Orthobiologics: Why Inflammation And Immune Stimulation Matter | Conversations in Regen Episode 19

In this expert discussion, Dr. Ariana DeMers, the Queen of Business Orthobiologics, sits down with Dr. Thomas Buchheit to explain the role of inflammation in regenerative medicine and how immune stimulation differs from traditional inflammation. They explore how clinicians can use inflammation and healing processes, recognize when pain is immune-driven rather than structural, and avoid common sequencing mistakes in orthobiologic treatments. The conversation also covers practical frameworks for leveraging acute inflammation to maximize outcomes, and how treatment approaches have evolved over time with the immune-plus-nerve framework. Additionally, they discuss the impact of natural anti-inflammatories like turmeric on the body’s healing response, the clinical relevance and future direction of autologous conditioned plasma (ACP), and promising new therapies, including GLP-1 medications for osteoarthritis. 

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Transcript

SPEAKER_00 0:00

We have been programmed to think of all inflammation as bad. And it's true, right? If you have a flat immune response to injury, you tend to chronify. So we've kind of demonized the neutrophil in all of our therapies. Regenerative therapy is kind of like a workout. You've got to suffer a little bit to get a good result at the end.

SPEAKER_02 0:39

So happy to have you here. I'll do a little introduction. But what we're talking about is we're talking about regenerative medicine and talking a little bit more about the controversial topics and talking about cutting-edge insights that are shaping the future of interventional orthobiologics. And I really am excited to bring to you today Dr. Thomas Backett. I might have needed two H's, not two C's, but that's okay. It's B-U-C-H-H E I-T, founder of Triangle Regenerative Medicine and Biologics in Chapel Hill, and former director of the Regenerative Pain Therapies program at Duke, as well as a pain medicine physician at Duke University, Department of Anesthesiology, Division Chief, Editorial Board of Pain Medicine, and he is fascinated with the neuroimmune mechanisms driving chronic MSK and nerve pain. So for those of you who don't know who I am, I'm Dr. Ariana Demers. I'm a board certified fellowship trained orthopedic sports medicine, surgeon, and regenerative medicine aficionado. I am a sought-after educator and a trainer in both ultrasound and orthobiologics. And I've successfully been able to move my practice away from insurance-based care, even in rural California. So definitely can be done and do mostly regenerative orthobiologic therapy, treatments for cash-based services in my practice. My most important thing is that I am passionate about helping physicians incorporate orthobiologics into their practices seamlessly. So we're gonna get started, and there's all sorts of fun stuff. These AI companions are massively fun. I have like a billion of them myself, but super interesting. They keep asking me all these things that they want me to do. So I'm getting bossed around by these AI things. Okay, so we're gonna start with this conversation. And really, we get to hear from internationally renowned experts in regenerative medicine. We get to explore controversial topics that maybe people don't talk about on the podium. And so I really love to have more of a fireside chat conversation about my favorite topic, which is regenerative medicine and orthobiologics, and maybe gain some actionable insights that you can implement in your practice starting today. So we will get started, and I'm gonna talk a little bit about my perspective on orthobiologic treatments. So my thought and my opinion is that orthobiologic treatments will be first-line treatment for musculoskeletal care in the next five years. The train is leaving the station, and if you are not actively offering these treatments to your patients, you gotta get on the train because it is leaving the station. Now, successful integration is sometimes difficult. I hear this all the time. We know ortho biologics is the best treatment for our patients, but how to be successful? So maybe you've tried some things, but you don't know the latest science, you don't know the techniques, maybe you're a little bit behind on ultrasound training, maybe this cash business thing is really daunting. You hear about marketing, you hear about sales, and you want to run the other way, and it's not your fault. Maybe you just thought that I'm just not good at this business thing, but clearly we didn't learn this in school, so it is not your fault. You know, some people are just struggling on the fact that they know how to do this, they know that this is the right thing, but how do you actually capitalize on this four billion dollar orthobiologics market out there? Yes, four billion dollars, and maybe some of us are thinking, man, I deserve more, but this is so hard. Why is it so hard? So how do we win? Now we are gonna be talking about the science today. Man, we are gonna go deep with Dr. Blackite in the science today, but we also need to consider how we talk about this with our patients so we all win. And while we need a system to make sure that we hit all the high points, we're not obviously gonna go over all of this today, but we are going to get a little further along the journey to be wildly successful in your orthobiologics practice, and we need a system. So to start, we're gonna start with that orthobiologics knowledge. So, Dr. Bakai, why don't we get down to business?

SPEAKER_00 5:55

Sounds great.

SPEAKER_02 5:57

My friend, we have questions. We are wondering a lot about you, and I've read your book and we'll go over your book a little bit more, but man, this book of yours has opened up Pandora's box, and I think that we would love to know how that mind of yours works. So, my first question is in your book, when you say immune stimulation, what does that mean in a clinically useful way, and not just biologic theory, of how is it different from inflammation? Like, we're using orthobiologics to stimulate our immune system, which is a new kind of concept that I haven't really thought about before.

SPEAKER_00 6:45

So, can you kind of help me understand how this new Yeah, no, it's a it's a fantastic question. You know, I I could summarize it by saying that when I talk about immune stimulation, I'm talking about good inflammation. Full stop. We have been programmed to think of all inflammation as bad. And it's true, right? Chronic inflammation, it's universally bad for us. It destroys tissues, it causes chronic pain. And because of that, I think we've all equated acute inflammatory changes to chronic. And it's just not true. If you think of good inflammation, what do we do when we exercise? You create inflammation, there's a recovery cycle, inflammation recovery grows stronger. What happens when we have a cut or a wound or a fracture? It's good inflammation. You recruit the immune cells to the area and it starts a healing cascade. And what I wanted to do in the book was kind of look at the entire field of orthobiologics and regenerative medicine simply within the immune cascade, within this cascade of good inflammation. It's confusing to, especially to the lay audience, right? When we talk about inflammation, because they've heard for so many decades that the inflammation is bad for us. And so that's why I tried to kind of change the language a little bit to talk about it's really about immune stimulation. So that those are really almost, I almost use this synonymously if that makes, if that makes a bit of sense.

SPEAKER_02 8:10

Yeah, awesome. So this is your way of clarifying the difference between acute inflammation, which we all need and want to have this healing response, versus chronic inflammation. Is that correct?

SPEAKER_00 8:30

Right. Yeah, and if we look at that paradigm of good inflammation, and good inflammation being acute, strong, short-term, and able to flip an immune switch, everything starts to fall into place and makes sense. It makes sense why exercise is good for us, it makes sense how we heal. And it also explains some of these things we've seen where you know there's been an increasing press on the challenges and the problems with recurrent steroid injections, with chronic anti-inflammatories. And that all makes sense because those are shutting down these therapeutic responses that our bodies normally do. I mean, we have these built-in healing systems that all mammals on this earth have, and we're shutting them down, you know, frequently. And so, my the what the focus of the book was how do we not do that and how do we harness, really harness these inflammatory pathways, harness this immune stimulation. And then how does this reflect in regenerative therapies? I think PRP is a great example. You can even look at you know, mesenchymal cell therapies and everything else, they're really just turning on different parts. But you know, if you look at PRP, well, let's let's go back and look at maybe what happens if we sprain an ankle. You sprain an ankle, you bleed, you know, you release platelets, you release this growth factors, it pulls in white blood cells, and you know, the full first white blood cell pulls in as the neutrophil, and then it pulls in, you know, monocytes that convert to macrophages, and then that's the immune switch that flips, right? It's the macrophage immune switch that flips. If that happens, you get a healing cascade. And if it doesn't happen, you linger. And there have even been a few studies out there that have looked at the risk of chronic pain if you don't have an immune response, an immune stimulation response to injury. One was with acute back pain, one was with jaw pain and TMJ, even looked at fibromyalgia. If you have a flat immune response to injury, you tend to chronify. And so, really, the book, in some ways, is kind of about the benefits of acute inflammation, for lack of a better term, and how that's kind of the backbone of regenerative medicine.

SPEAKER_02 10:44

Awesome. So, you know, I a lot of my patients have been told, and we've all been told, ah, you gotta get rid of the inflammation, get rid of the inflammation, anti-inflammatories, I like whatever you do, don't get inflamed. Oh, I gotta get this inflammation down. And, you know, as we go through this, it's like, no, no, no, no, no, no. Like, let's harness this and let's ride that wave to resolution. Do you think that a lot of our maybe like reason why we have these chronic issues is because we've blunted our natural immune response with all of these anti-inflammatories, like everybody's living on ibuprofen. Do you think that that in part that plays a part?

SPEAKER_00 11:27

Yeah, I think it's a great question. And I my suspicion is that we've probably accelerated the problem of osteoarthritis around the globe by soaking in anti-inflammatories continuously because our bodies can't go through these cycles, the cycle of repair and recovery. We've blunted our immune system, and it doesn't happen. And and we need to kind of reignite it. And that's where, you know, PRP and some of the other therapies come in come into play. It also explains, you know, there's been a lot of great literature, and you've talked about this in your podcast as well, which is a great discussion of the importance of dose with PRP. And it also gets, that's the same discussion of you've got to have that strong stimulus to flip the immune switch. And if your platelet count is too low, you're not gonna get there. If your white count is too low, you're not gonna get there. And I actually have a talk I've given before. It's called Don't Fear the Neutrophil, because we've also been programmed to think that all white blood cells, even in PRP, are not good for us. And that's just not true as well. Matter of fact, there was a study that Mark Parisi and Luda Daichenko and others did up at McGill and with collaborators in Italy and US and everywhere else. And they were able to very clearly show that if you don't have neutrophil activation, you can, you're more likely to get chronic back pain after an injury.

SPEAKER_02 12:48

Okay. So now you've opened Pandora's box.

SPEAKER_00 12:52

Yeah, so that I was hoping to. I was hoping to open Pandora's box.

SPEAKER_02 12:55

No, are you telling me that this age-old adage of the fact that we want leukocyte poor PRP may not be true?

SPEAKER_00 13:09

There is a clear role for neutrophils and white blood cells, not just monocytes and macrophages, but but neutrophils in that healing cascade. And yes, that's what I'm saying. I think we need white blood cells in PRP. It is part of the healing process. You can even go into research that's been laboratory research that's been done. If you have an animal that has the immune system blunted with steroids or NSAIDs, if you give them neutrophils, you can recapture the pain relief in those animals. You can flip that switch. And so we've kind of demonized the neutrophil in all of our therapies, but I am a big believer that you you need that as part of that as part of that important immune stimulus to heal.

SPEAKER_02 13:53

That is fascinating. I'm gonna go one step deeper. Where do you think, and this is our just question one, but where do you think we've gotten off track along the way where we were like, ah, get rid of the neutrophils, we can't ever have neutrophils, no white blood cells. Like, where do how do we go so far astray?

SPEAKER_00 14:15

You know, when I kind of do a deeper dive into the literature, especially on PRP, it is, I think, understandable where this incredible confusion comes from, because there are so many products out there and there are so many formulations. And, you know, again, you've talked about this as well. It's a really important conversation to say that if you've got 10 different PRP PRP devices, you've got 10 different PRPs. And I don't know all of where it came from, although I actually I've seen a couple of studies, I saw one meta-analysis that said you need to use leukocyte poor product for joints, but they also included some non-PRP studies in that, including ACS, ontologous condition serum. So clearly that's gonna bias you toward non-white blood cells because there's no there are no cells at all in that. But I I think that the data is increasingly clear. And we've had, I think it also stems from this fear of inflammation. We think that if we put white cells in, we're gonna cause inflammation and it's gonna do harm. And it's just not true. I remember seeing, it was a basic science study, they were looking at cell culture, and they were talking about the the harms of white blood cells in the PRP because it upregulated IL1, it upregulated T and F and all these inflammatory factors. But what the Helser showed is when they did expression analysis, they looked at the proteins that those genes produced in those cells, it also turned on all these healing systems. And so to me, it's just like a workout. You know, regenerative therapy is kind of like a workout. You've got to suffer a little bit to get a good result at the end. And if it doesn't, if you don't have a little bit sore afterwards, it probably wasn't a good workout. And I think you know, we have the should have the same philosophy with our ortho biologics as well.

SPEAKER_02 16:03

Yeah, absolutely. That's such a fascinating, such a fascinating topic. And it I always feel like we're now at the at the beginning, right? Now we've finally gotten to the beginning, and and before that was just all the preamble, right? So it's so fun. So for clinicians that are already doing PRP or ortho biologics for that matter, what do you think the most important sequencing change that they could make tomorrow? Like what piece of the puzzle do you think they're missing? Or maybe they've got it maybe backwards that you that you think needs to be clarified or or talked about a little bit more.

SPEAKER_00 16:49

Yeah, so for folks who are already offering orthobiologic therapies, right? You know, one thing I think is really easy to do is make sure everybody exercises before you pull their blood.

SPEAKER_02 16:59

Okay. Tell me more about that. Well, you know, one is a believer, make me a case out of this. Yeah, you know, well, so you know, everybody on the bike for 20 minutes. Like, tell me why.

SPEAKER_00 17:12

People have talked about platelet counts and exercise, and you know, maybe there's some truth to that, but there have also been quite a few studies of growth factor release and exosome release and all those other things that are in these ortho biologics that are are produced and magnified with exercise. And so there, I think there are a lot of things in blood that we are not counting right now that we magnify with a little workout. So I think that's clear. You know, a healthy diet. You know, I'm a big believer in Mediterranean diet, so make sure, you know, put your patients on a Mediterranean diet. There's been the discussion that comes up, and I have this discussion a lot with patients as well, of turmeric and Boswellian, some of the supplements before. I tend to have people come off those if they can. Now, the reality is if they're taking that and they can stay off their anti-inflammatory, then you leave it on it, right? Because it's better to be uh rather on turmeric than you know, high doses of naperson or meloxicam or something like that. But, you know, it it I always tell let people's immune systems kind of go wild a little bit. Turn it on, upregulate it, let it stimulate, and then three or four days later, after after they start to see that immune switch, because if you look at that immune cascade and and when you get macrophage polarization to that, you know, those healing macrophages, it's a few days out. And so that's when I kind of restart some of the supplements. But I think those are very easy changes to make and you know, a good diet handout and a good pay, a good thing to pay attention to for patients as well.

SPEAKER_02 18:41

So do you exercise every single one of your patients before you draw their blood?

SPEAKER_00 18:45

I try to.

SPEAKER_02 18:46

Okay.

SPEAKER_00 18:47

Try to. What do you what do you do?

SPEAKER_02 18:49

I don't, and I should, right? I I know the research, I know the science, and yet it it it's a it's a, you know, all of us docs are really good about doing the thing we've always done. And so when you make when you're like, shoot, man, I need a a compelling reason why I should make this change. I know it to be true, and yet I still don't do it. So I gotta figure out a workflow that works. Well, you know, I don't I don't have a bike in my office. Like maybe they can just go for a quick jaunt around. I I don't know.

SPEAKER_00 19:22

Yeah, and I I don't have a bike either, but I just tell them to go for a brisk walk if they haven't worked out in the morning. You know, you also don't want people coming in completely dehydrated either, right? So that's that's the downside. That's not that's not good, obviously. But but a late workout or a brisk walk around the block before you before you draw the blood, that's usually doable. Let's unless they're showing up late to your office, then it's a different issue, right?

SPEAKER_02 19:44

Right, yeah, yeah, absolutely. Well, we still have some questions for you. So we're gonna keep asking all of these really fun questions, but we're also gonna leave some time for some question and answer time. So, what do you think are the highest yield diagnostic questions or exam findings that would point you more towards this like chronic pain, immune, nerve involvement rather than structural integrity or something to that effect? Like, where are those aha moments where you're like, oh man, this we need an immunomodulator?

SPEAKER_00 20:23

Yeah. So I, you know, you I I I wonder if you might do the same thing, but obviously, you know, if you're looking at a joint, you're looking at stability of the joint, you're looking at there's an infusion, that's easy. I tend to tap on the nerves around the joint too, because you end up seeing a lot of people with a lot of nerve sensitivity, even with especially also with tendinopathies. And I tend to, you know, add things. I'll do a D5 prolo hydrodissection for folks if they've got a lot of nerve sensitivity around a joint. Because it does seem like, I don't know what you think, but it does seem like that it's kind of a whole joint issue, and it's not necessarily just the that medial compartment or just that labrum, but it's a whole joint. And and when folks have a sensitization of nerves, I tend to try to work on that as well. I'm also a big believer in, you know, looking at you look you looking at the color on the ultrasound too. If you're seeing, you know, the usual hypervascularity and increased signal there, I tend to talk about things like adding protein concentrates and other ways to kind of kind of cool things off a little bit for folks, help them flip that switch. What do you do?

SPEAKER_02 21:29

Yeah, so I think that you're exactly right. And I absolutely really hone in on this concept of knee organ. Just it's a comprehensive environment, a microenvironment, and it includes the interarticular space, it also includes the extraarticular space, it includes the ligamentous status, and I do believe that it also includes the nerve status, right? I just had a patient today. And she's like, oh, my meniscus is still hurting. And when she she points, I'm like, okay, first of all, that's not your meniscus. And that's not even in the joint line. So it's not even close. But she's pointing to this pez location. And I tell you, that is so common. I'm sure everyone's like, oh, it's just pez bursitis. But then when you pop your ultrasound, there's no bursitis to be had. So then the question is, is it nerve? Is it one of your genicular nerves? Is it a saphenis nerve? Neuritis? Is it a hamstring tendinopathy that is under-appreciated, underrepresented? Like, I think there's more to the subject than a simple intraarticular injection. So the likelihood that you are going to come to my clinic and get a simple interarticular injection is basically zero. Because I'm I guarantee you I'm going to find something else that's going on in the knee organ rather than just the simple interarticular space.

SPEAKER_00 22:56

Yeah, and your point of you know, pest tendinopathies is a really good one too. You know, you probably had the experience, I had this experience of seeing this in a lot, especially the trochanter, right? People always talk about trochanter brositis, and we were dumping in years ago, we were dumping all kinds of steroids and everything else down there. And you know, we got you know, you probably started, I started looking about 15 years ago at those and realizing that most of these people that came in brositis didn't have brositis. They almost all had gluten gluten-intendedopathies. And if you get that to heal up, they do pretty well. If you dump steroid and they do great for a month, and then they're back in two months to get more steroid.

SPEAKER_02 23:30

Right. You know, I think back to all the horrendous things I've done to my patients over the years just because I didn't know any better. You know, I used to have this protocol for, you know, lateral hip pain, bursitis, right? Where I would do a blind steroid injection. And then if they didn't get better, then I would, and I would send them to therapy. And then if they didn't get better, I would MRI. Um, what I noticed is nobody had bursitis, right? It was all gluten tetinopathy. Yeah. But yeah, I still didn't appreciate that until I read Jane Fitzpatrick's study, and it was like youth PRP, dummy. I was like, oh my, this is interesting. But no, it was even before that, there was a lot of conversation in the orthopedic literature about the fact that the the lateral trochanteric pain was like the rotator cuff of the hip, and that we had a lot of tetanopathy that was not appreciated, but we still didn't really understand that biologic component of it, and we were still dumping steroids in it for a long time. You know, I think Jane Fitzpatrick's follow-up study that showed the, in my opinion, the detriment that is the cortisone injection, right? So when you look at her follow-up study at five years, at least 50% treated with PRP healed completely, no evidence of disease. And in the 50% that didn't heal, they had all had previous exposure to steroid. So I think if you're exposing your patient to steroid, you are condemning them to worse results because they don't have that ability to heal. Even when you have subsequent exposure to PRP, right? It's devastating to think. You're like, oh my gosh, what have I done to all my patients?

SPEAKER_00 25:23

Yeah, but you know, we didn't know any better. 15, 20 years ago, I was, you know, we were all doing. That's what, you know, we didn't know of it. And it really wasn't until we all started looking and looking at the structures of the tendons and looking at the fact that there really wasn't bursitis in most people. And if there was, it was always associated with tendinopathy, and starting to think, well, then you think, well, how do we get the tendons healthier, right? And and the answer is really going to be growth factors and PRP and things like that. So it was really interesting, right?

SPEAKER_02 25:51

Don't don't dump steroids in it? That's weird.

SPEAKER_00 25:54

People felt a whole lot better, but it was it was really an interesting time because I think a whole lot of us all came to the same conclusion nearly at the same time, and from a lot of different a lot of different areas, but it makes sense, right? And also again makes sense with this concept of immune stimulation and good inflammation that we need this to heal. And to me, osteoarthritis and tendinopathies are just chronic wounds. You know, you don't treat a chronic wound with steroid, you treat a chronic wound with things that promote healing of the wound, right? And and it's not a big surprise that the first PRP publication ever done was by a wound surgeon. It was Dr. Knighton in Minnesota, it was 1986. He he was to heal wounds.

SPEAKER_02 26:42

Yeah.

SPEAKER_00 26:43

Makes sense, right?

SPEAKER_02 26:44

Yeah. So we still have more questions. Ah, this is so great. I mean, honestly, I read your book in one day. It was phenomenal. I loved it. And I was like, I I think I called you the next day when I was like, oh my god, this is this is amazing. So, for practical interventions, what do you think is the most practical, low barrier intervention that physicians who maybe aren't practicing having a lot of PRP in the orthobiologics in the clinic? What do you think is the the easiest framework, the easiest way to kind of talk about this need for acute inflammation, for immune stimulation?

SPEAKER_00 27:27

It it's it's hard, right? Because patients come in and they want to fix and they they're used to taking anti-inflammatories when they when they hurt. I I wonder if education, and I know education is very time-consuming, which is actually one of the reasons why I wrote the book. So I could give the book to patients and say, please read chapters 10, 11, 12, or chapters 4, 5, 6, or whatever it is. And it's really been nice because then I can start a conversation with them and then I can use the book to kind of finish it. And I said, so here's what we started this, but I really want you to do a deeper dive in it, you know, because they come in with fantastic questions, right? And and even if you have a longer clinic appointment, which I have longer, I've you know, fortunate to have longer appointments, we still run out of time because it would take nine hours to do a full explanation of what's going on, right?

SPEAKER_02 28:17

And so cost-effective. You you are correct.

SPEAKER_00 28:20

Right, right, right. And so uh to me, the book is a teaching tool. So I have handouts. I have I have handouts I use on on healthy foods and fats. I try not to use the word diet because the diet is a triggering word for many people. So I talk about healthy foods and healthy fats. I have handouts on on exercise. I I also do employ and look at some supplements. We've mentioned a couple of them before. To me, the strongest uh argument for them is if again, if we can if I can use them to decrease the need of the use of anti-inflammatories chronically. So I I to me it's the educational tools and those handouts, and then and then also the the book has been, at least for me, a really valuable educational resource as well, especially for patients who have an interest in in exercise, healing, want to get off medications, interest in PRP or stem cells or ACS or any of the other therapies, that they can go as deep as they want into it. Because this, you know, I think the science is, I worked really hard. I mean, it took me over six years to write the thing. So I worked really hard trying to make sure the science was accurate but understandable. And I had an editor who kept on me to make it understandable because there are lots of parts that we had to chop out for simplicity's sake. But in the end, I think, and I think and I hope it works for the lay reader as well.

SPEAKER_02 29:42

So yeah, it's really interesting because you, you know, the the way that you wrote the book was understandable to the lay reader, but what what I really appreciated is that you didn't dumb it down. And so, as a physician, getting into orthobiologics, really looking for that scientific basis and background, it's absolutely what I would consider a must-read primer for anybody that's getting into orthobiologics who hasn't really had the exposure or the or the ability to deep dive. You know, I wish I would have had this early on in my career when I was getting into it, because let's face it, orthopedic surgeons are not well versed in the orthobiologic world. We we spend a lot of time talking about surgery and widgets and then like how best to construct X, Y, or Z, but I think sometimes we forget that there is a biologic human attached to all the cool things that we can do. And so this this was such a thoughtful, well-versed scientific primer that is clear enough for the lay person, the you know, maybe not fifth grade level, but I think that clear enough to really help, but also smart enough and and deep enough to work an amazing magic for docs as well. So thanks so much for taking that. I mean, that's a lot labor of love for sure. I I do have kind of a question, and I would love if you could walk us through you know, this this consideration of immune plus nerve, and and like before you had this framework of thinking about nerves, thinking about immune stimulation, thinking about maybe central sensitization, chronic pain, you know, back in the day that 15 years ago you versus the today you, where do you treat cases differently besides besides clearly the trochanteric bursa problem? What other cases have you kind of done a 180 with? If you could kind explain it to us, maybe an example of that?

SPEAKER_00 31:58

You know, beyond what we've already talked about, I guess I could use myself as a case study as well, because I've had a couple of knee injuries, and I had one about 15 years ago, and I had another one a few years ago. And the first one I sucked myself in anti-inflammatories, and it was a slow recovery. It was a meniscus terror, it was a basketball game gone bad, the meniscus tear, and and I didn't have surgery. But it took me about six months before I was really back to function. And the second time around, I actually had a bigger injury, and I ended up just letting it flare. I didn't take any anti-inflammatories. I had colleagues that thought I was insane because I was limping around for a couple weeks. But, you know, I was I was skiing again a month later, so it wasn't a six-month recovery, it was a month, and I was, you know, still a little discomfort. Certainly it was nothing compared to what Lindsay Vaughn has gone through recently. But but it was a nice comparison of what happens if you suppress the inflammation to just let it run, let it let it convert, let the immune cells and immune stimulation occur and and work through that. And it was a little bit of a little bit of an individual, I guess, an end of one experiment for lack of a better term. But it was a nice illustration that again it hurts, it hurts to have a have a tear and to not take anti-inflammatories. But the recovery was faster. And I think it was a nice lesson for me as a little bit of a proof of concept in some ways, too. And so I use that example with patients as well, because they come in with issues and injuries and things, and so we can talk through that, and and that's helpful because it, you know, I'm less it it doesn't come across as me preaching to them because I've kind of gone through it myself. And so that that's an easier, you know, it's an I think it feels like it maybe an easier conversation in some respects because I'm just not telling them, you know, you need to hurt, you need to be off your anti-inflammatory, as I said, you know. I can tell me it does, it does hurt it. It's you know, but you're gonna heal faster because your body's gonna do the work, a lot of the work for you.

SPEAKER_02 33:57

Yeah, yeah. I I mean, I I I also share my experience with you know PRP. Definitely I've had simple interarticular injections. I've had my my most amazing claim to fame is I had a full tear of my collateral ligament on my index finger. And as a surgeon, that's kind of annoying, right? Where every time you go to use it, more than annoying. Yeah, yeah, it's very annoying. And I was like, gosh darn this thing, this is not healing. And so I finally put an ultrasound on after six months of ignoring it, and it was fully torn. I was like, well, shoot, man, this is a problem. And I went and talked to the surgeon, and he's like, Well, we can probably, you know, repair this, and you'll probably get back to work by like six to twelve weeks. I was like, probably, first of all, and second of all, six to twelve weeks? That's a problem. That ain't happening. So I got this brilliant idea that I was gonna just inject my and my time, my ligament and the joint and brace it and and see how it went, right? Holy smokes, it hurt like the dickens. I couldn't even put my hand below my heart for like two days, and and then I poorly planned as well because I had surgery like two days after a PRP injection, which is idiotic. But I will say that I was able to work and operate with a brace on, you know, that whole time period. And then the star of the story is I had complete healing of a fully torn collateral ligament that had been torn for six months, right?

SPEAKER_00 35:38

Because I'm an idiot, and that's remarkable, really.

SPEAKER_02 35:41

It really is remarkable, and so you know, the the the consideration is like, can this stuff actually work? And clearly I am uh a connoisseur, but I also have seen it work for me for those exact reasons that all of our patients come to see us because they don't want surgery, they can't take time off, like six to twelve weeks off. Oh, sure, because I'm independently wealthy, of course, you know, and so I think that's a consideration that we all have to put ourselves in our patients' shoes, and we tell patients a lot of weird things that we would never accept for ourselves. So I I I would agree that that end of one is a pretty interesting experience.

SPEAKER_00 36:28

It is, and it brings it home a little bit too, right? You know, I kind of consider myself a specialist in orthopedic limbo, and those are the folks I love seeing, right? It's the you know, it's the it's the patients who they can't do what they want to do, they're yeah, they've still got a little cartle left. They're not a candidate for joint replacement surgery, or they're too young, and but they can't do what they want to do, and you try to get them moving again. Because we all know that you know, movement, movement is key, right? So if we can get them back to the gym and and it does them a lot of good. Yeah, we can also talk about some of the misconceptions around you know the concept of a stem cell versus a mesenchymal cell versus as well. That's another Pandora's box if you want to open that one up.

SPEAKER_02 37:08

Yeah, yeah. So I think where I would like to go is like maybe clinician misconception, but maybe you know, referring physician where they want to refer you your patient for this stem cell injection, right? Oh, can you can't you just fix their pain with an injection? I want my pain shot, right? So, how do you communicate to clinicians what it is that we are actually doing? Are we using stem cells? Are we not using stem cells? Or what do like from a from a clear perception that maybe you know you used your book to kind of clarify this, but also is helpful for the non-orthopedic physician who may be wanting to refer to you. How how do you kind of clarify this for the layperson but also for the the referring practitioners?

SPEAKER_00 38:05

You know, I I think we're just finding ways to stimulate everybody's own healing response. And I feel like, you know, humans, we have built-in healing systems. Sometimes they get a little tired and a little worn out. And my job is to kind of get them, get them stimulated and get them turned on again. And so that's what I do. And when we can do that, sometimes it gets nutrition, it's exercise, and maybe it's prolotherapy, maybe it's PRP, maybe it's some of the other advanced, more advanced therapies. But all these are doing are turning on everybody's innate healing mechanisms. And so that's what I tell tell people we're we're working on. And I don't tell people we're growing we're not growing new tissues or growing new cells. I feel like we're I tell them we're we're making tissues healthier and and we're making making them function better.

SPEAKER_02 38:50

So yeah, and so to that end, you know, there's always this conversation about is it really regenerative medicine? Are we really regenerating cartilage? Are we really regenerating tendon? And I think and you tell me if I you're this is partially correct, is in part I think we are making tissues healthier. So are we growing new cartilage? No-ish, but we're not fully wrong. So can we comfortably call this regenerative medicine?

SPEAKER_00 39:26

You know, if you define regenerative as improving tissue health, then yes, right? You know, we're not right, we're not growing new ears or growing new kidneys in a lab culture, right? I mean, that's that's a that's a different world. We're not using inducible pluripotent stem cells or some of the other things that that people do. But we're improving tissue health. And so that's where I like to, that's where I like to leave things with the patients, is that I, you know, we have very very good tools to do that. And and with that comes pain relief, you know, very often, and sometimes it obviously takes a couple weeks for the pain relief to kick in, but that's how I like to, that's how I like to present it to to patients. You're right. I mean, you do recruit, so even if you're not, even if the cells or the tissues or the or the what you're injecting isn't growing and new cells long term, you are recruiting, you know, the the body's own regenerative cells to the area via those chemotactic signals, but that's that's a little bit of a different argument, isn't it? But it's still restoring tissue, it's restoring tissue health.

SPEAKER_02 40:33

Yeah, yeah, I I would agree. And and you know, if you are completely healing a tendon or a ligament, isn't that regenerative?

SPEAKER_00 40:41

To me, it would be.

SPEAKER_02 40:43

So, yeah, I don't know. Like, I think the jury's still out on that, and I think it's also semantics, but for the most part, I feel confident and comfortable to consider this as a regenerative therapy. I think we're we're not wrong. So, thanks so much for sharing. You know, the question is always okay, so we've we've done this massive deep dive on science. So, what does that next step look like? Well, clearly, you know, we want to be able to now take this science that we're used and we've done the deep dive on and say, okay, now that we have the a really clear understanding of the science, how do we use this knowledge to help the right patients, the ones who need our help? And so our practice launch system is part of the way that we define, and I think you've had a little bit of exposure to this, but our orthobiologic practice launch system helps you with your orthobiologic knowledge, how to attract the right patients, how to create a viable cash-based business, how to have high-converting consultations, and then clearly putting it all together for success. If you want the fast track, I'm gonna invite you all to Clearwater, Florida for our hands-on workshop and lab, the business of orthobiologics express course. This is a Saturday afternoon four-hour course about patient-focused branding, how to keep your orthobiologic patients from your practice and treat them, effective pricing strategies, how to use AI to expand your practice with tools and tactics for growth, proven solutions to overcome challenges and avoid the pitfalls that are common in cash-based practices. And then on Sunday, we have a lab about that we talk and teach lipoaspirate training for MFAT. This is a cadaver lab. We also review bone marrow harvest and concentration as well as getting your hands dirty for PRP and protein concentration processing. This is hosted by Apex Biologics, and the best part is there's no cost to attend. So if this is interesting, these are the dates for February, March, and April. Just scan that QR code and take a look. If you are wondering what your next step should be for your orthobiologic practice, whether you're just thinking about it in the middle of it, or learning how wondering how you can scale and grow that practice. If you want to take a little quiz that we put together, just scan this QR code and we will. This is Dr. Buckheit's book. It is wonderfully amazing. I love it. I I I do truly think this is a primer that everyone who's doing orthobiologics should be reading. The QR code is there. Please scan that QR code if you can't to find it. Just search Healing Joints and Nerves by Dr. Thomas Buckheight. And We will uh it's it's on Amazon. Go get it. It is definitely a really great book. So kudos to you. I think what we'll do is take some questions. Dr. Buckeye, thank you so much for joining us. It's been an amazing conversation. If anyone has any questions, please put those in the chat. I'd love to hear. And then we'll go ahead. I think we may have a QA, but I can't remember how to do that.

SPEAKER_00 44:32

And as you're doing that, I'll put a plug-in. Your course was great, Ariana. It was a great, it was a great course.

SPEAKER_02 44:36

So oh, thanks. Yeah, this one.

SPEAKER_00 44:39

Yes.

SPEAKER_02 44:40

Yeah, it's so fun. You know, it it's a it's a quick four-hour course about the you know the the top ways to become successful in cash-based business, right? And we haven't learned this stuff, we don't know this stuff, but what we have proven is we are physicians that know how to learn. So this is a teachable, learnable skill. It's just what we haven't gone to school to do this yet. So come to uh this express course, we'll go to school for a little bit and understand how we can best serve our patients with orthobiologics. I do have a question here. There's a question about the natural anti-inflammatories, like turmeric. Do you think it blunts that response or do you think it's an actual natural anti-inflammatory? Like, I I actually don't know. I use turmeric as one of my supplements that I use to get patients off of ibuprofenolib, any of those things. I add turmeric, I use fish oil, I use, you know, the berberine to make sure their blood sugar is stabilized. I use a a number of supplements to really kind of enhance their overall health and well-being to be able to, and I tell them, you know, listen, you're the pharmacy. I got I gotta borrow from the best pharmacy. We want the best pharmacy possible. So we're gonna try to optimize your your health and your cellular metabolism so that we can get the best things out of it. What's your thoughts on on these supplements blunting that natural response?

SPEAKER_00 46:13

I I do I do think they've probably blunted some. You know, I again I think if you're choosing between an anti-inf anti-inflammatory over-the-counter versus a turmeric and Boswelli or whatever combination you want to use, clearly there's significant benefits of the herbal versus the versus the pharmaceutical in terms of gut health, in terms of kidney health, in terms of all the side effects that you're avoiding. But those these these herbals, turmeric in particular, I believe, is an NF kappa B inhibitor, similar to some of the other ones, right? And so there probably is some inhibition of that immune stimulation signal. And so if somebody is on it and they, you know, they're getting great benefit of it, I'm careful of taking off, but I still tend to take it down a couple notches or even off prior to blood draw, for instance, for for PRP. I'm not sure if it's as important as taking them off their ibuprofen or naperson, but it's one more thing that that I think can can blunt that immune cycle a little bit.

SPEAKER_02 47:17

Yeah, yeah. I think that's interesting that you bring that up. And I I think that uh that's not you know, it does I was just looking it up, and you're you're exactly right, it's the NF kappa. And I so now I'm like rethinking everything I'm doing, right? I'm like, oh man, I don't know. But yeah, is what what's the lesser of two evils? I think we've shown that ibuprofen and a leave are less beneficial. But I think that's a great question. So I think the answer is that if you can be off everything, that's the best.

SPEAKER_00 47:50

I think I think that's the answer. If you can be off everything, that's the best. Let your body, let your body do the work and then go back on it after you've after, you know, three or four days or even four or five days of macrophage polarization, and and then get back on them. That's the ideal.

SPEAKER_02 48:05

Awesome, awesome, awesome. Okay, so now no one else is wanting to give me any questions, and that's totally fine. I have you all to myself, so it's this is perfect. Uh now in the book, you you talk a little bit about the autologous condition plasma. And can for those of you who are not like what is this? What is this deal like? Tell me a little bit about your experience with this and and maybe where where things are going from this standpoint.

SPEAKER_00 48:37

Yeah, I had a little bit of an interest in it because you know, autologous condition serum has been out for a while, and I was working with you know Peter Whaling and some other folks in in Germany from clinically and and from a research perspective. You know, people called it IRAP, and if you even go to the veterinary circles, they call it IRAP, which stands for interglucan 1 receptor antagonist protein, so IL1 RA. And everybody thought it worked because it shut down IL-1. IL-1, we know, will chew up cartilage in a joint, right? So IL-1 chronically is pretty damaging to cartilage. And everybody thought, well, this process that an incubation process, it releases IL-1 RA, it blocks IL-1, end of story. But it wasn't the end of the story because there's a recombinant protein out there in Ekinrah that, you know, your orbitologists use, and and that was tried in osteoarthritis and it didn't work. As a matter of fact, by the way, as a side note, if we look at all the trials that have been done for immune suppression and osteoarthritis, they've all failed. TNF and TANRCEP a TNF inhibitor failed, edilumab a TNF inhibitor failed, IL6 inhibitor failed, and IL1 inhibitor failed. They all failed, which again back to the story of suppressing inflammation doesn't cure osteoarthritis. It's a wound you need to heal, not inflammation that you need to just shut down. But there was the same process with with the autologous condition serum that we were looking at. So we did we start doing a deeper dive and just looking at it in the lab. And it turns out that actually a lot of it's driven by exosomes. We were able to show that you pull them out, it stops working, takes away most of the effect, you put them back in, puts the effectiveness back in.

SPEAKER_02 50:23

And these are these are autologous exosomes.

SPEAKER_00 50:26

Autologous exosomes. So, and you know, it's gonna be really interesting to see how the exosome story evolves over the next few years. You know, they've been a little bit tricky, right? Because a lot of them are manufactured off of cultured mesenquymal cells, and obviously culturing mesenquymal cells is not considered minimal manipulation in the United States, and so that gets very tricky. But I think the story is not going away. You know, this the possibility for exosome-based therapies is going to be interesting, and you know, I think if you look five years ahead, there's gonna be something out there.

SPEAKER_02 51:03

Um, you said something, and I really had a question about that because we, you know, you're right. They've tried to treat osteoarthritis with all of these immune inhibitors. Now, there are some very interesting things happening with the GLP1 medications that are showing significant improvement in osteoarthritis symptoms. And so it just it just dawned on me. I'm like, okay, well, that was a definite, oh, by the way, wow, this is cool. We found an arthritis treatment. Um what do you make of that?

SPEAKER_00 51:44

Well, so do you think that's because of the decrease in severity of metabolic syndrome and the folks who are on GLP ones?

SPEAKER_02 51:52

I no.

SPEAKER_00 51:54

You don't think so?

SPEAKER_02 51:55

Yeah, I don't think you know the issue. And I'll tell you what my experience about the GLP ones and what I've noticed over the years in my patients with these inflammatory arthritis, they they happen really quickly, right? So their symptoms start to resolve quite quickly before reversal of the metabolic syndrome. Yeah, so yeah, case in point, today I have a patient we started on GLP ones one week ago. She has significant improvement in her pain function, nothing else changed. She lost two pounds, she's greater than 300 pounds. Wow. Her metabolic syndrome is massively problematic. Did we change all of her hemoglobin A1C? Did we change all of her her cholesterol? Did we change all of her metabolic syndrome? Good god, no.

SPEAKER_00 52:55

What do you think's driving that effect?

SPEAKER_02 52:57

You know, it it's really interesting. The first time I heard anything about this, I was at I went to the peptide world conference, right? I'm like, ooh, great, I'm gonna learn all about peptides. This is gonna be great. And what uh 70, 80% of it was like diet, exercise, sleep stress, and then oh yeah, by the way, there's just peptides, and the most famous peptide is a GLP1. And what I came away from that conference was just showing that this peptide on all the main metabolic cellular health pathways was beneficial, so I think it is actually positively affecting your cellular health much quicker, and that's why we're starting to see this like almost miraculous decrease in arthritis symptoms pretty quickly, is because we're we're starting to affect the the cellular health pathways at that base level quicker than you know, you can affect the metabolic syndrome.

SPEAKER_00 54:01

Yeah, so it's gonna be really interesting to see how that story plays out. Somebody's gotta do a study on it. They can do a study in tendonopathies as well.

SPEAKER_02 54:09

Yeah, yeah. There's so much there. I mean, right, we just started the beginning, right?

SPEAKER_00 54:14

Right, right. Yeah, no, and I think you're right. That's a really important point, is that this is the very beginning. This is a it's a new field of medicine, it's a new field of science. We know so much more now than we did. When I started the book six, six, almost seven years ago now. There were so many questions, and some of those questions have been solidified. Even the simple simple questions of platelet dosing. I mean, that's so nice to have that information now. The importance of immune stimulation, the importance of white blood cells to stimulate this healing response has been clarified quite a bit with some really important high-level publications as well. And so the story is clarified, but they're still evolving. And it's I think it's a really exciting time.

SPEAKER_03 54:59

Yeah.

SPEAKER_00 54:59

I think in 10 years we're gonna look back and say, I can't believe we were doing all those steroid injections and doing all those anti-inflammatories.

SPEAKER_02 55:06

Oh my goodness, right? Like, literally, I think back and I'm like, oh my gosh, what was I doing? How could I have like injected cortisone in people's hips and been like shocked that they needed a hip replacement six months later, right? Like, I realized we didn't know that then, but at the same time, it proved true in my own practice and then was later borne out in the literature. And and so I rarely use steroids. I can't I use them so so sparingly that it's like it goes bad in my cabinet, right? Because I just don't use it. There's so many other options, there's so many good things. There's prolo therapy, there's neuroprolo, there's you know, even toridol intra-articularly, there's PRP, BMC, adipose, you know, protein concentrate, ACS, like there's so many things. Why reach for a steroid?

SPEAKER_00 56:05

Right. We've got a lot of tools now that we didn't have uh a while back, and it's really an exciting time.

SPEAKER_02 56:12

Awesome, awesome. Well, you know, thank you. Oh, deep tea agriwald just shared a graphic that illustrates the GLP power. Awesome.

SPEAKER_01 56:23

Yeah, I just shared it with you. Hi, how are you? I'm good. A nice graphic. I love showing it to patients that come in, and it's like first you want to rein in your metabolic health and make your terrain nice, and then you can add all these regenerative therapies, and things work so much more effectively, but it's hard for people to understand like their arthritic conditions and how that relates in the bigger picture. So I love that graphic is very simple for patients to look at.

SPEAKER_02 56:50

Yes, yes. Yeah, basically, you know, they these GLP1s are inhibiting that chronic inflammatory state. And so going back to acute inflammation is good, chronic inflammation. Do you think, DPT, do you think that it resolves that chronic inflammation, or do you think that it blunts the effects? Like what what what do you think the GLPs are helping to kind of do that?

SPEAKER_01 57:19

So I yeah, I think it's really dampening that metabolic cascade of inflammation. So that microenvironment is helped. So when you put any sort of regenerative therapy on top of it, the appropriate inflammatory response takes place, but you've mopped up what you can before you do that, right? So it's just more effective.

SPEAKER_02 57:38

Yeah, yeah. I think this medication, you know, has been helpful for my patients, helpful for primary treatment of arthritis. Some for some of my patients, this is all I'm doing for them for their arthritis.

SPEAKER_01 57:51

I've solved a lot of chronic pain issues just with metabolic management, and then I'm like, hey, maybe you should now think of something regenerative for that congenital hip dysplasia because it will bother you at some point. Yeah. But harm reduced, harm reduced, and so now you're doing things in a really nice, stepwise manner.

SPEAKER_02 58:08

So so good. Thank you so much for sharing that. That's so great. Gosh, I love I love this conversation. Thanks, Gosh.

SPEAKER_01 58:14

Me too. Me too. Thanks, Mom. Nice to meet you. I'm so glad.

SPEAKER_00 58:17

Oh, yeah, great to meet you. Thank you.

SPEAKER_01 58:19

I'm glad someone in anesthesia is thinking this way. Welcome. The both of you. One, two, ready, break. No, we've got a we've got a bunch of people. You have some work to do, but you've done so much, Ariana, for the field, so that's great.

SPEAKER_02 58:32

Thanks, guys. Well, we are over time, but again, this is the book. This is the primer you should be getting. If you don't have it, please go to Amazon. No, I don't get any kickbacks from it. I just think it's an amazing book. So please grab it. I think it will be one of those books where you read it and you go, oh man, this makes so much sense. So, Dr. Buckight, thanks so much for joining me. Thanks for taking six years to write this amazing book. And for everybody else, thank you so much for joining us. We'll see you back in two weeks. Look forward to another amazing conversation. And I am looking forward. Next in two weeks, we have Dr. Kristen Oliver from the Bluetail Medical Group joining us. So please, please, please come back, hang out with us. We love to have all of this conversation. Have a great night, everybody, and we'll see you in two weeks.