So, I want to thank Kevin for asking me to give this talk because it was kind of fun to go back and look to the past and we have a lot of young people. One of the things that is great about ANNA is it provides opportunity for residents and fellows so I thought I'd give a very, I'm not a huge history buff, but I think it's important to have some context in terms of where we've been so you can understand where we are and where we're going to be going. So this is the problem, it's a pretty simple statement. When cartilage is damaged or it degenerates it just doesn't heal so that's why we get to have all these symposiums because we're dealing with a biologically compromised environment. So just a brief overview, a couple of slides on the past. When I was a resident at special surgery, this was all we really had and this, you know, we were pretty good at arthroscopy, it was very efficient, but the only thing we could really do for our patients was to go in and debride a lesion and then hope it would minimize some of the mechanical symptoms and some of the inflammation associated with it, but inevitably in those who were not meant to get better with debridement they would come back with recurrent symptoms or not get better at all. This got a little play back then, in 1986 Lonnie Johnson, how many of you have not heard of Lonnie Johnson in this room? That's encouraging, okay, so maybe it's a little bit older, you guys actually read the literature, you're too shy to say. So Lonnie is one of the greatest innovators ever and this is essentially marrow stimulation but just abrading the surface, but it was a hard thing to control because it was using a shaver to denude the surface and it led to a lot of activity in the subcondyle bone. So Dick Steadman, this is one of his original videos and I went to visit him and microfracture was a real experience, I mean I think he did maybe three a day. It took a long time, it was very meticulous and the basic premise was violate, this was 1200 patients actually that are reported on the surgical technique first with Bill Rottke, Karen Briggs and Singleton and essentially it was, the way it was suggested from performing the procedure was to debride it, get through the calcified layer, try to get vertical walls and then create several holes so that our own mesenchymal stem cells can come into the region and we get fibrocartilage to fill over time. He always said when you didn't get a good result, it was either because you didn't do the procedure well or you didn't respect the rehabilitation required which was typically a protected weight bearing, it was a typical formal lesion. But we've since learned there are some other potential challenges with it, we question longevity and so forth, but clearly the concept of stimulating the marrow which started with Lanny Johnson and then led to Dick Stedman offered a very cost effective technique that could be done at time zero leading to fibrocartilage fill. So you'd see bleeding and then if you had the opportunity to get back for a second look which unfortunately wasn't that uncommon three to four years later, you would get fibrocartilage fill like you see here. Then there was Vladimir Bobik, Hangedi, who suggested using an osteocondyle autograft and actually one of the first procedures that was described was coming from the medial aspect of the patella and using that as an autograft tissue and then also the posterior aspect of the femoral condyle where you might see a HOFA fracture that was another source of graft, but these were using plugs to treat localized cartilage defects. Alan Gross gets a lot of credit, but there's many others, Lexer, Convery, Myers, Garrett who really need to be credited for our early understanding of using osteocondyle tissue that was fresh, tissue that was made available within the first 24 to 48 hours. And then this was really the first FDA approved opportunity using cell-based therapy and in 1994 and then subsequently in 1997 with FDA approval, we had cell-based technology on the scenes and I think since then we've only had one additional technology achieve FDA approval, which was agility C, CardiHeal, that's it, and someone can correct me if I'm wrong on that. So I was a fellow in 1997 with Freddy and we all miss Freddy very, very dearly and was one of the greatest mentors I've ever had and these are my fellows and this is when we had autografts, we had ACI and we had microfracture and debridement, but it was getting increasingly confusing as these things were coming on the scene because we didn't know where to do it and when to use it and this is the first algorithm and Roland DeAngelis is here, we go back to when Genzyme was Genzyme, then it was, I'll forget, it was Sanofi, then Varicell, I probably missed some company in between there, right Roland? So but you're still there, right, and hopefully you still have a pension. So at any rate, this was our first algorithm and what Andreas was alluding to, we said let's just talk about defect size and this is how basic it was, we're just trying to figure out when we're going to do these things and how do we make decisions and then we added on to it, well some of these things may be palliative, then they might be reparative and then it might actually be restorative if you use an osteocondylograft and then we got a little more sophisticated and Jack Farr and I were having a beer one night and we were talking about, we got to start thinking about this differently and we started talking about demand levels, low and high demand because you can do something super simple if you have a low demand patient, but then you can do something a little more complex if you have a high physically demand patient because let's face it, most of what we do is low related and it may have nothing to do with the biology breakdown, but just how much load we put on the joint and your patients are sitting at an exam table, they have no pain, they jump off, they have more pain, they go up and down stairs, they have more pain, they put on 50 pounds or they play football, they have more pain, right? So and then we say okay, we got to stop thinking about only the cartilage, but there's other things that are really important and it's not just this little box, but we have to think about comorbidities, most commonly malalignment and meniscal deficiency and if we don't address that, our patients don't do well. So that's where we were and this is where we are and this clearly doesn't include everyone in the present, I just love this night with all my cartilage friends, we were out for a great dinner and I can just tell you where a lot of the thoughts are from the speakers you're hearing today who are really the present in terms of how we do things and also part of our future. So this is where we are today, that was jazz, right, it was jazz, we were at the OLC and he did every single cartilage procedure known to man, known to people at that time and that's that middle picture on the bottom there and these are pretty accurate frequencies as far as I know in terms of what's being done today, starting with debridement, still lots and lots of debridements and then all the way down to osteoconagrafts which we're doing about 4,000 a year. So I use this a lot in these talks and I think it's important because there's such a poor correlation between how patients feel, their cartilage status and we know so little about the natural history of these problems that we really are not offered the privilege of thinking linearly about how we manage problems related to articular cartilage because there really isn't a cookbook approach. Now we try to have these algorithmic approaches like you see here and it's gotten really, really complicated. If you want to put it all in, you can break it down to tibial femoral and then patellofemoral and then start adding in everything from demand level to rotational things upstream and downstream and so forth, whether it's a primary revision surgery. So it's endless and it's really almost impossible to capture and recapitulate an algorithm based on something that's schematic, but at least it gives us a framework to think about it. And then I think the other important tenet and this gives room to this concept that skillful neglect is actually a form of treatment. So I've said this a thousand times and I wish I had originated this quote, but Voltaire did it best, that the art of medicine consists of abusing the patient while nature cures the disease. That's pretty much true for a lot of the things that we do in orthopedics and Lisa Rosenbaum is quoted in this article in the New England Journal of Medicine, the art of doing nothing. So doing nothing sometimes is okay depending on the particular problem. Patients will often ask us, now that I know that I have a cartilage problem, if I stay active am I definitely going to make it worse? And there's sufficient literature that says short of obesity, repeat surgeries and high level trauma, sports is not known to increase the progression of osteoarthritis or cartilage damage. So that's important because patients have lots of concerns. And I think we're getting more thoughtful today about who will respond to things like orthobiologics and who will respond to load reduction. And despite how good we think we are in restoring the cartilage surface, again, go back to that basic tenet that load is really the primary issue that we're dealing with and that patients will get an inflamed, achy knee with load or they may have a dry knee but it hurts with load. So the patient on the left might respond favorably, for example, to orthobiologics and the one on the right may need an osteotomy, a replacement, an osteogonograph, a dead piece of cartilage and bone. A lot of things can make that patient better and it may not have to be living cartilage. I know that's a shocker, but it's been shown to be true. And then we have the issue of chronology which is also important because you can take the same defect and put it in an older patient but they may not be as responsive. And that's, I think, because older people who live with the disease longer, and this has been borne out in outcomes, don't do as well because they behave more like arthritic patients than our younger patients who live with the same disease but for a shorter duration of time. So I'm going to emphasize this point again and again that load really matters because that's what brings patients into our office. If they give up on activities and that's acceptable to them, they generally don't come to us. So the bone is, I think, our focus and this is going to be our focus continuing into the future and it probably is what matters most because the lowest hanging fruit that we have is an osteotomy to correct alignment and you can treat a lot of things without actually addressing the biology with reducing load. So where are we in the present? In the present, we know that debridement can be a viable option, especially individuals who don't have long timelines to get better, even if it's temporizing. We know that subcondal drilling as a replacement for a microfracture awl can actually yield reductions in revision rates given the otherwise the challenge that happened to the subcondal bone. And you heard about OATS. OATS is a dominant treatment strategy for small lesions compared to marrow stimulation. So that's where we are in the present with that technology. We now have adjuncts to drilling such as mince cartilage, collagen scaffolds, and now this technique that's being just a new answer to an old theme using mince cartilage. You can do this arthroscopically, take healthy cartilage from the interconvular notch and put it into a defect, put fiber and glue over it. We know that MACE now is a next generation technique that using these custom cutting guides much easier. We know that osteokinographs actually may do better if you add bone marrow aspirate, a concentrate from our CT data. And then we get to the future. So where are we going? So this is a slide from Andreas Gamal. I think one thing that will get better for us is less invasive techniques. I don't think these have to be done arthroscopically, but certainly less surgical invasion, less soft tissue morbidity may be better for our patients in the future, a lot like that transition from open to arthroscopic cuff repair. This is some work that we're doing in our institution where we're looking at three-dimensional improvements in donor matching, looking at graft integration. Our CT study showed that graft integration is better when the graft is soaked in bone marrow concentrate. And getting to a higher level of sophistication, can we actually modify disease by looking at synovial fluid aspirates, IL-1-alpha and other things actually will track with patient reported outcomes. So that's the other thing that I think is part of our future. What's new on the horizon? These are the only two new things that I think are either just getting there or are close. CardiHeal was recently approved, the Agile C, and that will be handled at least currently with distribution by a public company that's Bioventus. And Asculop is near the end of their clinical trial, which is a cell-based technology using bovine pericardium or a type one collagen as a membrane. So we do have a couple of things that are on the horizon. And I'll just finish up with some other thoughts on what I would call predictive modeling. I think we're really excited to publish our good and excellent results, but I think one of the things that would be really helpful is how do we do a better job in the office to predict who's going to do well and who will not do well. So I owe a lot of this to my partner, colleague, and friend, Adam Yanke, and now Jorge Chala, where we're identifying some of the things that we've often thought about, such as BMI, duration of symptoms, total surface area, and alignment as being some of the key factors that lead to a good or excellent result if they're not corrected. And then this other one, which I think is really exciting, is how can we predict who will not respond to a simple arthroscopy and debridement, and who should otherwise avoid a staging arthroscopy and go on to definitive treatment. And this is the SIRT score, which is currently under review, which we can take a number of these variables, such as deflect location, their pre-op pain, their physical VR-12, and an Amadeus score, and say, how do you add it all up, and say, who's not going to do well with the simple scope, and let's go right on to definitive treatment. So I think some exciting things. This is some work from Eric Strauss, who's one of our former fellows. He's doing some exciting work, and maybe not that much different than some of the work that Christian Lauderman is doing, where they're using biomarkers to evaluate pre- and postoperatively from synovial fluid aspirates, and they basically are finding that some of these markers are correlated with severe cartilage injury, and these levels can be elevated with higher VAS pain scores postoperatively, and this may actually be a target for future therapeutics. So this is where I think, in part, where we're going in the future. And I just want to challenge you, do we really need new cartilage once it goes missing? So I know we all believe this is an important part of it. I think the real key issue is getting to these patients very early. Maybe there's an opportunity to provide some structure, sort of rebar behind a lesion, as we treat edema, which is a secondary phenomenon due to cartilage loss. We have active implant, which is not yet approved, but it's the same concept over and over again. We have the tigernia on the right, help me, what's the new name, what are we, MoxieMed? So all these things start to look a little bit odd, but they share the same premise. It's load reduction, okay? So we have to start asking ourselves the hard questions. When is cartilage important, and when is the bone important, and how do we translate that into our solution? So there's a large incidence of cartilage abnormalities that may never cause symptoms, so that gives rise to this concept of skillful neglect, especially when we don't have a firm understanding of the natural history of cartilage disease. I think we will do better once we fully understand the relationship between the pain, the bone, and load. And I still ascribe to, and not everyone does, but I still ascribe to the fact that maybe we can still contemplate doing the least amount necessary to achieve a successful outcome. So thank you very much.

cartilage damage

treatment options

cell-based therapies

osteochondral autografts

load reduction