That's a great talk. And based on your, following to your very last point, it would be great for the group to hear you say, tell us all that there are no approved stem cell products in orthopedics. There are no exosome products available in orthopedics. That's correct. There are no exosome products approved in orthopedics and there are no stem cell products approved in orthopedics. There are investigational new drug products. Those are being studied in appropriate settings. But I mean, exosomes are a great example of a challenge because just figuring out how to reproducibly make exosomes so you actually know what you're studying requires actually a pretty sophisticated, usually a university lab, because just trying to derive them from some ad hoc process leads to really, you don't know what you've got. Something we all deal with every single day. Every one of us in this room hears this from patients, so it's a message we need to hear. And there are plenty of places that are advertising that they've got these. Would you be able to share, because we get this a lot in our biologics meetings and so forth, what are the consequences to clinicians who promote cellular activity for some of the things that you heard about today when that sort of is very visible and that's the narrative? What do you say and how do you get involved? At FDA, luckily at FDA for clinicians, we just want people to stop. So generally we'll just say, we just send what is called, it has come to our attention letter, which basically says it's come to our attention that you're doing something wrong. Please cease and desist. We really hate to have to get Department of Justice involved and we only do so when someone's doing something really egregious, usually because real harm has come to someone. That's happened occasionally. And the other way that people get into trouble is not from us, but if people get kind of more, do more advertising, sometimes the Federal Trade Commission or the Securities and Exchange Commission can get annoyed at this. Thank you. None of us up here like attention, so it's good. Okay. We do have a few questions from the audience, so thank you for sending those in. One question, Dr. Rodeo, let's have you take this one. What post-op pain strategies do you use for patients if you're avoiding NSAIDs? And certainly we want to try to minimize narcotics in the perioperative period. So I do think, I think 24 to 48 hours of an NSAID maybe, it probably is acceptable. And I think I'll just get you to do that first couple of days, but try to use, I'll use Tylenol, I'll use a multimodal approach. If you have a really problem with the pain, you can use Gabapentin, things like that. But try to get into that first couple of days and then you're generally okay. So I've used Tramadol on occasion. You know, we obviously try to get away from opiates, but basically, Rachel, I think a couple of days of NSAIDs is probably okay, but I try not to be on it for two weeks straight. And then another question, we'll go to the shoulder again, Dr. Mazzocca, with the, with your Bursal approach, is there any effect with the lidocaine with epi that you might use at the beginning, for example, for portal injection, analgesia, or for insufflating the joints? And then what is the mixture of PRP to Bursa? What is your secret sauce? The Bursa is just whatever you can get. That's where the magic is. All the rest is a fibrin clot. We're trying to make an all autologous fibrin clot because that's kind of easier to get through regulatory pathways in our own hospital and with patients. So it's a three to one PRP, PPP to autologous thrombin, so three to one ratio. But you don't necessarily need that. That we just use to try to get it to stay. That's the problem. You know, Dr. Rodeo drains his shoulder, closes the portal, and then injects it in with a needle. Right? That's how you do your, yeah. So we know that stuff's squirting around, otherwise he would get, you know, you'd be looking at videos of the great clock going. And so that's the goofiest part of this, is the application of it, I think. Gus, are we ready, do you think, and what would you do, what would a clinical trial look like? Are we ready now to do something sort of like we've done with BMAC, a trial with and without with Bursa? You think now's the time to do it? Sure. I mean, we were surprised. We were surprised at how proliferative those cells are. And it's not something that we discovered. You know, Frank Golke's talked about it for 25 years ago, so they've known about this for a long time. And then Bursa's got, you know, it's variable. Some people have got a lot, some people have got a little. But there's always plenty. Why don't you put a collagen patch on, Gus, and then stick your stuff on top? I mean, the patch might work to, you know, clots adhere to collagen very rapidly. That's one more reason. You get back to this carrier issue, which we all deal with, how does it stay there? That's why I'd use the patch. So maybe put a patch in and put your stuff on top. Yeah. I think we can take two quick questions, and then we'll have to end. Thank you. Steve? Yeah, I got a question for Dr. Mazzocca. Why do you think that you're, you showed where you had a sufficient amount of colony forming units and yet you didn't have a good result? Why do you think that happened? Do you have any hypothesis or theory? Or are they just shooting duds? Or is CFU too much, too overrated? I don't know. You know, I asked a question yesterday in the biologic section about that. It seems we get hung up on the numbers, and the numbers don't seem to have much to do with it. I don't know. I use the colony forming units because at least that is something biologic that we can do, not just cells, you know, cell numbers. So that's why we use colony forming units. And we take a sample, we have an aliquot from everybody that we've done, and we grow them up and look at it. Now, counting colony forming units is not as an exact science as you may think. No, I know it's not, but, and then three to one versus four to one versus five to one versus eight to one? The tighter you make the clot, the cells don't live in it. So the better the clot, where you'd be like very happy and it sticks, they don't really live as well. So they need a certain amount. So that's why we came up with three to one. Dr. Harner is from the government. Can I have him go next? I don't want to cut him off. Yeah. Thanks, Brian. Just, Dr. Coyne, in your talk, you cited an article that said a 25% failure rate of meniscal repairs. I would contend that it's a 75% success rate, because if they do a meniscectomy, it's a failure. So I think that's a good number, because these are often tough tears, so I just want to bring that up. I'm not a strong clot advocate for tough, tough tears, but it's really a 75% success rate. Thank you. Thank you. And please, the last question. A question for Dr. Rodeo. When do you decide, or how do you decide what to use, an augmented patch or a VMAC or a combination of both? That's a great question. You know, I've used these biologics typically in the rotator cuff and revision surgery, bigger tears, poor tissue quality. We have no good data to suggest how you pick cells versus a patch, and that's, I always say, I start my talks by saying, you know, identify what's the biologic target. Until we know what we're trying to treat, that is, do we want to increase cell proliferation, vascularity, matrix synthesis, maybe influence the inflammatory environment? All those are important biologic targets, but they're all very different. Until we know what the biologic target is, number one, and number two, how our biologic formulation acts, we're not, we're doing this pretty arbitrarily. So the answer is, we don't know. And that's where we need further data to understand what we're trying to treat and what we actually, you know, the composition and the biologic activity of our materials so we can eventually match biologic with the treatment goal. All right. We are two minutes over. And so I want to thank our speakers. Thank you all. This was a great audience. And enjoy the rest of the meeting. Thank you so much.

stem cell

exosome products

orthopedics

investigational new drug

reproducibly making exosomes