Dasha: [00:00:00] Welcome to the Biomedical Frontiers podcast, where we explore pivotal research projects and disruptive innovations aimed at translating scientific advancements into tangible healthcare solutions. I'm your host, Dasha Tyshlek 
Ben: Cartilage is what's referred to as a soft tissue. It exists all throughout our body and one of the most important places where we have cartilage is in our joints. Cartilage provides both a low friction and a shock absorbing surface, so that joints can function, take loading, take impact, and basically allow us to move around. 
Dasha: So what can people expect in terms of, over their lifetimes, the health of their cartilage and or the deterioration of their cartilage. How do they find out that there are issues or problems that they need to address? 
Ben: One of the biggest clinical challenges is early detection and early diagnosis. Often, these cartilage defects form and are developing, sometimes for five years, sometimes for a decade, sometimes maybe more before people actually have significant pain. 
Right now today, if you go to the doctor with joint pain and you get diagnosed with one of these lesions, the frontline treatment is a purely surgical approach. The most popular one is still something called Ostrochondrialograft, which is the transplantation of cartilage and bone from a cadaver source the biggest challenge with osteochondralograft is it doesn't guarantee that you won't need a knee replacement even later, and then, it's also just very hard to get that graft tissue. 
What's really alarming is that knee replacements are becoming more and more common in a younger patient population and I actually learned a really alarming statistic recently that roughly half of the knee replacements that are done today are done on patients that are still in private payer insurance, so that essentially means people that are not retired. So, this is the paradigm that Nanochon sees itself entering and these are the areas of patient care that we really, really want to improve upon. 
Dasha: Welcome back to another episode of Biomedical Frontiers and today we're going to be talking about our cartilage, which is a very interesting topic and one that a lot of people don't know much about so I'm excited to be speaking to an expert. Dr. Ben Holmes is the CEO and driving force behind Nanochon, a company innovating cartilage repair and regeneration.
Holmes expertise in biomedical engineering has positioned Nanochon as a front runner in developing next generation orthopedic medical devices. Nanochon is creating durable, effective treatments for orthopedic patients, promising a future where advanced, reliable solutions are readily available to improve the quality of life for individuals with joint issues.
Before founding Nanochon, Dr. Holmes was the CTO at SonoStik, another George Washington University medical device startup. He has a Bachelor's of Science degree in Mechanical Engineering from University of Virginia and a PhD in Biomaterials and Nanomedicine from the George Washington University. Ben, welcome to the show.
Ben: Thank you very much. It's a pleasure to be here. 
Dasha: Well, thank you and Ben, I want to start first by talking about what is cartilage and its biology. What is unique about it in the body? 
Ben: Yes, excellent question. So, cartilage is what's referred to as a soft tissue. It exists all throughout our body. And one of the most important places where we have cartilage is in our joints.
Cartilage provides both a low friction and a shock absorbing surface, so that joints can function, take loading, take impact, and basically allow us to move around. The issue though is that cartilage does not last as long as we live, typically. So over time, cartilage loses its ability to stay durable, and it actually starts to wear away just like other mechanical surfaces.
What's challenging about cartilage is that unlike virtually all other tissues in the body, it's what is referred to as avascular which means it does not have a vascular system, so there's no blood vessels in cartilage. It's essentially mostly made up of collagen, water, and then there's a very small population of cells called chondrocytes, which are the primary cell in cartilage, but they exist at a very, very low density.
So, they have a limited ability to sort of maintain the health of that collagen matrix in the cartilage, but once you start to have significant wear, they have no ability to regrow that cartilage or repair any damage on their own. So, that's certainly a problem if you're a young athlete or an active person, who injures themselves and tears the cartilage.
But for most people, it's really just degeneration over time. So, the elements in that cartilage start to break down, they start to wear away. That leads to the cartilage surface itself, as I [00:05:00] mentioned, starting to physically deteriorate and wear away. And eventually people end up with this condition known as a focal lesion or a focal cartilage defect.
But the easiest way to think about these is they're essentially potholes in a road. So, they start relatively small. They eventually grow to about the size of a coin and that cartilage, once it's gone, actually leaves the underlying bone exposed. So remember, cartilage is essentially existing in a several millimeter thick layer over top of the bone in the joint.
And when that bone gets exposed, that's why people actually start to experience pain. And that's the point at which they actually typically go into the doctor to get diagnosed and potentially receive some treatment. 
Dasha: I've been seeing people talking about cartilage health and one of the things people sometimes mention is taking collagen.
Can you talk a little bit more about the composition of cartilage and nutrition or lifelong cartilage health? 
Ben: Cartilage is made up of a particular type of collagen, called collagen type 2. So, to kind of keep it at a high level, type 2 collagen has a particular structure and particular properties on the molecular level that give it these low friction water retaining properties and allow it to function in this particular capacity as like a low friction and shock absorbing surface for a joint.
So collagen 2 is the cartilage collagen, is how I've heard it referred to. And it's sort of a particular challenge because people are obviously really concerned about their health and they want to do whatever they can to preserve that cartilage and then also potentially even provide some treatment if they've started to experience pain.
I'm not a nutrition expert, but generally these types of collagen supplements that people take might aid in suppressing general inflammation, but it doesn't actually turn into regeneration of the cartilage itself. So taking a collagen supplement, is it really going to do anything to actually repair that damage in the joint once you've started to have it. And also, just like with any nutritional supplements, these things have not had to go through clinical efficacy or clinical validation.
So, you know, today, there really is not clinical evidence that taking those types of supplements even does anything. 
Dasha: So, what can people expect in terms of, over their lifetimes, the health of their cartilage and or the deterioration of their cartilage? How does that typically progress. How do they find out that there are issues or problems that they need to address?
Are there diagnostics? And if it's going in the direction of disease or deterioration, what does that progression look like for a patient? 
Ben: Yeah, absolutely. And so I think that's one of the biggest clinical challenges is early detection and early diagnosis. Often these cartilage defects form and are developing, you know, sometimes for five years, sometimes for a decade, sometimes maybe more before people actually have significant pain.
There are some potential early warning signs that cartilage is starting to thin and wear out. People will sometimes talk about feeling like a stiffness or a clicking in their joint. But again, this can sometimes be up to a decade before they actually have pain and actually want to seek out the treatment of a physician.
There are some groups that are working on early detection. There's a really interesting technology that's in development that essentially uses acoustics to try to hear these acoustic changes in the surfaces of the joint moving across each other. But it's very much something that's still in development, and I'm not familiar with it actually being fully clinically implemented yet.
And then at the same time, there's a limited number of options that could actually even treat people at this stage. So there are people that are working on it, and I think early detection and better early treatments are critical, but we're really kind of focused on this more moderate stage, which is the point at which people do typically enter the care continuum.
And so right now, today, if you go to the doctor with joint pain and you get diagnosed with one of these lesions, the frontline treatment is a purely surgical approach. So, there's a particularly widespread procedure known as microfracture. There are now some sort of alternatives to that treatment, but they all function on primarily the same principle, which is that the surgeon attempts to kind of clean out or remove that diseased cartilage.
So they leave kind of like a uniform hole where the cartilage defect was, and then they do something to try to stimulate the bone underneath. So in the case of microfracture, the surgeon will just drill little millimeter sized holes through the bone. [00:10:00] Some other techniques kind of involve either like rasping the bone or scraping the bone to try to get some kind of stimulation, but all these techniques work off the same principle, which which is really just you're trying to get the bone to form a clot and then form a scar tissue to stabilize that cartilage defect. 
So, the real problem with these treatments is that they're relatively inexpensive, they're fast and easy to do, that they're all done arthrostopically in an outpatient setting, but they just don't last very long because that tissue that fills in is scar tissue.
It's not real cartilage. So the big problem is that patients typically return to pain within two years of the treatment and you can't just keep doing a microfracture or debridement procedure over and over and over because the pain returns primarily due to degenerative changes in the subchondral bone, so that bone that's under the cartilage layer.
So you get a microfracture, you feel pretty good for, you know, two years and then you start to have pain again and you go back to the doctor. And that bone has significantly degenerated and is of lower quality and lower health than it was when you first had the initial treatment. So, after this two year period where people need a revision, the options get more limited.
And the most popular one is still something called ostrochondrialograft, which is the transplantation of cartilage and bone from a cadaver source. So literally, someone on the organ donor registry, you know, passes away, and they become an available source of graft tissue. 
A sample of cartilage and subchondral bone is taken from their joint, and then that's provided to the surgeon or the provider to be transplanted into the patient's knee, to try to restructure that cartilage surface. So, the biggest challenge with osteochondralograft is it doesn't guarantee that you won't need a knee replacement even later. So, patients still have mixed outcomes and still eventually need a knee replacement.
And then, it's also just very hard to get that graft tissue, just like it's difficult to source organs for transplantation, there's a limited supply of grafts. So, in a patient population of about 700,000 a year in the U. S., there's only typically 15 to 20,000 ostrochondroallografts done. So it's a very, very limited treatment.
There are some other options as an alternative to allograft. And they're really mainly cell therapy products. So there is one product on the market that takes cells from the patient themselves. There's a couple other products that use cells taken from a cadaver tissue source. But they all kind of function on the same principle, which is that you're collecting chondrocytes, the cartilage cells, You're growing them or culturing them in some kind of a laboratory environment and basically providing sort of a synthetically grown graft tissue that the surgeon can then implant into these defects.
But the big problem that they have is they don't really have demonstrated better outcomes than ostrochondrialograft, but they're anywhere from as expensive to six times as expensive and we're talking about an upper limit of around fifty to sixty thousand dollars just to receive the therapy, that doesn't include the surgery or all the other associated costs with care. And we're talking about a patient population that's primarily still in the private payer system So people that are not retired and on on Medicare But people that are still working and covered by a private insurance plan.
And so private insurers are looking at these cell therapy treatments. They're seeing really mixed outcomes but higher cost, and they're saying, you know, we want to avoid paying for these things. So, it's also made a challenging environment for these treatments to even get to the patient because there can be issues with coverage.
But at the same time, they're treatments that have not demonstrated a better outcome. So, even if you get a cell therapy treatment instead of osteochondralograft, you're still looking at progression of the disease and potentially needing that knee replacement, you know, 5 or 10 years down the road.
So that's the care continuum that patients experience today. You're talking about, you know, two or three surgeries, and then still needing a knee replacement at some point. A knee replacement has a whole host of known issues. It's a very well trodden and widely performed procedure, but it doesn't ensure a full return to quality of life.
Patients often say they still have pain if they try to do simple exercising or other physical activities. So, it really does restrict you basically just to walking in most cases. And then there's also a lot of risks with infection. You know, it could take up to a year to recover from. And again, it just does not really ensure a full quality of life of the patients that receive it. 
So, what's really alarming is that knee replacements are becoming more and more common in a in a [00:15:00] younger patient population and I actually learned a really alarming statistic recently that roughly half of the knee replacements that are done today are done on patients that are are still in private payer insurance.
So that essentially means people that are not retired. So, you know, you have a whole host of these known knee issues and risks and also, you know, sort of a low quality of of outcome, but it's becoming more and more common and it's sort of becoming more and more of a default for younger patients that if something better existed they could get a better treatment. So this is the paradigm that Nanochon sees itself entering. And and these are the areas of patient care that we really, really want to improve upon. 
Dasha: Yeah, I've been a lot of what you said is very alarming. A couple of things that really stood out to me was the 700,000 patients that need interventions before they're ready for knee surgery. So these are part of that younger population here. That's related to sports injuries potentially or other inflammation. And also on top of that doesn't include the knee surgeries, the knee replacements. My own grandmother recently had a knee replacement in this past year.
And I've gotten to see what the recovery from that surgery looks like. It's a very invasive surgery. That one is not done arthroscopically. It requires significant healing time just for the wound. Like you said, infection. We had to deal with that in our family where an early infection was setting in and there had to be a follow up procedure and you know, six months plus later, she's she's still in pain, just less pain than before the knee replacement.
So I've definitely seen that while this is the standard of care, and it certainly worked for several decades, it's not optimal for people. And to see that happening to patients who are younger is really devastating because really mobility is so important to long term health and happiness of people.
So I'm really glad to hear that you are tackling this. It also just struck me that we don't have early diagnostics for this, that kind of the first real indications you get is once the deterioration is at a point where it's affecting the bone. And so for our listeners out there who are interested in areas of high impact of research, that seems to be something to tackle, where we still are at very early stages of figuring out early diagnostic. I want to turn a little bit to your solution. You guys are focused on knee replacements. What are you doing differently from the standard of care where, it's either that scraping technique or you're using cell therapy or donor cartilage for replacement?
Ben: Yeah, absolutely. So we are really focused on providing a solution that can not only supplant allograft and cell therapy products, but also can really provide a robust frontline treatment to also completely replace those debridement procedures and microfracture. So we've been really focused on showing that our platform can not just be, you know, a better, more cost effective solution with some better clinical outcomes than tissue grafting.
But it's something that can really provide the type of fast healing and robust long term durability that could really make it a replacement for the microfracture procedures. So the implant itself is based on two key technologies. The first is the material itself and then the other is how we're making the implant.
So I'll talk about the material. It's a fully synthetic polymer composite. So it's basically just a couple of different types of polymers blended together, but that material has a highly aligned nano and microporous structure that simulates the collagen type 2 fibers. So it has a highly aligned sort of fibrous structure that looks like collagen.
So that gives the material mechanical properties that are matched to cartilage. So it actually can act as an immediate replacement for areas where there's damage or lost cartilage. And then that material also acts as a substate for cell growth. And a lot of our foundational research really focused on promoting the growth and development of MSCs, MSCs are a progenitor cell that exists in the subchondral bones, so they don't exist in the cartilage tissue, but they exist in that bone underneath.
So that material was really designed with recruiting and promoting the growth and development of these progenitor cells, which develop into new cartilage if you support them in the right way. So that's the material itself. And then the other component of our device is advanced manufacturing. So we actually use 3D printing [00:20:00] to take that material and manufacture it into a well organized three dimensional structure.
So there's the structural components of the material itself, but then there's also this 3D printed lattice that we create. And that actually acts as a really rapid recruiter of these cells So the primary way that they're they're delivered is when this is implanted surgically the bone does bleed and the device wicks up blood from the bone underneath of it and then and then supports the formation, the rapid formation of a clot which is also holding these progenitor cells.
So that initial healing process, what we found is it takes place much quicker, certainly much quicker than happens with the microfracture debridement procedures, but then also happens much quicker than occurs with the cell biologic products. So we quickly trap these cells in the cartilage layer of the tissue and over time interaction with the material actually leads to the formation of healthy cartilage as well as healthy bone.
So the implant itself is not patient specific. I always like to clarify that because people hear 3D printing and they think, oh, you know, they're going to image me and then they're going to match an implant exactly to my anatomy. That's not what we're doing. 3D printing is really a way for us to control that architecture and ensure that there's that proper three dimensionality to the way the materials arranged.
But the implant itself is essentially a button sized implant that can be easily plugged into these cartilage defect areas after the surgeon does like a simple drilling procedure. So we had surgical tools to introduce it. The primary important tool is just kind of like this drill, which just drills a hole where the defect is and then the surgeon just presses our implant into place, and it kind of walks into that hole like a puzzle piece. So, the implant and the way it's surgically introduced provide really robust mechanical fixation so the implant's not going to come out of place or dislodge, and then, the material itself also supports immediate loading.
So right now, especially when patients get a microfracture or when they get the cell therapy treatments. They have to be completely off their joint and off of their leg for anywhere from 8 to 12 weeks. So that's 8 to 12 weeks that you're in a brace, you're walking around on crutches, and you can't even start physical therapy until, you know, 2 or 3 months after the treatment.
Our device is designed to support immediate weight bearing, so that means that you know, you couldn't go out and play basketball the day after your surgery, but you can immediately start walking and you can immediately start rehab. So that provides a profound speeding up of the recovery process.
And then the implant material itself, as I mentioned, facilitates this really rapid integration with the body and really rapid healing. So you sort of skip some of the initial kind of like immune reactions or foreign body reactions that happen with other types of materials which can happen with osteochondroallograft and and which definitely can happen with the additional treatment from these cell therapy treatments or devices. So, we've shown in our animal studies that you actually get anatomical restructuring of the joint and complete integration of the implant within two months. So, that's incredibly rapid, typically takes six or eight months to achieve anything that kind of looks like that type of tissue regrowth.
And then, the differentiation into cartilage and healthy bone also happens very rapidly. So, we're about to start our first human clinical trial this year so we'll really be able to finally prove these claims. But based on the animal studies we've done, we think people could be considered fully recovered, you know, within four or five months after treatment.
Dasha: Ben, it's such an interesting approach and I hear that you guys have developed a technology that sort of has multiple facets of improvement. So I hear you say it immediately replicates cartilage and has mechanical properties, but also specifically it proliferates correct healing into the cartilage correctly, which what I also hear you say is when you do kind of a cartilage transplant, you could say, or cell therapy, there's something missing to stimulate correct growth of new cartilage, even though cartilage is introduced.
Can you explain that a little bit that, why is cartilage getting replaced better with your technology? 
Ben: Yeah, absolutely. So kind of going back to our foundational research, we were really interested in leveraging some of the mechanical stimulation pathways that specifically exist in MSCs. So they'll respond to chemical cues or biological cues, just like other progenitor cells will, but they also respond to proper [00:25:00] mechanical environments.
So that kind of comes back to inform the material design itself. So this material that has a structure that looks like collagen fibers, it's well organized and has a proper mechanical profile. So that really helps to stimulate the growth of those cells and the differentiation into essentially chondrocytes, so into proper cartilage cells. 
The other component comes from the 3D printed device itself. Our device has both vertical and horizontal channels in it, and the horizontal channels really just kind of facilitate infiltration from surrounding tissue and also provide an avenue for waste transport in and out of the scaffold.
But it also has these vertical channels, which are of a distinct design and architecture. And that's important because it's been shown that long horizontal channels actually also help to stimulate the development of chondrocytes. And that's because chondrocytes have a very particular arrangement in the highland cartilage, which is that they're sort of like aligned or stacked along these vertical tracks.
And so the 3D printed structure also provides this additional kind of mechanical cue so that as cells are growing up through the device and developing, it also ensures that they develop along this chondrogenic pathway. And so, we put a lot of time and effort into engineering these structures into our device, which can achieve a therapeutic effect, whereas, tissue grafting is just replacing it with a, with a big coherent piece of cartilage tissue and hoping that that, you know, integrates properly with the surrounding healthy tissue.
And then the cell therapy products are really relying on the delivery of chondrocytes and hoping that those chondrocytes themselves remodel tissue or potentially interact with some MSCs that, you know, come up from the bone. But what we found is that these structural elements and the effect of these structural and mechanical cues is vastly more potent.
And so that also means that we can get this regenerative effect and do in a better, more clinically relevant way, but we're doing it with a completely off the shelf synthetic device. And so that's the other really, really important component of what we're doing. It's that these tissue products and these cell products suffer from a real lack of efficiency and also high cost per procedure because they all have to be delivered or prepped on a case by case basis. 
Whereas, what we're offering the surgeon, and this becomes a really important topic of discussion because lowering costs and increasing efficiency is also really important for how surgeons are practicing medicine today, especially in the MSK space, our device is something that is fully synthetic, packaged, and easy to distribute. And so, our vision for this is that surgeons can go from this laborious process to source a graft or source of therapy to having our device sitting at the point of care, you know, in some volume in a box and can be pulled and used as needed for case, after case, after case, just like any other surgical consumer, like consumable, like a suture or like a surgical tool or something like that.
So that off the shelf component also is something that we think is really going to drive adoption and also just dramatically improve access for patients. So instead of having to wait two months or six months to get one of these therapy devices prepped or to receive graft tissue, the surgeon diagnoses you and then all that's really limiting your ability to get treated is how fast you can be scheduled in the OR. 
Dasha: Ben, one of the things we dive in on this podcast is the translational practices that ensure that when you're doing research that's meant to advance human health, how do you also make it practical and something that can then really make it out of the lab and into the clinic?
And there's so many things you've described about how you thought, even through the process of how the surgeon's going to use it and where they're going to order it and how much has to be manufactured or how easily it has to be available. I would like to kind of go back into your days as a scientist working on this project.
Could you share with us what you guys were doing early on in order to align your research and exploration and experimentation, to being able to then create a product that is going to solve multiple issues, both kind of clinical outcomes wise, but also this cost does fit into workflow, it seems like a lot of thought had been put into this upfront?
Ben: Yes, and I really appreciate that question. This is one of the things that I love talking about the most and I'm very passionate about. To put it simply, we sought out the feedback of our potential [00:30:00] customer very, very early on. And in our case, that would be sports medicine surgeons that are treating these pre knee replacement patients, right?
So we benefited from doing this, what's referred to as a customer discovery process in a very, very active and structured way. We actually, initially went through the National Science Foundation's iCorps program. So we went through a version of that program at the university level when we were still graduate students.
And then in 2016, when we formed the company, we went through it again at the national level through the program that the National Science Foundation directly administers. But all these programs sort of function in the same way. You come in with your initial concept of what your product is.
You come in with your assumptions about, you know, who the key stakeholders are and what value you provide to them. So that's referred to as the value proposition. What is it about your product that's going to make them willing to use it and pay for it? And then you have to go out and in person interview a hundred of your potential customers.
So, it's a very rigorous, fast paced process, but it really forces you to quickly have these conversations, generate this feedback, and then sort of iterate on what the potential value is that you can bring and so to kind of talk about Nanochon as a case study. You know, we originally thought that what we were developing was a better material for supporting a cell therapy. So our original vision for this product is that it would have this material we designed, but then it might also have other materials in it, and that it might even be impregnated with or embedded with live cells. And then, our other assumption was that we were really a direct competitor to the knee replacement.
So, you know, we thought, oh, we've got this better solution for really regenerating cartilage. Of course, patients are going to want to get this instead of a knee replacement. So a knee replacement surgeon is who our customer is. And after talking to, I would say, maybe a dozen knee replacement surgeons.
What we found is that, despite all of these known issues of knee replacement, they're really good at doing it, and they're really thinking about benefit to patients on sort of like a decades horizon. So what they were saying is, well, we know a knee replacement will last and provide some clinical benefit for at least 10 years and in most cases 15 or 20 years, and we're really good at doing them.
We've invested a lot of time and training in how to do them well, we in some cases have even invested heavily in a lot of capital equipment like surgical robots to do them faster and more efficiently. So we found that those surgeons really had no desire to change what they're doing. But it was suggested that we talk to these sports medicine specialists who are primarily doing arthroscopies and are almost exclusively treating these pre knee replacement patients that are either too young or the disease is not yet severe enough for them to just automatically be prescribed a knee replacement.
And, you know, after talking to maybe 20, 25 of these surgeons, it became very clear that they're in a very different paradigm. You know, there are these hosts of clinical issues with existing treatments as I've outlined. They're also looking at clinical benefit on the horizon of two years to five years.
They're not looking decades out so all the surgeons told us that they didn't consider any of the existing treatments for these patients to be a clinical standard of care. What they said is that everybody kind of picks the things that they're comfortable with and that they feel like they could perform well and then they generally just sort of commit commit to those treatments but they're always looking for better more solutions and then that kind of flowed into the potential I guess I'll say the potential value proposition of competing with these things like cell therapies where they outlined all these issues that they have with sourcing with loss of efficiency, not being able to quickly move their patients through the clinic to receive treatment.
And they're just losing a ton of time, and frankly, they're losing money as well, trying to make the existing treatments work, and so that also informed our return to the base technology, and made us really interrogate, hey, could this material alone have an effect? Do we need to pre culture it or pre embed it with cells or some biologics?
So that kind of flowed back into how we thought about continuing to develop the product and really kind of stress testing, can the material alone have an effect? And so that's really what we've been able to show at our subsequent testing in our animal models. Is that, you know, we have this well informed structure and this well informed material that really is enough to get significant clinical healing and then that flows back into the product being a much lower cost off the shelf device that can really address these pain points that the surgeons are having today.
Dasha: Ben, that's so interesting hearing about the NSF iCorps program. You know, I've heard [00:35:00] from many people how powerful that hundred interview regiment can be, in both discovering where the real root of the problem is, but also understanding all of this additional context that's needed to make a technology and a solution succeed.
But there's something that you said, that I want to kind of go back into a little bit, which is that for the knee replacement surgery in your initial discovery, you also heard that because there has been so much investment into making that the standard of care, and it is the standard of care, it's a very immovable behemoth.
It's going to be really hard to change, even if a better alternative comes around. I hear you saying you guys then decided to focus on an area where you could make a difference, but also people were more willing to work with you because the problem was seen. It sounds to me like you guys might get back to that knee replacement at some point because that's still a suboptimal surgery to perform.
And I'd like to get your thoughts on what that change, what is going to be required to drive change when you have so much infrastructure, training, and kind of expectation that that's just the standard of care. 
Ben: Yeah, I really like that question. And I think that this also really highlights how the development paths for these types of innovations and getting them from the bench all the way to the clinic and even to the market can be a long process.
And while you're going through that process, things can start to shift in the market. And so if you think all the way back to 2016, you know, those recent trends in how knee replacements are administered had not yet presented themselves. So at the time, the hip replacement was actually still the most widely done elected procedure.
In the last five years, the knee replacement has surpassed the number of hip replacements that are done every year. So I think that as we've developed, we've seen this this shift in diagnosis and treatment of osteoarthritis and this trend of knee replacements being pushed into earlier and earlier points in the care continuum and in younger and younger patients.
So I think that it's still something where we're very much focused on sports medicine and younger patients. But we've started to think about, you know, are there opportunities to provide a better alternative to early knee replacement, right? Because I think the surgeons that are starting to implement knee replacement are not necessarily the same surgeons that have just been, you know, doing tons of these on, you know, 65 and older people for years and years and years.
So I think that is the opportunity is that some sports medicine people are starting to do these early knee replacements, but they really have a lot of issues with it and they don't have the same sort of investments in training and time and it's not as big a part of their practice, so they don't necessarily have the same resistance to change, but I think also it's a question of staying focused on our core value while also thinking about how can we show some benefit for those potential patients. And so one of the ways we thought about that is just are there ways in our ongoing clinical trials to actually kind of expand the indication. And so one of the easiest ways to do that is just with age. 
So in the safety study that we're about to start this year, we're still restricting it pretty heavily, but we've already talked about designing the randomized trial that will need to get FDA approval to maybe incorporate patients that are a little bit older, still looking at ways to restrict the clinical severity of their condition. But you know, just simply saying, hey, we've also shown that this works in an older population, which if they had a better solution, wouldn't necessarily need to knee replacement.
It's just the default treatment. So it's actually a way to potentially pull some of those patients out of the knee replacement specialists purview and actually put them into the sports medicine segment. So it's really kind of building a channel to bring those patients into a different segment of care, if that makes sense.
So it's not necessarily trying to convince the really hardcore knee replacement specialist to use our product, but it's a way to say to the sports medicine surgeon, hey, this might be an option for you to treat some of these older patients that would just automatically get a knee replacement. So it's a way for them to effectively pull more patients into their practice. 
Dasha: Yeah, that's a really interesting strategy and thought process you guys have to go through as you plan the long term sort of product roadmap. I want to switch to a less scientific topic, but one that's extremely important in translation of technology, which is actually leadership.
So I learned about Nanochon when Ben and his team had recently won the Charlottesville BioSpark Competition, which is an annual competition here in Charlottesville, where about 10 plus exciting biotechnology companies, across the entire East Coast compete. And then I started seeing some of these other programs you've participated in like [00:40:00] iCorps mass challenge, MedTech Innovator.
And you're also a first time CEO, so you kind of went from the science lab, maybe being a CTO previously, technology focused, now to being really focused on fundraising, team building, all of this other stuff that goes into building a company. And so I just wanted to kind of explore the side of you a little bit.
So first, my question is, you participated in these high profile programs and what did you gain from each of these experiences? 
Ben: Yeah, so after we did iCorps, we've basically gone through some sort of accelerator or incubator every year, every year since the company was founded. So, there are a lot of these programs out there, and they all sort of focus at different stages of a company's life cycle.
So, we were always able to find a program that was appropriate for whatever the next step was that we were trying to reach. And not necessarily like have to go through kind of like the same sort of basic customer discovery exercise, basic lean startup exercise every time. So every year we went through another one of these programs and I think that they were really instrumental in helping us build, you know, a network of advisors and very experienced people that we could sort of pull into the orbit of the company to help us with whatever the critical experience gaps were, whether it was on engineering and product development, you know, whether it was on commercialization and distribution, you know, regulatory, clinical testing, all of these things.
And I think along the way, just to give an idea of the progression, you know, some of the notable programs we went through our creative destruction lab, which is one of the big health tech accelerators really focuses on companies that are at the point where they're ready to raise their first institutional round of capital.
So it does kind of take you through this structured mentorship and customer discovery process, but really focusing on talking to investors. So starting to think of investors as a customer in a certain way and thinking about what's important to them and what story you need to tell for them to want to invest in your company.
We've also now continued to go through even later stage programs, so we have been a resident of the Johnson Johnson JLabs Incubator, which really focuses on technology development and refinement and also engagement with a strategic. So someone that you might expect to come in at a later stage as a financial partner, certainly someone you might think about as a potential acquirer for your company and a platform to really commercialize the product.
So that's a program that when we were ready for it, really helped us with those things. And then this past year, we went through the MedTech Innovator program. And MedTech Innovator really focuses on companies that are sort of past the initial startup stage that really kind of fall into what's considered early stage.
And they say that they like you to be within two years of commercialization. So we're kind of roughly in that zone where, you know, the path to regulatory approval and going commercial with the product is actually closer to us now than the founding of the company is. So when you're ready for those types of programs, they all continue to help you build your network and network with the people that are appropriate for taking you from where you're at today to the next stage.
So, you know, we've always tremendously benefited from these programs. It's helped us bring on advisors and key people. It's helped us bring on investors as well. And then now it's helping us network with these potential strategic partners who might be ready to acquire us several years down the road.
Dasha: It sounds like there's a real great place for each of these types of programs in the journey. How did you know which of these programs were going to be the right fit as you guys went through the development of the technology and the growth of the company? 
Ben: Yeah, I will say some of it has been through the connections we made through those incubators, right?
So after going through iCorps, people that mentored us in iCorps said, oh, we think you'd be right for this Pharaoh one program. And that sort of like, kind of continues in a leapfrog fashion as you move forward. I'll say also that a lot of these programs do actively recruit. So, like, Created Destruction Lab actually approached us because they saw that we were a J labs company and something like MedTech Innovator is something that's very well known to any experienced person in the industry.
So, you know, a lot of it came also from just people that we built out our other investors and so on saying, hey, we think that this is the right time for you to consider this particular program. 
Dasha: That's excellent. Would you have any advice for earlier stage companies in terms of what they should be [00:45:00] looking for to kind of get them sort of started thinking about how their technology is going to translate into a product?
Ben: Yeah, I mean, I think the first and most important thing is that initial customer discovery. So, if you're going to go through one of these programs like iCorps, something else, something that really focuses on defining that initial product to market fit between what you're building and who's going to be the initial user of it.
Dasha: Well, personally, you started out your career in this technology role and now you're a CEO of a company. What was it like to go from that transition and what have you learned along the way in terms of leadership? 
Ben: Yeah, absolutely. I think that I benefited early on in my academic career from just having a lot of exposure to presenting and storytelling, right?
So we were fortunate enough to go through a lab that had a young motivated investigator who really wanted to get us out there talking about the research. So to put it into context, a typical PhD might go to one or two conferences a year. My co founder and I were going to four or sometimes five conferences every year to present our research.
So that just really got us comfortable with standing in front of an audience, talking about the technology, talk about what we were building and also to get comfortable in answering questions, because I think that's one of the biggest pieces of fundraising, is that you're going to present to investors and they're going to take you through, you know a long process, months, if not sometimes up to a year, just to really dig into every area of your technology, your clinical application and your business.
So, it got us really comfortable early on with those kind of like critical communication skills that are required to be the leader of a company. I'll also say that I think that we really benefited from hearing a lot of good, I guess I would say war stories, right? 
So I always sought out mentors, whether it was through these programs or just informally who had experience building companies and sort of knew what the pitfalls were, knew what the common mistakes are, and you know, a lot of them really just come around fundraising and legal issues and organizational issues.
And so I think hearing some of those stories about where people made mistakes and where they wish they'd done things differently and really trying to implement those really investing in good legal advice early on, both on the patent side, but also just on the, on the company formation and governance side. I think that we've really benefited deeply for doing a lot of that work early on and with good attorneys. And then I think from a leadership perspective, it's sort of learning how to trust your team.
I think as academics, we're taught to be very provincial and very guarded and very protective of the work we're doing. And I think that that is very much counterproductive for when you're inside a small and growing company. You really have to be able to trust your team, have good communication among your different team members.
And you know, really be able to make sure everybody's on the same page communicating regularly. And then also you, as the CEO or even as the CTO, very quickly as things progress and grow you lose the ability to do everything yourself, because you just don't have the bandwidth and there's not enough time in the day. And so I think also really learning how to how to trust your team, bring on people that you have oversight over, but you trust their expertise and you trust their ability to work somewhat independently, I think is also just a really important skill.
And I think ultimately at the end of the day, you know, respect, trust and open communication are the values that, you know, we at Nanochon have tried to build our culture on. 
Dasha: Yeah, those are great lessons and could be an inspiration to some PIs in terms of how they run their labs or what kind of training and additionally, I love that storytelling piece, like go out to more conferences, have more people ask you questions and challenge you.
The field of biomaterials and regenerative medicine is very hot. We've talked about it many times on this podcast, different applications, different challenges remaining to be solved. Where do you see kind of the field and the opportunities of this field for the next 5 to 10 years? 
Ben: Yeah, absolutely. So I think just in musculoskeletal health, it's really been a focus on solutions that can alleviate or negate the need for metal implants.
So that's certainly very prevalent in joint health as we talked about, but it's also very prevalent in spinal surgery, it's very prevalent in extremities, treatment, and very prevalent in cranial maxillofacial surgery. You know, metal in general has a lot of the same issues throughout the body, which is that, you [00:50:00] know, the metal itself will eventually wear out in some way, although that can certainly take decades.
But then there's also this challenge of you've got an inert piece of material like a metal existing in a biological environment. And so a lot of times, you know, metal implants fail because of the health of how the bone has grown into it or attached to it. So, there's also the very prevalent and known issues around infection.
 You know, infection is a big issue with total joints, but it's also a huge issue in spinal surgery. You know, infections can actually become very life threatening very quickly and also cause disastrous complications. And then this is also true in, you know, areas like dental and cranio maxillofacial surgery, where it's really hard to even ensure sterility at the time of the surgery.
So, I'd say in general, regenerative medicine in musculoskeletal health has a huge, potential value to alleviate the need and the complications associated with metal implants. So, that's an area that's really been a driver for MSK.
I would say in other areas of the body, I'm really excited about some of the innovations around I guess I would say suturing or closure or basically, you know, addressing how you close up internal structures in the body, like organs, blood vessels, connective tissue, you know, how you repair, how you repair those, those types of damage, which can just be the result of a surgery. So basically thinking about replacing sutures and staples with biomaterials, regenerative biomaterials that can provide, you know, better closure and then also regenerate and restructure.
So I think that's a really exciting area. And then I think in general, you know, the initial promise of regenerative medicine, when it really first emerged in the 90s and then again in the early 2000s was the ability to do a lot more complex repair like regrowing parts of the heart, whether it's heart valves or heart muscle, repairing trauma to other major organs and then also in, you know, the treatment of neuro diseases and neurological injuries. So I think that those types of applications remain extremely attractive just because they're such huge and life threatening problems and so I think that we're going to continue to see people to try to develop, you know, these really complex therapeutic treatments.
And there are some things that are now emerging again to treat things like liver disease and to repair cardiac tissues. So I think those, those huge problems will always exist. And I think as regenerative medicine gets more mature in areas like MSK and in other areas like general surgery, we'll continue to see those innovations flow into the really, really big problems.
Dasha: Those are all really exciting areas and I would like to add to it. We talked early on about early detection and in our previous episode on this podcast, we talked to Dr. Jonathan Hill, and Wasatch Biolabs where they're developing all these epigenetic tests using new techniques and epigenetic sequencing.
And so, one of the things he mentioned on that podcast, so relevant to this set of problems, is that we now have this ability to more quickly develop tests that test for biomarkers on our sequence. And sometimes you can pick up if a tissue is getting degenerated, if something is going on and it's leaching basically contents outside of that tissue and then it's circulating in your bloodstream.
And so, if people are looking for additional areas, there seems to be this whole world of trying to figure out how we can detect cartilage degeneration much earlier, which would allow so many more of these interventions to be, you know, whether it's lifestyle interventions or the use of Nanochon, to actually be taking place earlier, where there's much greater chances of great outcomes coming through.
Ben: Absolutely. And, you know, especially in cartilage health, I certainly am no expert in this and from what I understand, it's an emerging field, where there still have not been hard, actionable findings, but there are researchers that are looking very deeply at sort of the genetic component of cartilage degeneration, and it's sort of known that some people will be more susceptible to degenerating cartilage health and the development of osteoarthritis sooner than others and that there's probably a genetic component to that.
So I also think that's a really exciting area of research where you might be able to say, oh, like we've been able to find some genetic evidence, you know, years and years before you even start to develop this arthritis that you are more susceptible to it and that could inform things like, you know, earlier detection, lifestyle [00:55:00] changes and so on.
So I also think it's a really exciting area and one where if there's, you know, substantial advancement that could really dramatically and change what the care continuum looks like for these patients. 
Dasha: Yeah, well, Ben, is there any last call to action, anything that your company is doing that people can participate in or anything else that you'd like to call out on this podcast?
Ben: Yeah, absolutely. So, we're gearing up to start our first human clinical trial. This is going to be our initial safety study, the first time the device has ever been used in human patients, so we're extremely excited about that. And we're on track to start that study early next year, if not potentially doing a surgery before the end of the year.
So that's sort of our stretch goal is to push things along and actually potentially get a patient treated, before the end of the year. But in addition to these clinical efforts, we're also working on building up our manufacturing and product development capacities to really be able to prepare for supporting higher volume and higher quality production of our device, certainly for that larger randomized trial in 2026, and then also to provide a good ramp for actually producing the device for commercialization. So, we are planning on building our core engineering team, and potentially looking to onboard several people, to join us at our manufacturing site in Baltimore, Maryland, at the launch port.
So if there's anybody that's interested in a potential job opportunity and might be looking for something, you know, in the first quarter of next year, we are going to be actively looking for people. 
Dasha: Oh, Ben, that is so awesome and I will tell you and our audience that we have had some people write into biomedical frontiers, at virginia. edu and share with us that they've heard about companies on this podcast and were asking for connections. We love the idea of connecting talent to great companies and a lot of really great opportunities are in companies like yours, smaller startups that are working on innovative, transformative products.
So, this is something that we can do. Please write in if this is of interest and Ben's LinkedIn and other information will also be in the notes, both on RSS and YouTube so that you can click the link and connect directly. Thank you everybody for listening. Ben, thank you so much for coming on the show.
Ben: Thank you. It was my absolute pleasure. 
Dasha: Everybody have a great day. And if you loved these topics, please take a look at some of our previous episodes. Episode four in season one with Dr. Daniero and Dr. Griffin on regenerating vocal cords and in airways with novel biomaterials also focuses on some really interesting new applications of biomaterials and dives into the clinical side of things as well.
So you can learn a lot. If you're just joining the podcast, we love this topic. There's so much great stuff going on in this field. Thank you everybody. Have a great one.
David: Thank you for listening to Biomedical Frontiers, stories with innovators in healthcare. My name is David Chen and I am the Managing Director of the Wallace H. Culture Center for Translational Research at the University of Virginia. Our mission is to help bring promising new biomedical research and technology into the hands of the provider and the patient.
If you found this episode valuable, please let us know by subscribing, following, or sharing. You can learn more about our promising translational research projects on our website. See links in the show notes.