All right, I first want to thank you all for those who attended tonight. My name is Shannon Strader and I'm this year's RFC research representative. I am also the moderator and creator for the AAP and AR3T Orthobiologics and Regenerative Medicine series. The goal for the webinars is to provide comprehensive education for physicians in training and physiatrists interested in regenerative rehabilitation while reducing stigma, misinformation, and encouraging responsible advancements for the regenerative field. If during the session you have a question, please write in the chat box and we will answer as many as time permits. Thank you, Shannon. It gives me a great pleasure in introducing our brilliant speaker tonight, Dr. Borgstein. Dr. Joanne Borgstein is an Associate Professor of PMNR at Harvard Medical School and is the Associate Chair for Sports and Musculoskeletal Rehabilitation for the Harvard Department of PMNR Spaulding Rehabilitation Network. She is the Medical Director for the Mass General Brigham Regenerative Sports Medicine Program. She is the Medical Director of the Spaulding-Wellesley Rehabilitation Center. She's the Chief of PMNR at Mass Gen Brigham Hospital. Dr. Borgstein serves as a Team Physician for the Varsity Athletics at Wellesley College and Associate Director of the Sports Medicine Fellowship at Spaulding Rehab Hospital. A major area of clinical, academic, and research focus is in regenerative injection therapies for osteoarthritis and sports injuries. Thank you very much, Dr. Borgstein. Thank you. Thanks, everyone, for the invitation and for having me and for showing up after work today. I really appreciate it. And I'm excited to share with you a little bit of a journey and some information about responsible use for orthobiologics in sports medicine. So what I'm going to do is bring you a little bit through a journey that we took at Mass General Brigham and are still on the path of. What our process has been, I'm hoping, and I trust that I see future leaders on this call who will be going out into practice and clinical research and translational medicine to develop orthobiologic programs and advance the field. So in so doing, I put together a few slides on what we've done at Mass General Brigham and Spaulding over the past couple of years. And then we'll move on to discuss the newest AMSSM position statement and the BJSM, British Journal of Sports Medicine, editorial about responsible use of orthobiologics. We know, I'm sure you all know, this is an incredibly robustly growing market. This is even a little bit old, but multiple times of increase in volume over the past few years. It's a huge industry. And so we need to be a little bit mindful of that as well as we progress. And if you look at the, quote, stem cell, end quote, market, those that are advertising straight to consumers, the three biggest fields are orthopedics, pain management, and sports. So very, very relevant to what we do in the sports medicine and physiatry world. And really why we're here discussing this is because for years, and certainly we're not at point of any sort of cure at this point, there really has been a treatment gap from considering basic physical therapy and mechanical and health related lifestyle ways of managing osteoarthritis and chronic tendinopathy pain to the other end of the spectrum, which is partial and most often total knee or shoulder or hip arthroplasty. The cartilage, the surgical cartilage repair procedures have become more mainstay and are certainly advancing, but there is a gap here in the more moderate range of clinical symptomatology that we really have yet to fill. And it's often anywhere from five to 10 years when folks become symptomatic with knee osteoarthritis until they have joint replacement. And there's a lot of living to be done during that time. And so we can think about regenerative medicine or orthobiologics as a bridge therapy. Mass General Brigham, what we set out to do was to create, expand a regenerative sports medicine program. And again, I'm hoping this will be useful to you all as you go out into practice and hopefully academic practice. And our value statement was to develop a world-class evidence-based value-driven care supported by education and research via an interdisciplinary program. This is absolutely a team sport type of activity. And we've not assembled the full team, but as you go out there, you're going to need a good research team to collaborate with if you're going to sort of move this field forward. And for us, it's included some stem cell biologists, biomedical engineering, and certainly we hope to enhance our biotech collaborations. You do need support from legal counsel, policymakers, as well as scientists and clinicians. And of course the clinical team is not just about non-operative care, but it certainly includes regenerative rehabilitation or physical therapy and occupational therapy colleagues, optimization in terms of medical management and optimization for healing, coaching, strength and conditioning, as well as surgical and non-surgical sports medicine providers. Keeping of course in mind that we're all doing this because the patient is at the center of this. And as we go forward, all of this is going to become important in providing patient-centric patient care. What we did in our, again, in our institution is we put actually our network, can't say one institution, we put together an MGB, which is a Mass General Brigham sports medicine team, which included folks from all our representative hospitals across the network, included folks from orthopedics, as well as non-surgical sports medicine. And what you don't see here is robust help from all different departments across the Mass General Brigham network. There's administrative support, financial support, legal support. There's been so robust infrastructure to help the informatics that will go along with this and the epic phrases and all that goes along with standardization of a program across a network. So this is really, this is a labor of love, but it's definitely a team sport. We started as you might by looking at who's doing what across our network. One of the things that we are committed to is providing a uniform experience, product, and level of expertise across the entire network. Doesn't depend on any one person, but rather how we roll this out and how we expand it to assure quality across the network. We also had to define, as you will have to define, what we want to be. So what clinical offerings we want to have, and also how are we going to dovetail with and be a robust offering for research, both on the tissue level and osteoarthritis and tendinopathy. And those were the two that we decided that we were going to focus on osteoarthritis and tendinopathy. I'll talk a little bit more about our research infrastructure shortly. Well, at the same time, you can't live just in the ivory tower. And we know that we wanted this to feel like a smooth program for patients. We wanted people to feel they had personalized assessment and care. And we do want to be recognized or continue to be recognized as leaders in education, training, and academic productivity, and be very mindful of how we advertise, how we talk to patients, how we counsel patients. I'll talk a little bit about research infrastructure, biobank, biorepository, data platform initiative a little later on. But that's a major undertaking and important aspect of how we, and I suggest you consider going forward in the future. We also started by surveying industry leaders, both in the academic and in the private practice world, both in the United States as well as outside of the United States. We started with Italy, spoke to some folks in Great Britain. So there's a lot of discussion about what we want to look at and what the world leaders were doing to make sure that we are going to be helping in a global effort to move this field forward. The other issue we have to think about is all dovetailing into the discussion of responsible use is trying to standardize the workflows, the operating procedures, and all the patient-facing documents. So once again, folks, whether they come to Spalding or Mass General or Brigham and Women's or any of our hospitals, mostly, will have a similar degree of expertise and experience. This takes a fair amount of time. Happy to share this down the line so you don't have to recreate everything that we did. But a lot of this ends up being very sort of academic network or clinical network specific. And there's a lot of collaboration that goes along with physical therapists, surgeons, and et cetera to sort of make these happen. We also had to decide, and I'll talk to you about this in a moment, what we were actually going to offer and why, based on certain compliance aspects with regulatory and FTC components. We also have to decide, as you will have to decide in responsible use, who is actually capable of doing which procedures, what your standards are in terms of training and expertise, and also what the patient intake is going to look like. We decided that we were not going to be sort of a factory, if you will, and just line people up and stick a needle without guidance into a knee, but that we felt that the in-person, if you will, regenerative medicine or orthobiologics consultation, review what the patient's been through, review their non-interventional care. Many people come to us and will come to you who do not need any sort of injection, let alone an expensive orthobiologics injection. The exception to that was folks who were referred directly from one of our colleagues for a specific intervention. So again, all of this will dovetail into responsible use, so that you're always looking critically to make sure you're doing the right thing for the patient at the right time, and you're taking a conservative approach as you go forward. Of course, as, and again, talk to this in a moment, what you do might be institution-specific, but we look to our internal legal team at Mass General Brigham and Spaulding, as well as we had funding to get input from external counsel that would review some of the areas that our own internal legal team was not as familiar with or as expert in. So make sure as you go out there and use this responsibly, you stay up on the guidelines from the FDA and the FTC and stay up on the, you know, evolving literature. What we decided when it was all said and done is that we felt comfortable as of the current time to offer these combination of therapies, extracorporeal shockwave, needle tenotomies through automated devices or through percutaneous needling, prolotherapy, dextrose-based injection therapy, platelet-rich plasma, bone marrow aspirate concentrate, micronized fat transfer, and of course, the whole realm of surgical treatment for cartilage repair. So with that sort of intro as to how we thought about this and rolled out or are in the process of rolling out a more substantial program at our institution, I'd like to take a next 15, 20 minutes or so and discuss the most recent guidelines and position paper from the American Medical Society of Sports Medicine. And what I would tell you is that a group of clinicians, ethicists got together and the goal from these guidelines was not just to say use platelet-rich plasma for knee arthritis or don't use it for X, Y, or Z disease, but rather to provide a framework upon which you have the skills and the ethics and the process to sort of keep up and make decisions and A, how to implement this in practice, but also on how to maintain ethical and responsible standards. The actual physician statement did not address shockwave therapy. There have been multiple reviews. There's one by Allison Schroeder et al. And we do incorporate this into clinical practice. Shockwave therapy has mechanical and cellular effects that have been shown to improve tissue healing and do alter pain signaling. The biological effects can be as a result of mechanotransduction and affects cellular level. It can increase collagen system synthesis, and I've seen this clinically may actually reduce soft tissue calcification tendinopathy or calcification in muscle. The advantage of it may be to use in in-season athletes, similar to prolotherapy, best used in conjunction with physical therapy, and most evidence supports the use in chronic tendinopathies and fasciopathies such as plantar fasciopathy. There's some animal and clinical data looking at focused shockwave therapy for the treatment of bone marrow lesions and bone marrow edema, and this can be certainly very effective as part of a treatment for bone marrow edema, either in bone stress injuries or in subchondral bone in osteoarthropathy. So again, these were the authors on the position statement, and I'm going to go through, basically take you through the highlights of the position statement on responsible use. This was published just a couple of months ago. This is not meant for us to go through line by line tonight, but rather to tell you this is a resource for you to define the terminology consistently with what others are talking about. So some of the things we'll be talking about tonight, I'm referring to a bone marrow aspirate concentrate, the orthobiologic term. Now most people would consider that orthobiologics is a subset of regenerative medicine. Regenerative medicine is a new field of medicine. It refers to using tissues and tissue engineering to try to stimulate healing or improvement of a medical disease process, for which orthobiologics is a subset using biologic substances specifically to try to promote use in orthopedic injuries and potential healing perspective. Perinatal products are a group of products that can be from placenta or amnion. Platelet-rich plasma we will talk about is just blood enriched in platelets. It has cytokines and growth factors in higher concentrations than blood plasma. And prolotherapy is hyperosmolar dextrose. Occasionally people add sclerosing agents, such as phenol or polydocanol. We use hyperosmolar dextrose, which triggers inflammatory cascade and healing. It is specifically to focus on fibrosis junctions and thesis and intra as well as extra articular use. So just these are a couple of basic terms, but this is here, this is in the article, and it's for your future use. So I'm going to start by just giving you a really concrete summary of the basic and clinical science of PRP. PRP is plasma, platelet concentrate higher than whole blood. Variation in concentrations and platelet count are seen. It can further be broken down into leukocyte-rich or leukocyte-poor, and studies have looked at relative benefit of each of these for different types of processes. Most of the platelets are going to be released within the first 10 to 15 minutes of injection. That can be sooner if they're activated prior, but no need to do that because these will be activated in the body upon injection. And PRP is basically used to treat chronic tendinopathies and osteoarthritis. So in the bottom line nutshell is over the last, we sort of looked at the data for the last one to two years, and if you walk away with anything with PRP, the most robust data really exists for lateral epicondylopathy, for chronic tendinopathies. Gluteal tendinopathy has level one evidence. Plantar fasciopathy, adjunct for rotator cuff repair and rotator cuff augmentation. There are more mixed results for Achilles and patella tendinopathy, but these are, these are the big ones. These are the low-hanging fruit, and when you counsel your patients, this is exactly what you can tell them. For osteoarthritis, again, bottom line, there have been studies since then, but the most robust evidence for platelet-rich plasma, better than hyaluronic acid or steroid injections, most robust data is for knee osteoarthritis. There's at least 14 studies for that. There's insufficient evidence to be certain for other joints, although certainly some trending for more chronic moderate hip osteoarthritis and for ankle osteoarthritis, which clinically is honestly one of my most favorite joints to treat, as I think the robust response is usually quite consistent. As it relates to ligament and muscle injuries, there's really limited data for platelet-rich plasma and ligament injuries. There have been some rather robust case series from Luga-Podesta et al, looking at proximal, partial thickness, onocollateral ligaments of the injuries of the elbow, suggesting that there might be some improvement and even some healing that's been seen on subsequent imaging. No data, of course, for full thickness injuries, and generally these refer more to proximal than distal injury. Muscle injury, the data has been kind of mixed to weak. It's been looked at for return-to-play times after hamstring muscle injuries. there's actually some suggestion that platelet-poor plasma for muscle injuries may be a better option, but really, if you're looking for someplace to go and things to study, I think muscle injury is still ripe for further study. Cellular therapies. Now, these generally, what we refer to here are mesenchymal stem cells or stromal cells. These are multipotent cells that can differentiate into musculoskeletal cell lines, such as bone, cartilage, and adipose. What this really looks like and how this works in vivo is still not well understood. The thought is that primary action may be a paracrine effect and not actually a cell-differentiating regenerative prototype in most situations that we're using in the United States at this time. We know that there's a secretory function, an anti-inflammatory function, immunologic modulatory function, antifibrotic and anti-apoptotic effects of these cells. And although there have been some in vitro and animal data to suggest cartilage restoration, this really has not been shown at all yet in the forms that we deliver these cells in the United States. There've been some studies that have come on culture-expanded adipose-derived cells from outside of this country or under research protocols, which have suggested temporary improvement in cartilage, at least in the knee, for about a one to two-year period of time. But still, there's more to learn about this. And when you're counseling patients, this is what you need to make sure. I cannot tell you how many people come in and they're expecting that I'm gonna give them these, quote, stem cells that are gonna, quote, regrow their cartilage. So this becomes a very important and responsible use. Make sure you're up on the literature and stay up on the literature and are counseling appropriately. When we're looking at cell therapies, the common ones that we use in the United States are bone marrow aspirate concentrate and adipose tissue. These tissues, as we use them, have a small number of cells in them. And we talked about studies from Korea that suggest some cartilage repair. When it comes to what we have here in the United States, the best study joint has been the knee, but data is mixed. And I think the data at this point in time suggests safety and anti-inflammatory effect, interleukin receptor, antagonist protein improvement and modulation, but yet not a clear improvement in articular cartilage mapping and function. For tendinopathy, cellular therapies, again, have very, very scant evidence to support their use. There've been some studies looking at cell therapies such as bone marrow aspirate as an adjunct to rotator cuff repair to induce more of a healing and better response. This mostly comes from Hernigou et al and from Gus Mazzocca. And with higher level of cells, there's a higher likelihood of success. Using fat-derived products has not at all been well-studied. I just put this out here because although it's not been well-studied, we were able to publish some of our initial series and our clinical experience with this, especially in rotator cuff tears and in osteoarthritis, has been extremely positive. So again, I think this is something we need to look at. Similar clinical experience and serial healing has been seen, at least in our experience, both in the rotator cuff with small partial tears and the Achilles tendon with partial tears. So just a phenomenal at this point, but needs certainly further use. This is, again, not to go into too much detail tonight, but for you to know this is in the review, this is in the position paper. And what I wanna keep reminding you of for responsible use is that we stay in the sort of the legal safe zone, the FDA safe zone. So things like micronized fat, make sure that you're using an FDA compliant kit, make sure you're not enzymatically digesting this fat because that is not allowed, it's more than minimum manipulation. Amniotic tissues currently in their current form in bottles, essentially off the shelf. There's no company right now that has FDA approval for orthopedic applications, only the sheet form, and those are really more in wound healing. Nothing culture-expansive and nothing from amnionicorion at this point in time. Platelet-rich plasma and same day bone marrow aspirate concentrate with an FDA approved device is probably okay at the current point in time. Dr. Borstein? Yeah. Sorry, do you mind resharing your slides? I think we are unable to. We lost you? Yeah. Did you see them till now? They just lost? No, I think they lost prior, but we weren't sure because you were learning so much. Oh my goodness, you waited so long to tell me you didn't see the slides? Way too polite. Do you see it now? Yes, they look great. I'm sorry. So you have not seen any slides today. That's pretty sad. Well, hopefully you got something from learning. No, I'm learning so much. I didn't even realize. Please don't be shy in the future. How's this? Good? Great. All right. So let's move on and talk a little bit about regenerative medicine and introducing it to clinical practice with responsible use. Number one, we need to have a rigorous and structured approach. We need to consider the science, the clinical evidence, the feasibility and the regulatory aspects. First, we need to make sure that we know there's safety and efficacy data. We should not be making any unsubstantiated claims. And we really always need to be mindful of how this fits into the algorithm for treatment for specific conditions. We don't start with injection therapies. We only go there if other less invasive basic sports medicine principles have not gotten our athletes or patients better. We also need to be mindful that on average clinicians who are already in practice or who are finishing up residencies need to have additional training to become proficient in these procedures. And the plan should be in place for the provider and your staff to become proficient. It's not just you. Your staff needs to know how to process these samples, how to draw the blood, how to process the bone marrow, how to set things up for you and how to counsel the patients. It really takes a village. Our medical assistant, physical therapist, nurse, everybody is really on the same page in how to make these things happen. And it's our responsibility to keep informed on the regulatory landscape for biological materials and processing. Also, what does this take? We feel, and you know, AMSSM, and we feel this way at our institution as well, that you need to have basic proficiency in the assessment of these types of musculoskeletal conditions, how to examine someone, how to manage them. And there needs to be excellence in proficiency in image-guided procedures. Not only ultrasound, this could be fluoroscopy or they can be used in combination. Really need to be up on your anatomy, both diagnostically, being able to interpret MRI and ultrasound. And if people are ready in practice, then certainly there are options with courses. IOF is one example and the different academies training on ultrasound as well as on orthobiologics specifically. We don't yet have guidelines on content for sports medicine fellowships for orthobiologics per se, but maybe that'll be forthcoming. And we were speaking just prior to this about the need to maybe set what a curriculum for this should be, basic and advanced. The other really important thing that you might not think about is informed consent. This is tough. These consultations take an hour. We need to be honest and balanced in how we present these, because folks come in and are somewhat frustrated and sometimes a little desperate, and they're willing to put their resources into this. But we need to make sure that we're educating them about the risks of the procedure, what is known about these, what is not known about this, what is not known about this. We also have to make sure that we educate them that these are not necessarily standard of care. These are out-of-pocket expenses. We need to talk about the FDA and use our terminology and verbiage accurately and carefully. And if you happen to have any conflict of interest, that certainly needs to be communicated right up front. This is something you might not think of, and that is quality control. The institution needs to have a way of monitoring quality, monitoring for adverse effects, making sure you deliver a safe and standardized product. Unfortunately, I've seen situations, I've heard of situations where, not in our institution, but this was not the case, and people have had joint infections and other serious complications from this processing. So you need to have a safe and standardized product and way that you're going through this. You need to have an FDA-approved device and manufacturer. All of these things should be included in your safety and quality control. The time, the date, patient demographics, what you're treating, what the medications are, medical comorbidities, cancer, diabetes. You're not gonna probably be doing these in anybody with an active cancer diagnosis. Are they drug using, alcohol using, smoking? All of that would probably make them a less robust candidate for this, but needs to be documented. What the technique is that you use to process your sample, what equipment you use. We are putting in place devices to measure and record our cellular contents. Great if you could do this from the get-go. We have just been able to do this more recently. How this was delivered, where it was delivered. You need to have pictures that show what you're doing, how much you delivered, did you activate it, and did you do any needle fenestration? Additionally, we need to know baseline cell counts. We need to know the post-processing cellular count, changes in concentration, volume, and total cells, at least monitored in your lab periodically. It's not gonna be feasible to do that in every lab every time, but just be mindful of setting up some parameters. Critically important for the field is outcome measures. So we have been collecting outcome measures for years, but we are going to be improving this with more automated patient reported outcome measures that are tendon specific, joint specific, and that really should be pushed out to our patients at set intervals so that we can compare across our network. And so we have also the infrastructure to look back on these from a research perspective over time. We always have to be talking about informed consent, looking with a mindset towards conducting clinical and translational research. I hope, we hope that these procedures will ultimately be recognized and reimbursed by third party payers other than just workman's comp or professional sports teams, and also are gonna be absolutely mandatory when we have our continuing discussions with the FDA as well as third party payers to look at the cost effectiveness of what we're doing. The next publication that came from this was an editorial, which really was just a very quick summary of the salient points from the position statement. And I'm just gonna sort of summarize that for you so that we have some overall framework and some take home points that I want you to leave with tonight. And I think this diagram from the editorial is just beautiful. It's a beautiful to look at, but it's beautiful in terms of content. So what are we looking at here to summarize? There is a treatment gap that orthobiologics hopefully is starting to and will continue to evolve and fill over time. Obviously, we'd like to get to the point where we're not filling a gap, but we're preventing. We understand the pathogenesis of what happens, for instance, after an ACL injury and reconstruction that starts that inflammatory cascade, which leads to premature osteoarthritis. So while we're talking about filling a gap, the way this should go is to ultimately prevent, mitigate the progression or development of osteoarthritis in the future. So there are treatment gaps and there's unmet patient needs for both chronic and hopefully preventative aspect of osteoarthritis and chronic tendinopathy. Two, one must be aware, stay aware, stay informed of the regulatory aspects of this. Make sure any product that you're using is only quote, minimally manipulated and is used in the type of tissue from which it comes. It's called homologous use. So those two aspects of regulatory oversight need to be appreciated. In addition, always need to be mindful that we wanna use safe techniques. We want to ensure that we deliver our target with use of image guidance. We always wanna be mindful to use the least invasive, safest, most cost-effective treatment with the strongest evidence to support its use. And if that means you need to talk to your patient and say, you know, happy to do the bone marrow, but really I can't make a case for it in your situation. There's not enough evidence. And then talk them down. A lot of people come in with the expectation that they want you to do the stem cell stuff that they've heard advertised or read about on the internet. We need to be using consistent, standardized nomenclature, clinical protocols within an institution, within a network and across the country and world, as well as being mindful of our quality control measures and reporting. We talked about the ethics of this and informed decision-making, sort of setting the expectations of what they're going to be going through. Make sure you set the expectations in terms of return to play. This is sort of an overview of a time-related process. This is not a steroid injection that works within a few days. And they're not gonna be going back to sport right away. It could take a few weeks, sometimes a little bit longer. And that PRP and chronic tendinopathies that we discussed seem to have fairly robust evidence, especially in the knee and gluteal tendon and lateral elbow. However, to routinely recommend orthobiologics for other musculoskeletal conditions, we certainly need to advance the science. In our institution, coming back to our clinical implementation, we spoke about our standard operating procedures. You'll have to decide in your institution. We have decided we're going to implement a call center so that we can get patients to the right place within our network. Our networks, you know, you can be traveling a couple of hours from one end to the other and still be in our network. So we want to have patients get to the best provider. And then of course, I'm putting this in here because I didn't really emphasize for us and for you, everything that you put out there in an advertisement needs to be compliant with the FTC, okay? The aspect of it in terms of false claims, for instance, bone marrow acid can be used to reduce inflammation and treat osteoarthritis. Well, do we have proof of that? No. PRP can be used to repair an injured Achilles tendon. Do we have proof of that? No. So we need to make sure there are things that you wouldn't even think about. Patient vignettes, you put, you know, Mrs. So-and-so's osteoarthritis was cured or she felt so much better because she had bone marrow aspirate into her knee and that's a useful treatment for osteoarthritis. You are innocent and you're thinking, wow, this patient's story would be great, but it's making claims and it's advertising something that is not evidence-based. So when you really think about it, as an example, we started with our patient materials this much and we ended up using this much and it's bland and it's vanilla and it doesn't state a lot other than, yeah, we do this. And I'm sorry to tell you, but that's the way it needed to be for compliance, not only with the FDA, but with the FTC. So things that you might not think about, if you go home and look at your own websites, you may realize that you might not be compliant. The other aspect that I just wanted to emphasize is the research infrastructure. So we have started, we're using and putting a lot of money and effort into a robust database and biorepository. So we have coined and hope to register the name STARNET, Sports Treatments Assessment Research Network. With that, we have utilized the help of the Center for Innovation in Bioinformatics, Clinical Research Institute at our healthcare system. And we have worked with them. It hasn't rolled out yet. It's probably gonna be rolling out in the next few months, but we have been working for about two to three years on putting together and getting the resources to put together a framework so that every patient, no matter who they see across the network, will get a similar type of treatment, similar type of outcomes. And we will be having this in a database that is de-identified and ready for research purposes with a network IRB. And to that end, we will have our STAR Bank, which is our biorepository, as well as other electronic health records. We've been working to and sort of have codified what measures we want to collect. Our measures need not be your measures, but it needs to be done if we're going to set this up for future important research. And of course, many of you are in institutions and academic networks that will support. Okay, many of you are in academic networks. That's what the AR3T is about, Mayo and Pitt, you know, Ohio State and Emory. You know, there's so many out there, but it's really great when you start thinking outside of your own sphere. And as I sort of got more involved in this over the past few years, I honestly didn't even know that this great institute was gonna be such a great collaborator. The Wyss Institute for Bioengineering has turned out to be a great collaborator. Certainly our basic science research, as well as all the clinical networks, as well as our Institute for Health Professionals to help us look at regenerative rehabilitation. So we are not unique. This certainly exists in other institutions. I'm hoping in the future, we all collaborate academically to advance this field. And that's what organizations like the AAP and the AR3T are just wonderful and terrific for. So hopefully I sparked some questions. I'm sorry if you didn't see the slides. I'm happy to give them to you afterwards and share them. Thanks for being polite. No need in the future. Very sweet of you. I hope that didn't detract from the first, you know, part of the presentation. I'm happy to go back if there are any charts or diagrams I mentioned and you want me to go back and go over them. But otherwise let's just break here and the next 15 minutes, just talk. Comments, questions. Hi, Allison. Welcome. Everything is up for grabs and would be valued. How's that? We see each other now? Great. I had a question, Dr. Borkstein. Sure. So it's a lot when talking about informed consent, quality control, outcome measures, and process technique. A lot of that's, I don't even know if it's even taught at like many institutions except for yours and maybe a few others. Do you foresee with, you know, these injections and all the information you have to know if that will eventually become like a requirement to be able to qualify to, you know, have those specific injections, whether it's a specific sports medicine certificate or if it's a, you know, different kind of fellowship within itself. Those are great questions. Will there be some special secondary orthobiologics regenerative medicine super fellowship? Probably, maybe. I mean, there are folks who already offer that mostly in private practices. And certainly the standards, I knew I'm talking to the AAP folks and AR3T folks. So I really wanted to present what I thought a good standard of care and delivery for sort of robust academic future would look like. Having said that, the vast majority of people in this country doing this are out in practice. And so what they need to do is be mindful of the science that's out there. A lot of the ethical aspects, knowing your equipment, safe delivery applies. And I can't, I'm sad to say, I've seen horrific complications when these things are not adhered to in the private practice. You can have complications anywhere, but I mean, awful stuff out there with products being saved for a day or two, sent from one practitioner to another, flown in from elsewhere, off the shelf products, and all of that needs to go away because safety is the primary issue. And when it comes to data sharing and outcomes research in private practice, there are folks out there, there are networks that you can join as a private practitioner to pool data across the country. You don't have to do it all on your own. You could do it on your own, but you can just, they're not that expensive. Dr. Lange has one, there are, I don't want to endorse any one product, but there are a couple out there that can be a part of your practice armamentarium, and I think should be, quite honestly. In terms of quality control, it's like I, as one who, at one of my hospitals, there's private practice folks and academic folks, and the truth is I can't so easily control what goes on in the private office outside of my, quote, vision, if you will, but it is important that we herald the right aspects of this so that, you know, basically so that the field doesn't go under because of misuse and misrepresentation and greed and, you know, imprecision and sloppy, unsafe practices. And I think from what I hear, like sort of legally and FDA and our council, the FDA first is interested in patient safety. So things that are being done that may not be safe at the get-go are going to be the first targets of enforcement. Doesn't mean where any of us are immune, but I think that that's the real first target for enforcement. Thank you. Yeah, I agree completely. Thank you. Yeah. I had a question just regarding some of the future guidelines that may come out in terms of responsible use of orthobiologics. So I know you had touched upon this, that we really want to make sure we're giving the right patient the right treatment. So for example, your smoker with the multiple comorbidities may not be the best patient to receive an orthobiologic. Do you predict or do you think the trend might be going toward looking at patient characteristics when we are prescribing these therapies and what may these guidelines kind of reflect in that realm? Because I think that's something I feel really passionate about giving the right patient the right treatment. Yeah, yeah. Yep, absolutely. Yeah, I can't remember who published it, but somebody did start to put those factors out there in terms of giving a score, like a pretreatment score based on a variety of factors, for instance, alignment, grade of arthritis, medical comorbidities that might help us. Now, those are really just sort of epidemiologic and data points. They're not really cellular analyses that would help us predict, which I think is where we need to probably go. I'm sure there's... Not sure. I'd like to be sure that there's gonna be sort of a personalized regenerative medicine recipe, if you will. We'll take a little pupil swab or look in our database and say, you have this genetic profile and you're gonna do better with this treatment than somebody else, the same way oncology is going that way. Psychiatry is trying to go that way. So yeah. And then the other thing is, and this is sort of patient readiness for change. Can't say we use it as a carrot, but it's sort of like there's a carrot at the end of this. So I tell folks, I think you kind of be wasting your money. You haven't been exercising regularly. Your nutrition is not good. Your BMI is high. You have abdominal adiposity. It's pro-inflammatory fat. You're diabetic. I can do it, but chances are you're not gonna have a good response and you'll be throwing your money away. I'm happy to do it, but let's talk about lifestyle. And that starts a whole nother discussion. We have a whole lifestyle medicine service, people refer to, but it's often a motivating factor. And then folks come back in six months and they maybe lost a little bit of weight, gone through the physical therapy. And then they don't generally need the treatment or might not need the treatment. And we talk about nutrition, I'm sure as all of you do in your day-to-day practice, but we probably won't be treating folks, generally not treating folks who are really poor condition for this. I really think they're just be, they may work, we may get lucky, but you're not stacking the deck in their favor. And then you may be wasting your money or their money, sorry. Thank you, yeah. I think it's for at least one of the things that I have seen in maybe some private clinics is just like, okay, here you have the option for PRP, whether or not it's for you, shell out $600 and you get your shot. Yeah, yeah, we turn away, we don't turn away. We find alternatives, paths to improve pain. And the other thing in our state, not a lot of insurers, if you take knee osteoarthritis as an example, some insurers will still cover visco supplementation or we may do a one-time steroid injection still just to reduce the infusion and effusion and jumpstart their ability to comply with physical therapy and rehab. So we also try to do whatever we can that would be covered by insurance, a priority before kind of having that discussion about orthobiologics. Thank you so much. Oh my gosh, you're gonna have to fix this. You're gonna have to do the research and make it happen. I have a question. First of all, that was an awesome lecture. Thank you so much. You touched on this Starnet Biobank. What are the goals of this biobank? And are you just gonna be looking at regenerative medicine or are you gonna be looking at like global pain management? Great question. So we're starting a little bit more scripted, make sure our processes are good and that we have the staff and infrastructure in place to support it. So probably when we roll it out in the next few months, we're gonna start with shockwave and all orthobiologic procedures as well as surgical regenerative procedures as well. We'll have our biobank. We have freezers that we're getting in every location. We'll have a de-identified database. We'll ultimately have some central storage for specimens. So I think to start with, we need to roll it out with the orthobiologics because otherwise we'd be treating absolutely every person who came across the door, which would be thousands and thousands of patients. And that would be overwhelming. But the only real good use is ultimately if we can say, okay, well, this patient, everybody with Achilles tendinopathy is gonna be entered into the database. So whether they got dry needling or trigger point injection or just physical therapy, we should be able to follow some of these parameters. We don't need the star bank. We don't need the biobank, but we may need other parameters that we can measure and we'll measure PROMs and have our database over time. That's gonna be, will have to be wave two or three just because of the proof of concept that we can get this done and do it well. So there are initial research effort will be more in the orthobiologic, surgical and non-surgical and shockwave arena. Now, having said that, once we are really good at that and roll it out and get our processes down, we then have something that we can use to help apply for industry and federal funding because now we have an infrastructure. They did this so beautifully in ALS. You know, they set this, they've used the neuro bank in our institution at MGH, Sabrina Paganoni, you know, sort of helped to lead this and they had a robust infrastructure and then companies and research grants were obtained because, okay, we'll plug you into this group of patients. We'll plug you in here. So part of the reason we also wanna do this is to be able to support getting funding for what we want to do. And lastly, but certainly not least, and they did this again in ALS, is the framework is there to go multi-institutional. So it's all there and they can, once we roll it out in our place, you can bring in other institutions and they can run their trials and we can share data, we can share samples. So it's meant to be nimble and to be able to support collaboration with other research supported institutions. So good question. And there are gonna be lots of phases of this. I can only hope and pray we're as successful as the ALS team was. Part of their success, other than the wonderful people who did this, is that there's just not as many people in the country with ALS. So you can probably capture, you know, 20, 30, 40 institutions. We get into the millions and millions of patients if we did that. So we're gonna have to be a little bit more selective as we go forward. Thank you. Thanks, Jason. Thanks for coming. Thank you, Dr. Borgsten for the presentation. It was very good. I have a question regarding PRP. So you said that there were some good indications for PRP regarding some of the tendinopathies. And I was wondering if the severity of the tendinopathies will influence how you address the need for orthobiologics, and if you would be more aggressive according to the severity. Good question. So the three tendons that are probably the best studied would be the lateral elbow, glute tendon, and probably Achilles to some extent, rotator cuff to a lesser extent, but more in the surgical world. And yes, severity is really important. If somebody has a full thickness, you know, significant severe rotator cuff tear with retraction, there isn't a role for... I mean, there may be a role for PRP if they have some secondary arthritis, but you're not gonna offer them that treatment. Just the severity alone of the tissue and what it looks like would not be a contraindication. There are other things we may look at, neovascularization, presence or absence of tissue defects, but for just plain old garden variety tendinopathy, it might influence how we deliver it, right? If there's some calcific tendinopathy, we may do some fenestration in there. If there's a real defect, I might add a little bit of a tissue filler. But if you just have a thick, abnormal, common extensor origin that might look a little nastier than someone else's, it may not hurt anymore, and it might not necessarily, you know, fail to respond. I think that's part of the grading system that Clotel was talking about, is that how does severity... I mean, we've all seen nasty looking tendons get better easily and not so bad looking tendons and hurt a lot and have a lot of neovascularization. So it really, and is that related to pain? Who knows? So I think that it's a really good question and one that needs to be answered, but just a more advanced tendinopathy without any of those particular defects or characteristics, I would be okay with treating with just PRP. You could also use shockwave to some of these tendons. The nice thing about shockwave, Dr. 1040 and I have been working a lot in conjunction to combine our treatments. You know, if you think about treating a tendon, you're treating the whole muscle tendon unit, right? So shockwave can help with a muscular component to it in a way that's an adjunct to what we do with the tendon with PRP. So there's a lot of layers to answer that question. Exciting stuff, very exciting. Thank you. So any other questions? I don't know if there are. I'm happy to stay later. Yeah, I did want to clarify for everybody that the recording, we'll get your PowerPoint and we'll splice it with the recording. So it will be on the recording. Oh, how slick is that? Thank you, that's great. Yeah, and I apologize about that. I guess one question I do have is that you did mention about, I guess, differentiating between the bad apples and I guess like the academic research mind about advancing the field responsibly. Besides education, do you feel like there's a better solution? Because right now, I guess that's my fear is like going into this, I'm wanting to move it forward. I love the research aspect of it, but I do know that it's almost like a private world. It feels like in human, or at least it's getting a lot of like social media, like presence more than... I'd like to think that most people are inherently good and perhaps under-informed is what I would say. And academic or paraphrase doesn't really matter. There can be good and bad compliance just from not knowing what's to be done. And that's why these things like position statements and seminars and educational aspects are really important. So I don't know, I'm gonna still believe in the good of people and try to just really write and educate, and it's not just the practitioners that need to be compliant, it's the industry. So you might think you know something, but then a slick salesperson from product X comes in and says, hey, look, we have this J code and you can bill for this under Medicare, and you can just take this amnio fix off the shelf and we have data and blah, blah, blah. And they sell it to you because you don't know any better. So it needs to come from both sides, both from the clinician side and from the industry side as well. So it's tricky, but I'm not sure everyone is well-intentioned but I'd like to think if we get people well-educated that most people are well-intentioned. And if they're not well-intentioned, most people don't wanna be brought to task by the FDA, right, or the FTC, or have bad advertising. So there may be a little, you don't always stop at a red light unless you know that there might be a traffic cop there, right? So the thought of enforcement might alter behavior as well. And yes, I do stop at traffic lights, but you know what I'm saying, you know? Yeah, for sure, for sure. All right, any last questions? Okay, I appreciate you so much. This was so important. Thanks for the invite. I'm sorry about the slides again, but I see a lot of folks here who I think are really gonna be leaders in this field. And even if it's just a few folks, I hope we can work together in the future, thanks. All right, thank you all. Be well. Thank you. Thank you very much.

orthobiologics

sports medicine

regenerative medicine

treatments

safety

patient assessment

outcome measures

research infrastructure

education

collaboration