All right, good morning, everyone, bright and early. The good news about this is this is a really small group, so I think speaking on behalf of all of us, if there's any questions or whatever, we might as well just kind of have more of a discussion rather than a presentation, so feel free to flag us at any time. This is, of course, a rapidly evolving area, and for the first time, we've had to kind of change our mantra about this because there is so much stuff, and it's kind of hard to make sense, and especially in the area of osteoarthritis, into two big categories. One is what are we trying to do, one, to reduce the symptoms of osteoarthritis, and we have things that can do that, and the other one is the new area of things if we're trying to really rebuild, and there's some evidence and there's some techniques that are going to be coming right around the corner or present that can do that and emerging evidence on that, and that's what we wanted to share with you today. This is old slides, so I'm going to not spend a lot of time on older stuff and concentrate on the new, so I just wanted to put it up, kind of flash it up of the modern-day use of platelet-rich plasma. When we're talking about osteoarthritis, we talk about the yellow kind of PRP. This is the plasma-based. This has less of the platelets. It certainly has less of the white blood cells, and this is where most of the evidence is, although there is a little bit of conflict, and we could talk about that conflict any time with regards to the type of PRP used for osteoarthritis. Old slide, old slide showing basically a level one review, meta-analysis of only level one studies, and again, old news is that it works better than HA, its comparator, so that is again nothing new, and when you look at the specific subtypes of PRP, again showing on the graph on the right that the platelet-poor, sorry, the leukocyte-poor PRP has more evidence than the leukocyte-rich. Newer studies on some exciting synergies, so this is a level two study that shows that in summary it was, well, let me just back up and say that this was a study with three groups in it. One was hyaluronic acid. The other was leukocyte-poor PRP, and the third group is the combination, and this was a really well-done study. It looked at a lot of different things other than just outcomes, certainly synovial fluid markers, et cetera, and the summary then is the group together with platelet-rich plasma and hyaluronic acid performed better than leukocyte-poor PRP, and this is up to even a two-year follow-up, so kind of really substantial results of this and has led to more and more of this combination therapy now because there's data behind it, and certainly I think if you ask us on the panel, we have seen a significant improvement in symptom abatement when these two are used together, so something to consider. Something also to consider is a lot of the noise of the publications in this area of PRP. I wanted to address it right off, and that is PRP is not created equal, and also when we're talking about the literature, we cannot come to conclusions such as PRP works yes or no. Here's an attempt to do so in JAMA, so this is a well-done study in JAMA, and their conclusion was PRP is not supported for the use and management of osteoarthritis, and that, of course, that sort of claim is inappropriate and downright untrue, and we just talked about the level one review of all of those other studies that shows a significant improvement in symptoms. Well, how did this happen? This happened because this was one type of PRP. This was one manufacturer of a system, and it did not meet criteria for PRP in the first place, and not only did they not even measure that at the study of what was given to patients, but if you look back in the technical documents of this particular system, it just didn't have that capacity to generate modern-day definition of PRP and enrichment of platelets, so this was more like a platelet-poor plasma, and yes, this did not work for this particular trial, so that is true, but it doesn't mean PRP doesn't work, right? Those are two totally different things, and so we really need to be careful when we're going forward. We need to be careful of what PRP can and cannot do, and I think that there's high level of evidence that it can decrease pain in osteoarthritis. It can decrease inflammation, and this is the leukocyte-poor version of that. There's no evidence of restorative capacity, so again, it's on this side of the fence of symptom abatement and not the attempt to regenerate cartilage in any sort of respect. This is certainly something that we have to be diligent about because now there is greater than 30 different types of PRP on the market. This is manufacturing kits, right? This is kits that we can use in our clinic, and we've really got to be careful and ask our companies, what is the data that you have for your kit, not PRP, for your kit, and that's where we're running into the JAMA issue and these other ones, right? We're just picking different kits and saying yes or no, and we're giving large conclusions about those, and that's, again, the thing that's getting into trouble. More and more evidence that this leukocyte-poor and getting into the range of six to eight times concentration of platelets, and again, considering the use of hyaluronic acid as a combined injection is very reasonable because there is now data. Where is this whole field going? We want to look to the future because the future is now in biologics, and we can see that there are more and more companies that are exploring fractions other than the PRP or the platelet-rich fraction of blood, and so you're going to see more and more products coming across. There's many in development and beginning to go through the FDA system. That is because our blood is powerful, right? We know that there's so many things that we can get from our blood. Maybe we do want to get some enzymes as part of a therapy that we want. We certainly have inhibitors within the blood, and I want to give you an example of one of these, and this is a platelet-poor plasma that is enriching a molecule in our blood called A2M, and A2M is a very potent inhibitor. It's a protease inhibitor, and it's a really big anti-inflammatory molecule, emerging evidence, right? There's not really any level one data on this whatsoever. It's more of an example, really, of what's out there and what could be mined from our blood because in the basic science studies, you can see that as the level of this A2M increases, the level of inflammation decreases. So that's really the only part of this whole presentation up here because there's so much to talk about. Any questions on that just as we go through it? It was deliberately quick just because there's not a whole lot of new things, and I did go over the new things on it. So much to talk about as far as the tissue preparations and the cell preparations. This is now going into adipose tissue and the preparations that are really on the side of the fence of proven decreasing pain and decreasing inflammation, and I want to share that data with you guys today. There are really two FDA-approved ways with which you can process fat. I want to talk about the one to the right. This is one maybe we're more familiar with, the lipogems or lipogems, depending on where you're at, and this is a ball-bearing system that breaks down fats into little globules as well as screens, and the question is, really, what does this system do? And now there is new data to show what it does. And what this does is it takes fat as its whole, takes away the mature adipocytes, which can be inflammatory, so that should be not part of the fat preparation. So that's screened out and washed out of these preparations, and then what this system does is break down the cluster into more bioactive, as they would say, gems or little pieces of adipose. This does not create a cell mixture, right? So this has to do with, again, the cells that we want, the active cells, along with some matrix and it breaks it down into a globule, which they call the gem. This system also takes care of and takes away red blood cells, because in what we're trying to do in biologics, we don't want the red cells around, right? Those could be inflammatory within the joint. Really good basic science data, and this is really cool to show. So I remember back in medical school with lipopolysaccharide, right? And that's a very inflammatory, used by bacteria, some types of bacteria to create inflammation. And so then we see the lipopolysaccharide in culture with the cell line, and you see the inflammation skyrockets. If you do put in that same lipopolysaccharide, and then you put in the micronized fat, you see that it blocks that inflammation. Even with that potent stimulation of inflammation, you can't get it. And so this is a really powerful basic science study showing the mechanism of which the micronized fat can be used to decrease inflammation. What about pain inhibition? It's kind of across the board with cell and tissue therapy, and it's one of the reasons that it's becoming more and more popular, and more and more products are coming through the pipeline. Why? Well, here is a study just again with a micronized fat, and you could see these are across the board effect of the pain inhibition with the use of the micronized fat. So quite a lot of evidence, this is over 1,200 patients now cumulatively, and you see there's really no dissenting studies, it's kind of all of the same, showing a significant improvement in the pain. I think this is a really instructive study here. This is really testing how powerful, so to speak, micronized fat preparations are. And so this is a study with leukocyte-poor PRP plus HA. So we already talked about that that was again showing better results than PRP by itself. So here's a study of repeated doses of that synergistic combination of PRP and HA in comparison then to a single dose of microfragmented fat. And the question then is, which worked better? And the answer is, although you see a lot of improvement in both groups, right? So this is not to decrease the really significant findings across the board of the combination of PRP and HA, but it is saying that there was even better results with the micronized fat. So I think overall, it's kind of in that same category of effect, but certainly there's going to be some patients that respond to one, don't respond to other, and we have then now good data to show and to guide us that this is a very reasonable thing to use and kind of puts it in a hierarchy for us as far as the decision making of when we could use it for our patients in the clinic. Bone marrow aspiration, I just wanted to kind of show where we're at as far as this. So look for the top of the pyramid and you see Don Buford here showing the posterior superior iliac spine and really being able to localize that in our patients with a very reproducible ultrasound technique. And the benefit of this is that if you use that posterior superior iliac spine and you localize it under ultrasound, then you could just put this jam-sheeting needle of your choice of the kit and put it straight down. So it makes the technique of this very easy and reproducible and safe. Even with larger patients or whatever patients, it's very then safe to do it. So highly recommended technique. Certainly nothing's changed as far as the understanding of that the posterior and anterior iliac crests are the goldmine as far as bone marrow and increased cellularity. That's part of Hernigo's original studies and so that still maintains to be true. Where are bone marrow aspirate concentrates used? Well, we're going to talk about it's then abatement of symptoms, right, because this is an OA talk. So we're going to talk about that. It is also used across the globe for treatment of chondral defects as well. And we'll talk about that in the next section. But overall, here is some more recent studies that are showing again insufficiency fractures and you can see that with MRI to the right. This is after conservative treatment and decreasing weight bearing and still the fracture lines persist and so then really developing the theory of two different ways of approaching interosseous treatment. So the way to the right is in areas with which you as a clinician feel that there is a problem with pressure within the marrow space and you wish to decompress it or if you wish to apply calcium phosphate, you know, subchondroplasty, if you're wishing to do those things, the short route or the decompression route has a lot of benefit. The benefit is decompression of the marrow space with regards to the pressure. Totally different in theory is the biologic route and the biologic route takes the long trip across and then by definition goes through normal marrow. So then you're dragging that biology, you're creating bleeding along with it. You see it's a totally different biologic or totally different approach to interosseous therapy and so therefore you can be thinking about what are you as a clinician trying to do. Are you trying to stir up the natural part of biology here by dragging those and then this is maybe a better way of delivering again BMAC and bone marrow aspartate, et cetera, into that area because you're stimulating more of the bone. One of the techniques is again just taking again the long route as you can see here through normal bone and gravity is certainly going to have a component here, putting a reamer over the top, generally speaking it's around four millimeters of size as far as a reamer, taking the drill bit out and then you can inject your bone marrow or whatever you would like from a biologic perspective through that and what we see is that this has been a very powerful study when the beginnings of this, our numbers are low as we're getting organized as multi-centers of putting this together but we do see a significant effect and I think those in the audience, you guys can see this lunar pre-collapse, right, avascular lesion of the condyle. These are the no-no's, right, it's a certainly no-no as far as subchondroplasty is concerned but this is one that is on the border of being saved and you can see that with this sort of combination treatment in erosius that even on the edge lesions that we'll be able to make some significant improvement and preliminary data on the ability to remove bone marrow edema and to normalize the marrow space is pretty powerful when you look at it and so then again, numbers are low but at the same time, this is a big deal and there's many patients at risk that we just showed and so then this could be a valuable part of your armamentarium in treating the whole breadth of osteoarthritis. What we see as a whole with interosseous therapy is like most things in biologics, it's rapidly but it's emerging and so we don't have a lot of data, so we have around six studies, there's a couple more in the pipeline but what we see is around a 20% failure rate. So interosseous therapy has a lot of good, the numbers are somewhere in the 80% success rate on it but it's not 100 and so then that is the future research on how do we get that number, how do we avoid the failures, who are the patients that are responding, who are the ones that are too far gone, let's say are not responding, that is the 20% that we have to be better at but so far, pretty reasonable results in a hard to treat population. Won't spend time on this old slide but this is the new understanding of the etiologies of osteoarthritis and so what we have done is develop lots of therapies from the orthobiologic but there's a lot of other things being evolving now including medication pathways to block the emergence of osteoarthritis. This includes cell senescence pathways and so then you see the senolytic drugs that are now on the pathway for approval as well as again gene inhibition, IL-6 pathway, those are in development and going through the FDA system now. So stay tuned because then we're going to be, I hope, having kits available for us to be able to test our osteoarthritis patients to understand why they developed arthritis and then we can biologically target them in a much more specific way. Alright, well here's the real new stuff, okay, and so this is where we'll spend most of the time. I'm trying to talk fast because there's a lot of things we want to discuss as a whole group this morning so I'm going through this and I wanted just to touch base on some of the newer philosophical parts to cartilage regeneration and attempts to put cartilage back. This has to do with this whole stem cell line and the understanding of why we don't talk about stem cells anymore because we're not using stem cells, right, and so we talk about progenitor cells and we'll talk about that a lot this morning but this is, again, recognizing that we have Macy and adult chondrocytes and we're going to take one step more immature than that with the juvenile chondrocytes and I think it comes to everyone's mind. Why are we talking about it? Is it a biologic and is it different than adult chondrocytes and we as a group has spent a lot of time looking at the basic science of the juvenile chondrocyte versus the adult and understanding the differences between the two and there's a remarkable amount of difference. You can see it from the basic science perspective but also look on the graph here and this has to do really with a metabolic rate and the activity of these cells and you see that the genes and the metabolic rate markedly change after the age of 13 and as clinicians, yeah, because the kids, they heal their own lesions pretty well, let's let them go but when we get into the teenage years or adult, that process is much more fragile, right, and we're seeing that with the basic science now and the reasons why. I think this was one of our studies that we looked at the stemness of the juvenile cells and so what we did is we took the juvenile cells and we compared them to an MSC, right, a progenitor cell and asked how alike are they, yes or no, and you see that they share 250 gene products that are available. So there's a lot of immaturity of the juvenile chondrocytes. And so therefore putting it into our thought process about biologics. This is certainly available on the market and there will be more manufacturers, but more suppliers of juvenile cartilage. And I think the thing that we've really tried to do is to keep up with modern arthroscopy, right? And so really developing techniques and instruments. A lot of these are in development now coming right around the corner. So these should be out by this time next year with new cannula systems and ways with which these can be delivered. You see, we prepared the bed here, took out the calcified cartilage and then took out the saline, right? And then putting the juvenile cartilage in there and then layers of fiber and glue to create a cocoon. And so then, you know, with this technology pretty reasonable to do from an arthroscopic perspective it just takes a little bit of organization and we have some tips on that too. But again, here just one of our patients more recently, but there's power in this, right? These are patellar lesions and this is hard, right? As we all know. And so there is some big wins with this. So this is again, emerging. There's not level one data. There's no comparative data of this technique versus others but there are many studies that are ongoing. And here's just a few of them show just the same kind of results of most of the other cartilage therapies. These are in tough patients and that's where the teams that are using this are using this in tougher indications because it is a new technology where other types of cartilage transplantation haven't done great. And then we still have our two year data coming out. So that's a whole nother story, but here's our one year data. It looks very similar to your data. So we're gonna be sharing that soon as our number of cases continues to go up but across the board, I have a very reasonable choice as far as emerging techniques. The progenitor cell populations are resurfing. This is really brand new. And I'm gonna show you some across the globe ways with which cartilage restoration in osteoarthritis is being approached. But I wanted to share a philosophical change here that basically, and you'll see all of these technologies share together. Number one, they are not just injections, right? And they're not just going and cleaning up a meniscus, but they all are really about the preparation of the local environment. And so then as much as the internal environment of the knee, because that's where most of these studies are on, can be optimized, then that is the lens of the surgeon is trying to optimize that from whatever way. And that could be osteotomy, could be synovectomy, it could be chondroplasty, it could be meniscus, but optimizing. Second, stimulating subchondra bone. So essentially all of them have that in common. We'll talk about that. And then many of them are adding cells to this kind of three-step approach. Adipose cells are being used around the globe a lot for the simple reason that they're easy to work with. We can harvest them, because some of us have some extra to give, right? And at the same time, if you look at it per gram of fat, there is an incredible source of cells within fat. And so then the numbers are way higher than the other tissues. So that's why. Here is some of the data, and if you could just look at these MRIs, and I hope it's close enough to be able to see it. So this is grade four patients where there's nothing else to do besides arthroplasty. And so this is Julian Freytag from Australia. And so this is using the patient's own cells that are cultured, right? So this is again, gonna be available for us maybe next year, but much more likely in 2025. There's a few companies that are preparing and going through the FDA process for us to harvest a surgeon's cells, send it to the laboratory under FDA oversight, and then send it back, a little bit like Macy and ACI, but it is the adipose derived cells, so we could dose it. And so here's a study of 50 million cells, and you can see that there is some early enthusiasm of this. This is again, preparation of the bone with using abrasion arthroplasty along with it. So again, it's this one, two, three rule, but then some reasonable results from the beginning. Here's multiple studies across the board. Again, I don't wanna belabor this, but doing the same thing, right? But I wanna show these are level one studies across the board, and really what they have in common is pain and function are improved, and we talked about that, is the two take home messages of cell therapy. But for these studies, including Julian's study, showing significant cartilage regeneration of the surface, and these are through functional MRI T2 mapping. And so very specific MRI analysis on it. So some excitement, right? We're generally heading in the right direction. Even more excitement is these new studies, this starting in chondral defects, right? So this isn't necessarily osteoarthritis, but I wanna share it with you because this is Dan Serres' work. This is from the Mayo Clinic. This is through MidwayPoint or a little bit more through the FDA process. And what this is showing is ways with which we can stimulate immature cells with our cartilage. And as basic scientists, if there's any in the room, this concept of co-culture is very powerful. If you have an immature cell, an adult cell, and they can then talk to each other, and the messages from the adult cell can tell the young cell what to do, right? And that's very well known in basic science. And here is a modern day approach that uses that co-culture technique. And this techniques involve a couple of things. Number one, it involves some enzymatic degradation, hence it's an FDA, it's an IDE, right? It's a drug type of a pathway. And so then digestion of cells down from cartilage tissue down to a cell with some extracellular matrix. It doesn't digest it all the way. And that's called a chondron. And so then that is the autologous part to this. And then the other part is the allergenic part of it, where they're adding again, cells from a vial. Totally different, right? We are in the new frontier of stem cells in a bottle, but it is not that we're just injecting in there. We're being much more thoughtful, right? As a group on how that could be interacting with our own cells to really make a difference. And you see the results with the graphs. It's just been a fantastic thing. And so that's gonna, of course, then we're seeing, well, how much can we push the limit on this, right? Is it just cartilage defects? Is there just a size or can this go further? But again, interesting work, not too far around the corner to be available. Point of care trials. So this is one that we're doing. We're preparing the fat and we're getting again a gametia cell. So this is not stem cells in a vial. This is a grouping of cells and you see the white dot at the bottom, that's a collection of many different types of cells from fat that have been prepared in a way that's, let's just call it meeting current criteria, although this is controversial, of minimal manipulation, right? And the centrifuge system is FDA approved. There is some, but I don't wanna spend time. There's too much to talk about this and minimal manipulation as far as the syringe technique. Maybe I did wanna mention it, that this has gone through a litigation at the national level. Too much to talk about now. However, physicians doing their best and what they believe is best for the patient at the bedside is generally thought of as the practice of medicine. And therefore this was part of a case of manipulating adipose tissue and then deemed that that is within the right of the physician. So, long story, great conversation, but too much for today. So then this is one way to approach it. You're gonna see lots of similarities, right? To these techniques and including the similarity to the juvenile chondrocytes of preparing the area, right? Stimulating the bone, putting a matrix along with the cells and tissue in the area and then using the fiber and glue. So very similar philosophical strategies of rebuilding cartilage and starting again on cartilage defects. And then this doesn't dose, right? But we know from doing the basic science studies that this is techniques around 8 million cells for this. And here's the early data. And it's interesting for us, right? Of being aware of microfracture. And the comparators, this is a randomized controlled trial of micro drilling. And we see that there was no difference for the first year and look, they're starting to split, right? And then what do we know about the micro drilling and microfracture or that the results tend to deteriorate even though it's the FDA standard, right? That we have to judge ourself against starts to deteriorate two years. And you can see that the adipose tissue is starting to break off even though it's not statistically significant because we have too few folks in the trial. But here's the exciting part. The exciting part is that this is again, advanced MRI technology. So we're measuring what the defect looks like is cartilage composition. And then we are then measuring on the front and the back of the host normal cartilage. And what we wanna try to do is we wanna mimic mother nature, right? Get as close to highland cartilage as we can. So we want that ratio to be one, right? The same. And then we can see that the adipose derived cells are really approaching that number one versus the micro drilling. So again, early cool things. I'm just gonna pass through some of these because again, there's just so much to talk about. Here is a new strategy. This is over from Asia of dosing allogenic umbilical cord blood cells. And so this is one that is in trials in the United States now. And if you wanted to be a part of this trial, they are certainly enrolling institutions in it. Here's the good and the bad. The cool is first time umbilical cells, cells in a bottle, that time is now here, right? In FDA approved trials. So it's cool. It's right around the corner. Is this the technique that's going to get it done? I don't know, right? So this is really a microfracture like, right? Big holes in the subchondral bone. If you look at the MRI, that subchondral bone is disordered because of what we're doing. The results have been fantastic. Is this going to hold up? I don't know. But I'm a little worried about the use of the subchondral bone in this matter. Nonetheless, the cell component of this is striking. And then I think finally on this hole is the agility. And this is taking this whole thing to the limit as far as stimulating the subchondral bone. Creating an implant with which there is porosity to be able to hold channels that can come and allow the subchondral bone contents to come to the surface. This is one of the modern day philosophies that do not use cells, right? And so then the question is, again, early results have been really sensational, I have to say. And this is well researched. This is technology from Israel. But, and then, you know, again, no doubt on their improvement in pain and function. But I think the summary is going to be how much can we resurface? This is the only implant that's FDA approved, not just for chondral defects, but for any and limited size of lesions, right? So then can it resurface of osteoarthritis? And you put a big row of this, that is what the company is going to try to do next. I don't know what the limit is going to be, but stay tuned because it's a brand new philosophy and it does not use cells. And again, it is really about stimulation of the bone below. So that is it. A couple of things. Number one, here's where we're at. We're just trying to understand are cells required, right? And you see philosophies that have them and don't have them. Is a specific dose required? There are studies that have them dosed and do not have them. Is point of care processing? That's where we're trying to press the envelope. Do we need this big FDA pathways and companies to put things through? Or can we do something at the bedside? So we're trying, as a whole, we're trying all these things to hone down. But we weren't talking about this a couple of years ago. This is really exciting that the future is here with the use of cell therapy. So you see the significant advances over the last couple of years. So thank you very much. And I think we'll just do questions probably at the end for all of us, right? Do you want to go ahead and do a couple of them right now, which is that way you can run on cartilage while you're thinking about it? Yes, sir. Take a minute or two. Regarding the agility, the first thing that pops in my head is you're taking away a lot of bone to put that product in. What's the impact of if it fails that you have to do a total joint on the integrity of that vein? Yeah, yeah, exactly. Yeah, and we don't know. And I haven't used this product. I did want to report it because it's there. We're going to hear about it. And so I wanted to share with you some of the data because I was also and remain skeptical and for the many reasons, right? It's kind of also microfracturous. It's heavily weighted on the bone. And so if we put coral there, that means our regenerate cartilage is better, right? Than if we just did microfracture micro drilling, which we found that that wasn't the case. Is this microfracture plus, right? Because then there's a lot of additives with microfracture and matrices and those didn't quite hold up as well as we thought. Is this going to be the same because it's so heavily leveraged on that cell population? No one knows. But I think it's good to be cautious. It's good to be skeptical. The same thing with that other technology where we're drilling big holes in the cartilage and you have those MRIs and say, that's what we're trying to prevent. Or, you know, if I had a bone looking like that, I would do an osteochondroallograft, you know, in that. We're doing that to the patient. And, you know, is that going to add up to good results? So I think that this is really pushing the envelope. For us, it gives us a breadth of understanding of what's done in the world. And all of these technologies are actually coming to the United States that I talked about. This isn't anything more of, you know, let's go to Japan and then we could do it. No, they're coming here. So this is great for us to all know this as a group because we're going to have choices going forward for what we use. Any other questions? How about financing? For those of us working in an academic center, who pays? This is so exciting. Yeah, you know, some of these implants, so one we were just talking about, the coral, very inexpensive. So then that is obviously being worked through. These are nine-nine codes because there's nothing that matches. You could do a predicate code of, again, a microfracture, but that only pays so much. And so then you're paying for the implant is something significant. For some of these, there's not much cost to that, including the coral. Some of these stem cells in the bottle may be more significant, and that's what's going to have to be worn out. And that's the big market pressure that's going to be really important because you're right, there's going to be a limit with the payers until there's enough evidence. And then, and the companies know that, that they cannot come up with a process. And I think there are, without saying names, there are products on the market in this arena that got really expensive and it hurt. It hurt the usability because of reimbursement, cost to the patient, et cetera. And so I think that there's a big eye on that. So there's no specific answer to, truly, to your question because these are new technologies. But I think that is very thoughtful. And what I did want to say, though, some of these are not very expensive. So it's doable from the cost perspective, even if it was cash pay. Yes? You want me to do one more? So it seems to me, at the end of the day, there's a lot of technology, a lot of research, a lot of effort and resources putting into developing various degrees of fiber cartilage. And is that really where we are? I mean, is that what we're making here? And I'm not sure if I'm right or wrong at that. And what's the quality of this tissue? I saw some of the MRIs. And with that said, nothing approaches zonal cartilage. And is the goal, really, is the standard osteochondralogram where you get zonal cartilage out of a package? So, you know, lots into that. And Scott, feel free to chime in. So we are, the goal of this is not to produce fibro cartilage, right? It is to use more immature cells and to create an environment that that cartilage becomes closer and closer to hyaluronic cartilage. Whether or not it actually gets there, but we're closer, right? And our functional MRI scanning is proving that. So we are, that is not our goal. Our goal is more durable cartilage. And the question then is the strategies with which we could do that, right? I'll give you, again, the example of the chondron, plus the cells. And then if we have that crosstalk and we already have matrix that's produced, et cetera, are we going to create a more of an environment because we have a cell mixture of adult and immature? So that is just kind of one of the philosophical parts to this that we hope the answers no to the fibro cartilage. I think it's a very great question when we talk about agility and the corals, like, well, aren't we just doing the same thing with fibro cartilage? Not knowing yet, right? That hasn't had that burden of proof and that study of how good of cartilage that is there, but it's certainly not the goal as we go forward. And then finally, you know, osteochondral allografting. Is it here to stay? Absolutely. Is osteo, well, this is a philosophical thing and Scott can chime in. Is osteochondral allografting going to change? Yes. So then we have that whole part. But what about osteoarthritis, right? Is osteochondral allograft really a choice when we have multiple lesions and we get into the osteoarthritis side of the fence? That's where it's not an unlimited technology, at least as of now. And I think that's going to grow in its own part, but we need these other types of technologies because osteochondral allograft will always have its limits. You agree? I think you raised an important point that we need to truly interrogate the reparative tissue. The microstructure, the composition, the material properties of regenerative tissue need to be more carefully studied. And then ultimately the material properties, how that, not just the tissue reform, but how it integrates to the native adjacent tissue, how it integrates to the subcolonial bone, and ultimately how it functions long-term. So I think you raised an important point that are we truly regenerating normal tissue? And it's a complex unit, the whole subchondral bone unit, subchondral bone to cartilage. So let me see how I get out of this. And how do we...

osteaoarthritis

cartilage regeneration

platelet-rich plasma

adipose tissue

micromfracture

stem cells in a bottle

implants

reparative tissue