PRP And Exosomes: Here's What Orthopedic Doctors Must Know | Conversations in Regen Episode 13

PRP And Exosomes: Here's What Orthopedic Doctors Must Know to avoid confusion, elevate care, and navigate emerging science.

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Are you unsure how to navigate the growing debate around PRP And Exosomes: Here's What Orthopedic Doctors Must Know? Are you wondering whether exosomes or platelet rich plasma therapy offer reliable, evidence-based outcomes? Are you frustrated about the regulatory gray zones, misinformation, or lack of standardization in regenerative medicine? In this conversation, I open up the most pressing and misunderstood topics shaping orthobiologics today so clinicians can finally gain clarity, confidence, and direction. Drawing directly from my discussion with Dr. Don Buford, we explore where exosomes truly stand, how PRP evidence is evolving, and what orthopedic doctors must realistically expect when integrating these therapies into practice. If you've been craving straightforward explanations on exosomes, exosome therapy, PRP injection pain management, or regenerative medicine orthopedics as a whole, this deep-dive will help you understand the landscape more clearly.

In this episode, we will walk you through the real-world insights from our fireside chat—from the hype surrounding exosomes explained in practical terms to the crucial distinctions between extracellular vesicles, autologous approaches, and the regulatory limitations surrounding their use. I share my personal perspective on how orthobiologics injections are being misinterpreted, why exosomes regenerative medicine is still in a formative stage, and what clinicians must consider before adding these treatments to a cash-based practice. You’ll hear exactly how PRP therapy continues to evolve, why platelet dose matters, and what we can fairly conclude from existing PRP evidence without making exaggerated claims. I also unpack how busy orthopedic, sports medicine, and interventional orthobiologics specialists can approach data collection, patient-reported outcomes, and practical quantification tools without feeling overwhelmed.

As I reflect on the video, I also highlight what Dr. Buford and I believe is coming next—including the future of research design, collaborative registries, orthobiologics standardization, and the essential mindset shift needed for successful practice integration. If you’ve ever felt uncertain about the legalities around exosomes, how to discuss biologics with patients, or how to build a profitable yet ethical regenerative medicine practice, this episode lays out a grounded and reasonable roadmap. Nothing here promises magic; instead, it provides realistic expectations, thoughtful insights, and strategies clinicians can apply immediately.

For more guidance on interventional orthobiologics, regenerative medicine, PRP training, and pain management orthopedic insights, make sure you connect with me directly. Subscribe, comment, like, and explore the other videos on my channel so you never miss the newest updates on orthobiologics, PRP injection explained breakdowns, exosomes, and evolving clinical strategies. 

Building a successful cash-based orthobiologic practice is not a single decision. It is a series of the right decisions made in the right order. The Business of Orthobiologics offers three distinct programs designed to meet physicians at different stages of readiness — whether you are just beginning to explore PRP, ready to build a full practice system, or committed to going all-in on a comprehensive transformation.

Learn More here: https://thebusinessoforthobiologics.com/programs-explanation 

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Transcript

SPEAKER_00 0:00

If the only penalty is you have to stop what you've just been doing that was wrong for the last four years, that's not a disincentive for anybody.

SPEAKER_01 0:06

I believe that orthobiologic treatments will be first-line treatment for musculoskeletal care in the next five years.

SPEAKER_00 0:15

So I think it's totally unfair to hold orthobiologics to a higher level of evidence than we hold orthopedic surgery to. There's a lot of useful information you can get from a nice cohort study, which is like a level three study, and it can be retrospective. Nothing wrong with that.

SPEAKER_01 0:53

And maybe some other more controversial things. So we're gonna talk about some controversial topics and cutting-edge insights that are shaping the future of interventional orthobiologics. For those of you who don't know me, I'm Dr. Ariana de Meurs. I'm a board certified fellowship trained sports medicine orthopedic surgeon and regenerative medicine enthusiast. I am an educator and trainer, not only in orthobiologics, but ultrasound as well. And I have successfully moved my rural Northern California practice away from insurance and I focus on cash-based orthobiologic procedures. And most importantly, I am passionate about helping doctors to incorporate orthobiologics seamlessly in their practices. I have a very exciting guest. We are going to be talking about evolving orthobiologics, data, axisomes, and the future of collaboration. This is going to be a conversation with the one and only Dr. Don Buford. He is an orthopedic sports medicine surgeon and regenerative medicine pioneer. He is the founder of Texas Orthobiologics. He is current president of Interventional Orthobiologics Foundation. And he is an advocate for PRP quantification and the responsible use of orthobiologics. So I am just really excited to welcome you to our show. Thanks so much. Thanks so much for joining. I'm excited for everyone to join. This is more like a fireside chat rather than a lecture. This is gonna be really fun to just kind of pick your brain and explore some controversial topics in orthobiologics and regenerative medicine, gain some actionable insight. So you can start implementing this in your practice immediately. And then there's gonna be a live QA section for all your burning questions. So if you have questions, please put them in the chat, put them in the QA section, and we will get to everybody as possible. We'll see. There's a lot of people on tonight. So if you're wondering about something, someone else probably is too. And so we're gonna get started. I'm gonna talk about a bold statement. I believe that orthobiologic treatments will be first line treatment for musculoskeletal care in the next five years. Now, sometimes that is easier to dream if you're actually doing it. But successful integration of orthobiologics is sometimes difficult. And a lot of people are looking for how is it that you can have a successful orthobiologics practice? You know, we know orthobiologics is the best treatment for patients many times. But how are we able to be successful? Maybe you've tried some things, maybe you don't know the science. Maybe you're a little wondering about technique or cash business or marketing or sales. And here's the deal it's not your fault. Maybe you just thought, I'm just not good at business, but here's the deal. We didn't learn this in school. Maybe some of you are struggling, right? On how to be successful, how to capitalize on this $4 billion ⁇ biologics market out there. So if you are thinking that you deserve more, or if you're thinking, why is this so hard? Go ahead and just pop in the chat what you are struggling with the most. And maybe we can get you some insight and maybe we can get you some success at the end of tonight. So how do we win? Now, while we are talking about the science today, we also actually need to talk about how to consider talking about these treatment options with our patients. So we all win. So you need a system. Now we're gonna go over this all today, but we are gonna get you a little bit further down this journey to be wildly successful in your orthobiologic practice. And so we're gonna start with our orthobiologic knowledge today. And so this is when we're gonna get started. We're gonna get started, Dawn. We're gonna get going. So, Dawn, we have questions. We have a lot of questions. But let's get started with the first question. And this is quite controversial, right? We're gonna be talking about exosomes today. Uh, and exosomes are one of the most hyped and maybe one of the most under misunderstood topics in regenerative medicine right now. So my question is, are they the next frontier? Or are we still years away from clinically responsible use?

SPEAKER_00 6:16

Well, I have questions too. Looking forward to the exchange. First of all, thank you for the invitation to visit with you once again. I'm always appreciative. And uh as we all say, we all learn when we spend some time like this together talking about topics that we all love. So, with exosomes, I'm gonna give you first a background in terms of how I understand exosomes and the direction that they could take us, and then really where we're at right now. And I'm sure that most of the people on this webinar understand that exosomes really come from one or really two two places primarily within orthopedic uses. We usually have cells that we culture, and then we harvest the exosomes from a cultured cell population, and that method of making exosomes has been deemed making to be making a drug by the FDA, partly because the FDA has already had already ruled that culturing cells was making a drug. So the byproduct of culturing cells was also part of that drug-making process. And that's why we're in this kind of regulatory quagmire with exosomes right now. But the key point, though, that I came to understand when I first started looking at this was the cells that are making exosomes don't just make them haphazardly, they make them in response to what their environment around them is. So if you grow a cell culture in a hypoxic environment, you will get a different set of exosomes than if you grow a cell in an aerobic environment around a healing tendon, for example. I'm just being a little bit ridiculous in the example. But basically, the exosomes that are produced by a cell culture are really specific to that culture. And for that reason, it's going to be really hard to have one bottle that is applicable for all clinical applications, in my opinion, as I understand it. Now, we've had a company that now is touting the fact that they can make autologous exosomes by doing a third spin on the platelet poor plasma. And they're, as I understand it, very close to getting FDA approval for that. And that would be a way to capture the exosomes that are in the plasma portion of making PRP after we've done a spin. And so that would be an autologous solution, but we still have kind of the same problem. We don't know the content. And so now, as far as where we're at right now, clearly they're identified as a drug. Nothing the FDA has ever put out has spoken otherwise than their ruling and their opinion that exosomes are a drug and they need drug clearance, which we don't have. Not even for the autologous ones at this point. The current clinical status is such that we don't have a lot of clinical research supporting the use of exosomes. And I don't just mean in the US where it might be a little bit harder because we would have to, you know, ostensibly do an IND, you know, FDA-approved IND study, but even from other places outside the U.S., last year there was a paper published by some Iranian authors, very detailed Iranian team, that looked at, let me get the numbers right, they looked at 28 patients and bilateral knees, and in one knee they injected five CCs of placental-derived exosomes. In the other knee, they injected five cc's of normal saline, and they got MRI scans pre-injection and at the six-month post-injection mark. And of course, they ran through all the patient-reported outcomes and all the functional scores and pain scores. And long story short, they found zero difference. No difference between normal saline at five cc's and placental-derived exosomes at five cc's. Now, you know, I don't want to fall into the same trap that we sometimes accuse other authors and editors of making by saying that means exosomes aren't going to work. But it does mean that in that study, placental-derived exosomes, and that well-designed study, this was a triple-blinded study, that they did not have any significant advantage over placebo. And so even with a very specific narrow conclusion, that's still not encouraging right now. It means we have a lot more work to do if we're going to show that exosomes can move the needle better than things that are already really well established, like PRP and bone marrow concentrate and microfat and these other things that we have, not to mention the energy modalities. But long-winded answer. But I think there is a future there. I just think it's going to take some really thoughtful people and probably a little more refinement on what's in the exosome package before we can really call it a useful clinical drug in orthopedics.

SPEAKER_01 10:43

Yeah, awesome. Yeah, thanks so much for sharing that. Now, what is the so there's a conversation about exosomes and then there's a conversation about extracellular vesicles or EVs? Are those the same? Or are they different? Or do we have to be more specific as to what we're talking about? You know, should we be maybe talking about where it was cultured, how it was cultured, what environment it was cultured in? Is it autologous? Is it allogenaic? Is it, you know, do we have do you think that there's gonna need to be a very clear discussion and you know, apples to apples comparison?

SPEAKER_00 11:28

Yeah, I think yeah, that this will probably happen long after I'm practicing medicine, and maybe even long after my son has been uh, you know, through his career. But ultimately, if we're able to specifically culture cells in a specific environment, say we have a great model for an osteoarthritic joint, it may even be as granular as to be an osteoarthritic knee versus an osteoarthritic hip if we find that there's differences there in the synovial plophral or whatever we're studying. But at that point, when we can identify those differences, and there's gonna have to be some AI involvement because the computations of how these things interact is huge and complex. But one day maybe we could have a vial of exosomes where this is for neoway, you know, and this is for hippo, and this is for cuff tendinopathy, and this is for you know tendinopathy around the elbow. It may be, I hope it doesn't get overly complicated. It may just be we have a tendinopathy vial, you know, a chondrosis vial, and maybe a disc vial for lumbar disc or something like that. But I think it's going to have to be more specific than just saying we have exosomes, we don't know what's in them. We're gonna dump it in and then hope the body knows what to do with that.

SPEAKER_01 12:40

Yeah, so you know, you see exosomes marketed everywhere, right? And so can you just buy them off the internet and take them to your doctor and be like, hey, can you inject this for me?

SPEAKER_00 12:54

Yeah, I sneak around chat groups and things in terms of orthobiologics, I should clarify. But you would be surprised what people talk about doing. There's people online selling these things to other people online, nobody's clinical at all, just based off of, hey, my bro or my gal friend told me that this works. Ditto with peptides, obviously. And uh so so yeah, you can get them through sources that are not vetted, that are in no way, shape, or form guaranteed to be safe or even to have what's in the vial. We've all seen that. Even from companies that were supposedly vetted, didn't have what was advertised back in the day when we were looking at bottled stem cells.

SPEAKER_01 13:30

Yeah, absolutely. Great, great conversation. You know, I think it is you want to be cutting edge, but you also want to consider like patient safety, your license safety, who the licensing bodies are. So I think you thanks so much for kind of giving us that clarity about what's legal in this country at this time. So I guess we'll have to stay tuned, right? So I still have questions, right? So when you talk about over-engineering, thanks for looking at that. But in the ontologous world, are we over-engineering PRP? Or have we finally gotten to a point where we're able to standardize it and we're all able to talk about it in a clear enough language for everybody to understand what we're using?

SPEAKER_00 14:24

I think we're obviously much farther along with PRP than we are with any other ortho biologic in terms of understanding the dose-response relationship at this point, especially since we have a measurable metric that can be done in the office on the day of the procedure. That's really cool. I think that's probably unique, although I know we can get cell counts, total nucleated cell counts, but that's not quite the same. So at this point, it's actually a pretty good place for us to be in right now clinically. I think we can make a lot of useful um recommendations to patients for multiple orthopedic conditions that are backed by level one, two or three evidence, where we have dosing data for soft tissue pathologies and for arthritic uh or joint pathologies as well. Not or and also for that matter for things like ABN and fracture pathology, too, where we know dosing data. And so that's what a more mature scientific approach tends to be, where you've got a dose-response relationship, you have a targeted dose, you can meet that targeted dose on the day that you're giving the drug.

SPEAKER_01 15:27

That's some pushing is it a drug?

SPEAKER_00 15:30

Well, okay, so it's a biologic. It's a biologic, but uh call it a treatment. So I think in terms of platelet dose, which of course is volume times concentration, I think that's where we're at. That's the current state of the art in terms of quantifying PRP. People are talking now about monocytes, and they're 100% accurate. Luckily, we get a monocyte count with our hematology printout, even on a three-part differential. So that's something that's easy to add into our world to check and to quantify if we find that's clinically useful, more than the platelet dose. There may be some ways in conjunction with the platelet dose that matters, but right now, if you only gave me one metric to track for my PRP treatments, it would be the dose. It would be the volume times the concentration. Yeah, we'll see what happens with the monocytes in terms of tracking that. I think the leukocyte rich versus leukocyte poor has kind of fallen by the wayside. I don't think that matters anymore. I think a lot of people have shown that dose is more important than leukocyte content. So I've only used leukocyte poor or leukocyte neutral. You know, we created that third category where the leukocyte count content is still basically less than 11. And it may be above baseline five, say the patient's leukocyte count, WBC is five. You make the PRP and it's seven, but is that really leukocyte rich? We just call that leukocyte neutral, versus if it's 25 on the white count, then yeah, that's leukocyte rich. So whether it's leukocyte poor or neutral, that's all I've been doing for the last, oh gosh, seven, eight years. And as you know, like you do, we track every case. There's been no change in outcomes at all. So I think that's really the state of the art with PRP in terms of how we quantify and how we deliver and report what we're delivering. I I hope we never get so granular that we have to look at things like basophils and eosinophils. I hope. But if somebody figures that out, if somebody figures that out, more power to them, then we'll shift, you know?

SPEAKER_01 17:19

Yeah, so that that brings up a really good point. So you both you and I are looking at hemocytometer data every patient, every time, every draw. Um, but there's a lot of people out there saying, oh my gosh, like I can't, like that is cost prohibitive. That is like I don't do enough volume to do that. What would you say to them? Is it cost prohibitive? Or is this should this be maybe standard for knowing if you're going to be doing injections, what you're actually injecting?

SPEAKER_00 17:54

You know, I think it's it may truly be cost prohibitive for someone who's not very busy in the field, and it's a big enough monthly payment on their hematology machine that they're worried that they're going to not be able to make that work. I think the better, I shouldn't say better, but I think the busier clinicians that care about their outcomes and what they're doing, I think you have to have a hematology machine because we don't have any other way to quantify. And so, you know, that's you know, like an orthopedist not having an X-ray machine. You know, it's hard to make statements about things if you just don't have a way to measure them.

SPEAKER_01 18:27

Yeah.

SPEAKER_00 18:28

Or ditto for ultrasound or MRI scan, you know, sometimes you just need a way to quantify what you're talking about. Um say something really smart about it. So they're not, I mean, they're expensive, but you know, somewhere between eight to twenty thousand dollars, depending on if you're getting a three-part or a five-part machine. If you split the difference and say it's going to be thirteen thousand dollars, yeah, it's a lot, but you know, you run that over three years and it's it's manageable. But then they need to understand that if you're doing this on a cash pay basis, which knock on wood, we should all hope we continue to be able to do, that you charge appropriately to account for the fact that you are quantifying what you're doing and that you are providing that next level of care.

SPEAKER_01 19:06

Yeah, absolutely. Absolutely. That's what I tell everybody. I said, you know, do you need it? It's not like do or die, but is it nearly critical? I wouldn't do, you know, in the rare instance that I don't have account, I feel very underprepared for my patient. And I don't, I don't enjoy injecting without knowing how what it's quantified. I'm like, oh my God, how do people do this? So, and you can price accordingly, and so you can bundle that in. It's another $25, $50, $75 to ensure that you know what you're injecting.

SPEAKER_00 19:47

And the part that's hard to capture on the back end is if you use that as part of what you're presenting to your patient population is the value that you're providing, you may be getting eight more patients a month into the office because of that message and the value. And that more than covers your extra $70 per injection. It's just hard to match those two numbers up, but I'm certain it happens.

SPEAKER_01 20:09

Absolutely. And, you know, speaking of measuring, you know, I'm just gonna put a shameful plug, like everybody needs to collect their data. The patient reported outcomes has to be done. I don't care if you, you know, have you found anything that it makes it easy to collect data, you know, from a spreadsheet to an app to some kind of AI tool.

SPEAKER_00 20:33

Well, it'll be interesting to see what happens in the AI world. I'm sure there's going to be some amazing things that happen that make it even more automated. But basically, ever since they started, I've been using Data Biologics, which was built from the ground up, to be an orthobiologic-specific registry. And so as they've grown, I've kind of grown with them and used them for my cases, and they've kind of expanded their reporting package and the ability to look at your data in in ways that you can really drill down to a body part, a biologic, and even a dose and see what your graph looks like. And you can benchmark that against the universe of other clinicians that are using data biologics, and there's got to be about 280, maybe almost close to 300 now. So there's a fair number. And it's not so much for bragging rights because I can't pull up, you know, Ariana versus Donnie, but I can pull up Donnie versus the rest of data biologics. And the point is, I just want to make sure that my chart looks pretty close to everybody else. I mean, you know, if it's better, great. I don't want to be a lot worse because if I'm a lot worse, I need to figure out what everyone else is doing and what I'm missing, you know. And so again, it's just a way to, it's not really even gamifying it. It's just a way to make sure that you're incorporating best practices because you've got an environment with data biologics clinicians that everyone's kind of thinking about the same thing in a thoughtful way. They may be using different biologics. It's not, it's agnostic in terms of treatment. It even includes non injectable, it includes shockwave laser, it includes all sorts of things. And so you can really track your outcomes for almost any orthopedic therapy that you can use on a patient. So I love that platform. I'm sure there's others. And like I said, I'm sure that AI will somehow make this even more fantastic going forward.

SPEAKER_01 22:16

Absolutely. Awesome. Well, thanks so much. We now have a question about IOF and Toby uniting together for the next conference. Do you think that this coherence, bringing this together, could bring coherence to the orthobiologic field? Or do you think it's gonna maybe unite ignite some new debates on direction and standards? Like, where do you see that?

SPEAKER_00 22:45

Well, I think you know, bringing those two organizations together, you know, it was a years-long process and it was truly a labor of love amongst people that really deeply feel the need for education and training and standards and ethical practice and this growing, vastly you know, growing subspecialty. And getting all of those people together just seemed like the right thing to do. You know, after COVID, when we all pivoted for the most part to telemedicine for a lot of things and attendance went way down at all all the in-person meetings, coming out of that period, that's when we started saying, gosh, you know, we need to start looking at ways to combine these efforts so that we're not asking clinicians to be at two or three or even four different meetings a year where they're essentially seeing the same speakers, or if not the same speakers, the same topics. And just do things really change that fast where we need a meeting every quarter. You know, I've been to both meetings for years and years, maybe more than a decade, as I'm sure you and others have. But we really thought there was going to be a way to combine the two organizations in a way that preserved both of their identities and made the overall curriculum in teaching stronger. And we're excited. We've already done a lot of groundwork for the IOF Max with Toby meeting in June. And we've got, I think we've got like 12 or 13 international faculty that have already agreed to come either across the pond or coming from you know far west to come visit with us, share what they're doing. And so it's going to be a truly collaborative meeting. It's going to double the size of the meeting. And so instead of three or four hundred, we're going to be looking at numbers that are back like we used to see before COVID. We're going to be looking at six, seven hundred, you know, eight hundred. And when you get that many people together that are all really curious and interested, only good things can happen. So there'll be a lot of small breakout sessions, but the key is to maintain the identity and to really try and accelerate the growth in the field.

SPEAKER_01 24:46

So, you know, I know IOF has new initiatives from the searchable video library to the new grant program. Is this helping to reshape what collaboration and research look like in this field? And do you think that it is the more we can put forth, do you think it's helping to accelerate the adoption widespread?

SPEAKER_00 25:11

I think so. And for those that don't know, which would be mostly everyone, because we're just starting to do it, one of the most common questions we were getting at the IOF was do you have a reference of ultrasound pathology? Because people would go to IOF meetings or instructional lectures at different courses, or go to my course, and then you know at the end of that long weekend, they're energized and charged up, but they want to have something to go back to and check on a regular basis. Like they've got a they've got a clinic tomorrow where they've got three new elbows coming in, and they want to go back and review what lateral tendinopathy looks like? What should I be looking for tomorrow? And so that's a common request that we were getting at IOF, and we finally just sat down and said, you know what, IOF should be the provider of this sort of information. We have a great ability to warehouse knowledge from all of these IOF members. And so we're just about to announce that. Some of that burdens on me, so my bad for not having it out, but we'll have it out before the end of the year, before everyone leaves for Christmas break. You know, mid-December it'll be out. And it'll just be a place you go to submit like a two-minute clip of any pathology. There's obviously no charge to submit, you're just contributing to the library and assuming that it's accepted by the people that'll be grading the video clips, it'll get added to the library with recognition, and it'll be kind of a living evergreen, you know, online library where people can go and your membership can go, and they can type in lateral elbow, they can type in a pathology, there'll be lots of different ways to search it. So I think that'll add to the education, you know, to the mission of IOF in terms of education. So I'm really looking forward to that actually. You mentioned the other thing that we're doing, which is grant program for research, yeah. Very excited about that. So the Jerry Malonga Fund has graciously agreed to sponsor an IOF grant program, which is now up and running. And basically, IOF members can submit grant proposals to the IOF executive director, who's Jillian. And uh they we don't have a defined dollar amount, but basically up to about $10,000 can be granted or given to somebody with a good clinical or basic science idea. And the use of the grant is essentially unlimited as long as it pertains to the study. I mean, you can't go to Vegas, you can't go to Vegas and put it on black, but but if you do IOF wants half, but that grant can be used in terms of supporting the protocols, in terms of buying supplies, in terms of getting statistical support, you know, whatever someone needs. Because another common issue that we had at IOF with people will call up and say, Hey, I have this great clinical idea, but I don't have a statistician. I'm in private practice. How do I make all this work and how expensive is it going to be? And even a simple study, if you want to do it well, you know, it could cost you $10,000, $20,000 if you're gonna put 30 or 40 or 50 people in it. And without industry support, or if that's your only method of support, sometimes you're just kind of locked in and not able to do what might be a great idea otherwise. So IOF wants to support those people that are interested, that are just looking for a little bit of help to push their idea across the finish line and get a study up and running.

SPEAKER_01 28:21

Yeah, that's awesome. And you know, that what a perfect use for the Dr. Malangas fund. You know, as people may not know, he was definitely one of my mentors, and he is absolutely sorely missed every day. So to be able to now have a research grant program in his name is awesome. Awesome, awesome.

SPEAKER_00 28:45

So I just say one other quick thing about that because you know Jerry's son, Luke, has been spearheading this and has been fantastic. Luke is also one of the principals at Data Biologics. And so the grant recipients will be able to track their data with Data Biologics. The only real ask that IOF has is when you finish your project, you present it to us at one of our IOF Max meetings and publish it in one of our. There's a journal project I can't talk about yet, but we're looking at having an official IOF journal as well. And so that would be some other another resource for somebody to get their research published.

SPEAKER_01 29:17

Amazing. Amazing, awesome. Well, IOF is doing great things. Of course, you're at the Hum. So of course they are. So we still have more questions, and then we'll be doing a little QA session at the end. So our last question is you know, if we could redesign how evidence is generated in regenerative medicine and orthobiologics, what would that look like? Meaning, you know, do we have to have randomized controlled trials or does real world data is it good enough? Is it actually better than the randomized controlled trials that we all live and die by in the evidence-based world?

SPEAKER_00 29:58

Yeah, man, that's a great question. You know, I you know, I was one of the authors on that paper that documented that in orthopedic surgery in our specialty, the average level of evidence is three. So I think it I think it's totally unfair to hold orthobiologics to a higher level of evidence than we hold orthopedic surgery to. So three are better. Okay. There's a lot of useful information you can get from a nice cohort study, which is like a level three study. And it can be retrospective, nothing wrong with that. And so all that would be is we're gonna treat, we're gonna treat 20 people this way, 20 people that way, and at the end of six months, we're gonna see how they did. That's a level three study, but as long as you don't randomize it, but you can go back and see how they did. That could be a level three or better study. I think we need to do that. Real world data is fantastic, but it's nice to have some sort of control because the placebo effect is so strong. Yeah, and that's always a confounding factor, and it's always something that a naysayer will point at, and at least you can have a little bit of a stronger conclusion if you can say, yes, we did treat 20 people with normal saline, like in that exosome study we talked about at the beginning of the webinar. If they didn't have that, it would be hard, it would be a little bit harder, a little bit less solid of a conclusion. But I like the idea of having some sort of comparative group. It doesn't necessarily have to be placebo, it could be to steroid, it's a bad word, but it could be to steroid. I mean, if you have a partner that's only doing steroid and you case control your patients, so you could do that. It could be to you know, PRP versus another biologic, because we now are at a point where we have pretty good PRP data as a baseline. But as long as you have two different comparative groups, I think that makes any conclusion a bit stronger. But what do you think about this idea? Because I've been thinking about this, Ariana. What if at least annually we had a bunch of people, um, a bunch of smart guys and girls sit in a room, or maybe it's at IOF Max, or maybe it's at, you know, however we do it, format like this, and we come up with 20 to 30 study ideas that are lacking. Obviously, it would be dominated by exosomes and bone marrow concentrate, at this point, even peptides and some other things. Just come up with 30 ideas and just put that up on a, I mean, as long as you don't care about who does the work, we just want to get these 30 questions answered. We think these are really cool questions that could be answered. I would love to have that kind of repository posted somewhere and have some of our clinicians that are in environments where they may be able to do a study that I can't do because I'm not in an academic setting, or we may be able to stimulate a multidisciplinary study if two or three people sign in to be part of a study group. It's looking at this study question. And right now it's really hard to do that unless you just, you know, call on friends and family if you have a great study idea that needs to be multidisciplinary. So I just I've got I've always got five to ten ideas for a study, and I can only run one or two at a time. There's only so many ways I can divide my patients, right? So I love the idea of having like a study board or a study group whose sole job is just to say, these are some great ideas, and you know, it's not eBay. We're not selling these ideas. These are just great ideas. If you want it, grab it, you know.

SPEAKER_01 33:10

Yeah, democratization of you know, our field and you know, housing the ideas, how giving some maybe some support. Absolutely. What do you think are the most uh meaningful endpoints? Because, you know, like the study that you were just talking about at the beginning of this conversation, you know, they rechecked MRI's in six months, and I'm thinking, why? Like, is that really meaningful? MRI, do we actually expect normal saline to affect cartilage thickness? Do we actually expect axisms to affect cartilage thickness? I don't know. Maybe we do. Do you think structural endpoints are appropriate? Do you think patient reported outcome endpoints? You know, I'm kind of torn, right? Because from a clinician standpoint, do I re-MRI all of my patients? And if I did, would that change what I did? You know, looking at what we have our experience with in the surgical world with the rotator cuff tears, right? Do we re-MRI every single one of our rotator cuff repairs? No, we do not. Should we? Maybe. I think it'd be really unfortunate findings because we know what the data says that we ain't that good, right? We forgot that there's a biology part to it. But is structural data endpoints, are they the end-all be all? Should that be included, or is patient reported outcomes good enough?

SPEAKER_00 34:49

I think whenever possible, we should include structure. Because if you don't look, you won't find it. And if you don't look, you'll miss it. And you just gave a great example of how important that can be in orthopedic surgery. You know, if we hadn't had some thoughtful people decide to go ahead and get MRI scans, we would have never known that, you know, 20% aren't healing, you know, in some studies, much, much higher. But and then we finally that that raised enough awareness that that people that were sure that they were, you know, the initial response is, well, they're doing something wrong. They don't know how to fix a cuff. But you start to learn that's kind of the human condition, you know, the cuff is tearing, not because it's a traumatic episode, it's tearing because the tissue's kind of you know degenerating.

SPEAKER_01 35:34

And it's a biologic deficit, right? What a perfect opportunity for orthobiologics, right? Dr. Hernegy's showing that exactly, you know, application. So I always struggle with that. Like, is structure the end of that? Because we all see those knees where they look horrible and they don't hurt, and they look fine and they do hurt, right? So, like, is there that correlation?

SPEAKER_00 35:56

Well, it's not correlated. You know, there may be some, there is some correlation. Let me walk that back a little bit. We do know, for example, that cuffs that are intact, those shoulders tend to be stronger than shoulders that have a full thickness cupcraft. So there is correlation. Now, if you're talking about an arthritic knee, I had a great example of a patient today, and her husband hit the nail on the head. And he's like, So wait, so this isn't going to change, you know, this stem cell injection we're considering is not going to change her x-ray. And I'm like, No, it's not going to do that. But I may be able to take her pain down from an average of six or seven down to two or three. And we've got, you know, hundreds of people where we've had that happen. And he said, Well, then why would I care if the x-ray change? And I'm like, Exactly. You know, I don't care. I would love a treatment where the x-ray did change, but until we have that, patients really want to have less pain and to be more functional.

SPEAKER_01 36:46

Right.

SPEAKER_00 36:46

But I still want some of us to be able to pull up the structural input too, because one of these days we are going to have something that changes structure. We've already had some hints at it. And it may be the dosing issue, we need to be higher and higher. Um location issue, we need to be intraosseous and in particular. But unless we track the data in some of these high-level studies, we'll never know.

SPEAKER_01 37:08

Yeah. And then the final piece of this data collection and real world registries and uh research, you know, people always say, well, if we had proof that it worked, would we get payer acceptance?

SPEAKER_00 37:24

I don't know. You know, there's so much that figures into that, I've decided, from because they obviously can't claim it's experimental. They stopped claiming that PRP, for example, was experimental many years ago. Now it's just a non-covered procedure. And so the question is, what would they need to have to get it covered? It's clearly not X number of level one studies, because any number that anyone could pick out of a hat were past that. Yeah. Must be some other explanation because they're not stupid. I mean, these are people in charge of multi-billion dollar companies. And it must just be that they're so locked into their business model that they control totally vertically integrated, they control every aspect of their business model down to the point that if they're losing money, they can raise premiums and not lose money anymore, or decrease payments to us, like they do every year, and always make sure their stock price is going in one direction. So, and then there's the whole political aspect of it, right? And so it gets into things that no longer are tied to medicine. So it gets out of my it gets out of my area where I'm comfortable. But the other big question is do we want them to cover it? We lose autonomy every single time they cover something.

SPEAKER_01 38:32

I don't, I want nothing to do with that business. You're exactly right.

SPEAKER_00 38:37

I mean, if they're going to cover it, and it's the argument I made at the one of the meetings earlier this year, if they're going to cover it in a way that respects the value that we're delivering to patients, in a way that respects the value the patients are getting, like TRICARE, for example, the five years they covered PRP for Neoate, their average payment was about $2,100 for a PRP injection for a knee. And I think that's fair. I think that pretty closely represents the value. And people will say, well, gosh, that's more than a partial menisectomy. Well, yeah, I think we're delivering more value than a partial minisectomy. We're not doing anything destructive. We are, if it's done well, we're giving people a chance to have significantly less pain for, you know, if it's done well on average, 18 months, maybe two years, and none of the risk, you know. So when TriCare covered PRP at that rate, that was an encouraging sign, but then it went away. And I don't know if it's ever going to come back. The more likely scenario is they cover it, and even if they give us a little bit of a teaser where they pay $2,000, you know, two years later it'll be $600.

SPEAKER_01 39:38

Yeah. In every scenario, that is what I can imagine. Because I don't, I have never seen my reimbursements go up ever. Well, we have a couple of questions from the audience, if you'd be so kind. I have a couple of questions here. So let's see here. In platelet-rich plasma research, we're moving towards reporting platelet dose. In BMAC MFAMXM space, what steps um should we be taking to establish similar standards for characterization so we don't find ourselves trying to retrofit consistency after large volumes of non-standardized data is already published. Like, how do we solve that conundrum in part, right?

SPEAKER_00 40:22

Yeah, it's hard. You have to, you know, we do have a total nucleated cell count. We can get that on the day of a BMC procedure. You can even run adipose through that, I believe. Although you'd have more experience with that than I do. But you can get a total nucleated cell count. The problem is all of the total nucleated cells are not mesenchymal stem cells or even hematopoietic stem cells.

SPEAKER_01 40:42

Yeah.

SPEAKER_00 40:43

So it's a proxy. It's the best kind of quantification proxy that we can do. And there have been papers published that have used that as a proxy and come out with pretty good evidence showing that, for example, for knee arthritis, your if your total nucleated cell count's 800 million or higher, is it million or billion? 800 million.

SPEAKER_01 41:03

It's 400 million, I think.

SPEAKER_00 41:05

Above 400 million. Yeah.

SPEAKER_01 41:07

Is that floor?

SPEAKER_00 41:08

Yeah, those patients did better, right? At the higher dose. And again, higher dose people did better. You know, imagine that. So without a total nucleated cell counter or without a hematology machine, if we're talking PRP, then you've got to make your clinical practice based on worst case. Like what's the lowest platelet count my normal patient may have, which is like 150. So if you don't have a hematology machine, what I tell people is then you've got to draw enough blood is if every patient that walks in the door has a platelet count of 150, and then you set up a practice where you're meeting whatever your number is, I won't tell you what your dose is, you can decide. But if you're trying to get a dose of 10 billion and you're saying everyone that comes in the door is at a platelet count of 150 and you're only drawing 60 cc's of blood, how are you ever going to get to a 10 billion dose? You can't. You just can't because there's starting with 10 billion. So same thing with bone marrow. If you're expecting to get to a certain dose because you're matching a protocol that had great results over a long term, and that protocol was drawing 150 cc's of marrow, how are you gonna get there if you're only drawing 60 cc's of marrow in your office?

SPEAKER_01 42:10

Yeah, yeah, exactly. Well, that really that's gonna add one of the there's one of the questions. Is one able to make adjustments to the platelet dose when using a hemocytometer? And I would say absolutely yes. That's why I use a hemocytometer so that I can adjust my dose before I inject. I don't know if you're doing that as well, but I definitely I do that time.

SPEAKER_00 42:31

I do. It's nice, you know, we live in a world right now where we don't really have any studies showing that we can overdose. Okay, there's not studies yet showing that we can overdose a knee with platelets. And there's plenty of registry data where people have put in 20 billion, 25 billion, even 30 billion platelets without a drop-off in clinical outcomes. So I don't really use it to cut back on my dose. What it would allow you to do if you wanted to, if you had an efficient PRP kit, you could draw less blood to get to the same outcome, particularly in a location where you don't need as much volume, and it would allow you to make sure you're hitting whatever dose you want. But in a bigger joint like a knee, I routinely draw 120 cc's. And if the profit count happens to be 300, which is great, it means I'm starting with like 36 billion platelets, and I'm probably going to inject like 30 billion platelets. Yeah. If you look at the chart, the chart is still down low at two years, they're still at a pain score at like 2.5 at two years, statistically. So you just have to think about you know what you're able to do in your practice and then craft a strategy around that. That's the kind of thing that that you help people with every day. I know it's kind of thing we talk about at places like IOF and Orthosono, too.

SPEAKER_01 43:46

Yeah. So then the question that we have a couple more questions. And so, what is the next step? You know, what are the takeaways? I think you just honed on one is if you don't have a hemocytometer, air on the side and aimless. Oh, right. I would aim for pretend that every patient has a playlist account of 150 and pretend whatever kit you use has a 50% efficiency rate, right? So if you do that math and pretend that's worst case scenario and you still can get dosage, you know, re reliably I draw at least 120. I can't think of the last time I draw I drew 60cc. I just would hate to be caught short. And sometimes, you know, you get surprised. You're like, oh, what you're 150. Shoot, man, you wouldn't have thought. Okay. Well, thank goodness that you know you will have enough to go round.

SPEAKER_00 44:40

And it's not, to be clear, it's not that you have to hit like 10 billion gets bandied about a lot. It's not that you have to hit 10 billion to have a successful outcome. There's plenty of research showing that you know, if I'm at 7 billion, am I gonna you know throw my hands up and go back in and say we have to start over? No. Okay. Something's wrong if I'm at three or four billion, okay, unless there's been clotting or some other problem. But the point is, more people, at least in my experience, more people will respond and respond better and for longer at the higher doses. So it's not so much that I'm looking for a particular number, it's just that I believe the higher doses, I get a higher percentage response rate, better pain relief, better functional outcomes for longer. So why wouldn't I want to do that? I've already got the needle in the arm, I can draw an extra 60cc of blood until I see a drop-off. I I and I haven't seen it in years and years, so that's why I do that. If you're going to be at the lower end, then again, using the knee as a model, if you're gonna be at the lower end in the 4 billion or 5 billion range, you might want to consider doing multiple injections.

SPEAKER_01 45:49

Yep. Yep. I mean we've seen data that shows that you know a series of lower dose PRP injections performs as good as the single dose high injections for a cumulative dose that's high, right? So definitely, if you're worried, we know that when you have a non-responder and you redose them, you can turn them into a responder. And so it just has to do with dosing. So I think that's the main takeaway. I know everyone came to talk about exosomes. There is a question about exosomes. There's already groups that are selling exosomes, and many practitioners are buying them and using them. Those practitioners always tout their helpfulness for MSK conditions. The question is why do you think they aren't concerned about the ramifications of using these? Is there a specific consent that absolves them from being targeted or you know, having some adverse action taken against them?

SPEAKER_00 46:45

When the cops pull me over and I show my little receipt from my drug dealer, they're gonna let me off. No. There is no consent that lets you off the hook if you're using a what they call a misbranded or adulterated drug. So I mean, on this question, the FDA's been pretty clear. They've actually released guidance specifically with exosomes in the title. And they've released public warnings against exosomes. And so it doesn't mean they can enforce it against everybody because they're not the FBI who's busy doing other stuff right now. But that's a whole nother webinar. But but you know, the FDA really hopes that their letters and the actions that they do take will raise awareness for the other clinicians who will then act accordingly. And so they're taking a big leap of faith that human nature is not going to be influenced by cash pay procedures, and I think they're losing that. I think they're losing that bet. They have to enforce more. I think that and the penalties have to be far more severe than they are now. If the only penalty is you have to stop what you've just been doing that was wrong for the last four years, that's not a disincentive for anybody.

SPEAKER_01 47:59

Yeah. I always talk about, you know, because people always ask me, they're like, well, how can they sell that? It's like, do you speed in your car? They're like, well, yeah. I'm like, is it legal? Well, no. What's the likelihood you're gonna get pulled over and get a ticket? Pretty unlikely. Everyone else is going the same speed. Even if you do get pulled over and get a ticket, how what is that gonna really affect your life? Are you gonna go to jail? No, you just like go to traffic school and pay a fine, right? So you're right. The enforcement is low and the penalty is low. Therefore, I think people are gonna continue to do that. Is it right? Is it legal? No. Are you willing to risk, you know, penalties, fines, your license? Maybe not, right?

SPEAKER_00 48:46

Tell me if you think this is true. It would go away overnight if the FDA or the state medical boards and state, you know, chiropractory boards or whoever, nursing boards, suspended a license for six months. It would go away overnight.

SPEAKER_01 49:02

Yes.

SPEAKER_00 49:03

Yeah, there's no question about it.

SPEAKER_01 49:05

Yes, yes, because you know, they can track you, they can figure out how you bought it, where you bought it. They like that's not the hard piece. So if they're now have crawler bots that are looking all through all the transactions, which are not safe, done tomorrow. Oh, you're you have a license. Okay, suspended, boom. Just like when you get a ticket, a speeding ticket, or like a toll ticket. If you go through the toll and they take your license plate and you're like, oops, sorry. You know, same thing. Absolutely. Well, so you know, what is the next step? How do you become successful? How do you have a successful orthobiologic practice? Well, we have our practice launch system, which is that orthobiologic knowledge, attracting the right patients, creating a solid cash-based business, creating high-converting consults, and then putting it all together for success. And that's our practice launch system for the business of orthobiologics. So if you want the fast track, it's really simple. We do a workshop every month. It's called the Business of Orthobiologics Express course. It's in Clearwater, Florida. I do it every month. So the next time this is available is in three weeks. So if you want the fast track, you can register for the Business of Orthobiologics Express course, and we can talk all about that. And then the next day, there's some hands-on workshops for BMAC and out of post harvesting, PRP, and protein concentrate. So there's a QR code. I'll make it a little bit bigger. That's that Bob or Business of Orthobiologics Express course. Now, you guys are in for a treat. If you can wait until January, this is the course. If you want to learn how to do ultrasound, this is the Las Vegas Regenerative Medicine and MSK ultrasound course brought to you by the one and only Dr. Don Buford. He's been doing it a long time. It's still the most practical regenerative medicine and ultrasound training course since 2008. I was there in 2010, so I would agree that has been a very practical. I didn't even take another course until 2018. So that one course can get you not only started, but going for a very successful orthobiologic practice. And tell me if I'm wrong, is it a whole day of regenerative medicine?

SPEAKER_00 51:37

So this will be the first course after all this time. You've gone to a full day on Thursday. And so what that allows us to do is for the most part, all Thursday afternoon will be live demos. We're going to do probably six live demos on Thursday afternoon of various sorts, you know, BMC, adipose base, PRP, different joints, different locations. And go ahead, you can talk about the special, go for it.

SPEAKER_01 51:59

Yeah, the special is that Dr. Beauford, for you guys only who are on this call, who have hung around, get a special. If you want to come to Orthobiologics, the Orthosono course, the Regenerative Medicine and MSK Ultrasound Training course, he's gonna give you $300 off. The code is Bob, Business of Orthobiologics 2199. That is a steal. So that's a three-day course, a full day of orthobiologics and regenerative medicine, and then two full days of ultrasound training, not only didactics but live models. It's a phenomenal course. And of course, I'll be there as well. So, you know, if you want to hang out, we can do that as well. So I'm so excited for this. This is phenomenal. We never have enough time, and so the fact that you've put on that full day, it's so it's a Thursday, Friday, Saturday, and then we do another advanced technologies training course on Sunday as well. Now, I'm looking at the questions. There is one more question, so I will do that. The question is platelet lysate being used in the United States? And if so, is there a standardized-based method to isolate it?

SPEAKER_00 53:20

Yeah, you've had experience with it too. So the answer, the short answer is yes, of course, it's being used in the United States. You know, I have colleagues that use it particularly in lumbar spine applications. Yes. You tell me when I say something wrong. But in terms of a standardized way, the way that I'm most familiar with involves freezing and then thawing it out. But I've heard a couple lectures on some other ways that sound kind of interesting. But let me let you let me let you take that ball.

SPEAKER_01 53:46

Yeah, absolutely. So just so we're clear, place it platelet lysate means that you take the platelets and you break them open, take the growth factors and filter out the platelet bodies. And those are used a lot of times for nerve-based applications like epidurals, like carpal tunnel, like any kind of hydrodissection around nerves, anywhere where you're really worried about an inflammatory flare. And so you're right, there's a couple of ways. Dr. Ben Rosson gave a really nice kind of overview. There's a freeze thaw method, there's a modified method, there's an ultrasonification method, and really any way that you can think to break open that cell, right? So there's a lot of different ways to break open the platelet. How do we lice cells? So go back to biology and look up because there's some freeze thaw, there's some UV, there's some ultrasonification, osmotic, there's a lot of ways that people are using that just a scientific basis to be able to lice the platelets. There's an alternative way, which is called platelet release, where we're just activating the platelets. That has not been shown to be as effective. So platelet release is just activating PRP and taking the suprinate. Lysate is actually breaking open those platelets and taking all of the payload of the growth factors. So people are doing it in the United States. You know, if you were to ask Scott Bruder, he would say that's not legal because it's manipulation. Then when you ask him if platelets are really cells and is blood outside the HTPC, then he concedes that maybe that's true. So it is a little bit more of a gray zone. I believe there was a book chapter that was published by Dr. John Kanab recently, K-N-A-B, on platelet lysate. So that I would urge you all to make a take a look. I don't, I think it's out, but uh if it's not, it's coming out soon. So I that's where I have for platelet lysate. I do want to invite you all to our newest member of the family. This is called True MD. We are hosting a two-day conference to transform your practice. It's in Phoenix, Arizona, February 7th and 8th. And this is going to be with me and some leading regenerative experts and business experts, marketing experts to be able to grow a thriving, patient-centered, profitable orthobiologic practice with proven systems, pricing models, growth strategies that you can implement right away. It's a two-day course. So this QR code gets you on the wait list, and registration is going to be opening in about 10 days. So get on the wait list. We have a limited number of people that we can accept because this is workshop style. This is not sit and listen and lecture. It is get things done so that you can go home on Monday and make more money and be successful. The final piece is I wanted to just make sure you save the date for the IOF Toby Max conference that's in Denver, Colorado, June 17th through the 20th. Really exciting stuff back in Colorado. Combo meeting. It's gonna be amazing. So please make sure that you save the date for that. If there are any other questions, please don't hesitate to put them in the chat. We'll stick around for a couple more minutes. But otherwise, thank you so much. I really appreciate Dawn. Thanks for joining. And everybody else, thanks for joining. This has been phenomenal. A really a great conversation about where we're at in the field of exosomes. It really is exciting and very interesting. I am very interested in the opportunities and what's going to happen in the future. And I think it's really also we're not sure, right? Are we going, are we pushing more to culture expanded cells or are we pushing more to EVs and an acellular product? Or maybe we use those for different things.

SPEAKER_00 58:06

Exactly.

SPEAKER_01 58:08

Awesome. Awesome. Well, if we have no more questions, I don't see any questions. Let me see. Maybe we have some other questions. I don't see any. I really appreciate your time and we look forward to another conversation in region in two weeks. This is gonna be quite an exciting uh conversation in region, so stay tuned for the invite. I'm really going to be excited about my newest guest. We're gonna keep it a little secret, but just to say, outside the US. So we're gonna have some international flavor coming in from in in two weeks. So all right, well, that is a wrap. I hope everybody got their fill of the illustrious Dr. Don Buford, and uh otherwise, we will call it a night. Thanks so much, everybody.