Next, we have Burt Mandelbaum with Precision Medicine. How to choose the right type of PRP for the different conditions, orthopedic conditions. Thank you, Burt. A pleasure to be here, and great to see the synergies between Anna and the BA, and it's amazing to see these logos sitting together. But why are they together? And for you as the attendee, what are we looking for? We're looking to go back to your practices on Monday and having a way, not only in terms of what you do, but how you think of it conceptually, technique, and technology, and putting it together going forward. Now, when you really look at it, Thomas Edison certainly discovered the light bulb, but he said, you know, what I really did was discover a thousand ways of how not to make one. You know, we're in an evolution. This field is dynamic. It's changing radically. All kinds of consequences, day in, day out, and for us as sports physicians, our world looks like this. Injuries, the burden that's greatest, are really hamstring strains, and baseball, and football, and soccer, ACL meniscus tears, and osteoarthritis. So upon that, we as sports physicians have become very interested in this world of biologics. Now, conceptualists take away this, as you can see, the vegetable suit. It's alphabets. There are five things you have to know here. One is Buffy Code versus plasma. We're going to think a lot about the platelet concentration, the white cell concentration, will we activate the PRP or not, and lastly, what the dosing is. So again, conceptually, please take away, those are the most important concepts. The products that you get brought have a wide variety of numbers of platelets they deliver, as you can see on this slide. You can see Angel System will be 2%, 7%, Genesis, Harvest, Magellan, GPS, give you very different products, not only in terms of platelets, but in terms of white cells. And again, as you learn, they have different consequences depending on that. And if you use Angel PRP, you can dial in exactly what you want along the spectrum. So again, it's very different than you as what you do in your surgical practice. So let's think about which PRP for what condition going forward. And we'll start, as you've heard from Ashish before, this is one of our athletes going to the goal, and all of a sudden, you see the quad over, stretches, and creates this hamstring injury. In baseball, it's $29 million per year, in soccer, $7 million per year. You've heard from Dr. Betty talk about the issues, and the literature goes all different ways, but we look for one study, and here it is, it came out recently, that shows for grade 2 hamstring strains, you in fact had 32.4 days for the conservative group, and 23.5 days for the PRP group. But most importantly, the recurrence rate was so significantly different. And I point out here, they use this Biomet GPS system, which is very different and significant. When it comes to TENET, as you hear, there's a lot of basic research looking at leukocyte rich versus leukocyte poor. More leukocytes creates more growth factor release, and tenocyte proliferation going forward. So again, understanding nuances are very important. Again, we've heard from Pietro early, talking about randomized control trials. It kind of turned and switched in about 2016, showing in favor. But what's really learning is that it's the concentration of platelets going further up that has the positive impact. So we're learning more as we go forward. How about the ligament? And understanding here for MCL injuries appears, just in one study, PRP appears to be effective in improving outcome in our athletes. And lastly, when it comes to ACL injuries, which are quite significant, we understand how we can interact. Martha Murray has given us the Bayer, 14% re-injury rate in two years. The reconstruction, 6%. We're more focused on how to take the 6% to 3%. How to do that, and you can see in this study, 48% reduction in healing with PRP. But how do we do it? And there I am with the graft, and you can see here, we're using calcium chloride. We're infiltrating the graft, like you see. And then in this particular case, we dialed in 7% ANGEL PRP. Why? Because it has lots of platelets, about seven-fold greater, but also WBCs, and injecting it directly into the graft. Hopefully, we would achieve this 48% reduction in healing time with the PRP. As we move on to meniscus repair, you've heard great studies being presented by Seth. In vitro studies show that with PRP, you can increase matrix synthesis with greater MRI expression, a biclican, a decarin, and an in vivo study showing better healing of meniscus tears in these animal studies. When it comes to clinical studies, and I think David Flanagan's study is most helpful, you can see here that PRP increased the survival of meniscus repairs, and they're very statistically different to P-less and 0.008. And why? They use two types of PRP. The ANGEL PRP in a biomed, there was no difference, but they also activated it with calcium chloride. And again, these little nuances become really important to understand. As we move on to cartilage, we think about this study. Rita Kandel from Toronto has given us the effects of PRP on cartilage, and what she found was just using it in the media. 20% PRP showed superior compressive mechanical forces, but also increasing the gag content going forward. So again, as orthopedic biosurgeons, all of us become extremely powerful. And lastly, we'll end in early osteoarthritis. This is a 25-year-old professional soccer player already having narrowing of the lateral joint length. And again, we talk about the turning between catabolism and anabolism. That's what we're doing overall. In understanding the interrelationships of this milieu, here you have Jerry Mao's video looking at MSCs in the center of the artery, moving their way towards the PRP. Why? Because they're being summoned, and they proliferate. And then we see the MSCs become more trophic and immune-modulatory overall, and having a positive effect on the metabolism of synovium, the cartilage, the meniscus going forward. And there you have it. That's really one of the most important things is just PRP really affects this environment going forward. And we also learned that PRP mechanism actions are quite significant, and there are many different ones, and there is the literature accordingly. Unintended consequences. Two different PRPs in the work by Lisa and Brian show that just using a different PRP increases the white cells, and it becomes more catabolic. If you lower the white cells, it becomes more anabolic with respect to interleukin-1 and MMPs. So again, the consequences of making these decisions are really critical going forward. And again, this balance between catabolism and anabolism, that PRP really should have an anabolic and anti-inflammatory effect. In terms of efficacy and evidence, again, we've got lots of evidence, 4,000 articles giving this information, but the literature is quite robust. But we pick out those articles, like this one, that shows you need 10 billion platelets. It's crucial for PRP to have the most long-lasting effect on cartilage going forward. So again, we're learning. This is an extremely dynamic field. It's changes, it's heterogeneous, but we've got to learn going forward. And this comes from our BARB study, our early first 20 patients in the BARB study. And what we find here is that the platelet counts in PRP create, as Scott has pointed out, responders and non-responders. But you can see the platelet count of the responders is statistically significantly different than the non-responders, nuances and details that we have to pay attention to. When we think about this, we're unready for the PRP 3.0, the adjuvant combinations. What happens when you take HA and put it with PRP? What it does, the HA induces a release of more TGF-beta and PDGF accordingly. And as you can see in Brian Cole's study, that patients with NeoA were injected with PRP and HA had a greater improvement than HA alone. Again, 3.0 in thinking about this thing. And most importantly, the activation with calcium chloride. In this systematic review, they found that activating with PRP was more effective in terms of improving pain and functional knee scores with osteoarthritis. So we'll end with this, and this is the take-home message. For all of you who are going back on Monday, this is how you need to think about what you do. What makes a difference? Consequences are important. You can see there the injury, platelet count, low, moderate, high. White cell, low, moderate, high. Activation or not, and dosing. Muscle strains, as we'll learn, moderate and high from the literature with respect to platelets. Moderate and high with respect to WBCs. Also activating, and one dosing. For the rotator cuff and tendinopathy, as you've heard from Jason and Pietro, moderate, high platelets, and even getting higher, it seems. Moderate high WBCs activating in one to three doses if, in fact, you get the opportunity in tendinopathy. In terms of ACL and ligament healing, moderate, high, moderate, activation, and one dosing. Meniscus repair, inject into the meniscus. Moderate high, moderate high, activation, one dose. And lastly, with respect to cartilage, low, low in terms of OA. Analyze that accordingly, maybe moderate. In terms of WBCs, platelets as high as we can. We activate this, and again, from the standpoint of cartilage repair, you get one dose. When you get OA, it's one to three times, plus or minus, high molecular weight HA. Thank you very much. Thank you, Bert, that was great.

Platelet-Rich Plasma

Orthopedic conditions

ACL tears

MCL injuries

Hyaluronic acid