Well, good afternoon, everybody. We have a great session coming up. We'll start with Dr. Matt Provencher. He will talk to us about innovation in sports medicine surgery. Dr. Provencher is from Vail, Colorado. He has a very accomplished career. He spent time in the Navy. He's a professor of surgery and orthopedics at USUHS, director of our fellowship in Vail. He's also served in Navy SEALs for many years, has published over 420 articles, written seven textbooks, and is certainly a thought leader in innovation. So go ahead, Dr. Provencher, please. Thanks, Mark. Appreciate it. Is Tokish here? I'd like to debate him again. I want to recount. No, it's all good. Thank you, everyone. And John, Allison, great program. Dean, fantastic stuff. What a great day. We're just going to talk a little bit about some of the things that have happened in the last five to 10 years and some of the things that are coming down the pipeline. There's a lot of other stuff here. So I'm not going to cover cartilage and cuff and all these other augments and biologics. But some of the things that we are delving into and making our lives better and our patients' lives better are super important, I think, to the future. And working closely with our vendors in terms of helping us do better for our patients, I think, is really important. This is probably the most exciting areas, preoperative planning. And if you really look at the literature on where we are in preoperative planning, it's here to stay. It's getting better. We're doing a lot better with it. Now, of course, our hip and knee colleagues have found that the robot, although there might not be too much evidence on the early side, it's helping us do the procedure potentially a little bit more reproducible and a little bit better. We may have robots coming in sports medicine, but it's not here yet. What is here and what the future is is certainly patient-specific instrumentation. And this has truly changed the game. I've done osteotomies now for 25 years. And we all know the principles of how to do osteotomies around the knee. But now we have patient-specific instrumentation. Now, many companies are helping us do this to really make our lives a lot better and to get something down to a point-something degree or a point-something percent in terms of where we want to correct it. When we're looking at our 3D planning and how we do this, we have patient-specific 3D-printed models, 3D-printed plates, 3D-printed options and screws to be able to do this. We also have three-dimensional modeling, really been looked at closely with the shoulder and shoulder arthroplasty, but certainly our young athletes that are getting early arthritis. This is becoming more and more concern and keep our weekend warriors in shape from an arthroplasty standpoint, super important. And so being able to do the surgery ahead of time on the computer, we've never been able to do this before. I didn't have this at the beginning of my career and I wish we had it a lot earlier because I now have much less stress in the operating room, picking implants, picking what we need, picking what we need to choose. And it's really helped de-stress this. The other thing is 3D models. I've been doing this for about 15 years now. 3D printers, used to my first one I bought cost me about $15,000. Now these are all over schools and elementary schools are about 500 bucks each and can really help you plan this modeling. And then what about interoperative and looking at this? This is the future. This is already here. We have many different types of goggles and Oculus, Google Glass, some of these other things that are now helping us place implants in the right position, getting the right landmarks, reproducing anatomy. This is the future. It's here to stay. And this is one of the most exciting areas in sports medicine. Well, what about shoulder instability near and dear to my heart? We know that bony augmentation is here to stay. It's a huge problem. We're getting better at it. We still have a lot of work to do, but we know that the glenoid doesn't take a joke. And now a big part of this is just looking at the glenoid track and looking at three-dimensional imaging on this in terms of how we do this. Back in 2007, we found unique use of allografts. And now I'm proud to say that this is, I think, really stuck. We have some more work to do on it, but the distal tibia fitting the humeral head is just an example. And now we have studies that are looking at the distal radius, the end of the clavicle, and now reproducing other parts in the body to be able to go other places. But I think this study highlights how the law of basically human nature and the law of nature in terms of how the radius of curvature is preserved across the universe. And so these radius of curvature of joints is really preserved across the universe and how we can get super creative by using allografts around the body to reconstruct the anatomy. I also think understanding anatomy, we've had a ton of explosion of interest in revisiting anatomic studies across many joints. This is just an example of looking what happens after procedures and then three-dimensionally modeling this in terms of helping us do a coracoid transfer better to find out where the nerves are, the vessels are, where the exact ligaments are, and again, at the end of the day, restoring our anatomy better based on three-dimensional planning, understanding everything else. Well, what about the distal tibia for the glenoid? We now have the talus for the humeral head. We did another project and said, well, I said if the tibia fixed, the talus should fit the humerus. And again, it's really hard to get a fresh humerus, so why don't we start using a talus? Here's a great example, reverse heel sacs. It's an all cartilage lesion. And now we're able to use the talus, again, another way of using a nice, dense corticocancellous graft, and you can get Woodshop 401, but again, what's easy with this? 3D planning, 3D printed models to be able to reconstruct this. And so up to about 42 millimeters, this fits really well, and you get a really nice restoration of curvature and a graft that you can get in five days from graft companies, and to be able to really help our patients at the end of the day. Well, what about instrumentation, sutures and configurations? There's been an explosion of this in terms of really evolving from just a cylindrical suture. We now have sutures that have some level of creep and strain. They have biologics, they have collagen, they have antibiotic impregnated. We also have tapes in a variety of different sizes. And if you look at some of the bracing concepts or suture augments or internal brace concepts, and you look at some of the work out of Birmingham or Jimmy Anders, Jeff Dugas, Lyle Kane, many others, just in the elbow world, this has helped change the game for our athletes with using tape-type sutures across the elbow, not to mention the knee, the shoulder, and many other areas. And we're looking at double row rotator cuff repair, which has clearly been around a long time, but now using all knotless and all suture-based constructs. Never even would have thought we would have had this, would have been able to use around the body. And now we're looking at knotless fixation. Knotless fixation, amazing. I didn't wanna believe it. We had knot discipline. You had to learn how to tie knots, a sliding knot, a non-sliding knot, a Revo, a Weston, a midshipman knot. We had all these different types of knots. Frankly, my fellows, I'm not sure even know how to tie them now, and I'm not sure it's necessary because it's so good now. I didn't wanna believe it, but it's really good. The mechanics have stood up the test of time. Really, every company has this, and now there's different, again, different tape sutures that may be helping us with our capsular repairs because there's less of a giggly-saw effect across the capsular soft tissues, and we're getting these really nice reconstruction of the anatomy. I think that's the biggest area we've improved is reconstructing the anatomy and putting this back, using our technology partners to make this better. And lastly, visualization and scopes has helped us really change the game. Some of the technology, there are many companies now that have this chip-on-tip technology, so our GI colleagues have this in the GI world. The bottom left of that screen there shows you what a GI scope is like or an endoscope is like, and now we're able to put that chip-on-tip technology to the use in orthopedics by really making small, needle-like scopes that are able to be inserted in the joint in the office. Are you kidding me? We never do an arthroscope in the office and have the ability to do that. It's really amazing stuff, and that is gonna help us change the game. The ability to have two scopes in two different areas of the joints, the ability to stitch images and videos together so you get more of a two-dimensional, maybe even a three-dimensional picture in the near future, which is coming. Here's another new innovation that looks different. This is all just through one scope, but just with a touch of a button, we can switch basically from a 70 to a 30 and not have to unscrew the scope or change the lens, and so another really cool area. Lastly, our therapy and how we monitor our patients, super important, personalized recovery, injury prevention, and watching this is really important. Our wearable market continues to expand. There's a new one on the market almost every 15 days, and this is a little bit hard to keep up. It's overwhelming, but we do know that some of these are gonna stick, and we're already using these to help monitor our patients. We also have remote patient monitoring codes, CPT codes, now CMS-approved, ever since January 1st of this past year, and we're able to, companies that help us monitor our patients better and actually get paid to do it and paid to interact with our patients without them even coming into clinic, but we're actually getting better data than probably even when they're in clinic because they have a wearable, and these wearables, I think, are here to stay. We don't know exactly what's gonna stick, but there's probably gonna be something that will help us, and then lastly, this telemedicine and watching patients and how they're doing is gonna really help us change the game down the road, so there's lots of innovation in virtual reality and teaching and how we teach our residents, our medical students, and fellows. I think virtual reality, augmented reality, is gonna be here to stay, and bottom line, there's lots of innovation coming our way, and it's really been an explosion in the last five years, so I wanna thank all the great innovators and thinkers out there because it's certainly helping our patients. Thank you. Thank you, Dr. Proventure. Dr. Proventure, before we go to our next speaker, I just have a question. You know, over the next five years, Dr. Proventure, you took care of the New England Patriots and has a team physician. What innovation do you see over the next five years that you would love to have had at that time to help your team and your players? I saw personalized medicine, fitness. What do you see in the near future for that? Yeah, it's probably everything. You know, it's everything. It's stealing a model from AOSSM, keeping people in the game, Dr. Philippon, and getting them back to the game quicker. It's all about return to sport, return to sport confidentially, or confidently, and then getting them back to play reliably and so that they don't re-injure themselves, injury prevention, so that's some of the stuff I wish I had a little bit, but it's getting so much better, and the next five years promises to even help our athletes better. We're gonna see people come back. You know, the Aaron Rodgers story of coming back, you know, eight weeks after an Achilles repair. Look, it probably really wasn't gonna happen, but the press liked the story, but even to think about that would have been unfathomable five to seven years ago. Thank you. Thank you. Our next speaker is Dr. Ramkumar Prem from training at HSS. All AI application in sports medicine. Currently, he's practicing in California. He's dual fellowship trained in sports medicine and joint replacement. He's passionate about hip and knee preservation. He established the world's first laboratory dedicated to application AI in orthopedic surgery, authored multiple articles, over 125, and regularly contribute to Forbes and edits for arthroscopy journals. Looking forward to your talk. Thank you, and thank you to AOSSM for the invitation. Not really sure what I'm doing next to this esteemed panel, but I'll take it. So I'm gonna talk about AI, and it's a evolving journey for me. And so this is kind of the major disclosure that this is just a personal experience, not intended to be comprehensive, and I am arthroplasty and sports medicine trained, so you'll have to bear with some arthroplasty stuff, but there's a lot of people along the way that have helped me. The actual disclosures are things we talked about, nothing that actually affects the talk. Format of the talk, essentially, is help start this lab six years ago, and there's basically three clinical interests. And it comes down to risk calculators, wearable smartphone devices, and basically surgical execution. And the biggest clinical disinterest I have is in automating clinical care. And so we're gonna just comment a little bit about generative AI. So simplified AI is essentially computer automation, and it's based on pattern recognition. And that pattern is based on the data that we have. So data essentially just mirrors the model, and it's not that complicated. And so the way I think about things is there's non-generative AI, which is what everyone has pretty much seen in the literature up until this point, and that's just a reflection of what's going on from our own data set. Then the more unsettling thing for me that we'll talk about is generative AI, which is producing or generating information. And so I'm just gonna go over quickly. You'll see this talk starts with evidence, then slowly becomes more personal philosophy. But the first limb that I wanna talk about was AI as a communication tool that we've seen. This, back in 2018, was essentially the first publication using machine learning around arthroplasty, where a lot of my arthroplasty colleagues were frustrated with the amount that they were getting paid for primary joint replacement. Despite the risk of the patient that comes in, we were able to show that higher-risk patients do deserve higher remuneration depending on that risk, and that can be determined based on something preoperatively. Secondarily, at the time, the political atmosphere wanted to bundle hip fracture patients. Turned out to be, for all the surgeons, that's not a very smart idea, because again, risk, at some point, was essentially unjustifiable, because it's essentially a different population. Another example is essentially using machine learning to predict future injury, and it just basically shows that machine learning itself as a model is better than regression when you have tremendous amount of data. It's not perfect, but it's better. Another example is basically looking at cartilage lesions. We've talked about this. There's so many different ways we approach cartilage, whether it's looking at the imaging, bone edema, alignment, preoperative function. Turns out, based on this data set, the most important factor was preoperative mental health. And looking at CAT scan imaging data, similar with hip arthroscopy, you're getting the theme here that machine learning takes multiple different variables and helps you discern what is actually important to the top. To an administrator, this is important because it almost helps codify what we as clinicians actually know is what's going on, but this helps turn this into an algorithm. This goes so on and so forth. Basically, the theme is you can predict future things within a certain risk model. Same concept. We did this with MRI, but now moving on to AI as a patient experience and a recovery tool, like what Dr. Provencher was talking about in remote patient monitoring, where we're essentially looking at some of my patients' step counts, what their opioid score is, what their outcomes, and it's basically based on all these sensors that come from your smartphones that then passively gets kicked back to your phone, marrying a whole bunch of data sets to come up with point of care demands. And so essentially, you can actually alter the way we see patients. We saw with COVID, there can be a lot more virtual visits. And again, bear with me for the arthroplasty stuff. If you ever have to deal with revision arthroplasty, turns out that AI is pretty good at detecting what implant is in so you know which reps to call, and it's pretty darn good at images. And so it's shown up to 100% accuracy, 99% accuracy with what kind of implant you have. And this is my current focus, where we look at CAT scan imaging, and we're essentially creating face masks based off of real anatomy, and that's the stuff that Dr. Provencher was talking about, where we're getting better at dialing in anatomy, and we're able to calculate, based off these face masks, off of hip to ankle CTs, multiple, multiple metrics at the same time, automatically, with 27 different metrics. These are just examples of that. This is essentially a quick slide that basically shows we can decide that if you have more than nine anatomic outliers, that essentially means that you are, as a patient, an outlier, and therefore, perhaps, you should be treated a little bit differently. So it helps offer some patient-specific elements. And these are examples of all the anatomic variations that we treat, and this helps, through imaging analysis, what AI helps us do. And another example of a cluster map of showing how patients, before their total knee arthroplasty, can be segregated, based on various anatomic metrics, to really show how we dial in our surgical plan. And this is essentially what I'm currently focused on, where we're looking, and I found this video important to show, because the future of this kind of research requires Python education, where you can actually code, and go through images, slice by slice, and actually pick where, in this case, where the CAM lesion is, what you wanna take out, how you wanna do the resections. A lot of hip arthroscopists understand that alpha angle's an imperfect metric, but really, it's a volumetric assessment that needs to be looked at in a three-dimensional model, and this is what I spend most of my research on, trying to help focus. And so, getting back to where we are now, there's hope versus hype. Back in 2018, I got a series of rejections, and no one will ever care about machine learning, and now I'm up here, and it's very confusing how the hype cycle's gone. Now, for every 178 publications, two are maybe original studies, one is a commentary, and so we've probably had the pendulum swing a little bit too much. It's probably gotten out of hand where people are flooding these journals through a Trojan horse method where there's some bad AI research out there, and these are essentially my eight lists. The first is gratuitous use of AI when it's probably not necessary. Another one is people who say ML and AI are the same, and AI and machine learning, they're very, machine learning's a subset of AI. And another quick tell is when a study is labeled, is there a bug? I swear to God. Is when a study says machine learning or AI shows, proves, or demonstrates. That's the equivalent of saying a t-test shows statistical significance. It's not gonna work. And then finally, if you're gonna do a study, you have to show the full open code. That's essentially the methods of this kind of research. And quickly, I'm moving down the list. Essentially, external validation's important, and these chat GPT-based things are essentially, it's too soon to tell where we're at. And there are some guidelines on what is important. And so, getting back to the very, very editorial aspect of this is that there's, I knew there was a bug, okay. So, generative AI essentially confronts our three greatest irreconciliations in medicine. I think right now, content creation is based off of foundational data. I already told you everything we've done is based off data. Secondly, simulation events or fake news are being generated in en masse. And you know, societally, I don't think we've actually ever reconciled with misinformation and fake news from the election, the pandemic. Do you believe CNN? Do you believe Fox? Academically, we haven't really reconciled with what surgical techniques and outcomes. And you know, this is further muddled by the absence of clinical practice guidelines. And so, are you a quad believer? Do you believe in the in-space balloon, all these certain things? And clinically, I don't think we've really exactly reconciled with what medicine is. Are we a profession? Are we a business? Should we just give people what they want? This is crazy. Anyways, so, anyways, generative AI really, really blurs the lines. It basically creates things en masse. In case you're not aware, for anyone on social media, which is pretty much everyone, there are fake individual accounts being created that generate an average of $10 million a year. And I know you guys probably can't read that font, but they create fake individuals that people follow and interact with, and they have their own sponsorships, and they dial up and down the personalities. And these fake accounts are essentially sponsored by Nike, Chanel, Dior, and, I'm gonna kill it, hold on. All right, no, I'm not. Okay, so, it's interesting because you're seeing what people want. It's not real, but they're okay with it, and that's crazy. And the truth, and the thing about generative AI is that the truth does not matter. But the truth is everything what we do academically, clinically, culturally, in medicine. And so, you really have to decide, would you rather be on an SSRI for the rest of your life or have a fake partner? And at that point, we've already decided that do you necessarily need to talk to your surgeon, or will a PA be enough, or will a nurse be enough? Or how about just a bot if they can answer all those questions? So, and then what's very disturbing is that you're seeing studies slowly come out that say, well, do we need real clinical data? Everyone I hope in the room would be like, yes, you need real clinical data for research. But beware of the word augmentation because it's a very slippery slope once we let generative AI come into research, and it's essentially creating fake data en masse, and you can modulate to whatever perception you want it to be. And I'll shut up very soon, but limited language models, they're not as bad as they look. You can customize them. You can do a pretty good job with it. The excitement in healthcare is essentially... The excitement in healthcare is basically that there's disproportionate administrative overload, and there's a lot of burnout. I think this is a sign that I should just stop talking. So there's an opportunity to automate redundancy, concisely communicate, coordinate care. And burnout's bad, generative AI. How am I using it? I basically use it to automate replies to patients. My first year of practice, I want to know what's going on with my patients, but they don't know that 80% of it's AI generated on my replies. Secondly, non-generative AI, I use the implant identifier before I go to a revision arthroplasty. And then finally, risk stratification to help patients understand. I'll leave you with this very unsettling way. I can write papers, or anyone can write papers very easily. We're talking about how to write a systematic review right in the text message chat bot. And it's very easy. It's very easy. So we have to be careful. So I'll leave it at that. Thank you, Prem. A great, great talk. I just have a quick question before we leave the podium. So you said about the data, and I think all of us agree that AI is a great tool, but how do you... You need accurate data, right? You need to have the perfect data, otherwise you have fake data, you can create a model that's... So how do you prevent that over the next 10 years from happening in our field? We have to be better stewards of the actual data that we have, like great things like Moon and Mars, that's our workhorse. We can't be allowing fake augmented data to run amok. It starts at the foundational level with which we gather data, but the things that we'll never be able to get is the things that people like with your experience, you can tell who's going to do well based on the interview and interactions you have with the patient before you take them to a... For a hip scope. That's never going to be really codified, except unless when we have visual sensors and we can read body language and that sort of thing, but that'll probably happen too. Thank you very much. Great talk. Thanks. Our next speaker is Dr. Seth Sherman. He's going to talk to us about CARDS lesion and what's available and what's coming. Seth is from HSS, he's currently the team physician for the Stanford football team. He's a third generation team physician and surgeon, which is pretty amazing. And he's a thought leader in his space and we're looking forward to your talk, Seth. Thank you so much, Mark. It's an honor to be here. Thanks to Alison and Jonathan. We're going to talk about cartilage lesions, what's available and what's coming. My disclosures are mostly online, but for this particular talk, we need to be specific about relevant disclosures. I'm going to leave them up as I ignore the moth. And I'll just say that it's been a privilege to innovate in this space. Many of us who do this are site PIs. Some of us are educational consultants. We get research funding and I think this is how we drive this innovation forward. So hopefully that helps to clarify here. From a 10,000 foot view, we need to practice evidence-based medicine. So what that means in the cartilage space is look at the amount of data for autologous cellular products and for osteochondral allografts. And then look at the paucity of data for everything else. We have many of these products that are in the exhibit hall. And they come from less stringent FDA pathways. And they have animal studies and maybe retrospective case series. But they do not have the rigor of the data of the big two that I showed you. So it's just food for thought as we start. So what about third generation autologous cultured condocytes? So we have expanded FDA indications now. It's technically easier. There's opportunities for accelerated rehabilitation. This is really our first tissue engineered product, uniform cell distribution on porcine membrane. And we have custom cutting devices that make this quite easy. We can do this minimally invasively. So that's really exciting. We looked at this in the lab, looking at the traditional manual cutters versus custom cutters. And fortunately found really no differences in the viability. So it's dealer's choice on technique at this point. And this information is obtained from an internet search. This is not made on behalf of any company. But the third quarter of 2024 is likely to bring the launch of arthroscopic technique. These kits target two to four centimeter defects. And this may influence up to 20,000 patients. And so what's new with osteochondral allografts? We can make these look very good at time zero on the surface. But what's lurking behind the surface? You can see that there's no free lunch. And we still have challenges getting the bone to heal. I think this is the real active zone for research. And we're using things like pulse lavage. We're looking at pressurized CO2. We're trying to load this with biologics to try to augment healing. And Jason may talk more about some of those tools in his talk in a moment. However, is this really working? The clinical data on that is conflicting. And so we kind of took this also back to the lab. And we saw some interesting things that need further study. First off, when we do pulse lavage alone, which is really the standard to get rid of the marrow element, really the plug doesn't lose any weight at all. When we combine that with pressurized CO2, it loses a substantial amount of weight and then gains back almost 100% of its weight in the biologic of choice. So food for thought needs to be borne out clinically. But I think that's exciting. Now we'll move on to clinical trials. These are not available for clinical use. So here's another culture-expanded autologous chondrocyte seated on a biphasic collagen scaffold. And so this study is now in phase three. It's in collection of the data. There's no more enrollments. There are excellent outcomes in Germany. And so time will tell what role this may have to play. Interestingly, these similar culture-expanded autologous chondrocytes can be mixed with an in situ polymerizing hydrogel. And this can allow them to be basically implanted arthroscopically. There's some early data in this from Europe. We'll see if it gets larger studies and makes its way to the United States. This is excellent work from Dan Saris and Aaron Critch and others at the Mayo Clinic. And basically what they are doing, they're debriding the cartilage defect. They're taking some of the mince cartilage and they're making autologous chondrons. They're then mixing that with allogenetic MSCs and in a single stage are implanting this back into patients. And so they have a phase one study. You can see the demographics here. These are the typical defects that we're treating in our practices. Fortunately, so far no treatment-related adverse events. We can see clinical improvements up to two years. And Aaron was nice enough to share one of his patients. So here's kind of a typical lesion that they're treating. You can see the preparation, the implantation, and the MRIs preoperative up to six months showing excellent regenerative fill and really quiet subchondral bone. So what's new in microfracture plus? We can look at things like autologous matrix-induced chondrogenesis. And you can see the schematic there basically augmenting the microfracture bed. There is a lot of data on this from outside of US. This is not available in America at present. The SECURE study is ongoing. Looking at standard microfracture for small to medium defects and maybe using microfracture plus to try to expand those indications for larger defects, time will certainly tell. Now we transition to early osteoarthritis. This to me is a big game changer. We're looking at the aragonite scaffold. So this is essentially sea coral. And you can see how there's modified porosity. So there's a bone phase and a cartilage phase. And when through rigorous study, they learned basically that there's a magnet effect. So it attracts your own cells essentially to make bone and then to regenerate cartilage on top and also around those scaffolds. This had a very large FDA study. This is now approved for clinical use. We talked a lot about this study, mostly because it's real world kind of indications in patients. And so this study had much older ages than others. This study had higher amounts of malalignment up to eight degrees, higher BMIs, less meniscus. So these are kind of the common patients that we see. And what's most striking is this is really the first study that bridges the gap not just for focal defects, but all the way into osteoarthritis as I'll show you in a moment. And so you can see the broad range of pathology that it tried to tackle and did tackle in the FDA study. This was particularly striking with larger lesions like the ones that you see here where the differences between surgical standard of care were larger. And then you can see again, most strikingly, mild to moderate OA, KL grades two and three. Not things we treat with most of our cartilage tools at present really did quite nicely. So here's kind of just a quick look at what these cases look like. Here's the regenerative fill on MRIs at two years, and really significant increases in the KUS scores, which was the main outcome study. Here you can look again at an oval-shaped condyle defect. We can see how you don't have to fill the whole defect. You basically just have smaller plugs filling parts of it, and it regenerates throughout the entire thing as you see here, quiets the subchondral bone, and improves the patient-reported outcomes. What else in osteoarthritis? This is not approved in the United States. Human umbilical cord MSCs on a HA substrate. And so this is quite promising technology. You can see the schematic of how it might work. Here is how they implant this. And so basically, similar preparation to basically potting a plant with the MSCs and the HA substrate. Phase three out of Korea is promising. And look, arthroscopies for osteoarthritis show regeneration. Again, this is not here in America. Briefly transitioning to the subchondral bone. We're learning so much more about the subchondral bone and its importance in cartilage restoration. We've learned about sick subchondral bone and a variety of pathologic conditions that really inhibit our ability and capacity to heal. This is basically one way to treat this. This is my friend Rachel Frank. She's basically targeting one of these bone marrow lesions, subchondral drilling, and then she's filling it with a biologic of choice to try to get the lesion to heal. I think moving towards the subchondral bone health is a critical part of the innovation. This is another way to think about it. Others are trying to use rebar or support of the subchondral bone underneath the sick cartilage and using mineralized rafting screws to do so. So time will tell on that clinical study. What about the future? We're hearing rumbles of synthetic cartilage products that are making their way through early phase studies. These certainly would increase availability of cartilage treatments and also implications for very accelerated rehabilitation. And lastly, I bring it back to this. The joint is an organ system. We of course have taken a whirlwind tour through cartilage, but we must not forget everything else or we'll never get good outcomes. Meniscus, stability, alignment are key. We just wrote on the concomitant procedures when and why we might do them with Owen Hurley and his excellent team. These innovations, as Matt alluded to, in unloading are outstanding and I think game changing and a meniscus transplant are critically important. And so this is an exciting time for cartilage restoration. Many emerging technologies and evolving techniques, but we must practice evidence-based medicine. And this of course requires rigorous review of new tools, carefully weighing them against gold standard and time-tested options. I think the future and the evolving treatments here must target the osteochondral unit and look to combat not only those focal defects, but broaden to give us tools really to combat early osteoarthritis. And I thank you very much for your attention. Great talk, Seth. What do you think, you talk about the bone, the subchondral bone. What's the biggest breakthrough you see in the next few years about treating the subchondral bone to help our cartilage lesion? I think that one, recognizing the importance of subchondral bone, I think has been the biggest innovation to date and really these new tools that are developing. I would say that one, we have to use the biologics that we have, deliver them appropriately and then follow the clinical outcomes and ensure that they're giving us better bone health. So I think that hopefully, and many of us are thinking that it's going to be something like bone marrow aspirate or aspirate concentrate. And if it's not the case, then we have to continue to search onward. Complex problem. Thank you very much, Seth. Thanks, Mark. Great talk. Our next speaker is Dr. Yankee. He's going to talk to us about the future of augments and rotator cuff. He's a product of Rush program, med school residency fellowship, works extensively with Dr. Cole over there. He's an associate professor of orthopedic surgery and also a true innovator in his space and looking forward to your talk. Thank you. Thanks. Thanks for that introduction. And thank you to the program chairs for including me here. You know, it's amazing when you look at the rotator cuff repair space compared to the cartilage or the arthritis space, even if you look at clinicaltrials.gov, both in the US or abroad, the number of trials in rotator cuff for cell-based technologies, growth factor technologies is just totally eclipsed by the arthritis space. And I think that there's a lot to learn from that space that we can bring into the rotator cuff to improve biology because we know that's one of the main reasons we fail. So I am a consultant for two companies that have implants that will be discussed in this talk. So we've heard this in other rotator cuff talks, but I want to at least touch on it briefly. You know, the idea is to restore the enthesis and structural success usually leads to clinical success in the long term and durability and strength is usually there if you get structural success. And so we all know that in multiple orthopedic spaces, you can have patients that re-tear that are still doing okay, but how long will they be okay for? And if you're going to go in there and repair it, I think we would all rather get back to normal. And so we want to figure out why we fail. And there's many authors and studies that have tried to contribute to this. We know that age, tear size, fatty degeneration, things like this can increase our risk for failure. And we tried to summarize this, this actually came out before the Rohy score, which I'll touch on also. This is a very busy slide, but let me try to help it make sense. So these are studies that looked at rotator cuff repair failure by MRI evidence of re-tear and the studies that occur up at the top controlled for the most factors. And so the top had 12 factors and as you go down, they control for less factors. And what happens is you can see that certain factors that were significant when less were controlled for drop out once you start to include other factors that are more relevant. And I think it's a helpful way to try to understand the literature when you see some studies that have conflicting results. And so the three that pop up here that are basically significant in an 80% or more of all studies, regardless of number of factors that are controlled for is always tear size, contraction, fatty infiltration, muscle atrophy, age is a little bit of a mixed bag here. And I think that just has to do with what cutoff the studies used. And so that's not the same cutoff for each study. And this really is how we should look at how much concern do we have that we're going to fail and then should we augment and should we consider biologics or other structural augmentation. The Rohy score has been an amazing step in the right direction here to try to predict our need to do more than just to repair, or maybe we do something completely different like a balloon spacer or an arthroplasty. And these types of predicted analytics, this is the first phase, the next phase needs to be seeing if we actually make changes, can we actually change these numbers. It also gives you a nice structural framework to go back to the literature, which we'll do a little bit here and say, well, what was the actual risk of failure in single arm studies when you look at interventional studies that don't have a case control model. And it doesn't take many of these factors to significantly reduce your healing. So once we get over seven, there's certainly quite a bit of concerns. There's lots of talks and studies on augmentation. I'll try to cover some of them that I think are a little bit more interesting or new, but also have clinical relevance. There's things that are going to be stem cell or growth factor based viral vectors that are so far from clinical utility that I won't get into the weeds on those too much. But really the categories I'll cover, biologic application, graphs that are in an onlay, and then we're going to focus quite a bit on interpositional graphs, because these are something that I think are really developing quite a bit and don't have as big of a footprint yet, no pun intended, I guess. So with biologics, I know that Dr. Dragoo is going to give an amazing talk on this, so I won't belabor it, but I think everybody should know, if they don't already at this point, that PRP in the setting of rotator cuff repairs has no clear benefit in reducing retear rate. So no good evidence to utilize PRP to reduce retear rate in cuff repairs. We repeated a study that was done out of Europe looking at bone marrow aspirate concentrate for the benefit of rotator cuff retear reduction. And this was in patients that we had about 30 patients in each group, and we looked at retear rates one year post-op using Sugaya's score and found that there was at least a one-point difference between those patients that had BMAC utilized versus not. And that mirrored our European colleagues and has very similar findings. So there certainly is a role for biologics and just a matter of picking the right one and how to deliver it. The delivery is something that really can be used in conjunction with the interpositional graphs, which we'll talk about. Onlay obviously has a lot of coverage at this meeting and others, so I won't get into a lot of detail there, but that clearly plays a role as well and is probably the most standard way to augment cuff repairs at this point. Interpositional graphs, as I mentioned, have the ability to be a different delivery device for biologics. And this is also nice because it can be done in the operating room. You don't have to wait for something to go through a 351 or a complicated FDA pathway that may never make it to market. Similar to what Seth showed in the cartilage world, there's actually only two products that have ever made it through all of those rigors and made it to the market, and he covered those too. So I think it's important to know what we can really do realistically. These are the onlay graft options, including biceps autograft, but again, there's plenty of talks on that, so I'm going to skip past that. Interpositional grafts, I think, are growing. These are at least three different types of them that exist. There's several others that are working on coming to market. The one on the left is currently at market because that's a pure allograft. I'll talk about it in more detail, but it's a partially demineralized graft that goes at the area of the enthesis. The next one is a demineralized bone fiber that's actually created in different shapes, but it's still technically an allograft, it's just manufactured. And there's other ones like this nanofiber scaffold that are made out of PGA, PLCL, and there's different compounds that can be utilized that are absorbable, and they usually start to resorb around three months. If we take a look at why we should even think about this, it's because almost all the studies, or at least the review of the studies in conglomerates that look at bone marrow stimulation at the footprint show that it just doesn't help improve our healing rates. And if we're going to have failure at that interface, eventually it'll pull through the sutures and retract immediately. So if we can improve that biology, then we should be able to improve our overall success without adding, hopefully, unnecessary cost. And so some of the studies supporting this nanofiber scaffold started with Tony Romeo's work over at CSU, and this was a transacid equivalent type repair utilizing the scaffold. And what they showed in this model was that there was increased presence of Sharpie fibers in this setting, so there was some benefits of restoration of the normal anthesis configuration. There was no significant inflammatory response here, so it wasn't viewed negatively. Still not normal, and obviously there's no models of normal rotator cuff repair that really exists today at all. But certainly nothing concerning in a negative way, because some people think if you're going to put stuff in that space that you might actually create like a non-union generator between that. And luckily, we don't see that even in these that have a higher resorption profile. Their study also showed the ultimate load to failure was significantly better with the utilization of the scaffold at the interface. They were able to follow this up with a clinical study of single-arm 33 patients, and again, this is where we can kind of apply that Rohy data to see what a comparison group could have potentially looked like. The patients that were included had largely single tendon tears, small to medium tears, and so these were not necessarily large or massive tears, and the average age was under 70 years old. And so these didn't have necessarily a high risk coming in, but again, the MRI post-op showed no clear signs of the graft causing issues with resorption, cysts, fluid around the tendon, so there's no local reaction. Their re-tear rate was about 9%, and they all had good clinical follow-ups, so this is the type of information that we're going to need to continue to have to know, ideally with comparison groups and RCTs with more rigor, so we really know when to indicate these. The other one I want to discuss is this biphasic interpositional allograft. So this is currently available. Again, it's just a regular allograft. It just has some processing associated with it. You can see that image on the right is the density of the calcium that's left. So it's decalcified on the superior 2 3rds. Inferior 3rd still has mineralization from the cancellous bone layer. And the idea is for it still be a biologic delivery device, mere tendon, and what tenosites would migrate to on the superior surface and bone deep to that. And so we did a similar study to Dr. Romeo's study at CSU in a sheet model here. Again, very similar findings. So there was relative improvement of the enthesis restoration at our final time point at 12 weeks in this study. And we had no local soft tissue reactions either. So again, first thing, make sure we're not causing harm or damage. And then we were able to do a clinical study taking a look at this with a match control group and a match with quotes. Because we actually couldn't match age, which is a significant confounder here. The patients that had the graft were significantly older, which we know is a risk factor. So keep in mind the graft was put at a disadvantage in this setting. And looking at patient-reported outcomes, there were significant improvements in all groups. No difference between the two, however. Similarly, looking at strength, significant improvement in strength throughout. No difference between the two. But then we took a look at MRI at 12 months in Tsugaya scores. And the retail rates were significantly higher in the control group. And so there was a reduction from 45%, which is pretty high. Obviously, the Tsugaya score is a little bit tough if you've ever done that grading. There is, unfortunately, quite a bit of variability there. But there was a significant reduction of about 15% between these two groups in the first clinical study that's been done for this. And so that's something that needs to be done with more rigor to try to build this out to have more adequate power. I just want to show a very brief video of what some of these can look like. So this is with having medial anchors already placed. We pass the sutures medially. And we debrided the footprint to get a good bony bleeding bed to help incorporation of any interpositional graft that's utilized. In this setting, that's the biphasic graft that I mentioned. Again, it's very spongy. And we measure that out to be the size of the footprint that we're trying to restore. And once you have that and the medial sutures are passed, you basically can deliver it through a cannula. It seats with that mineralized portion inferior. And then you just pull the tendon over and either tie down or use knotless mechanisms, which I tend to use medially, which is much easier. Just zip tie it down. It holds it down. Then you put your lateral row in after that. But we also will soak that in bone marrow aspirate concentrate. And you can deliver biologics directly into that site. And I think it's a great way to try to hold them there. Similar to what Seth showed with osteochondral allograft, that cancellous bone really does have a good ability of soaking up biologics. That's something else to consider. So that's kind of where we are now. What really does already exist? There's other aspects that I think are going to be very helpful with growth factor delivery. Hydrogels, delayed release of biologics, both at the enthesis as well as in the subacromial space, the use of bursal tissue, minced and particulate at the time of surgery, work that Gus Mazzocca and others have done. And those are things that have been well-described and certainly have a lot of promise. Human recombinant parathyroid hormone has been shown to improve the healing at the interface, both in these rabbit studies as well as in some other studies that looked at their use in association with a nanofiber sheet. The other studies have also looked at the injection of this into the muscle to try to reduce fatty infiltration, which we know can be very difficult to reverse, if not impossible, with just a repair alone. And so I think that as we don't want to hook up a dead horse to a carriage, so the whole goal here is to have something healthy, connected, and functional long term. I think there's a lot of exciting things coming down the road. So that's the current model. Thank you for your time and attention. Great talk, Dr. Young. Just a quick question. To follow up on your nanofibers, time delivery nanofibers were growth factors. You're an expert in biochemistry. Can you think we see that in the near future, like a time release, like a TGF blocker to optimize the environment, or like you said, the parathyroid hormone? Is there a regulatory path for that that the FDA will let us use it? Yeah, it does exist. It's very difficult. And the thing is that by the time you try to pick a horse in the race, the evidence to support what you were trying to do may have changed. And it is a very complex space. And even other studies that have tried to recreate the arthritic synovial fluid environment, for instance, if you take the top five cytokines that show up in an inflammatory arthritis situation and you apply it in a lab model, the genes that that activates compared to if you actually just take the actual fluid and the exact concentration are completely different pathways. And so even if you take the top five cytokines, it's hard to reproduce what's happening biologically. So I think that just means that we have to try to look at things on a global scale. And there may not always be a magic bullet. Thank you very much. Thank you. Our next speaker, last speaker, is Dr. Jason Dragoo. Thank you very much. Dr. Dragoo is a professor and vice chair of academic affairs for the SU department of orthopedics. He's a pioneer in the field of orthobiologics. He's the annual chair of Region of Medicine and has developed many procedures in that space. He strongly favors orthologous procedures. And we're looking forward to your talk and guide us in the future of orthobiologics. Well, thank you, Mark. And this is an interesting viewpoint, right? Because the title is What Works. And traditionally, and especially a part of an innovations conference here, we have really cool things in biologics. I mean, really earth shattering things that are happening in this area. But I'm going to talk about none of those today. Instead, it's kind of a little bit of a biologic reset, right, in 2024. Where are we at with regards to evidence? If you guys are going to start with use of biologics, where should you begin? And where is the data? And it's interesting because if we go over this list of applications orthopedically, it's a smaller list. And maybe the question in 2024 is why. Why is there a short list? And it's because of really these two factors that show variability. There's variability in the biologic itself, in the preparation. This is an incredibly complicated chemistry game and biology game. So if you prepare things differently, you're going to have different results. And same thing as we all know, all patients aren't created equal. So if we're putting this in a patient's body, they're going to have different factors on their own. So when you then create literature, you're going to see variability. And at the end, I want to show you maybe a road map of how we're going to get around this and figure out biologics going forward. So here's the short list. You see that there's a couple of things in green and a couple of things in yellow. And we'll go over these here together. And again, this is where the data is. And so if you look at the use of biologics, and especially in osteoarthritis, there's a couple of categories that we need to establish. And that is as physicians, what are you trying to do? Are you trying to make the patients feel better and decrease their inflammation? Are you trying to restore their joint? And so then those are two different objectives. So let's go over some possible use of biologics for that. Now, the tried and true is platelet-rich plasma. And the question is, does it work? What is their data in osteoarthritis of the knee? And so this is a systematic review of all level one studies and it is in comparison to hyaluronic acid. And the answer is, across the board, per the plots, the answer is yes. It's more powerful biologic than hyaluronic acid. The little bit of confusion is, okay, well, what kind of PRP should we use? And most of the data is showing that it's the leukocyte-poor formulation. But again, I'm gonna go through some issues with that nomenclature and show you maybe where we're gonna go in the future with regards to PRP. But PRP then is more powerful than hyaluronic acid. But some emerging data is suggesting that if you put those two together and combine HA and PRP, that you're gonna have more of a synergistic effect. So here's a real good trial that's comparing the use of PRP plus the combination of hyaluronic acid and leukocyte-poor PRP. This is a really good trial because not only are they following outcomes, but also the synovial fluid and how this is biologically changing the joint. And what we see is some fascinating data that the combo of these two was more powerful than the PRP itself. So we're creating a little bit of efficiency charts with regards to our biologics. And that's interesting, but also interesting that for the first time, these biologics are showing an effect up to two years. So overall, we're getting somewhere with the treatment at least of the symptoms and inflammation of osteoarthritis. And again, repeating that there's no evidence that PRP can help regenerate articular surface in osteoarthritis. Well, then there's the next layer, and this is the so-called cell therapy kind of, because in the United States, we cannot machine tissue down to the cell level. But what we can do is break it up into bioactive fragments. And that's what these two technologies are showing. Now, let's go over some data here because this is an FDA approved system to the right. We have access to this, and there's actually multiple manufacturers of these devices. And so then what's the proof that something like this, this bioactive fat would work in osteoarthritis? And here's how the science is done. And so if you look at the big part of the graph, you see that that is lipopolysaccharide. This is an inflammatory mediator that's placed on cells and WAMO, just like in bacteria, that this leads to a very vigorous inflammatory reaction. But if you do the same thing and you put that LPS and you put this bioactive fat on there, look what happens. There's no inflammation. So it quenches the inflammatory response, and this is the proof that the bioactive fat is there acting as an anti-inflammatory agent. What about the clinical data? You know, do these things really work? And here's a meta-analysis of many studies, over 1,000 or 1,300 patients. And if you look at all these studies together, you see that they're all on the left side of the chart, all showing a decrease in pain. So kind of uniform data across the board when you look at the efficiency of this. And there's even a new study that is comparing, again, the results of this bioactive fat comparison to combo of HA and PRP in comparison to PRP itself, and showing even better effects as far as its pain-relieving capacity. So again, slowly we're learning more about efficiencies of biologics that we can choose for our patients going forward. All right, well, what about the Holy Grail? You know, is there any data to suggest that biologics actually, in the face of osteoarthritis, can grow back some cartilage? And you'd be surprised in the worldwide literature that the answer is yes. And we're gonna cut this down, right, just to randomized controlled trials, so just the highest level of evidence. And when we look at the world's literature, 10 out of 15 randomized controlled trials using cell therapy show a significant increase in cartilage thickness. So it's out there. No, we don't have this in the United States yet, but it is around the corner. So therefore, it is worthwhile for us to begin conversations here in the United States about this sort of technology. Now, I wanna also say that we don't wanna be confused by this sort of paper, because this is not talking about bone marrow aspirate, and it is not talking about amniotic products, et cetera. This is culture-expanded cells. And when you look at this further, the data shows pretty clearly that where do we need to get these cells from? Pretty clearly, the answer is adipose tissue. That's a science reason of why those cells are working better here in the regenerative environment. But we're also now narrowing down worldwide on a dose. And that's really important for us in the United States, because there are some companies that will have autologous ability for us to autologously harvest cells, send it to their laboratory, and then grow them. And then we'll have to say, well, okay, well, what dose do we want as physicians? And this will set the base of our clinical trials, which are coming up later on this year and next year. Well, what about that worldwide literature? Is there really level one evidence to suggest this is true? And this is a short list of the level one trials showing that a couple things, number one, decreasing pain, number two, increasing function, and three, increased thickness of cartilage with T2 mapping and T2 star. So this is physiologic MRI imaging to show the thickness changes. So real data, and again, coming soon to the United States. This is something Seth and I talked about, because we didn't know whose talk should this be in. This is this aragonite implant, and there's only one, right? So there's only one manufacturer of this. Is it a biologic, or is this an implant, or maybe it's a little bit of both? But it's interesting to talk about, because it leverages cells within our own body, right? And without that, it won't work, right? There's nothing intrinsic about the implant. It has to leverage the cells in the subchondral space. And so then this is interesting to talk about, because, and again, I won't spend time, because Seth did a great job with this, but it showed the data, show me the data. Well, the data's there. But the question is this, and I challenge everyone to this, and maybe we can talk about it, and that is, this is FDA-approved for chondral defect treatment, true, but it's also authorized for regional arthritis. And the question is, you see there's two implants and a little bridge of osteoarthritis between there. Is this powerful enough biology to be able to really treat the osteoarthritis as well? And I think the jury's still out on that one. But no doubt that this really does lead to cartilage fill over time. Well, what about the rotator cuff? And again, Adam did a great job with this. But if you keep up to date with the literature on this, which is a lot, and you look at the reviews of this and the power of the evidence, there is evidence to suggest that PRP and bone marrow cells can improve the structural healing of a rotator cuff surgery. It's an augment. But it's also true, as Adam said, that there's no evidence that this improves the clinical scenario of the rotator cuff tear. The outcomes measures are not different. So what does that mean to us as physicians? Maybe it means that we selectively use biology. And if we have a patient where we're really worried about their healing capacity, maybe it's then we invoke these adjuncts to rotator cuff because we're talking structure, we're not talking clinical outcomes. The literature is muddy with regards to formulation. So I can't tell you what's the better type of PRP to use. It's really untenable when you read the literature. It's too variable, and we'll talk about that. And then if you need to choose a cell source, you would choose the bone marrow cells. More data with the use of the bone marrow cells. What about teninopathy? Teninopathy is pure variability. And there's many reasons why. So this is tough when you read the literature. Overall, bottom line is, if you want to use biologics for teninopathy, a couple of things. Number one, use the leukocyte-rich formulation. It has the most data. All teninopathy is not created equal, and that's especially important for biologics. So the best data is in the treatment of patellar teninopathy, gluteal teninopathy, and of course, tennis elbow. The poor data is in the rotator cuff. Rotator cuff teninopathy, not a lot of data to suggest that it works. Or Achilles teninopathy. But there is some very emerging important data with cell therapy that I want to share with you, because it's likely to be the answer in the future. And I just want to show you this variability of the literature. So here is two randomized trials that I was involved in. One showed a positive response, and guess what? The other one didn't. And this is just classic for how are we preparing the PRP and the variable conditions of patellar teninopathy. So this is what you read in the literature. But here's the best evidence of teninopathy. This is a great study from Spain. That, again, is using doses of cells. And they were really the only ones that have been shown that you can change the structure, you can reorganize the tendons with teninopathy with the doses of cells, 20 million cells in this particular case. And all things are pointing to this is going to be the future of tendinopathy treatment. What about PRP for meniscal tears, sorry, meniscal repairs? Variable, again, it's interesting to read the literature, isn't it, that you have the last two here, you have a systematic review that says yes, and a systematic review that says no. What are we supposed to do with literature like this? And it shows, again, the variability of the literature and the interpretation of the data that we have. So we need some help going forward with this. And I think I wanna propose some things to everyone here today. We've gone over the problem of this variability and two sides of it. Number one, the preparation of the biologics, and number two, the intrinsic patient factors. What can we do about it? And I propose to all of us that there's really three things that we need to do to go forward with this. Now, I know this is small, but I hope if you take a picture of this, you can see it on the camera. But this is our work together, okay? Any of you in the audience that are investigators and are running clinical trials, these are the minimum criteria that we all need to use in our studies. That's number one. But just as importantly, let's hold our investigators to this by all the reviewers in the audience. We need to hold accountable science and not to put variable things in the literature. And we need to, as reviewers, kind of really require that these minimum criteria are held. So that is the plea here today. And that will really help us go forward with our literature. Second, our current way of subdividing biologics is not okay. It's not granular enough. And so in the future, what we're gonna have to do is we're gonna have to know exactly what we're putting in our patients, right? And this is the dose products of biologics. And there's a lot of work being done to change this, right? And we always have this example that we have a muscle ache, we want 200 milligrams of ibuprofen. We know, as physicians, we're getting 200 milligrams. But when we're using some of the biologics, we don't know the dose. And in the future, that's not going to be true. And here is just the beginning of the literature that's gonna be coming across that we're using absolute counts, we're using doses to treat our osteoarthritis and other things. And I think that's really going to get us far. And again, tendinopathy, again, same thing, and no one dose of cells. So stay tuned for that. But I think the biggest thing that's gonna change the paradigm in biologics is national repository networks. And many in this room are a part of this biorepository network where we are collecting the biologics, that portion of the biologics, and we're collecting data. And we are then collecting how patients do and we're putting in the responders and the non-responders so we can learn why do some people respond to biologics and some people not? I just want to take a couple of seconds to show you that this PRP that we thought we had down, it was a leukocyte-rich, and we were already beginning to be wrong in the fact that we want lymphocytes because lymphocytes in this preliminary data are showing a much better responder rate. We show that also increasing platelets also better responder rate. So in conclusions, we have a short list of the true data of the treatment of biologics that show efficacy, but in the future, we're gonna have a much longer list. And this is going to be a project with all of us together to change the literature and the science of biologics in the future. So thank you very much. Thank you. Thank you. Great, I know we're a little over. I don't know if we have time for questions from the audience. A few questions, we're kind of over a little bit, but if anybody has burning questions, we have a great panel here. Okay, well, thank you. Thank you, gentlemen. Great panel, great education. Congratulations. Thank you for your great work.

Marc Philippon, MD

Adam Yanke, MD, PhD

Matthew T. Provencher, MD, MBA

Prem N. Ramkumar, MD MBA

Seth L. Sherman, MD

Jason Dragoo, MD

sports medicine

surgery innovations

preoperative planning

robotic assistance

3D modeling

artificial intelligence

biologics

patient-specific instrumentation

augmented reality

evidence-based medicine