Hey everybody, I'm amazed this many people are like awake after my bedtime, this is impressive. So anyway, and I actually live in the central time zone, so that's sort of depressing. So I'm here today to speak a little bit on hamstring injuries. And the title of this is hamstring injuries and strains, but one of the things I wanted to point out is that as we often know when we see a hamstring injury, even if it's involving the muscle itself, it usually extends into the myotendinous junction and the tendon itself. So I did put a little bit in here about using biologics and tendons too, because to me when I treat these, oftentimes I'm treating the tendon and the muscle. And so I wanted to kind of put those together in this. So we're going to discuss both hamstring tendinopathy as well as muscle strain. And we're going to discuss a couple of different biologics, orthobiologics, including leukocyte rich and leukocyte poor PRP, which by the time you leave here, if you don't know the difference between those, at least you've learned one thing, right? So we're going to kind of beat that into your head, I guess. And then we're also going to talk a little bit about platelet poor plasma and the role it might have on this type of injury. So before we actually go into discussing those injuries, I'm going to dial back to a little cell biology, because we all love cell biology, right? And what's important is to delineate between the differentiation versus proliferation of myoblasts. So when you have a myoblast that differentiates, when you look at the differentiation of myoblasts, that leads to increased muscle fiber production. And that's what we want when we're trying to repair muscle. When you look at myoblast proliferation, that leads to scar tissue. You're not increasing muscle fiber production, but rather you're increasing the number of myoblasts and fibroblasts. So when we look for an orthobiologic or any type of product that will improve or repair muscle, including hamstring, we definitely want something that can differentiate. This dials it down a little bit more, even. And so you can see that on the right side of your screen, myoblasts, when they proliferate, basically release myostatin, and you don't really need to know all this, obviously, and that will increase the myoblast cells. But there's a definite difference between that and differentiation, where that myoblast produces myoD and heavy-chain myosin and MYF5, and that leads to skeletal muscle production. As you can see, there's a definite differentiation between these two processes. And this study by Dr. Lee in 2013 was excellent for us that use orthobiologics or biologics, and it showed that PRP, unfortunately, does not lead to myoblast differentiation. So PRP, in PRP, there's tons of growth factors, we all know that. But three of the growth factors that are there are TGF beta-1, PDGF, and myostatin. And these are anti-muscle growth factors. PRP in this study was shown to stimulate myoblast proliferation versus differentiation, and like we showed in the last slide, we want differentiation. So this cellular study, or this cell-based study, really said to us, well, is PRP good for muscle regeneration? So then I went out and did as extensive a literature search as I could, and I found a total of nine studies that had been done looking at platelet-rich plasma and hamstring muscle injuries. And of those nine studies, six of the studies showed no statistically significant improvement in pain and or function. And that was 286 total patients, and two of those studies done in 2015 by Hamilton and Rearink were both randomized double-blind control. They were level one studies. So that's pretty good. Now there are three studies that did show a positive effect or a statistically significant improvement. Those were case reports, but there was one randomized control, excuse me, one single-blind randomized control trial, and that was of 28 subjects. But I like, I think this 286 patients weighs on me a little more than this 30, but it's interesting to see that out there in the literature. So I also, this is another study that Dr. Dragoo, there's a lot of Dragoo studies here. I think Dr. Dragoo's published like 28,000 studies, so just an attaboy out there. So this was actually a really interesting study, and he presented some of this data at the Toby Conference a few years, probably it was five years ago. But this actually, this little study has changed the way I practice, and this was the, looking at the effect of a, I shouldn't say leukocyte, but a platelet-poor product on human skeletal muscle myoblast differentiation. And they had three products that, four products that they treated muscle injury with. One was a leukocyte-poor PRP. One was a leukocyte-poor PRP that they did a second spin to to remove the platelets. The third was a modified PRP where they just removed those anti-muscle growth factors. And the third was platelet-poor plasma. So everyone here who does PRP, I don't know how many of you know, but you always have that PPP in the bag that you usually throw in the trash, right? Well, there's some important stuff in that stuff you throw in the trash, okay? So in this study, the leukocyte-poor PRP led to myoblast proliferation, which again, we know is not what we're looking for when we're trying to repair skeletal muscle. But the leukocyte-poor PRP with the second spin to remove the platelets and the platelet-poor PRP led to myoblast differentiation. On this side, you can see the little red circled box at the bottom shows where the 2% PRP under high-power imaging showed really a paucity of myotubules or multinucleated cells, whereas the platelet-poor plasma on the far right, circled in blue, in that 2% second spin, so basically the platelet-poor products showed the myotubules and multinucleated cells and the repair of muscle tissue. Another animal study here showing to the two slides, you can see the PPP, which led to muscle regeneration versus PRP on the right, which led to fibrosis. So I'm going to back off of muscle for one second. So what I can tell you right now that this has changed is that previously when I would inject a hamstring or any type of muscle injury, I would go and I would inject PRP. So I stopped doing that and I started using my PRP at the tendon and my PPP in the muscle. And I have starting to pull some data, it's very early because I just started this a couple years ago, but anecdotally it has been awesome. So when I get that data out there, I'm looking forward to publishing it. But let's go to tendon as well. We've been talking about this previously, about leukocyte-poor versus leukocyte-rich platelets, PRP in tendon. And this is a rabbit study that, again, Dr. Dragoo was involved in. And I thank him for the use of some of his slides as well. And it was interesting to show that at about five days, the leukocyte-rich PRP had a greater inflammatory response. But then at 14 days, there was really no big difference in between the two. But what's important about this study is really the basic science, including cellular responses by different substances and different injections, it's really important to look at this first so we can understand the cell biology, apply it to an animal model, apply it to the human model, and then actually start to do studies on it. Looking at tendinopathy with PRP, I just pulled a couple meta-analyses to make it easy. Of this, only 5% were hamstring tendons. But it did show that this meta-analysis showed that PRP was safe and effective. Unfortunately, most of these studies didn't indicate to us if they were using a leukocyte-poor or a leukocyte-rich PRP. This meta-analysis, though, by Fitzpatrick had over 1,000 participants, and it did show that leukocyte-rich PRP, it was more effective in treating tendinosis in a leukocyte-poor product. So then I pulled all my hamstring tendinopathy studies I could find out there, and I found five, and I may have missed some. But of the five, four of these studies, the first four that are listed, showed a statistically significant improvement in pain and or function when PRP was used to treat hamstring tendinopathy. But if you look over to the right, all four of these four used a leukocyte-rich product, whereas the single study at the bottom by Levy that did not show a statistically significant improvement used a leukocyte-poor product. So the take-home points on this really are that PRP itself doesn't lead to myoblast differentiation, so therefore, theoretically, would not lead to muscle regeneration. But platelet-poor plasma, which is, again, what we usually just throw away, does lead to myoblast differentiation. So also, leukocyte-rich PRP is preferred over a leukocyte-poor PRP for tendinopathy. So tomorrow I'm going to do a little video technique on injecting muscle and tendon and hamstrings. And so the thing that I like to tell, and you'll see this tomorrow as well, is you've got the stuff you normally throw away, and if you're treating the tendon, use your leukocyte-rich PRP for the tendon and treating the tendon abnormalities, and then go and treat the muscle or myotendinous abnormality or abnormalities with the actual PPP itself. And like I said, I have been having people return improvement in pain and a quicker return back to play and practice by using this. It's actually been astounding to the point where I thought it was just hokey-pokey to start with, but anecdotally, it's been great. So anyway, thank you.

hamstring injuries

biologics

muscle repair

platelet-rich plasma

platelet-poor plasma