My role now is to talk about orthobiologic injections and how I use in my practice. Now, orthobiologics has gone through tremendous innovation recently, and now we're at that early adopter phase at this point, but we're not there in all areas. And what I want to talk about is hopefully not really abusing the gap between hope and knowledge here, so we'll give evidence and really rationale for how we practice going forward. Also understand the FDA says we have to be safe, we have to be effective, and it has to be approved. As a consequence between all these different interventions, we need to make sure we're minimally manipulated, which narrows what's approved and what's not. Now going forward and taking care of our patient populations, my population looks like this. So we'll talk about patellar tendon, ligament issues, cartilage issues, and osteoarthritis. So let's start with the patellar tendinopathy. We look at 19 studies and six randomized controlled trials, you actually find that also surgical trials find that it is very helpful, especially in those after and with ACL reconstruction. We give it a yellow going forward because of the conservative management, as it appears in some evidence, but it's limited, but we have to continue to move this along going forward. We give a green using it intraoperatively. When it comes to the MCL, some great data shows that PRP increases tensile strength in a clinical case report by our colleagues, Jeff Dugas et al. And as a consequence, we give a green going forward, especially in the athlete population. If we look at the tremendous work that Martha Murray and her group have done in the BEAR trial, but we find that there's a 14% re-injury rate in the BEAR group versus six for ACL reconstruction. So when it comes to the situation that we talk about athletes with this high rate also in this study from Ochnik et al. in 2016, we don't use this in the athlete population. We're focused on ACL reconstruction and we find some great data as Radich from Chile, Santiago, has shown a 48% reduction in healing time with PRP. So we're focused on how to make our ACL reconstruction graphs better. How about BMAC? Unfortunately, in this study by Silva et al., he doesn't show any evidence and shows no effect going forward. How about the meniscus? Dave Flanagan and his group have looked at PRP in non-ACL reconstructed group and shows that PRP improves survival. So we use, in fact, PRP with meniscus repair. How about osteoarthritis? Quite significant in our populations going forward. It's a significant issue. So we have a menu from corticosteroids, glucosamine, hyaluronic acid, PRP, cytokine modulation, stem cell variety of kinds, exosomes, amniotic fluid, estrogens, and WNT pathway inhibitors. So let's talk about how we think about this and how we use it. Well, we've been working with a group, Virtuallytics, that does machine learning. We come out, we see all the different studies and how we rate those and we find efficacy is scalable. There's a spectrum. There's nothing binary as we evolve. So we are an evolution going forward. So let's look at various things. Kristen Latterman has given us ACL injured patients, randomized to different four groups, and finds that, in fact, Triamcinolone improves the overall situation. So we give that a yellow going forward. We'll have to look to see if there are more studies. How about glucosamine, chondroitin sulfate? Mike Ciccotti, systematic review, has shown us that it has a positive effect, but variable efficacy, but a statistically significant effect. So we give it a green and we use it with our cartilage issued patients. HA, the data, basically decrease inflammatory response, protects cartilage going forward. And the studies abound. There are large numbers. And we, as a consequence, give it a green going forward. It's been used for over 20 years with good efficacy. How about PRP? PRP, with all those 1500 growth factors, has a positive effect, according to Rita Kandel on cartilage repair, by stimulating, summoning the MSCs and also causing them to proliferate when they get there. We also know, as a consequence, we give it a green light. And why? We look at these studies, PRP versus placebo, Womack, six months, positive effect, PRP versus HA, nine studies, and six and 12 months, three studies, and we give it a green going forward. How about this systematic review? PRP is superior to HA for pain at six and 12 months going forward. And so we now have expanded that to the use of PRP and HA. Why? Because it induces the release of TGF, beta-1, and PDGF factors from the PRP. And we give it a green in this regard based on that. You can see here, systematic review and meta-analysis by Zhao and their group from China, showing efficacy and safety with PRP and HA using it synergistically. So we give that a green going forward in clinical practice. How about BMAC? In everyday clinical practice, Jorge Schall has looked at this, showing no significant evidence going forward. But we give it a yellow simply because we have to learn more as we go forward in evolution. How about lipogens, fragmented adipose tissue going forward? We got a nice study coming out of International Orthopedics that indicates 87 patients showing positive responses. So we give a yellow going forward. We need more study. And this study comes from 2021. We look at exosomes showing up, very exciting, but we need some clinical trials before we use this in everyday clinical practice. Amnionic fluid, some good data. We've been part of a randomized controlled data trial with Andreas Gamal, Jack Farr, Brian Cole, Dave Flanagan, and others. And in fact, data showing quite positive overall in two studies being published so far in this regard. And we give it a yellow going forward. We need more data, but results are promising. How about stem cells? This study by Tom Vensness and his group, 2014. Again, it turns out stem cells not ready for prime time at that point. Maybe inferior. We give them a red light. And when you look at this study, my friend from Porto, Jao Espargara-Mendes, looking at intraarticular injection of culture-expanded, things we can't use in the USA, showing with or without PRP, show efficacy going forward. But once again, we're not released to use this by the FDA. So we give it a red at this point in time. Lastly, we're going to focus on estrogen, coming from Australia, showing the presence of greater estradiol, showing less of an instance of total knee replacement. And why? Because in fact, estradiol has a very positive effect, as you can see in this study, on cow explants. Single load compression, strain 50%, 96 hours, they all died. But if you put estradiol in there, and they reduce cell death and improve gap. It's very exciting in that regard. So we ask our patients to see their OB-GYN, their specialists, to focus on their estrogen levels. And lastly, the WNT inhibitor, SM4690 from Samumed, or now BioSplice. Very exciting. Clinical trials going forward. For the moment, we give it a red, but it is evolving. So we end with what we call the orthobiologic sports doctor's prayer. The ability to help when we can, the judgment to know when we can and we cannot help, and the wisdom to know the difference. Remember, never exploit the gap between hope and knowledge. Stop right there. Thank you very much and have a good day.

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