Regenerative medicine modalities is widely used in clinical practice. Despite the broad adoption in many scopes, confusion surrounding appropriate recommendations compared to surgery, patient benefit, and nuances regarding application still exists. This multi-disciplinary roundtable will explore three common pathologies seen in musculoskeletal orthopedic settings and discuss surgical interventions compared to non-surgical regenerative medicine modalities.
Participants will be able to discuss the surgical options for patients with the below listed pathologies.
Participants will be able to discuss appropriate PRP preparations for the pathologies mentioned. Identify appropriate times to consider regenerative medicine referrals for patients.
Topics for discussion: Knee Osteoarthritis – PRP/Stem Cell/A2 Macroglobulin if compared to arthroscopic debridement Rotator Cuff Partial Tears – PRP options and surgical repair Surgical Indications for Biologic Augmentation
Speakers: John M. Tokish, M.D., Orthopedic Surgery Steven K. Poon, M.D., C.A.Q.S.M., - Sports Medicine Arthur J. De Luigi, D.O., M.H.A., Physical Medicine & Rehabilitation Moderators: Anikar Chhabra, M.D., Orthopedic Surgery Welcome and thank you for joining today's webcast. I'm alan chips from broadcast Met and I'd like to thank Mayo Clinic for their longstanding partnership and for agreeing to participate in today's webcast during today's webcast engagement tools are available for your participation. You have the ability to chat, ask a question and even take notes that will be emailed to you after the program. With that being said, I'd like to turn the program over to our moderator Dr chopra. Thank you. Welcome and thanks for joining us for this webinar panel for a discussion on biologics. This webinar panel is titled appropriate musculoskeletal applications for regenerative modalities. Regenerative medicine modalities are widely used in clinical practice today despite the broad adoption in many scopes, there's a lot of confusion surrounding appropriate recommendations regarding should you use biologics and surgery. What are the benefits to patients? There are a lot of nuances also and how to get the biologics and what type to use. So this multidisciplinary roundtable will attempt to clarify some of the myths regarding biologics use, including the science indications, risks and things. You should ask your doctor. I'm excited about this because of the excellent panel. We have assembled all from Mayo Clinic Arizona. So I'm gonna first introduce the uh the male clinic Arizona members who are on this panel and then we'll start with the with the panel first myself. I'm dr anna car chopper. I'm the chair of sports medicine and I'll be moderating at Mayo Clinic Arizona. I'll be moderating this session second. We have Dr J. T. Toke ish who is a professor of orthopedics. The fellowship director at Mayo Clinic Arizona of the sports medicine fellowship And he's also the P. I. The biologics association registry and bio repository here in Arizona. Dr Jason de Luigi is the chair of physical medicine and rehab and also a professor uh in that department here at Mayo Clinic. Arizona dr steven poon is an instructor in orthopedics and team physician of Arizona State University Athletics and Arizona Diamondbacks. What we've done with this panel is we've set up uh this so that we have three different specialties. Dr poon is family practice trained. Doctor de Luigi is PM and are trained and dr token is an orthopedic surgeon. So having different perspectives about biologics I think will highlight the differences and how we all different groups use biologics in our practices. So first let's start on the biologics background. So dr poon for our audience. Can you define some common regenerative modalities including prp including the types of Prp stem cells and neon and a two macro globulin. Thanks dr it's an honor to be here with this esteemed panel of my colleagues. So there's a lot of confusion as you mentioned regarding the different types of regenerative modalities. It sounds like a very intimidating but also attractive sounding names. So I often break down the different classifications of these regenerative modalities into different subsets. We have our blood products like the prp then we have our surgical products and then we also have the harvested products. So with the prp, what that stands for is platelet rich plasma. And it's a general mechanism by which a patient has their blood drawn similar to a lobotomy draw, but just in a much larger volume. And then that whole blood is spun down rapidly in a centrifuge. And their different commercial kits that are used to process that and extract the liquid component which is plasma with a concentrated layer of of cells which include the platelet cells which are active in the body's inflammatory system. And then sometimes that's processed a little bit further into high white blood cell or white, low white blood cell counts and utilized in different clinical applications in the body, from joints to attendance. From our surgical standpoint we have these tissue matrices including the Ambien products and actually dr Turkish is a leading expert in this particular field but it's used to augment um healing during and after surgical procedures. It tends to be a product where it's augmented into the repaired areas in the surgical areas and it releases a high concentration of growth factors to help encourage healing in the various parts of the body that has been indicated for whether that's graphs or tendon repairs. And then we have our harvested products which includes the the stem cells. Now, a little word of caution here that I always tell my patients is that stem cells. It also has been around the nomenclature has been around for a while, but we're talking specifically about in this realm of what we call mesenchymal stem cells and not undifferentiated stem cells. And most of the time it's harvested either through a bone marrow, aspirate, drilling through the iliac crest or through a fat aspirate. There are other products that have been on the market previously, but the FDA has issued some strong warnings um in terms of removing these products, including placental cells. So the word of caution I would have for that is anybody who's got placental cells. Um take a long, hard look and take a pause of that because the FDA has put a very hard warning on utilizing these products and marketing them towards um regenerative modalities because it doesn't contain any live cells whatsoever. And then the last category is a new and emerging area including the alpha two macro globulin. Now, this is a protein in the body. Um that's still being studied for various uses in the muscular skeletal realm and it's been utilized elsewhere mostly. And it actually has been shown to inhibit some of the proteins that caused the cartilage degeneration within the joints. So we're still building a body of literature for this. But this is definitely a promising field that we can go. And it also falls under the blood product concentration um realm. Thank you dr poon as you can tell, it's obvious why there's a lot of confusion around biologics just from the first question. Um there's lots of different types of biologics there's different preparations whether how you inject them, how much you inject them. There's still a lot to be learned about biologic. So there are a lot of misconceptions. So thank you dr poon for that background. We'll delve into some of some of those things you mentioned in more detail throughout the throughout the webinar. So doctor Turkish, you're a leading expert in biologics. You run the bowel registry bio repository the registry here in Arizona. You're on the academy panel for american a category surgery panel for biologics to try to help normalize it and to send the right messages to patients. So tell us what your thought is and I'm gonna let you have freedom to to sort of go in whatever direction you want with this. But tell us about the current state of biologics and biologic treatments as it relates to M. S. K. Question? Uh M. S. K. Pathologies nowadays there are a lot of different ways you can go with this. But what do you feel biologics that now? And where do you see it going in the next few years. Thanks. And it's an honor to be with you all. I I think that the the key terms in terms of biologics right now. Current State 2022 is promising but we should sort of temper that because everybody's looking for. The promise is outweighing the science. Right? So there's a lot of promises being made out there because hope is something that's very reasonable and and the truth is is good science takes time. So the current status is is that there are a number of places where biologics has clearly established itself as a as an adjunctive treatment modality. But the claims that are being made out there by private clinics and and uh and other places I think are a little bit ahead of themselves. So one should exercise caution in this regard when we think about what, what can be done. Uh There is no evidence that we have yet that we can actually regenerate or regrow things outside of the lab or outside of animal models. So I think I would be careful if people say we're going to, you know, reverse or regenerate things. But the biologics have been very good adjuncts in terms of helping with patient reported outcomes increasing pain and inflammation and uh and helping preserve structures that that we need to sort of function normally. I think steve did a nice job of summarizing the they're in the US. We have a much more limited ability to practice with this because the regulatory environment is so careful with the FDA products like PRP, which is a blood product and spin it down and inject it back. It's probably the most studied and actually the science on that has emerged to be a very effective treatment regimen in many in many areas. But other things such as stem cells and were even cautious about using the term now? Because uh because this concept that they're going to turn into new cartilage or new tendon or new things really has not yet panda. So there's other areas in cardiology and sort of neurology that these areas are promising in but it remains a little bit challenging in regards of musculoskeletal medicine. One of the things I'm proud about with Mayo is that Mayo is a is an institution that has um committed themselves studying the science And so while we are very committed to cutting edge technologies, those cutting edge technologies have to be done hand in hand with science and research necessary. So I guess I I guess I would say that one of the reasons that I've been so proud of our institution is that they've committed financially ultra structurally as well through the center of regenerative medicine to say yeah we're gonna support you guys with the resources that you need in order to not only provide these people for our patients and also figure out and study them appropriately so that we can bring the science to our patients instead of just hope that's great dr Turkish. Thanks for that dr de Luigi. There are a lot of other types of injections injectables that we're familiar with that we use with muscle skeletal applications. Cortisone hyaluronic acid um anti inflammatory injectables, things like that. Why? And when should patients consider using biologic treatments rather than these time proven other injectables that we've been doing for years. Thank you, Doctor Scarbrough for having me a part of this group. And that's a great question. That's that is a topic that I speak with with every one of my patients. When we have a regenerative medicine consult, I always make sure that we talk about all these traditional injections, which has been known to be the standard for decades and many still rely on these in the 1st and 2nd line treatment. Of course we know that there are are time tested and we have great data on how long they last. But there are some limitations with data with the duration of time that they may last the number of injections they may be able to do without potentially creating harm particularly with corticosteroids. And now there's even more concerns with some of the insurance coming from the hyaluronic acid acid. So I still offer and use these agents and many clinical scenarios, particularly for acute pain and inflammation lowering the pain level to kind of, you know, get them to be able to be more uh functional at that time. Uh and and sometimes also as a buffer prior to a biologic later. You know, many persons are still worried about the out of pocket costs. Uh and there's with the biologics. So there's still some use for the hyaluronic acid in those areas. So when we're looking at it particularly There's certain clinical areas where the Ortho biologics have been shown to be a little bit more effective from that standpoint. There's growing evidence and lateral condole itis, knee osteoarthritis for example. But if the patient has diabetes or has had numerous corticosteroid injections in the past may have contraindications for corticosteroids from based on other medical complications that they may have. There would be concerns and obviously, you know, with with decreased coverage for some of the hyaluronic acids from the commercial pairs. Now they that may be limited as an option. So if they don't have if they've maxed out corticosteroids are no longer getting effect with them? That is definitely a time to consider the potential for Ortho biologics. Great, let's move on to some indications and questions regarding when to use these biologics. Doctor Doctor, can you tell us about the current indications for prp both leukocyte poor and leukocyte rich, as you mentioned earlier in the background section. Tell us when you would use these in your patients uh and when you would jump to them, do you jump to them right away or is this something you try other modalities first. Yeah. Great question. Thanks. DR Tower. So, you know, I'm gonna lead off this part by just picking backing off with DR TOK should mention is that in summary, you know, I think I tell my patients is a lot of times the marketing is ahead of where the research is. Right. So we talked about indications and um it's also important to really understand that the FDA um it doesn't necessarily have an approved label on these uses. But it's been cleared. The products that we utilize have been cleared by the FDA for use in clinical practice. So some of the uses that we have are for these different types of injuries and ailments. But as far as the true FDA nomenclature of indications were still kind of putting the little brakes on on that. But back to the gist of the question is that for the PRP I mentioned that we process the blood down and we concentrate the some of the cells down and it can include um some more white blood cells or fewer white blood cells from a relative concentration standpoint to inject into it. So basically we separated out that a lot of the literature that we've seen over the last 5 to 7 years especially has been that the fewer the white blood cells into a joint space the better and then the more white blood cells in essence into a structure like a ligament or a tendon is useful. So Dr de Luigi mentioned something like lateral african colitis, tennis elbow in particular, that's been showed promising outcomes with PRP but when we look at these it's over a longer period of time. So not necessarily comparing at two weeks, four weeks or six weeks with cortical steroids but we're looking at it at three months, six months, nine months and 12 months. And that's where we see the benefits from this. So, other promising studies from the soft tissue standpoint as aside from the tennis elbow lateral to condole itis, we've seen these in proximal ulnar collateral ligament injuries in the elbow and also for gluteal tendon. Open these in the hip. Thank you dr poon So so what I'm hearing from you is these these are leukocyte rich preparations that are used in tendon. Open these to try to help regenerate some of the blood supply and try to help with the healing process. Is that is that a safe thing to say? Yeah, that's that's correct. It's activating the body's inflammatory cascade and and initiating some of the signaling cascade to help with the healing and pain reduction aspects public. And so part of the leukocyte poor or the low white blood cell count utilizing the joints. And I think that's something we were going to touch on in a little bit as well. Yeah. And that makes sense. You don't want to cause an inflammatory response within the joints. Seems to be counterintuitive. So that's a great summary of that. So doctor tokens, how about and neon, I'll let you uh talk about something you're very passionate about and neon and what your thoughts are in the use of Ambien. And what indications it has now and maybe in the future. Yeah. Thanks. I think ambience is a really exciting area that we have done some initial research on. I should disclose to you that I have a little conflict of interest here and that I've got several patents in this area and so you should take what I say with a grain of salt but I think I can speak both generally and specifically about what its indications are. I think any regenerative modality is key to understand three things. Most scientists agree that if you're going to get a regenerative response you need to sell you need a signal and you need to scaffold those three things. That's those are the three keys and neon is unique and that and that it provides all three. Now I should just without getting in the weeds tell you this the FDA is very strict about um the use of cellular prod in giving those things to other people. So it's illegal outside of a very specific I. N. D. Or investigational new device in this country to give uh stem cells if you will or am neon cells. And so that was actually sort of finalized and clarified last year by the FDA. And the next day some 33 companies stopped marketing it and stopped doing it altogether. Which is good. But so we use an Ambien product here at Mayo and uh I should tell you that the keys of it are is that it does not have a cellular product at all. But really what it is is an al a graft transplant. So for example many people come in and they have surgery done and we use a graph products all the time. Right? So we use umbilical cord and we use that umbilical cord as a as a product that we can then transplant into patients as an ally graft. So a couple of things that are important about that number one is I told you that it's required that you have a cell a signal and a scaffold. The real question that we're struggling with right now is where does that cell come from? The promise has been? Well we're gonna give you those cells. These are what the so called mesenchymal stem cells are. But what we've learned is is that taking the cells from the outside of your body is probably not what's going to happen and what's going to signal the correct regenerative process. The cells that are probably most active in a regenerative process are sitting right in your blood vessels there these peri vascular satellite cells. And so really if you can deliver a signal to the body your body will recruit your own M. S. C. S. To come to the site that they need to lay down those materials with. So with and neon for example what we did is is here at Mayo we we ran them through our own independent lab. I was blinded to. It wasn't part of the analysis to see what are the growth factors that are actually there. What are the signals. And what we found is is that they're they're very very concentrated and high in angiogenic or those um those growth factors that enhance new blood vessel sprouting. So it's particularly effective in patients who have uh disease pathologies that are related to loss of blood supply. So what is that? Well that's tendon apathy is perfect pretend empathy in the sense that rotator cuff, tennis, elbow achilles tendinitis those kinds of things is a problem because our blood supply is sort of peter out over time as we get a little older. And so if we can supply something a growth factor profile that will stimulate angiogenesis we may actually be able to regenerate or at least support the regeneration process in that regard. And so am neon from that standpoint. We use it as a as an in office product sometimes and then we also use it as an adjunct surgery. And I think it's particularly effective in places where I'm concerned that the healing process needs stimulated by blood supply. We've also done a number of studies in the setting of osteoarthritis. We've compared it to other M. S. C. S. And in the lab and the guinea pig model of osteoarthritis. People don't know this but guinea pigs are one of the greatest models study because those little guys develop spontaneous osteoarthritis at a very young age. Sad but they develop osteoarthritis in their knees. So we're able to study the natural process in that and when we insert Ambien into those uh into those knees, it actually blunts the osteoarthritis response as well. So we're really excited about the possibility of this being an adjunct for arthritic treatment down the road. But as I said earlier, science is gonna have to be done in order for us to follow this up and see if the claims are are well grounded in science. That's great. It sounds like there's a lot of potential and what I see happening is, you know, we have a lot of different biologics right now, hopefully we'll be able to concentrate these two several products rather than multiple products based on the science in the future. I think that might clarify some of the confusion based on science and and that's hopefully in the future. Uh instead of dealing with 20 five different biologics, we're dealing with three or four for different indications. So that might be a nice uh nice uh future glimpse of what might happen. Dr de Luigi talked to us a little about the indications for uh stem cells and a to m also, Yes, thank you. You know, um you know, as you know, dr poon and Tokyo and shared. You know, even with those products that they just discussed, there's a lot of variations. So to add a little bit more, you know, complexity to this conversation. We're going to add in three other potential agents, Right? So, you know, bone marrow aspirate, lipo aspirate and alpha two macro globulin. So, you know, again, with all of these that the literature has been trailing, but it's it's gradually increasing over time. So trying to find out that right indication. So there are people that are out in practice that, you know, they will try to extrapolate, you know, one study to multiple body parts, but they may not all work out exactly the same. So, you know, for here, I'd say, you know, so there's no relative indications from that standpoint, but they are growing. So, you know, when we're looking at it, you look at the bone marrow aspirate. It's been compared to relatively equal efficacy with prp uh in in in a head to head study. But then most of the other studies have been compared to placebo or corticosteroid or highly ironic acid. So, so there has been mixed with that, but most of them been favorable, you know, So, for, for osteoarthritis, but again, there's less, there's less literature with the bone marrow aspirate than there is with the platelet rich plasma. Uh you know, similarly, there's also less, you know, literature for bone marrow aspirate for soft tissue, but it is growing some in that area, you know. So when we're talking about, you know, micro sized fat or, or lipo aspirate. You know, there are some more studies that are coming out with that as well. They've been utilized for things like you know plantar fasciitis uh and also for knee osteoarthritis. And so there's a study that's kind of come out that was look compared to corticosteroids and there's another one that's going to be starting here that's coming out with comparing micro sized fat to normal saline. So again they're still in the relatively infancy stage of the true literature from that standpoint. But some early results are definitely favorable. But again persons may extrapolate some of those treatments into those areas. Again with the adipose derived stem cells. You know, there's the benefit of some flurry potential and and and high energy in those areas. But like dr tokens had said it's more the medicinal signaling cells so utilizing that MSC you know acronym but changing it more to medicinal signaling cells when they are there. They will help then help drive and stimulate other cells and signal them to come to the area and help overall the healing process. Alpha two macro globulin is probably the one that uh you know it has potentially the greatest promise right now when we're thinking about a new opportunity. But it has been the least study because it's it's really come into the uh really coming onto the frame here relatively recently in the last few years. You know. Um there was a recent N. H. Study that had showed cessation of progression of traumatic osteoarthritis after treatment that had been done and this is a primary area that be utilized. So again that knee osteoarthritis. Again a lot of studies are surrounding that and this is where I think we're gaining a lot of more of the evidence potentially for the use of these other Ortho biologics. Great so um following up I have a question from the audience I think is appropriate. Um are there any certain co morbid conditions in a patient that would preclude you from having biologics as a treatment? I know that's a loaded question depends on the pathology that we're treating. But there's something you look for in your patients that would say okay you're not a good candidate for biologics because of this. Co morbid condition dr sorry? Oh yeah thanks. Yeah so you know definitely with there's a lot of patients when developing arthritis or chronic tendon on these it's a product of time and unfortunately you know time gets the best of all of us in some cases and we all have different types of co morbid conditions. So we always evaluate each patient individually right But some some areas especially if there's any type of active malignancies we try to avoid doing any type of blood products like prp for this. Sometimes patients need to be on certain types of blood thinning medicines for other conditions heart related or neurovascular related and sometimes we need to discuss whether those products need to be held prior to using regenerative modalities such as prp and so that's that's an in depth conversation with the patient but also there are other consultants from those realms. So oftentimes again though the act of malignancies in that standpoint is the one that we utilize but not all of them are are the same. So again having an in depth discussion with your physician with the person who's providing it. But also their primary physicians and their consulting specialists would be very very important for each person who's considering a regenerative process. Okay um one other question I'm gonna throw out from the audience right now. Anybody have an opinion about M. R. N. A. DR Toke ish. Any any uh anything to add about that like like messenger RNA for so for example retrovirals like we've seen a revolution in in in in virus technologies and vaccinations I think is what you're pointing to. Yeah. So so these are I mean you want to talk about understudy these are the least studied of the new emerging kind of biologics that are out there. But but here's the promise. Right so M RNA technology is exploding and anybody all of us have lived through the covid 19 pandemic, understand that several of the virals the antivirals and the vaccinations that are out there took advantage of this M. RNA technology. So so just to kind of give you a little um very quick and high value overview of this, you might look at it and you think of it this way there's a there's an emerging technology and genetics called CRISPR technology and many people are familiar with this but CRISPR is the ability to go and take single genes out. Think of it like your word document on your computer, your word processor where you can take and delete a certain section and cut and copy a certain section else. Well when you consider the genome on this process where the genetic blueprint which has worked out for the human genome now they are now able originally theoretically but now in practice to be able to edit out certain genes in that area. The most promising one has cleared some of the FDA trials and some of the ongoing trials happens to be in like sickle cell anemia. So for example they have demonstrated in a few early cases cures which is astonishing and and really really exciting in terms of being able to edit out the pathologies that might lead to this. Okay so then it got really popular because the covid era they were able to knock out the spike protein with some of these M. RNA technologies and injected via viral vector. So the concept and the promises beautiful. So if but the problem with for so for example arthritis or apathy is these processes are not governed by single cells. They're incredibly complex. And so the editing process which may be possible theoretically is going to take a ton more work to figure out how it goes. Is it gonna happen someday? I believe it will. Is it ready today or should you go to your local stem cells center and get it done now? I would tell you I would caution greatly against that. But there is great promise in this area and I think down the road we're gonna be able to offer some of those. That's great. We've we've touched a lot on osteoarthritis. A lot of our population suffers from osteoarthritis. And as dr poon said Father Time is something that we can't stop. Uh let's talk a little bit about the research. I think this is probably one of the most studied areas with biologics with osteoarthritis. I know mainly in the knee but also in other joints. Uh Dr can you tell us about the results of biologics and types of biologics with Oa with degenerative joint disease? Yeah. This is gonna build up a little bit on what doctor do Luigi had said earlier as well is is I mentioned before that prp is the most studied of all these modalities, right? And and the low leukocyte concentration, low white blood cell concentration injected into the joint has shown more favorable outcomes compared to the the leukocyte rich prp into the joints as far as me osteoarthritis. And again, early studies really compared it to corticosteroid at 24 and six weeks and a lot of those outcomes studies from, you know, the mid aughts? You know, 2005 to 2010. Really didn't show those benefits with Prp. But as we've studied it further, become more nuanced and how we understand the role of PRP has been shown that when you look at it for a longer period of time again those 369, 12 months that the patient reported outcome scores are much higher functions. Better. Pain is reduced over time. But you know, we don't have anything to suggest that these things are are reversing arthritis. There's nothing that we have on this planet right now that we know of that reverses arthritis. So but the P. R. P. Studies are showing that it can help mitigate pain and help prolong functional improvements for patients over a longer period of time. So then the other studies that Dr DE Luigi mentioned the B max studies the bone marrow aspirate the lipo aspirate. Those are really compared to Prp um in this realm. And a lot of them have been shown to be roughly equivalent with maybe the PRP is slightly superior in this case as far as the osteoarthritis. So some of that is extrapolated as far as the hips, the shoulders and other small joints. It's widely used in clinical practice and in other joints but the knee is far and away. The one most studied and we utilize that data to extrapolate to the other other joints, primarily just because of the broad nature and depth of the data that we have? That's great Doctor de Luigi, can you talk to us about the process of injecting biologics is ultrasound necessary? What are the benefits of doing that? Is it worth the cost and added time? Uh What are your thoughts? Great. Thanks. The process of the of the injection of biologics begins with equipment that one's using depending on which of the different, you know um treatment type cells that we're utilizing whether it be fat or or the bachelor, strong reflection or bone marrow or pRP. So you know, so again it's going to be harvested and then it's going to be spun in the centrifuge and then it's going to be separated. So with that, you know, there's going to be different spin time spin rates. And these were also yield different concentrations of cells. You know? So so when we come to the actual injection, once we get that, you know, again, the more accurate the the needle placement to the area pathology, the more likely they would benefit. Right? So if we are if you want is injecting without image guidance, we would have the assumption that we're delivering it in that area. But we maybe, you know, not delivering it exactly where we wanted to. So there may mitigate the amount of effectiveness in that area. So that was one of the potential advantages of ultrasound guidance that does not provide radiation to the patient compared to Flora Skopje? Uh you know, ultrasound. You know. Again you are able to see the soft tissue uh you know, where you may not be able to see the soft tissue target. You know, with Flora Skopje or other agents comparatively, you know, you know, if we're opening patient up in the surgical procedure, you get to directly visualize it. So, but the sonogram has that opportunity. It is an added expense to the clinic. You know. Often, you know, it's with the injections right now, they're bundled into the cost for the patient when we're utilizing traditional inject eights. But with the many times it's bundled still into the price when we're talking about cash based. So there is not typically an upcharge from from that. You know. Again, it could be cost dependent regional and institute based. So oftentimes there is an added cost to the clinic to have the ultrasound. There is the added cost to the clinic from that standpoint. If they're not getting a reimbursement from that standpoint. But usually it's not passed along to the patient for an additional charge. We're not typically during the PRP and then charging the ultrasound guidance feed to their insurance. Uh you know, and comparatively between all of the Ortho biologics PRP injections are typically less uh you know, cost to the patients. Their kits also cost less the equipment that you need to buy in the kits as part of those kits are less expensive because we're not having to harvest, you know, bone marrow, you know, or the or doing a micro lipo aspirate? You know, to get that micro fragmented fat in that area. So, so there is definitely a cost increase for those higher end uh cells that you would harvest compared to a veena puncture that that is done daily from that standpoint. But typically, you know, that's where some of the other costs could be passed along. Right? So, you know, most institutions will charge significantly more for the bone marrow or the lipo aspirate injections than the PRP injections from that standpoint. Great doctor Turkish. Um you know, arthritic patients and specific for osteoarthritis. When should somebody be considering surgery rather than biologic treatment? And we're talking about arthroscopic debris, mint versus arthur plasticity. Is there ever a reason not to try biologics? That's a great question. I think that uh the main barrier to try and the biologics is cost. Right? So PRP is not free. And uh and so there is a cost associated with it. One of the most attractive things about PRP. Is it your own stuff? It's your own blood. So for example, we we've done a lot of research in the area of am neon but that's an al a graph that's somebody else's tissue. Right. Which and so we have great tissue banks that screen for disease and everything else. But when patients often have a question about, hey, what are the risks of this with PRP the risks are pretty minimal because you're giving the patients their own product. That's true of the of the fat products as well as bone marrow products as well. So I don't think there's a downside to trying. Of course, the the real downside is of course it doesn't necessarily always work the real challenge. For example, in prp we know that it can be incredibly effective, but we also know that there's a responder group and a non responders. So one philosophy to answer your question would be, well, try it on everybody and if you don't respond then you can move on to a certain like arthroscopic debridement. We also, as you well know, and a car, we have patients that are great responders to that surgery and many who are non responders to that. So it's always an individualized discussion. But in general, the P. R. P. S. And most of the biologics, Jason we've been talking about, they're pretty safe and so they're reasonable to try. It's just a function of the cost prohibitive, you know, measurement and then, you know, ultimately, uh joint replacement is at the end of that realm, but an incredibly effective treatment tool in our hands as well when patients get to that point where they say, look, I need to finally cure this and get definitive our joint replacement colleagues do a great job with that. That's great. I'm going to throw out a question from the, from the audience here, that I think I'm gonna throw out to the panel let anybody answer this. And I think this is a great question and we see this a lot in our athletes that that we're treating. Um do any of you utilize a protocol where you combine high molecular weight H A hyaluronic acid with prp how often can you repeat this combination? And if you did do this, do you ever give H. A. To finish that series after the combo treatment? So I'll let anybody chime in with that question. I think that's a great question. I'm happy to go ahead. I was gonna say, you know, I I I have done it on on on occasion, you know, So with some trepidation, this was a high performance athlete that we had spoken with. So, my concern sometimes is that you could have we already have reactive sina Vitus with hyaluronic acid as a known potential complication. Um and injecting them simultaneously could increased that reactive process, you know, you know, but you know, based on the consensus that we had shared um and and the and the and the provider that was talking, they they have done high level um studies then that have yet to been published or on the way to being published that that have been done and they had shared that they have not seen it in great amounts, but and they're getting good results with it. So they have continued on with those treatments, you know, that patient that I've treated did have the reactive side of itis. Their knee swelled up significantly. We had talked about draining it and then going back and doing just the prp again alone. Uh So that again with those reactive side of itis is with the highly ironic acid. That would be my my area of trepidation. But others in clinical practice have shared that they have not seen that quite frequently and an end of one is still an end of one. But you know when that end of one hit what I was concerned about it makes me even more uh more trepidation to that area. Doctor Turkish anything to add to that. Have you used this in your practice? Yeah. In fact just the science on it has there's been a very good study brian coles group out of rush brian's done a great job in biologics. And they looked at a fairly high level study looking at H. A. Uh and Prp alone versus combined. And what their data found was was that the combination of P. R. P. And H. A. Actually surpassed either of the other two groups. So for those of you using it out there in in practice, especially in knee osteoarthritis, this is a promising area to consider. Yeah I agree. I think because of dr cole's work it seems to have taken off in the professional sports world it seems to be a common place to use this combo combo treatment. Uh So I think that's something to keep in your arsenal, especially with your patients and having a discussion with them. Let's shift gears a little bit from osteoarthritis to attend an open these. This has been probably more studied than anything else with biologics. So let's start with first doctor token. Talk to talk to us about your indications and techniques for using biologics for, say, achilles, patellar or media or lateral apple kinda light is very common things that affect our everyday athletes. Yeah, so I think the premise here is that we have not traditionally been very good at this. That's where we start, right. When we talk about rotator cuff repair, which is where is sort of where I live rotator cuff repairs. If we look at the quote unquote retail rates or what we like to call failed to heal rates. These things are in the 25 to 40% region on this. And so for a long time we as orthopedic surgeons thought, well we need a better mousetrap. We need stronger constructs. And believe me over the past 20 years, we've evolved to these incredibly strong constructs that are so strong that now the failure mode is that the tissue fails, which is where you want to be as the mechanics or a carpenter, right? You don't want your construct fail. Now it's very rare for our surgical constructs to fail. The problem is the tissue. So we've now moved from an area where our focus is mechanical engineering and we've moved into the biochemistry. In other words, it's not a mechanical failure anymore. It's a biologic one. And so if you have a patient who is at risk for failure, certainly rotator cuff. Uh and the and that would one might argue all patients right. But certainly in revisions or an older patients or smokers or patients who have advanced fatty degeneration or large tears and 1000 other risk factors you you should consider adjunct biologics in those rotator cuff patients that you have. Now, that's just the surgical side there. As you know, we all have these conversations with our patients, most patients if they if they can want to avoid surgery. So one of the really kind of interesting things about it is is that we can now bring these treatments to the clinic. So instead of saying, look, I'm gonna use a biologic and surgery, I can have at least a conversation of saying, look, I can use a biologic for surgery. And so the nice thing about that is is that if we try it and it works perfect. We've avoided the trip to the operating room, the logistic boss of complications. So that should be, I think foremost on everybody's mind. But in those situations where patients fail those, we can take them to surgery and used them as adjuncts. I would say that I would say I'm probably adjunct uh probably 70 to 75% of my rotator cuff surgeries for example have some sort of biologic adjunct now most of that is autographed but sometimes it's autographed and sometimes ambience. Sometimes we use the patient's autograph biceps as well. So there's I think an increasing effort to optimize the results of those both non surgically. That's great. That's great dr de Luigi. Can you talk to us about the post op rehab After biologics injections with both patellar and achilles tendonitis. Is there a protocol that you use? How often you know, how long do you shut down your patients after biologics? Do you limit their mobility? Do you limit therapy? You know what what sort of your general protocol after biologics? Uh injectable treatment? Yes thank you. You know with those two indication particularly you know there I am a little bit more restrictive you know from from that standpoint when I when I do the when I do my injection of the an Ortho biologic there's a little bit of needle defenestration that they're trying to create a little increased vascular charity from that standpoint from localized bleeding and trying to break up the tissue planes allow that prp or other biologic to spread through that area. So because of the. Needling aspect oftentimes I would use you know brace knee sleeve or patellar strap the patellar tendon or walking boot for my achilles tendon. The first two weeks or more relative rest trying to really be china just doing regular activities of daily living. You could use immobilization if you needed to but oftentimes with the walking boot for the achilles that has been shown to be effective. I do limit. Nsaids for the first two weeks after the procedure, we want to make sure that you know, there's not that there's not decreasing those healing cells that are coming there and the other platelets are coming ice. Also as a vaso constrictor, which then limits blood flow to the area. So I tip and say using a heating pad or just having the sleeve over the knee would create more heat to be generated and trapped in there. And that can also be palliative but also adds that they're having something that's done there. And as a physical reminder that you know not to push it. So I go a little bit more slowly with these patients because you know, the leg extension right? The patella tendon is the only attachment for the leg extension at that point. So, you know, and the quadriceps muscle is a very strong and attendance. So after that Needling there's a potential risk that it could rupture if progress too fast and depending on the level of pathology that was there and similar with the achilles tendon, we can bear our entire bodies weight on one achilles tendon from that standpoint and so just being a little bit more cautious with the progression of the strength training. Now there are times when you could accelerate it, particularly when you're talking about your professional, elite athletes. And I always say to my patients, not because they're better patients, that they have access to daily medical care, right? They oftentimes have, you know, two or three athletic trainers and physical therapists that they could see every single day and every team physician is on speed dial, you know, if there's any concerns leading up to that. So, so would you say dr de Luigi, would you can you give us a timeframe of return back to full activities after saying achilles or a patellar tendon? Uh Prp injection, uh would you say it's 2 to 3 months, would you say it's longer less than that? What's your what's your just to give the audience a general idea of what they're looking at, you know, compared to surgery. If they were to get this treatment? Absolutely, yes. So, so with both of those, it's going to be around 6 to 8 weeks is where I was telling them where we could potentially really see that biggest difference. But it can be that because eight weeks then two months, it could be in that 2 to 3 month range for them to go back to full speed, but that can also vary depending on the level of pathology, but I usually tell them where I really want to focus you at is where you're going to be between that six and eight week mark from, from where we're at you can get better sooner. It can take a little bit longer. But I want to make sure that you're in that trajectory between that six and eight week mark. And I think it's important to note there is risk early on obviously in that inflammatory phase after you inject there is risk of complications in terms of rupture of attendant and things like that. So something for our audience to know just because it's a minimally invasive procedure, it doesn't mean that um negative effects can cannot happen. So remember that and make sure you just talk to your physician about that. Um And staying with the theme of tendon open these dr poon I know you do a lot of uh 10 Ganapathy injections around the hip gluteal tendon on these. Can you talk about the literature and the results for that? I know there are a lot of patients who as they get older have a lot of hip tendon open these and have a tough time with everyday life. What are your thoughts about those? Yeah, this might be the most challenging question you've given me so far and because I can literally spend and have spent you know 60 minutes talking about this one topic alone. So the the big picture overview is that the gluteal tendons, the attachment, the grater trot canter tends to be the mediating factor for pain in the lateral hip area. So the what we used to call electro can't eric bursitis we actually see is more of these gluteal tendons and with any type of tendon apathy and I guess not taking for granted you know are the definitions that we're using. We're talking about product tendon degeneration, so normal tendon fibers are organized in thin ropes, but over time because of stress because of injury, the tendons can stretch out, they can fray a little bit some of these interstitial frame and they can thicken so tendon open. These are simultaneously an issue of overgrowth and also lack of healing from that standpoint. So with that it can develop some instability in that area. So there's a lot of really actually some really great studies being done out of Australia. There's dr Fitzgerald's group out of there has done a really nuanced study over two years looking at prp compared to cortical steroid and the lateral hip. These these glorious media attendance and they've shown that in the first six weeks as we would expect it, corticosteroid has a little bit more benefit. But when they tracked out the prp up to two years, those patients who had improvement from the Prp maintained that improvement starting at eight weeks. And then the last published study was up to two years out and even the patients who received cortical steroids um in the original group they gave them the option to convert the prp they were on the same timeframe. Eight weeks after the prp had improvement sustained for a year out after that. So a very, very promising area for um for PRP injections into the glute glute medias tendon specifically. That's great. Let's switch gears a little bit. Let's talk about surgical indications and and want to use biologics. Doctor tokens has the orthopedic surgeon in the group. What are you doing in your practice to augment some of your surgeries with biologics treatment? Does the literature support this? Are we still in the in the research phase that we don't know what's really gonna happen. But it's something we offer page offer our patients because they're hearing about it in the media and in the newspapers and with professional athletes. Uh go through your thought process when talking about adding biologics to your surgical procedures. Yeah, So I think that there's it's a little bit of both. Right? So there is, there is emerging science now. I'm happy to report. So for example, in tendon empathy, I can tell you that there's been a number of very well done studies that have shown that the addition of PRP for example, especially if we treat it in a solid form Has decreased retail rates. So for example, Alan Barber sort of lead us with this with a great study that sort of begun this revolution if you will and showed that he could cut the retail rate or the failure to heal rate almost in half if we use this then in 2014 there was a study out of France that should that if you used um bone marrow aspirate in the area that you could cut the retail rates in half and 10 year results were much better. Now. That study was was really eye opening for everyone and said oh my gosh if this is real this is this is a major step forward and I will say that that study has been repeated a few two times and the results are a little bit more cautious right? We always say in medicine that nothing ruins results like good follow up. So that's not been shown to be as quite as miraculous. But there are studies that have followed up one large one here in the U. S. That has shown that there is promising effect in the area of rotator cuff. So here's what I would tell you. We we are we have a high failure rate when it comes to getting attendance for example to heal. And we have a high failure rate when it comes to getting patients who undergo for example arthroscopy for the of osteoarthritis. And so for rotator cuff which is just one example we there's now good data out there that will allow me to help a patient predict what their failure to heal radar because we know what the risk factors are there now scores clinical scores where they come in and I can say hey buddy you're 70 years old, you're you have a chronic retracted tear, you have retaliate changes. You have multiple comorbidities and you lead an active lifestyle. Those five factors with your M. R. I. Findings and everything I'm seeing on physical examination. If I go in and do a perfect repair, you will fail at 80% of the time patients look at me like my goodness, 80% I fail. I say yes it's not the mechanics, I can put it back but it's the biologics. So with that and I would say if you you know what your what your your your sort of aptitude for failure is for us, it's not very high. So if you if we think you have a significant risk not healing that tendon, we're gonna add it. So for me, one of the more interesting aspects of this is is that in conjunction to rotator cuff there we often do a biceps tina thesis because the biceps pathologic and so one of the techniques that we've pioneered here is that we take that biceps and then we put it into what looks like an olive press, we take your biceps that we normally would throw in the garbage but we take that and we put it into this olive press and it makes a beautiful match. We take that patch. Once we're finished with your rotator cuff and we put that on and set it down now that patch contains live penis sites tendon cells and we know that tendon cells are one of the most potent activators of those local stem cells it calls the local stem cells to the area, induces them to lay down extra cellular matrix. It's your own cell and it's a very powerful sort of adjunct. So from that standpoint I would say that biologics don't necessarily have to be high science. They can be using patient's attitude using what they're already gonna be retarded if we think that there's a biologic uh angiogenic problem meaning we just don't think you have any blood supply. Sometimes I get patients that have failed to 34 repair attempts. Those patients where I think there's a blood supply problem. Well then I might move into something that I think might stimulate that blood supply a little bit more. Uh as to the stem cell concepts and everything else. I think from a rotator cuff standpoint and from an arthritic standpoint we still have to consider those? That's great. Those are some great tips of how you approach your surgical patients. Um it's a very humbling profession where in when you're talking to patients about an 80% fail rate uh with your surgery. So um I think this is a great great future of where we can use biologics to help us as surgeons. Uh Let's uh let's talk a little bit about insurance. Um dr poon dr de Luigi insurance often doesn't cover these biologic treatments? How should patients approach this? Do they have any other options? You know? How about insurance during surgery? Is that different than insurance during clinic and covering these biologic treatments? What are your thoughts on that and how should patients be approaching that? That difficult dilemma? Yeah. I think that leads to immediate discussion you know Dr de Luigi and myself when we have our agenda of consultations just laying it out front. Hey unfortunately most insurances don't cover this. There are a few exceptions right? There are few insurance companies um and it's sporadic and you have patients would have to just check with their own. Um But for knee osteoarthritis and lateral epic condole itis are the two indications that I have seen insurances be willing to cover when they do approve of that. Um Otherwise some patients have the options of using their essays or their H. S. A. S. For coverage on that these uh these modalities. But that leads to the greater discussion. Is this right to you because we talk about harms right harm to the patient. Is there an infection risk anytime you do a procedure? Yes. Is there a risk of allergic reaction? Usually not with the autologous products? The prp but harm to the wallet is really a patient harm as well. So that's a part of the discussion that I have with them to see if if that's right for them as a treatment plan? Yes. The following on it is still one of the most challenging things you talk with with patients because you know, you, you know, you're trying to talk to them about the best care options, Right? And it is, it is a challenge when you're talking about one of the options that may be beneficial to them is going to add a significant cost that may be cost prohibitive to them. But you know, I think the more research that we get on specific tissue types as dr poon mentioned and shows consistent effectiveness, I think that the insurance companies will start to start to approve it more frequently. And those two topics are those two tissue pathologies, lateral pecan colitis and the osteoarthritis are the two that I always quote are the most likely to get approved first in a car. I might just add, you know, their people may not understand the process by which insurance companies uh, fund things. And so, uh, maybe a minute or second on that. So for example, it's not just a willy nilly decision by many insurance companies, right? We always sort of think of them and saying, well they're they're making business decisions, etcetera for sure. But there is a process by which you can go through and establish a billing code. Right? And so I'm, I'm deeply involved with the, with anna, the Arthroscopy Association North America. One of our mission statements is advocacy trying to make sure that we allow patients to have access to the same care regardless of their economic situation. So stem cells, if you will or biologics is unfortunately right now kind of a treatment care pattern for the wealthy. Right. And that's I think that's a problem. We need to find ways to do that. So how do you do that by the way you do that is through level one science. If you can get randomized clinical trials that are published in the literature and peer reviewed, that allows you to take those data, take it to something called the Rock and the governing bodies that determine coverage decisions. And once you have a level one study or to level one studies and several backup studies, that evidence then allows you to obtain a code for it. So when we talk about, how do we make these these treatments available for all of our patients? We've got to do good science. I think that's where I think we and others are trying to help lend a hand and leading the way. That's great. Um, some great advice for our patients. So we don't have too much time left. I have a couple more things I want to touch on. Uh, I'm gonna go through each of the panelists here. What one question should patients ask their doctors prior to getting biologic treatments? Uh Dr poon, let's start with you. You know, this touches on what I just said before. What makes the procedure that you're offering to me worth the money that you're asking for Dr de Luigi, what would you have your patients ask their providers? As as doctor Turkish mentioned there are a lot of stem cell clinics around every city and they seem to be popping up on every street corner. You know, are these places you should go to and if you do go, what are you gonna ask them before you get your injections? Yeah, that's great. You know. So, you know, one of the things that I think that always take start was when my patients ask me, what would you do if I were you and what would you do if I was your mother or father? Right. So from that standpoint, what would you tell them? So that's one of the things that I usually would if I were to tell my patients, that's what I would say. But also, you know what experience you've had in treating this this specific condition, you know, from that standpoint. So that's where I I really enjoy our consultations, Mayo clinic. I do let them know, you know all the times my goal here is to talk to you about all the science, you know that that's there if you choose to go somewhere else and get the treatment because you find it cheaper and you think that they're better than what we can offer you? I understand that because what we control our costs. But my goal is always to make sure they tell you what all your options are risks and benefits. And then you can make the best informed decision. You can have dr Turkish, what would you have your patients, what question would you recommend them asking their doctor? Yeah. I think I just uh pile on what steve had said about, you know how our patients are really savvy when they come in. I will say this and I'm sure this is true steve and Jason's practice as well and as well as yours antique cars, we probably spend I certainly spend more time talking patients out of biologic treatments than talking them into. We never talked them into it. And the reason is they come in because they've read some blurb on the internet and they're convinced me the latest and greatest I want to be treated just like you treat a coyote or just like you treat you know, one of the elite athletes that you take care of. And and a lot of times you look at it and say look I don't mind spending your money. I just don't want to waste it. And so the thing that any any provider, any doctor that is going to be talking to you about about stem cells or biological treatments, they should be able to explain it in a way that makes sense enough for you to understand. And it should be science based. So the questions you should ask are you should as a provider be ready for a long conversation. It's not just this is what I do and I've had good results because if that's the answer then that's fraught with all kinds of, you know, secondary gain issues and and problems with recall bias and all these other things. But that provider should be able to explain it in lay terms well enough for you to understand and make an informed decision. And then ultimately you have to have trust in your provider, you have to be able to look at the person across the table from you and say, look, I'm not an expert in this area, I'm relying on your expertise and eventually you have to decide do I trust this person that they're acting in my best interest, both medically and financially or not. And that's what I tell patients to look for. That's great. That's great. So let's talk about the future uh dr poon, where do you see biologics in 5 to 10 years? Yeah, I think the breadth of evidence now that we have laid the groundwork for it, I think it's can continue to expand. We talked about the alpha two macro globulin, you know, that's a promising literature um or utilization for arthritis and I think we're gonna find a little bit more in terms of of more specific indications. So instead of, we're just gonna do prp for this, you know, 57 years ago, we weren't talking about leukocyte leukocyte poor necessarily. Right? Like now we are, but those are some of the evidence or the published studies that have come out. That's what we're gonna see more over these next few years and say hey these little tweak nuances of the specific indications and utilization for individual processes, dr tokens. What promising research is occurring now that will change how you view biologics is something that I know. That's a loaded question. You can talk for hours on that. But what what would you summarize as uh most exciting for you as a provider? Yeah. You know what it is? It's the it's the marriage of different subspecialties. So ai right and big data registries that's the future. Right because in order for us to understand how this stuff works and whether it works when it works you have to have an incredible amount of data. And so the big promise here is deep registry data. So for example we have mayo are leading an area with the biologics association in their registry and bio repository six C. Including H. S. S. And Cleveland clinic and Sinai University of Colorado um stanford. All the groups have come together and said look let's get to the bottom of this and let's put science behind these things. So you're gonna get thousands of patients who will be put into registries. We will take samples of the stuff that we actually put in them. Then we can analyze that and relate it scientifically to where it is. There's another project that's being supported by bio mayo clinic center for individualized medicine where they take a nasal swab? It's called their tapestry project. And they've approved us to do this with our cohort. So if you have knee arthritis and we're putting you into a Prp study, you're gonna get a little nasal swab. You'll send it off, then we've got your genome and so then we can take a look and say All right, what what is your genomic profile that relates to people who respond who don't and those who don't respond because there is a responders and non responders group. How does that relate to the growth factors that are in your individual prp So for example, people don't know this but there's over 800 proteins in prp And frankly we don't know which of those proteins yet are the drivers on all these. Right. The biggest study in the literature is only studied about 15 of them. Our study will will triple that. But it still doesn't study 800. So the question is is can we put big data and ai analytics machine learning protocols in place to where we can accelerate the research. Super exciting and realistic in terms of uh doctor led right now, many different specialties are involved in biologics treatments. So you just look at this panel, we have, you know, three different fields completely different. But they're all doing similar things in terms of biologics treatments. How do you see this changing in the future will one specially sort of take the lead to minimize confusion for patients of where to go. Or do you think it's going to keep being a multidisciplinary field where many different groups are are performing biological injections, where what should we tell our patients of where to go? Should they see dr poon dr de Luigi doctor Turkish, I mean everybody you guys are all doing biologics but not really. Um there's no direction on where a patient should go. So how would you recommend patients uh deal with that dilemma. That's a great question. In an optimal world, you know, a patient would have a consultation with the three of us simultaneously so we can all kind of have the same panel discussion with them, you know. But you know realistically that's probably not going to happen, you know? Um you know, it would have to be a large, major change in overall, you know, if they had their own specialty, right? So if the american board of Medical specialties had musculoskeletal regenerative medicine, you know, but there's going to be pushed back from the existing academies possibly from that standpoint and the boards uh you know, and outside of musculoskeletal medicine I I see or biologics continuing to grow, we have phenomenal physicians here that are in dermatology, they're using it for alopecia, you know, others during Lorenzo regeneration, you know, I think one of the potentially landmark aspects would be regenerative pancreas for diabetic, you know, issues over time, you know, and whoever is going to get that is going to radically change the way we treat diabetes over time. But I think it's going to continue to grow. What I think we can do is best is come up with a consensus amongst amongst the various specialties of where of where levels of expertise have and and making sure that we share that. You know, there's there's differing viewpoints that were coming from but but we're going to try to homogenize that into a unified, you know, you know, discussion point. And so I always try to talk to you know, my patients about that, you know, and saying that, you know, I want to make sure that you know, you have the best information to make the most informed decision. And if you want to have a different opinion, you could see dr Penner dr Turkish and and talk to him about that. Right? So, you know, and from that standpoint and we're all, you know, at the end of the day, we want you to make the best decision that's going to work for you. I think that's a great point. What we've done here at Mayo Clinic in Arizona is we've created the regenerative medicine department which is uh comprised of multiple different specialties uh everybody you see on this panel as part of that department. And so at least it gives patients a go to place um that they have somebody who has some knowledge about it can then help them guide them to the right provider. Um We're running out of time but I have a couple of interesting questions that are gonna be a great way to end this session from the from the uh the audience. Um Two quick questions. Uh Do you see a future role in precision medicine or biomarkers helping direct the selection of and use of specific biologics? I think that's a great question because I think it sums up a lot of what we're talking about in not knowing exactly what biologics to use thoughts from the panel. I think I'm going to just pump up JT's project here because he's put an incredible amount of work into this bio repository study. And when we talk about truly game changing elements in the world of regenerative medicine that has the potential for it because then you get to really figure out okay, what is the particular compound within these things that are effective for you? So we know there are some good P. R. P. Studies, we know there's some bad pRP outcome studies, we just don't necessarily know why all the time. Right. And I think that's the bridge that we don't have yet, but JT's by repository study. Mayo clinics a leader in that field is gonna help us really determine where we can find the answer to the why. That's great one last question I'm gonna throw out to the panel. Um And I think this is a philosophical question. I think it's great with the media marketing and what's happening with biologics. Uh This is coming from one of the audience members because there is limited evidence that clinically significant tissue regeneration occurs. Why are we caught using the term regenerative medicine to describe biologic based procedures? Should we have alternative nomenclature? I think that's a great way to think of this. Especially in the current state with the science that we have J. T. I'll let you uh jump on that one. Yeah. Whoever put that question in is exactly right and uh and and wise in this regard in fact Arne Kaplan, the quote unquote inventor of the stem cell, doesn't use the term anymore. So it's moved over towards as Jason correctly described it later medicinal signaling cells for the MSC instead of stem cells because they're not stem cells and they don't act as that in vivo. So there is a tremendous amount of nomenclature that has to be sort of redefined and and that's okay. You know the science is gonna take us where the science takes us there will be necessary shifts as we learn more in fairness it's not you know it's not that the people that pointed a stem cell were wrong or at any sort of secondary motive. It's just that's where the status of the research was as we evolve we're gonna have to change some of our nomenclature as we go forward. And I think that's a that's a very positive thing. Um I think the other challenges is that is that as we learn and go forward, there's going to be different emphasis points on on different aspects of the care was the cell. Now we're moving really much more into the signaling mechanism, right? And then there's going to be the scaffold as well. So all three of those role of all three of those aspects play a major role in it. We just have to evolve with science. That's great. I'd like to thank everybody for this exciting and informational webinar to have our three world leaders and biologics uh to be able to spend their time this morning to answer questions. I really want to thank you for for for a job well done. Um here at Mayo Clinic Arizona, as I mentioned before, we do have a regenerative medicine department uh house under the Mayo Clinic sports medicine department. So if anybody out there is interested in getting more information, we're happy to uh to get you in at any time point. So please call the Mayo Clinic sports medicine department uh and the center of regenerative Medicine here in Arizona. So thanks again for your time and um I hope I hope we can do this again in the near future