and it has to regrow something, you know, in the damaged area, it turns into something called fibrocartilage. And that cartilage is completely different in terms of function. So it's just not going to serve the same role that it needs to serve when it's in your joints.
Yeah, that's a great question. So the, so your tissue as all of your tissues are in your body, are very specifically organized so that the tissue can function the way that it needs to. So with cartilage, you have distinct zones within your tissue, and those zones are really important for you to be able to, what we talked about earlier, be able to take a step and have that load transfer to your bones without feeling pain. So your shock absorbers. So when you have damage occur, that tissue doesn't have the same organization. So typically your cartilage tissue that's in your joints is called articular cartilage. When that tissue becomes damaged and it has to regrow something, you know, in the damaged area, it turns into something called fibrocartilage. And that cartilage is completely different in terms of function. So it's just not going to serve the same role that it needs to serve when it's in your joints.
Host-Christine Fennessy (05:15):
So how does this then play a role into developing, say, osteoarthritis?
So how does this then play a role into developing, say, osteoarthritis?
Lesley Chow (05:20):
So once you have damage, your path to osteoarthritis is inevitable. Osteoarthritis is, um, considered a disease that's a whole joint disease. So once you have damage to your cartilage, it leads to other pathologies that we're still understanding. We still don't really know what happens and we don't know what are the key players. We're learning something new every day about the onset of osteoarthritis. And so once osteoarthritis starts, it's very difficult to stop and it keeps progressing to the point where you lose your cartilage and then eventually it starts damaging the bone beneath your cartilage known as the the subchondral bone.
So once you have damage, your path to osteoarthritis is inevitable. Osteoarthritis is, um, considered a disease that's a whole joint disease. So once you have damage to your cartilage, it leads to other pathologies that we're still understanding. We still don't really know what happens and we don't know what are the key players. We're learning something new every day about the onset of osteoarthritis. And so once osteoarthritis starts, it's very difficult to stop and it keeps progressing to the point where you lose your cartilage and then eventually it starts damaging the bone beneath your cartilage known as the the subchondral bone.
Host-Christine Fennessy (05:58):
And so is that when things like knee replacements are become inevitable?
And so is that when things like knee replacements are become inevitable?
Lesley Chow (06:04):
Yes. So your cartilage doesn't have nerves, um, and vasculature, and that's actually by design. So when they're, when it's acting as your shock absorbers, you don't wanna have nerves there because you don't wanna feel the load and you wanna transfer the load to your bones. But that same setup that, you know, makes it so that cartilage doesn't regenerate. Once it's damaged and it can't reform, we're then talking about the load now gets transferred directly to your bone, and that can be very painful. So when you have bone touching bone, you have nerve endings in your bones, and so therefore you feel every step that you take.
Yes. So your cartilage doesn't have nerves, um, and vasculature, and that's actually by design. So when they're, when it's acting as your shock absorbers, you don't wanna have nerves there because you don't wanna feel the load and you wanna transfer the load to your bones. But that same setup that, you know, makes it so that cartilage doesn't regenerate. Once it's damaged and it can't reform, we're then talking about the load now gets transferred directly to your bone, and that can be very painful. So when you have bone touching bone, you have nerve endings in your bones, and so therefore you feel every step that you take.
Host-Christine Fennessy (06:42):
And, and so when you have a total knee replacement, how does that exactly eliminate the pain of osteoarthritis? Is it because you don't have, uh, the nerve endings in that, um, prosthesis, is that right?
And, and so when you have a total knee replacement, how does that exactly eliminate the pain of osteoarthritis? Is it because you don't have, uh, the nerve endings in that, um, prosthesis, is that right?
Lesley Chow (06:56):
Yes. So the pain that you experienced with osteoarthritis is a total joint problem. So it's a total joint disease. So you're feeling you have damage to your cartilage, it progresses and it begins damaging the underlying bone to the point where you lose mobility. Um, and it's just so painful to even take a step. And so the only solution at that stage is to just remove the tissue completely. And so when they remove it, they completely resect out the joint and they replace it with an artificial joint that's typically made out of metals.
Yes. So the pain that you experienced with osteoarthritis is a total joint problem. So it's a total joint disease. So you're feeling you have damage to your cartilage, it progresses and it begins damaging the underlying bone to the point where you lose mobility. Um, and it's just so painful to even take a step. And so the only solution at that stage is to just remove the tissue completely. And so when they remove it, they completely resect out the joint and they replace it with an artificial joint that's typically made out of metals.
Host-Christine Fennessy (07:27):
And so this is, it's a good solution. It works obviously to very painful, right? Yes. But, but part of the issue that you're trying to solve is that this is also very expensive and these things aren't, they don't last forever, right?
And so this is, it's a good solution. It works obviously to very painful, right? Yes. But, but part of the issue that you're trying to solve is that this is also very expensive and these things aren't, they don't last forever, right?
Lesley Chow (07:41):
Yeah. So it is very, um, so I think maybe another way to think about it is that, um, the onset of osteoarthritis is not well understood, and the progression of it is not, we know what happens, but once you reach a point where you really can't go back and try to repair, that's usually, um, when the patient starts feeling the pain. And so what we're trying to do is intervene a lot earlier before the patient starts experiencing pain. You know, people don't go to the doctor until they're debilitated, they're having issues. And when that's the case, then they're usually at a stage that's so late that the only solution will be, wait as long as you can and then have a total knee replacement. And the issue with that, the reason why they wait as long as they can is because the total knee replacement doesn't last forever.
Yeah. So it is very, um, so I think maybe another way to think about it is that, um, the onset of osteoarthritis is not well understood, and the progression of it is not, we know what happens, but once you reach a point where you really can't go back and try to repair, that's usually, um, when the patient starts feeling the pain. And so what we're trying to do is intervene a lot earlier before the patient starts experiencing pain. You know, people don't go to the doctor until they're debilitated, they're having issues. And when that's the case, then they're usually at a stage that's so late that the only solution will be, wait as long as you can and then have a total knee replacement. And the issue with that, the reason why they wait as long as they can is because the total knee replacement doesn't last forever.
Lesley Chow (08:30):
And so we're saying 10, 20 years, but if you're a patient that's in the forties, that's not a reasonable time to have a replacement because you're gonna outlive your implant. And so we worry about that because if somebody's gonna outlive their implant, that means they have to have a replacement surgery and that surgery is not gonna go nearly as well as the first surgery. So there's, we call those revision surgeries. And the reason why it doesn't go well is because you have tissue that's, you know, it's undergone a lot of trauma. You've replaced it with a metallic implant, and then the bone that's surrounding and supporting that implant. Um, usually when you have a replacement, it's because that that tissue's been damaged and so now you're trying to throw in another implant into tissue that's already damaged and it does just doesn't go as well.
And so we're saying 10, 20 years, but if you're a patient that's in the forties, that's not a reasonable time to have a replacement because you're gonna outlive your implant. And so we worry about that because if somebody's gonna outlive their implant, that means they have to have a replacement surgery and that surgery is not gonna go nearly as well as the first surgery. So there's, we call those revision surgeries. And the reason why it doesn't go well is because you have tissue that's, you know, it's undergone a lot of trauma. You've replaced it with a metallic implant, and then the bone that's surrounding and supporting that implant. Um, usually when you have a replacement, it's because that that tissue's been damaged and so now you're trying to throw in another implant into tissue that's already damaged and it does just doesn't go as well.
Host-Christine Fennessy (09:18):
How would I be treated today if I've damaged my cartilage very recently? How would I be treated today given our current understanding of, uh, regenerating this tissue?
How would I be treated today if I've damaged my cartilage very recently? How would I be treated today given our current understanding of, uh, regenerating this tissue?
Lesley Chow (09:29):
Yeah, so there's certainly a number of different interventions that they can do surgically that are clinically done. So you could have a procedure, um, like microfracture where they'll remove the damaged tissue and then they puncture into your underlying bone to get your bone marrow to come out. And that bone marrow has stem cells that can help or generate the tissue. You can also have chondrocytes, which are cartilage cells from a different region of your tissue, usually a non load bearing part of your tissue. They grow that up in culture outside of the body. And then you come in later and have those cells injected into your defect or your damaged tissue site. There are some biomaterials that they can implant. So there are a variety of different techniques depending on the severity of the injury, depending on honestly the surgeon and their preferences. But unfortunately, it all still produces that fibrocartilage that I mentioned before. It's producing a tissue and it's, and I liken it to, you know, like sticking gum on a leaking pipe. It's a, it's a solution and it, and it offsets the need for, uh, an implant, a total knee replacement, but it leaves you in the same situation of eventually needing additional interventions later so that tissue's not gonna respond the same way.
Yeah, so there's certainly a number of different interventions that they can do surgically that are clinically done. So you could have a procedure, um, like microfracture where they'll remove the damaged tissue and then they puncture into your underlying bone to get your bone marrow to come out. And that bone marrow has stem cells that can help or generate the tissue. You can also have chondrocytes, which are cartilage cells from a different region of your tissue, usually a non load bearing part of your tissue. They grow that up in culture outside of the body. And then you come in later and have those cells injected into your defect or your damaged tissue site. There are some biomaterials that they can implant. So there are a variety of different techniques depending on the severity of the injury, depending on honestly the surgeon and their preferences. But unfortunately, it all still produces that fibrocartilage that I mentioned before. It's producing a tissue and it's, and I liken it to, you know, like sticking gum on a leaking pipe. It's a, it's a solution and it, and it offsets the need for, uh, an implant, a total knee replacement, but it leaves you in the same situation of eventually needing additional interventions later so that tissue's not gonna respond the same way.
Host-Christine Fennessy (10:48):
Okay. Okay. Now this might be obvious given everything that you've just said, but I was just hoping that in a nutshell before you describe your actual research Yeah. What is the problem that your re that your specific research is trying to solve?
Okay. Okay. Now this might be obvious given everything that you've just said, but I was just hoping that in a nutshell before you describe your actual research Yeah. What is the problem that your re that your specific research is trying to solve?
Lesley Chow (11:04):
Yeah, so we, we are very interested in the fact that that tissue's so organized and we know that that organization is very specifically related to its function. So it needs to be organized so that it can serve its role as that shock absorber. And when you disorganize it, it just can't do the job the same way that it needs to do the job. And so what we are trying to do is understand more about how that tissue regenerates. 'cause it has a capacity to do so. It has a capacity to produce tissue, but what we don't understand is why does it not produce tissue in the same organization that it was in the first time it formed? And so what we're trying to do is think about in all different ways, right? So we look to development in nature as a inspiration to help us understand how does that tissue form in the first place.
Yeah, so we, we are very interested in the fact that that tissue's so organized and we know that that organization is very specifically related to its function. So it needs to be organized so that it can serve its role as that shock absorber. And when you disorganize it, it just can't do the job the same way that it needs to do the job. And so what we are trying to do is understand more about how that tissue regenerates. 'cause it has a capacity to do so. It has a capacity to produce tissue, but what we don't understand is why does it not produce tissue in the same organization that it was in the first time it formed? And so what we're trying to do is think about in all different ways, right? So we look to development in nature as a inspiration to help us understand how does that tissue form in the first place.
Lesley Chow (11:58):
When the, um, during the tissues development, we're also looking at what is it that the cells respond to? So what is it about our material that gets cells to do certain things? So we're kind of coming at it at different angles of can we replicate what happens during development that we can try to, you know, reform that tissue the way that it was in the first place? Or could we just try to understand what do the cells do when we give them different biochemical cues when we give them different physical cues? What, you know, sort of home can we give them to get them to do what we want them to do with the idea of yeah. Spatially organizing that tissue. Again,
When the, um, during the tissues development, we're also looking at what is it that the cells respond to? So what is it about our material that gets cells to do certain things? So we're kind of coming at it at different angles of can we replicate what happens during development that we can try to, you know, reform that tissue the way that it was in the first place? Or could we just try to understand what do the cells do when we give them different biochemical cues when we give them different physical cues? What, you know, sort of home can we give them to get them to do what we want them to do with the idea of yeah. Spatially organizing that tissue. Again,
Host-Christine Fennessy (12:37):
Can you just, for the lay person who might be listening to this, just, just explain briefly what you mean by organized tissue versus disorganized tissue?
Can you just, for the lay person who might be listening to this, just, just explain briefly what you mean by organized tissue versus disorganized tissue?
Lesley Chow (12:46):
Yeah, so each of your tissues in your body, so all the different tissues, your skin, your organs, like your kidney, your bones, your cartilage, all of these tissues are organized in very specific ways, meaning the different components that make up that your tissues, they are placed in very specific places within that tissue. And if you take it, so the, the example that I like to give is if I, if I took your tissue and I put it in a blender, it would no longer function the same way, right? We can agree that that for sure would not work, but you could argue that all the components are there. So why wouldn't it still function the same way? But that's because it had to be organized in a very specific way. So a good way to think of it is the way that a building is built, you have a certain structure that holds up that building.
Yeah, so each of your tissues in your body, so all the different tissues, your skin, your organs, like your kidney, your bones, your cartilage, all of these tissues are organized in very specific ways, meaning the different components that make up that your tissues, they are placed in very specific places within that tissue. And if you take it, so the, the example that I like to give is if I, if I took your tissue and I put it in a blender, it would no longer function the same way, right? We can agree that that for sure would not work, but you could argue that all the components are there. So why wouldn't it still function the same way? But that's because it had to be organized in a very specific way. So a good way to think of it is the way that a building is built, you have a certain structure that holds up that building.
Lesley Chow (13:36):
You know, the building that were our College of Health, our new college of health building, the health science and technology building, we saw from the ground up how that was being constructed, and it had to be constructed in a very specific way. So that gives us a great way of thinking about you need, um, you know, that physical structure, the, the materials are all placed in very specific locations, otherwise it's not gonna be a building. And so this is the same idea with tissues. All of the different components that make up your tissues need to be specifically placed in a precise location, otherwise that tissue's gonna respond differently. It's gonna have different mechanical properties, it's going to have different chemical properties and so on.
You know, the building that were our College of Health, our new college of health building, the health science and technology building, we saw from the ground up how that was being constructed, and it had to be constructed in a very specific way. So that gives us a great way of thinking about you need, um, you know, that physical structure, the, the materials are all placed in very specific locations, otherwise it's not gonna be a building. And so this is the same idea with tissues. All of the different components that make up your tissues need to be specifically placed in a precise location, otherwise that tissue's gonna respond differently. It's gonna have different mechanical properties, it's going to have different chemical properties and so on.
Host-Christine Fennessy (14:16):
Okay. So now take us through your research. Help us understand what your lab is doing exactly to solve this problem.
Okay. So now take us through your research. Help us understand what your lab is doing exactly to solve this problem.
Lesley Chow (14:24):
The approach that we're taking is trying to, um, construct a material that will help rebuild that tissue the way that it is originally. So respecting the organization of the tissue, um, as it was formed, um, after development. And so the approach that we're using is similar to the way that you would build a building. We have all of our different components that we need to construct the building, and then we're using 3D printing to control where those different components are going. And so this allows us to find out what is it about our material that can drive the formation of the tissue that's more similar to the native tissue. And then because we're taking this modular approach, we can mix and match the components, put them in the locations that we want them to be in, and sort of build that home for the cells in a way that we can really drive the formation of, of the tissue that we want to form.
The approach that we're taking is trying to, um, construct a material that will help rebuild that tissue the way that it is originally. So respecting the organization of the tissue, um, as it was formed, um, after development. And so the approach that we're using is similar to the way that you would build a building. We have all of our different components that we need to construct the building, and then we're using 3D printing to control where those different components are going. And so this allows us to find out what is it about our material that can drive the formation of the tissue that's more similar to the native tissue. And then because we're taking this modular approach, we can mix and match the components, put them in the locations that we want them to be in, and sort of build that home for the cells in a way that we can really drive the formation of, of the tissue that we want to form.
Host-Christine Fennessy (15:19):
Oh, okay. So is the idea that, you know, you're building this platform, would you be implanting it?
Oh, okay. So is the idea that, you know, you're building this platform, would you be implanting it?
Lesley Chow (15:27):
Yes. So the, the idea is to make a material out of materials that can degrade. So we're make, we're using polymers that will degrade in the body, and then we're decorating the surface of these materials with biochemical cues that signal to cells. And the idea is you would take that material and you would implant it in the damaged tissue and it would signal to the cells in the body, Hey, you should maybe grow more tissue here. You should grow more cartilage here. You should grow more bone here. Um, and we're trying to make something that you could implant that will help that tissue form in the way that it's supposed to form. So if you remember I mentioned before how you could regrow tissue, it's just not organized in the way that it needs to be organized. And so we're trying to give it a little jumpstart. We're trying to say, okay, I know that you can do it, but I need you to do it in an organized way. So if we give it a home for all the cells to live in and to see their microenvironment, the goal is to have it so that the cells can infiltrate into the tissue or into the scaffold, and then that scaffold will tell the cells what to do, how to produce the tissue in the right way.
Yes. So the, the idea is to make a material out of materials that can degrade. So we're make, we're using polymers that will degrade in the body, and then we're decorating the surface of these materials with biochemical cues that signal to cells. And the idea is you would take that material and you would implant it in the damaged tissue and it would signal to the cells in the body, Hey, you should maybe grow more tissue here. You should grow more cartilage here. You should grow more bone here. Um, and we're trying to make something that you could implant that will help that tissue form in the way that it's supposed to form. So if you remember I mentioned before how you could regrow tissue, it's just not organized in the way that it needs to be organized. And so we're trying to give it a little jumpstart. We're trying to say, okay, I know that you can do it, but I need you to do it in an organized way. So if we give it a home for all the cells to live in and to see their microenvironment, the goal is to have it so that the cells can infiltrate into the tissue or into the scaffold, and then that scaffold will tell the cells what to do, how to produce the tissue in the right way.
Host-Christine Fennessy (16:41):
Okay. In in, in terms of this idea of telling them what to do and, and giving them these cues, can you talk a little bit more about what you mean by the cues?
Okay. In in, in terms of this idea of telling them what to do and, and giving them these cues, can you talk a little bit more about what you mean by the cues?
Lesley Chow (16:49):
Yeah, so these cells have a natural propensity to regrow that tissue and regrow that matrix. Um, it's just, as I mentioned before, they don't know how to do it, right? And so what we're trying to do is tell the cells that have the ability to differentiate into other cells. So you have stem cells that exist in your bone marrow. We're trying to get those specific stem cells known as mesenchymal stem cells to differentiate into the cells that produce cartilage to the cells that produce bone so that they can form that tissue that they need to form. We also are trying to signal to the cells that exist on the edges of the defect. So you already have cartilage cells, you already have bone cells that exist there. We're trying to get them to help regrow the tissue and support those stem cells that are infiltrating into the scaffold.
Yeah, so these cells have a natural propensity to regrow that tissue and regrow that matrix. Um, it's just, as I mentioned before, they don't know how to do it, right? And so what we're trying to do is tell the cells that have the ability to differentiate into other cells. So you have stem cells that exist in your bone marrow. We're trying to get those specific stem cells known as mesenchymal stem cells to differentiate into the cells that produce cartilage to the cells that produce bone so that they can form that tissue that they need to form. We also are trying to signal to the cells that exist on the edges of the defect. So you already have cartilage cells, you already have bone cells that exist there. We're trying to get them to help regrow the tissue and support those stem cells that are infiltrating into the scaffold.
Host-Christine Fennessy (17:44):
Okay. And so what are, what's the nature of these cues that you're giving them
Okay. And so what are, what's the nature of these cues that you're giving them
Lesley Chow (17:49):
We're providing biochemical cues that are replicating some of the biomolecules that exist in the native tissue. So our thought process behind that is that if we are providing the cues that they would normally be seeing, we're hoping that that gives them the signal that, oh, this is the type of environment I would see in cartilage, so I should turn into a cartilage cell, or this is the type of environment that I am, I would see if I were in a, in bone tissue, I should turn into a bone cell. And so we're trying different chemical cues to get those cells to go down the path that we want them to go. Um, so we are basing this off of our own group, our own experience with it, and other groups as well who have looked towards understanding how cells respond to these specific chemical cues. But the nice thing about our platform is that we can change the biochemical cue so we can make it be something else if we're not seeing the response that we want. But the key thing is we have a strategy that enables us to control where each of those cues are within one single material that can be implanted.
We're providing biochemical cues that are replicating some of the biomolecules that exist in the native tissue. So our thought process behind that is that if we are providing the cues that they would normally be seeing, we're hoping that that gives them the signal that, oh, this is the type of environment I would see in cartilage, so I should turn into a cartilage cell, or this is the type of environment that I am, I would see if I were in a, in bone tissue, I should turn into a bone cell. And so we're trying different chemical cues to get those cells to go down the path that we want them to go. Um, so we are basing this off of our own group, our own experience with it, and other groups as well who have looked towards understanding how cells respond to these specific chemical cues. But the nice thing about our platform is that we can change the biochemical cue so we can make it be something else if we're not seeing the response that we want. But the key thing is we have a strategy that enables us to control where each of those cues are within one single material that can be implanted.
Host-Christine Fennessy (18:57):
And is that strategy because it's being 3D printed?
And is that strategy because it's being 3D printed?
Lesley Chow (19:00):
Yeah, so the combination of the molecules that we are synthesizing with the 3D printing altogether enables us to control where multiple biochemical cues are going, um, within one material. So the nice thing about that is that we don't have to, you know, glue two different materials together. We don't have to do a lot of post-processing after we've made a material. We can just print one thing and implant that as is. But the 3D printing really enables us to really precisely, you know, control where each cue is gonna be. So the advancements with 3D printing have been really beneficial to us. And then combined with our technology of being able to synthesize materials that will present the different cues on the surface, that allows us to really create whatever material we want.
Yeah, so the combination of the molecules that we are synthesizing with the 3D printing altogether enables us to control where multiple biochemical cues are going, um, within one material. So the nice thing about that is that we don't have to, you know, glue two different materials together. We don't have to do a lot of post-processing after we've made a material. We can just print one thing and implant that as is. But the 3D printing really enables us to really precisely, you know, control where each cue is gonna be. So the advancements with 3D printing have been really beneficial to us. And then combined with our technology of being able to synthesize materials that will present the different cues on the surface, that allows us to really create whatever material we want.
Host-Christine Fennessy (19:53):
Wow. And so what is an example of the type of environment that, um, cartilage tissue prefers? Like what, what would be the, what would be the biochemical cue that would signal to a cell, Hey, turn yourself into some cartilage.
Wow. And so what is an example of the type of environment that, um, cartilage tissue prefers? Like what, what would be the, what would be the biochemical cue that would signal to a cell, Hey, turn yourself into some cartilage.
Lesley Chow (20:05):
Yeah, so the cartilage has a variety of different extracellular matrix molecules. So we call them ECM molecules. So these extracellular matrix molecules include things like collagen 2, proteoglycans that are very important for the load-bearing response, Um, known aggrecan, hyaluronic acid, all these different biomolecules exist within that cartilage and are known to push stem cells like mesenchymal stem cells towards differentiating into cartilage cells. Just seeing that in their local environment is known to push them towards that behavior. On the bone side, we have hydroxyapatite, which is a mineral, it's the primary mineral component in your bone, and as, as well as other types of collagen, collagen one, collagen 10, and so on. The, the thing is, is we'll never make something as complicated as the native tissue, but what we're trying to do is what is what is a cue that we could give them that sort of, you know, signals them, Hey, this is bone, this is cartilage, you should become a bone or a cartilage cell and then let them do the rest. Um, because we're never gonna be able to reproduce the tissue synthetically as well as nature did it the first time. So we are trying to take a more regenerative approach and, you know, push them towards producing the type of tissue that we want them to produce.
Yeah, so the cartilage has a variety of different extracellular matrix molecules. So we call them ECM molecules. So these extracellular matrix molecules include things like collagen 2, proteoglycans that are very important for the load-bearing response, Um, known aggrecan, hyaluronic acid, all these different biomolecules exist within that cartilage and are known to push stem cells like mesenchymal stem cells towards differentiating into cartilage cells. Just seeing that in their local environment is known to push them towards that behavior. On the bone side, we have hydroxyapatite, which is a mineral, it's the primary mineral component in your bone, and as, as well as other types of collagen, collagen one, collagen 10, and so on. The, the thing is, is we'll never make something as complicated as the native tissue, but what we're trying to do is what is what is a cue that we could give them that sort of, you know, signals them, Hey, this is bone, this is cartilage, you should become a bone or a cartilage cell and then let them do the rest. Um, because we're never gonna be able to reproduce the tissue synthetically as well as nature did it the first time. So we are trying to take a more regenerative approach and, you know, push them towards producing the type of tissue that we want them to produce.
Host-Christine Fennessy (21:28):
Now is there anything that you can share so far about your results or anything surprising that you and your team have discovered so far?
Now is there anything that you can share so far about your results or anything surprising that you and your team have discovered so far?
Lesley Chow (21:37):
Yeah, so the coolest thing that we have discovered is that the cells do respond differently when we have the two cues. So you remember I talked about presenting biochemical cues that drive it towards cartilage, and then another set of biochemical cues that drive it towards bone. We are able to construct a single material that has both of these cues within the same construct. And what's really interesting is that we thought that, you know, having the cues towards cartilage or having the cues towards bone would drive that tissue formation if you had a single material with just one of the cues. But for some reason, the cells are really responding to having both of the cues in the same environment. And we really don't totally know why. But I think that's exciting part. So we know if we take a scaffold, so this material that we're printing and we print it with both the cartilage promoting and then the bone promoting biochemical cue, that will produce a more cartilage like and more bone like response than if we had them separately in two different scaffolds, which is really not what we expected to have happen.
Yeah, so the coolest thing that we have discovered is that the cells do respond differently when we have the two cues. So you remember I talked about presenting biochemical cues that drive it towards cartilage, and then another set of biochemical cues that drive it towards bone. We are able to construct a single material that has both of these cues within the same construct. And what's really interesting is that we thought that, you know, having the cues towards cartilage or having the cues towards bone would drive that tissue formation if you had a single material with just one of the cues. But for some reason, the cells are really responding to having both of the cues in the same environment. And we really don't totally know why. But I think that's exciting part. So we know if we take a scaffold, so this material that we're printing and we print it with both the cartilage promoting and then the bone promoting biochemical cue, that will produce a more cartilage like and more bone like response than if we had them separately in two different scaffolds, which is really not what we expected to have happen.
Lesley Chow (22:47):
What we think is happening is that these cells are communicating with each other. I liken it to like having a hotel where like the upper floor, the cartilage floor, and the lower is our bone and the cells are kind of sending signals back and forth within that single environment that's amplifying the effect. The other thing that we have just now started discovering is that if you take those same biochemical cues that we have split into two different compartments within a single material, if we actually just mix it all up so that you have all the biochemical cues, homogeneously presented both of them, and there's no spatial organization between the two compartments, the cells also respond differently. So they actually need to be separate to get one response, and then if you mix them, they respond differently. And so I think that's pretty cool because it's not enough that you have, this goes back to my analogy about putting things in a blender, right? It's not enough to have the components there. They actually need to be organized in, in a specific way to get them to produce the type of tissue that you want. So if you mix up that organization, you're gonna get a different type of tissue that forms. And I think that's really exciting.
What we think is happening is that these cells are communicating with each other. I liken it to like having a hotel where like the upper floor, the cartilage floor, and the lower is our bone and the cells are kind of sending signals back and forth within that single environment that's amplifying the effect. The other thing that we have just now started discovering is that if you take those same biochemical cues that we have split into two different compartments within a single material, if we actually just mix it all up so that you have all the biochemical cues, homogeneously presented both of them, and there's no spatial organization between the two compartments, the cells also respond differently. So they actually need to be separate to get one response, and then if you mix them, they respond differently. And so I think that's pretty cool because it's not enough that you have, this goes back to my analogy about putting things in a blender, right? It's not enough to have the components there. They actually need to be organized in, in a specific way to get them to produce the type of tissue that you want. So if you mix up that organization, you're gonna get a different type of tissue that forms. And I think that's really exciting.
Host-Christine Fennessy (23:59):
Wow. So, so what is next then? What, where are you now in the research?
Wow. So, so what is next then? What, where are you now in the research?
Lesley Chow (24:05):
So we're finishing up those studies that we use human, um, stem cell donors. And we are trying to show that it works in multiple donors, 'cause that helps us understand how different people will respond. And then our next step is to implant these in vivo in a rabbit model. And that rabbit model will help us understand we're doing everything in culture under very controlled conditions. When you put it into an animal, it's a completely different ballgame. And so we're trying to understand what will happen if we take our scaffold and we implant it inside a defect in an animal.
So we're finishing up those studies that we use human, um, stem cell donors. And we are trying to show that it works in multiple donors, 'cause that helps us understand how different people will respond. And then our next step is to implant these in vivo in a rabbit model. And that rabbit model will help us understand we're doing everything in culture under very controlled conditions. When you put it into an animal, it's a completely different ballgame. And so we're trying to understand what will happen if we take our scaffold and we implant it inside a defect in an animal.
Host-Christine Fennessy (24:43):
So further down the road, like what could it mean for my hypothetical self who just very recently, you know, rector cartilage, what could your research look like potentially in my life?
So further down the road, like what could it mean for my hypothetical self who just very recently, you know, rector cartilage, what could your research look like potentially in my life?
Lesley Chow (24:55):
So the, the dream would be we can make a material that's very simple. It can sit on the shelf at a doctor's office, somebody comes in with an injury, they remove the damaged cartilage, and then you just implant this material. Um, you can punch it out to the shape that you need for the patient. And then the, the idea would be that that specific scaffold that you implant in the defect site would help your tissue, your native tissue, your native cells, the cells that you already have in your body to populate that scaffold and then produce a tissue that's exactly the same as your native tissue. So as if you had never had the injury in the first place, as that tissue's forming, your scaffold is dissolving away, and then there'd be no trace at all that anything had even happened, that you'd even had damage in the first place. And that would be amazing, right? So you could have this done in an outpatient procedure, and then instead of you eventually forming osteoarthritis, we would sort of, you know, get to it before you go down that path of where you'll need a total knee replacement. Um, so that's, that's sort of the vision that we have. I mean, it's gonna be a long road to get there. Um, but that's really been the dream that a lot of us in the field have been chasing for a long time.
So the, the dream would be we can make a material that's very simple. It can sit on the shelf at a doctor's office, somebody comes in with an injury, they remove the damaged cartilage, and then you just implant this material. Um, you can punch it out to the shape that you need for the patient. And then the, the idea would be that that specific scaffold that you implant in the defect site would help your tissue, your native tissue, your native cells, the cells that you already have in your body to populate that scaffold and then produce a tissue that's exactly the same as your native tissue. So as if you had never had the injury in the first place, as that tissue's forming, your scaffold is dissolving away, and then there'd be no trace at all that anything had even happened, that you'd even had damage in the first place. And that would be amazing, right? So you could have this done in an outpatient procedure, and then instead of you eventually forming osteoarthritis, we would sort of, you know, get to it before you go down that path of where you'll need a total knee replacement. Um, so that's, that's sort of the vision that we have. I mean, it's gonna be a long road to get there. Um, but that's really been the dream that a lot of us in the field have been chasing for a long time.
Host-Christine Fennessy (26:14):
Wow, that's so exciting. Are there other applications, potential applications for your research? Like could it be applied to burn victims, for example?
Wow, that's so exciting. Are there other applications, potential applications for your research? Like could it be applied to burn victims, for example?
Lesley Chow (26:23):
Yeah, so what what I like about the platform that we've developed is that, you know, I talked about the Lego pieces and these modular building blocks that you can mix and match and change the chemistry. And that's actually sort of by design, you know, we did that on purpose so that we could translate the same technology to other tissues. So as you mentioned, you know, skin is actually a very complicated tissue. Um, it has, again, the same sort of idea that I talked about. It's very well organized, that's very critical for it to function the way that it does. And so we'd like to be able to take our same platform and translate it to saying, helping burn victims regrow that skin without having to have massive skin grafts that can lead to other complications. So having a material that you could print to the size that the patient needs, um, that has all of those chemical cues that help regrow that tissue, that would be really fantastic.
Yeah, so what what I like about the platform that we've developed is that, you know, I talked about the Lego pieces and these modular building blocks that you can mix and match and change the chemistry. And that's actually sort of by design, you know, we did that on purpose so that we could translate the same technology to other tissues. So as you mentioned, you know, skin is actually a very complicated tissue. Um, it has, again, the same sort of idea that I talked about. It's very well organized, that's very critical for it to function the way that it does. And so we'd like to be able to take our same platform and translate it to saying, helping burn victims regrow that skin without having to have massive skin grafts that can lead to other complications. So having a material that you could print to the size that the patient needs, um, that has all of those chemical cues that help regrow that tissue, that would be really fantastic.
Host-Christine Fennessy (27:22):
You know, you mentioned when we spoke previously that you have knee problems and that if you could have had an intervention as a teenager, you know, you might not have a doctor telling you today that you might need a knee replacement in 20 years, which would make you an very young person young for, for something like that. So do you wanna say anything about why this line of research is important to you personally and what keeps you motivated?
You know, you mentioned when we spoke previously that you have knee problems and that if you could have had an intervention as a teenager, you know, you might not have a doctor telling you today that you might need a knee replacement in 20 years, which would make you an very young person young for, for something like that. So do you wanna say anything about why this line of research is important to you personally and what keeps you motivated?
Lesley Chow (27:51):
So, I had an injury in my teens. I played soccer and I had a surgery. I had a couple of, um, interventions early on. But knowing what I know now, those interventions were never going to be long-term solutions. And so now, um, I'm in my thirties and I have issues with pain. So going downstairs especially can be particularly uncomfortable sometimes, and I have limitations with what I can do. I will also admit that I'm not the most compliant patient. Um, so I was not supposed to be running, I wasn't supposed to continue sports to the extent, but I did anyway. So I'm now at the stage where I have enough pain that I will need an intervention. And the fact I mentioned before about, uh, you, you know, patients only go in when they have pain and when they have pain is when they've already, um, lost enough of their tissue, they've had enough damage that it's irreparable at this stage.
So, I had an injury in my teens. I played soccer and I had a surgery. I had a couple of, um, interventions early on. But knowing what I know now, those interventions were never going to be long-term solutions. And so now, um, I'm in my thirties and I have issues with pain. So going downstairs especially can be particularly uncomfortable sometimes, and I have limitations with what I can do. I will also admit that I'm not the most compliant patient. Um, so I was not supposed to be running, I wasn't supposed to continue sports to the extent, but I did anyway. So I'm now at the stage where I have enough pain that I will need an intervention. And the fact I mentioned before about, uh, you, you know, patients only go in when they have pain and when they have pain is when they've already, um, lost enough of their tissue, they've had enough damage that it's irreparable at this stage.
Lesley Chow (28:53):
You know, I, I know that it's going, it's inevitable and I just don't see any reason why anybody else should have to have that. Um, so, you know, the technologies we're developing won't help me. I'm already too far gone. But you know, when I think about, especially, this is especially a problem for women playing sports. So young women playing sports are more likely to have the same injuries that I've had, and if we could intervene earlier, they don't have to face those sorts of issues later in their life. They can have a long, healthy life without having to deal with, you know, mobility issues. And I'm far too young to be having some mobility issues, and so it's only gonna get worse from here. Um, and also just the impact that that'll have on our healthcare system. And it also would be an intervention that could be done more widely. So our materials are relatively cheap. You could have an implant done in outpatient procedures. I mean, this is, you know, my, my dream for it, but I just see something that's much more accessible, something that could be done in a much more affordable way and really decrease the need for just ongoing intervention.
You know, I, I know that it's going, it's inevitable and I just don't see any reason why anybody else should have to have that. Um, so, you know, the technologies we're developing won't help me. I'm already too far gone. But you know, when I think about, especially, this is especially a problem for women playing sports. So young women playing sports are more likely to have the same injuries that I've had, and if we could intervene earlier, they don't have to face those sorts of issues later in their life. They can have a long, healthy life without having to deal with, you know, mobility issues. And I'm far too young to be having some mobility issues, and so it's only gonna get worse from here. Um, and also just the impact that that'll have on our healthcare system. And it also would be an intervention that could be done more widely. So our materials are relatively cheap. You could have an implant done in outpatient procedures. I mean, this is, you know, my, my dream for it, but I just see something that's much more accessible, something that could be done in a much more affordable way and really decrease the need for just ongoing intervention.
Host-Christine Fennessy (30:11):
That's it for today's show. Thanks so much to Lesley and to her very patient dog who you may have heard in the background for taking time out of a busy semester to share the important work that she and her team are doing. You can read more about Lesley's research in the fall issue of Resolve. It goes online this week, and we'll have links to it on the episode page. For more information about all the academic programs at the P.C. Rossin College of Engineering and Applied Science, and to find our show, head to engineering.lehigh.edu. Music in this episode is by Blue Dot Sessions. You can send us story suggestions or feedback on X at Rossin podcast. Thanks for listening and stay safe.
That's it for today's show. Thanks so much to Lesley and to her very patient dog who you may have heard in the background for taking time out of a busy semester to share the important work that she and her team are doing. You can read more about Lesley's research in the fall issue of Resolve. It goes online this week, and we'll have links to it on the episode page. For more information about all the academic programs at the P.C. Rossin College of Engineering and Applied Science, and to find our show, head to engineering.lehigh.edu. Music in this episode is by Blue Dot Sessions. You can send us story suggestions or feedback on X at Rossin podcast. Thanks for listening and stay safe.
About the Guest
Lesley Chow was an associate professor in the Department of Bioengineering and the Department of Materials Science and Engineering at Lehigh University. Her research combines tissue engineering, biomaterials, regenerative medicine and 3D printing to develop new approaches for repairing cartilage and bone, with the long-term goal of preventing osteoarthritis and reducing the need for joint replacement surgery.
Episode Details
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