See, Tom, I could do the rebuttal, then you can't come back up, but I'm not going to. So my next topic was ACI is the holy grail for cartilage. And I'm not sure who came up with these things, probably my colleague, Dr. John Kelly. So I have no disclosures as well for this. So you look up the holy grail, it's a thing that is being earnestly pursued or sought after. So when we think about our articular cartilage, what are we really looking for? We're looking for something that is compatible, adaptable, durable, dependable, viable, and even potentially predictable. And so my task here is to show that autologous chondrocyte implantation, when you're managing cartilage problems, is that holy grail. So for those of you that aren't familiar with where we are at this point, as far as how we treat articular cartilage in the United States, one of the common things is something called MACI, which is basically a two-stage procedure. You obtain articular cartilage biopsy on the first procedure for later implantation. As you can see in this one, the defect is prepared, stable borders, any fiber cartilage is removed, a template is made, and then a membrane that is actually grown with cells in it is implanted and without sutures. You can use sutures just to tack down corners if you desire, and it's held in place with a fiber and glue. So essentially, we have a cartilage problem. We're treating cartilage with cartilage, and we're trying to match the contours that are available. So the overall thought is replace cartilage with cartilage. Now this is an example of a 26-year-old individual who actually did have a root tear on this picture here, but he had a significant articular cartilage injury to the medial femoral condyle. At the time of arthroscopy, you can see the injury to the articular cartilage in a loose body. Twelve months later, you can see good articular cartilage filled with autologous chondrocyte implantation both on the sagittal and the coronal images. And if we look at a different technique, this was referred in to us. This was another patient in the Philadelphia area who had had an articular cartilage problem. It was treated with an osteoarticular allograft, and the person still had pain. One of the questions was, was the contour of the medial femoral condyle causing the problem since it was not the same contour? An MRI had been obtained, and the MRI showed significant bony edema around the area of the osteochondral allograft. Further evaluation of imaging showed that a portion of the plug had actually healed and a portion did not heal, and there was an actual fracture line through that portion of the articular cartilage. At the time of arthroscopy, you could see delamination of the graft, and eventually this graft was removed, and you can see this area where the graft had never actually healed. This was salvaged with an autologous chondrocyte implantation with a partial sandwich technique. If we think about, it's also adaptable. It allows treatment for challenging curvatures that may not be amenable to osteochondral allografts, non-contained defects, multiple defects, irregular shapes, and even different angles. And so this is an example of probably the worst patella dislocation I've ever treated. This person had patella dislocation just playing basketball, first-time dislocator, and not only had an injury to the medial facet, but actually had a complete fracture of the medial facet. And we can see the classic bony edema on the lateral aspect of the trochlea. On imaging, you also saw, though, that the patella probably really dislocated inflection as they took off an articular cartilage defect off of the central portion of the lateral femoral condyle that you can see arthroscopically on this image. You can see the fragment actually here in interior, but there was also an articular cartilage defect probably on the relocation of the lateral aspect of the trochlea. We had to put the fracture back together. We used two small frag screws for managing that. There was a central defect in the patella at that location, and you can see this was actually the area of the cartilage that had sheared off on the relocation maneuver. Imaging six months afterwards shows good fill of the articular cartilage defect on the trochlea region and then also centrally on the femoral condyle. It also is idyllic to be adaptable to cover. This was a traumatic. This is one of my partners, Dr. Carey, who I included on this presentation. This is one of his patients in which had a traumatic damage to the distal and medial aspect of the patella. This would be very hard to treat with an osteochondral allograft, but could be treated with an autologous chondrocyte implantation. This is another difficult, challenging one for an osteochondral allograft. This is a very posterior, and to get this knee to have an orthogonal position to drill and to put in an osteochondral allograft would be very challenging in this location, and so this is much more amenable to autologous chondrocyte implantation. Dr. Cull also did some work that was published recently and basically looked at comparative studies, randomized controlled studies, looking at different techniques and found that the autologous chondrocyte implantation was more durable and better able to restore hyaline cartilage than microfracture. Osteoarticular allografts were not included as a word on any randomized controlled studies to be included into the study. It was also shown to be dependable. It was dependable in the summit study, showing to be superior over microfracture. This was in addition to the study I just showed you from Dr. Cull's work. And it was also not only dependable, but durable. We do think about longevity, and as Dr. Carter just mentioned, when we talked about transplants, it is important that we follow things out. So here we do see this is followed out, and there's a much better durability with ACI. One that showed us that first was Dr. Lars Pedersen. In his studies, he looked at two-year data, then he had longer-term follow-up at approximately nine years, and basically showed that his improvement that he saw at two years did persist. He was also able to repeat arthroscope many of these individuals and actually did indentation probing showing that the quality of the tissue that had successfully implanted was durable, very similar to the native host adjacent to it. Dr. Cook, a veterinarian, has shown us that with osteochondral allografts, the amount of viable cells matters. And what he really showed is that you need to have this 70% viability. And so most of the grafts you're going to get, whether it's an autologous chondrocyte implantation, osteoarticular allograft, is going to be above 70%. In a study in cartilage, again by Dr. Cole, he showed that basically the length of time matters. He showed that for grafts that were less than three weeks in storage, they actually had pretty good viability. Grafts longer than three weeks, the viability started to decrease. And in his papers, they wrote, suggests that storage for more than three weeks is detrimental to the tissue, and this likely contributes to allograft failure. What was really interesting was the implantation. When they did the typical surgical implantation on these grafts, what they found is that at the superficial layer, there was a 29%, 30% decrease in cell viability, and overall a 20%. So if you start off at 80% and you lose 20% of that, or 30% of that, you're down really in the 50 to 60, 55 to 60% ranges in that location. So now if you go on and you think about ACI, they also report on their viability. And you get this when you get your implants, and you can see that typically the viability is over 90%. The last thing I would touch on is that it's predictable. You can actually schedule these. So we deal with a large collegiate population who does not have the flexibility in the middle of semesters, and they very much like the ability to say, I would like to do it right after my finals. You can do that with autologous contraceptive implantation, which you can't predictably do with osteoarticular allografts. So if you're looking for something that's compatible, adaptable, dependable, durable, viable, and predictable, I would say that ACI is your thing. So a few years ago, it was felt that the cup from the Last Supper resides now in the Basilica of San Isidoro in the northern city of Leon, Spain. And I would say that the Holy Grail of articular cartilage resides in the northern city of Cambridge, Massachusetts. Thank you.

autologous chondrocyte implantation

cartilage problems

damaged cartilage

patient's own body

cartilage defects