Ken Zaslav from Northwell, New York, who talked to us on cartilage repair. Great, we're gonna move from soft tissue to articular cartilage, and we're just so happy to have Dr. Randelli in sagasco now as the newest member of the VA. When performing articular cartilage repair, we have long recognized that the knee is an organ. So we know now, and we've been teaching everybody for 10 or 20 years, that all comorbidities must be corrected along with the cartilage repair, not just repairing the surface. So you want good ligament stability, good meniscus, and good alignment. But I think what we now realize is that controlling the local synovial environment as well as the bony environment may be just as important. And we need to try to get an anabolic state instead of catabolic, and decrease the articular inflammation and we're hoping that injectable biologics will be a way to provide this option. There's an excellent article that was published by Dr. Sherman and his group. You should take a look at Orthopedic Journal of Sports Medicine. So what is the evidence preclinically that exists? There's at least eight animal studies that have shown that if you add PRP to osteochondral autograft implants, you will get significant improved histologic integration and surface regularity, although these differences may diminish over time. Two different authors, Sun and Zhang, have compared scaffold implantation with and without PRP. And the PRP augmented groups for cartilage repair show increased presence of chondrocyte-like cells and more HA, sorry, hyaline-like matrix. What about the effect of PRP on cytokine and protein analysis? Again, in those oats and scaffold studies, you had better type II collagen, more GAGs, and with PRP augmentation. And interestingly, if you added CPM, even better GAGs and type II collagen. And Al Getgood has shown that scaffold use with PRP compared to PRP alone produces a greater immediate burst of growth factors and anti-inflammatory cytokines in the first 24 hours. Clinical studies are still very few and scant. Ciclary showed 52 patients with scaffold and PRP added to a marrow stimulation technique and noticed significant improvement in coup scores at three months, two years, and five years. And Aaron Critch out at the Mayo has reported on 12-month MRIs of 23 human patients with either scaffold alone, scaffold and PRP, or scaffold and BMAC. And while the bony incorporation was the same in all, the PRP and BMAC groups had superior cartilage fill, but only the BMAC had really good-looking T2 mapping at the end. The largest study to date on this type of procedure is really Dr. Gobi's work. He has done a one-stage cartilage repair with a hyaluronic acid-based scaffold combined with activated bone marrow-derived MSCs, and he's followed it at two and five years with significant improvement in both the microfracture group alone as well as the microfracture with HA up to two years. However, at two years, like most of our microfracture studies, we started to see the results go down, whereas with the HA scaffold and BMAC, it goes up continually through five years, and now he has followed it out to 10 years showing persistence like we see in Macy. So pretty good results here. What about adding BMAC to osteoarticular allografts or osteochondral allografts? Oladeki has shown that if you add BMAC, you get superior radiographic integration of bone with less sclerosis. That's a six-month mark. Kennedy has shown similar findings in the ankle when you compare it and with better MoCART scores, and Adam Yanke reported in a single prospective blind study that at one year, those with BMAC-soaked osteochondral allografts versus those who did not have BMAC-soaked, although they integrated similarly, there was better WOMAC and PROMIS pain scores at one year. Doctor, this is one of the most interesting things I think going on right now. Dr. Dan Saris worked first in Utrecht for over seven years on this project, and now at the Mayo Clinic using allogeneic MSCs from a bank that he saves along with a way to improve your minced cartilage procedure. So if you take a patient's damaged cartilage from the scope and mince it in the lab and mix it with these allogeneic MSCs with collagenase, you get a nice little mixture and you release growth factors, cytokines, and here we are. Then you can add it to a fiber and glue and put it in, and their data now has been published at five years at the American Journal of Sports Medicine. So it's a small number. This was a phase two study, 35 patients with a mean age, as you can see. The most important thing is there was no real foreign body response or serious adverse reactions from using these other person's MSCs and pretty good results at the five-year mark. We've been working with this new Agile C-Coral implant. It comes from aragonite, which is from C-Coral. If you look at the electron microscope on the right, you can see that the coral looks just like bone on electron microscope, and then on the top third, there were these drill holes of a very specific proprietary diameter that brings these MSCs to become chondrocytes. Here's an example of a two-month explant that was taken out due to infection, but you can already see, even at two months, direct osteotransduction of the implant, which is acellular. Now you have osteocytes forming real bone, and in the cartilage source, you can see that the cartilage grows in from the ingrowth. It's actually chondrophilic and also comes up from these micro-drilled holes, and you can see the T2 MRIs and histology are quite nice. Here's that same explant, and you can see the MSCs coming up the drill hole. When they get to the top, they turn into plump chondrocytes, and this was our first in man. The histology looks quite good. This cyclist, after five years of pain, went back to cycling in Slovenia, and then we have since published the recently, just two weeks ago, in AJSM, the pivotal study from the FDA, got FDA approval, has statistically significant superiority over the standard of care, and what's important about this study is half the patients had KL0 and 1 focal defects, but half the patients had KL2 and 3 arthritis, and now the indication includes patients, all patients with joint surface lesions for this cartilage implant for cartilage repair except those with KL4 arthritis. So, in conclusion, biologics can improve microfracture and osteochondral autograft. We need more clinical studies on this, and now newer, less expensive, single-stage technologies are available now and on the horizon to utilize patients' own or allogeneic MSCs to improve cartilage repair. Thank you very much. Thank you.

cartilage repair

ligament stability

injectable biologics

platelet-rich plasma

clinical research