We'll spend the next few minutes talking about biologics, both as a standalone as well as an augmented treatment to surgical procedures. And then we'll move on to talking about osteotomies in more detail. And finally, talking about how to put this all together. How do you actually execute on the cases that we're discussing? And we'll have time for questions, answers, and case presentations in just a little bit. So my disclosures haven't changed in the last 20 minutes. So how can we improve surgical outcomes? Biologics and biologics, those are the two. That's how we really improve our surgical outcomes as surgeons. This is what we have control over. We can't always control the patient-specific factors, but we can control the mechanics and we can control the biologics. Are biologics the answer to everything? Well, it's certainly a hot topic, not just in orthopedics, but in medicine in general. In fact, when you look at the media, the media would tell you that for the small price of X amount of thousands of dollars, you can take this subluxated arthritic hip and with a couple injection treatments, turn it into a normal hip. This is in my area. This is what we see. And more importantly, this is what our patients see. And they come in thinking biologics are the answer to everything. And that should make everyone in the audience look a little bit like this. Like, is that for real? And it really is not for real. And this is what is the problem. When you irresponsibly use biologics, you can have problems, major problems, leading to multiple surgeries for patients, multiple complications, morbid outcomes, et cetera. And so there are problems with biologics, and we have to be responsible about their use. I said this slide, or I mentioned this slide earlier, and it applied to surgical treatment, but it also applies to biologics, particularly in the U.S. environment where patients are often paying cash. They want to know, if I'm paying for this, will it work? Or if I'm paying for this, can you guarantee me an outcome? Not so much if I'm getting the treatment. When it comes to biologics, the question turns more into, because I'm paying for something, I expect a return on my investment. So it's a little bit of a different discussion when it comes to biologics. And the key is to manage expectations. And the biggest take-home is to please not over-promise what these injectables can do. Hopefully you over-deliver, but please don't over-promise, because there's not a whole heck of a lot biologics can do with bone-on-bone arthritic hips, bone-on-bone arthritic knees, malaligned joints. Whenever we talk about biologics, it's important to understand what is allowed and what's not allowed. And if any of you were at the Biologic Association Summit this Wednesday, we talked a lot about this. There was a memo that came out on June 3rd of this year by the FDA talking about the new harp down on biologic products and treatments. Now it's actually not anything new. This same memo was brought out to public in 2016. However, there was a discretionary period from the FDA for the last four years. That discretionary period is now over. And so if you advertise biologics, say, on your practice website or in your media or whatever you might do, and you're advertising something that's not accurate or false, the FDA can send you a letter and you can have repercussions for that. So it's important to know now more than any other time what is and is not allowed. Typically biologics, at least in the United States, that are allowed are products that come through an FDA 361 HCT slash P pathway. This is a pathway for products that are minimally manipulated and for homologous use. This has a lot of wiggle room. What is minimally manipulated? Is shaking a bunch of cells minimal manipulated or moderate manipulated? Is taking bone marrow out of a bone marrow bone, putting it into a machine minimally manipulated or more than minimally manipulated? Is taking bone marrow and putting it into a joint or into a tendon homologous use? Same for fat. Same for amnion. So lots of vague in this FDA ruling, but it's important to know that this is what the rules are. They can't be more than minimally manipulated and they have to be for homologous use. What's not allowed, at least in the United States, if you're not part of an IDE or FDA clinical trial, and that doesn't mean you can have an IRB at your institution and call it a trial and use these biologics in this way. It has to be an FDA trial or part of an IDE. And what's not allowed includes all of what you see here, culturing cells, taking cells out of the procedure room that you're working in and doing something to them and bringing them back in, sorting the cells, adding growth factors or adding enzymes. The challenge here is when we look at the literature and we see papers that show improvements with cellular therapies and biologics, many times it's due to the enzymes. It's due to the culturing. So careful what you read. Your patients might find those headlines, but that doesn't mean you can offer that treatment here in the U.S. From 30,000 feet, what happens? We have an injury. It could be as simple as a paper cut, but let's say a meniscus tear in this case. Growth factors from our own body come to that site of injury. That's how our paper cut clots. And then hopefully you get some repair or healing. The purpose of the field of biologics is to optimize the growth factors, to then optimize the repair. Growth factors come in two flavors, good and bad. We want to optimize the good and we want to deoptimize or turn down the bad, and that's the holy grail. Once we figure out how to do that, whether it's with an injectable or with a procedure or likely with a combination of these two things, then we have some real efforts here. Then we can really hopefully improve the biologic environment of the knee joint, of the shoulder joint, of the hip, of the ankle. We need to increase our intrinsic good growth factors and decrease our catabolic growth factors. What are our orthobiologic options? Well, it ranges from anything from visco-supplementation, hyaluronic acid, to blood products, most commonly PRP, to cellular-based therapies, including bone marrow and adipose-derived therapies, but also synovial-derived, peripheral blood-derived, and bursal-derived, particularly when we're talking about the rotator cuff, placental tissue-derived therapies, as well as isolated growth factors. These are all the tools in our biologic toolbox. I'm going to spend a minute on visco. Visco was very popular about a decade ago, then got a bad rap due to insurance coverage in the United States, and it can be really hard to get for certain payers. And now it's having a little bit of a resurgence because we're better understanding the role of visco-supplementation, particularly as an adjunct to, say, PRP or as an adjunct to surgical procedures. So visco has a lot of different therapeutic properties, but one of the most important ones is proteoglycan synthesis. So depending on the type of visco that you're using, be it high molecular or low molecular weight, you can get some biologic benefit out of a visco injection. There's a lot of different formulations, so you need to know what you're putting in your patient. You need to know where it's from, particularly if they might have an allergy, how many shots you're going to give, if you're going to give it at the time of surgery or as a standalone procedure, and if you're going to combine it with something like PRP. So what's PRP? Well, let's go back to medical school for a second. As we all know, blood's comprised of red cells, white cells, and plasma. Plasma is the, thus, non-cellular portion of the blood, which contains platelets and growth factors. PRP is referred to as a sample of blood plasma that's greater than two times the concentration of platelets above baseline levels. That can be 2.1 times, that can be 2 million times, or anywhere in between. And therein lies the problem with understanding PRP and why, despite decades of level one research, we still don't have a CPT code for PRP that's usable. Because it's so hard to compare PRP product A to PRP product B, because we still can't agree on a definition of what PRP is. There's multiple different systems and preps. What we do know is that platelets have a normal biologic role for tissue healing. As I mentioned, they contain growth factors and proteins, so when they get activated, their alpha granules release a variety of growth factors and proteins that allows us to clot, that allows us to have healing at a site of injury. And PRP tries to concentrate those platelets so that we get maximum bang for the buck at the site of the injury. There are a variety of different PRP systems, and to date, no single system has been proven better than another. But you do need to know what you're putting in, in terms of low versus high platelet concentrations, low versus high white cell concentrations, and you need to know if you're using a single spin or, more commonly, a double spin or a buffy coat spin, and understanding what the keys are for the end product that you're using. Treating a joint for cartilage restoration or preservation, for example, is different than treating a tendon, and a tendon is even different from a tendon because we have acute tendinopathies or tendon ruptures. We have chronic tendinopathies or tendon ruptures, and so the varieties of different biologics that we use need to take those factors into account, and remembering that more platelets is not always better, remembering that more white cells is not always better, but less white cells is not always better, so it really depends on what you're using. This paper by one of my co-fellows, Drew Lansdown at UCSF and Lisa Fortier out of New York is a phenomenal review of the different types of PRP, so if you're interested in getting better educated, I would encourage you to read this paper published in Operative Techniques in Sports Medicine, and if you can't get access, I'd be happy to send you a copy. This is a great paper to really simplify in an elegant way the different types of PRP and to understand what you're putting into your patient. Does PRP work? Yes. No. Maybe. So it just depends on the literature that you read, and this is what my pup Murphy would say about all that, and so you can find an abstract in the literature to support any single thing that you want to support. If you want to tell your patients PRP works, you can find literature to back that up, and if you want to say PRP is voodoo, you can find literature to back that up, so the big question is getting into the weeds and understanding what the PRP is that you're using and is it appropriate for that indication, and why is it so confusing? This paper was written by Jorge Chala out of Rush, but when he was previously working at the Stepman Clinic with Rob LaPrade, looking at the different types of papers published about PRP in over 100 papers, just over a tenth reported on every step in processing. This is the problem, and this is one of the charges of the Biologic Association. We are going to require that every paper we put out and every paper we review has standards, has methods, is reproducible, so that anyone in this room could go take those methods and apply it to their own practice and understand, and hopefully get a reproducible result. There is a critical need for standardization and consensus. What about stem cells? I put this in quotes because we don't like the term stem cells, however, that's what our patients know. That's what they come in asking for, so as clinicians, we have to be willing to understand this term, what it means, and more importantly, what it does not mean. And what exactly are stem cells, so to speak? Well, if you ask the NIH, they have one definition, and if you ask the ISCT, they have another definition, so even the world's experts in medicine can't decide on what the definition of a stem cell is. The bottom line is a stem cell, or a mesenchymal stem cell, or MSC, is founded in native tissues, such as your bone marrow or your blood or your adipose, but at very low concentrations. In fact, we like to use the term MSC, and Arne Kaplan, who's coined the term mesenchymal stem cell, changed the nomenclature to talk about mesenchymal signaling cell, or mesenchymal stromal cell, but it all boils down to MSC, to really include the definition of what the cell does, but get rid of what the cell doesn't do. And so the challenge is our patients know it as stem cells, as I mentioned, and so we have to be able to use that term intelligently in the public, but here in an academic setting, we need to better understand, and MSC is a better term. Well, let's talk clinically. Where do we get MSCs? We can get them from the bone marrow. Clinically, this is a bone marrow aspirate. It can come from any number of places, as you can see here, and the pros and cons are pretty obvious. The pros are it's easy to do. The cons are it can be costly, depending on the system that you're in. You can harvest from a variety of different locations. How do you know where to go? Well, there's literature to tell you where to go, and the literature would tell you to go to the posterior superior iliac crest for the highest yield of cells in the aliquot of bone marrow that you're harvesting. However, that's never been borne out clinically. It's never been shown that cells from area A are more important or relevant or a better number of cells from clinic site A are better than clinic site B. So how do I do it? I take the procedure that I'm doing, and I make it easiest for me. So if I'm doing a knee procedure, unless I'm part of a study, I'm typically taking it from the proximal tibia. It's very easy, and I don't have to go to the hip. If I'm doing a shoulder procedure, I typically take it from the greater tuberosity, as long as there's no cystic changes in the greater tuberosity. You could argue that there's more cells when you take it from the crest, but I've yet to see a study to say that that matters. Again, more is not always better. So we have to better understand that, but that's how I do it in my practice. What about fat? Fat has had a resurgence in 2021. Fat is a lipoaspirate, not liposuction. If your patients ask, you're not going to make them skinnier. And you take the fat from the abdomen, the flank, or the thigh. You can also take it arthroscopically from the infrapatellar fat pad. And essentially, you mechanically process to wash out all the cell debris, all the tumescence fluid that you used to inject the area that you're harvesting so that you can make the fat more readily achievable. And you get a final sample that's rich in MSCs within the extracellular matrix. One of the benefits of fat is over bone marrow is that there's no significant decline of cell number with age. And fat is contained, as we know, adipose tissue. It's contained within a structural scaffold. That's some of the pros and cons of fat. I wish I had a little bit less of the structural scaffold, you know, during the summer and beach days. But if I'm talking about biologics, I'm thankful for the structural scaffold. Because it helps hold those cells in place longer than, say, a clot of bone marrow. And adipose can contain 150 to 500 times the concentration of MSCs compared to bone marrow. And that may be advantageous. Again, we don't know that. And there's never been a head-to-head study clinically. So we don't know that more cells is necessarily better. But common sense would tell us that it probably is. There's a variety of different types of adipose preparations, similar to PRP, similar to bone marrow. You need to know what you're putting in. You need to understand the size of the molecules to see, is it right for the clinical application that you're working on? Amnion. This was a hot topic at the BA Summit on Wednesday. Because amnion is very difficult to understand. Is it homologous or is it not? Where does it fit into this scheme of biologics? What I can tell you about amnion is the products on the market now are pulled from the market. And you have to be part of one of the clinical trials to use an amniotic injectable. That being said, this is a point-of-care technique that does not require harvest from the patient. This is an allograft technique. And there's no donor site morbidity for that reason. And you can do it as simple as a steroid injection in the office. The early clinical results from at least one of the companies that have published are favorable with regard to safety and efficacy. So certainly more to come on amnion as the clinical trials continue in the United States and abroad. What about needle arthroscopy? So this is a tool that I use, and Armando mentioned this, in terms of potential staging arthroscopy for cartilage restoration procedure. I employ needle arthroscopy in this setting in the office for biologic delivery on occasion. Often I just use an ultrasound. But also for cartilage staging for future cartilage restoration and joint preservation procedures. I do believe, as the technology improves, this is going to become part of our standard of care. But I will caution you, after doing several dozen of these, you have to have the right patient who's willing to undergo this in the office and be part of this without passing out. That being said, as you can see from this video of a video, the view is quite nice, and you're really able to see a lot and potentially save your patient a surgery or directly visualize your delivery of the biologic. So to take it all home, we have multiple tools in our biologic toolbox, and we will get into some of these during the cases. But I want to leave you with the thought that there are still more questions than answers. And I'm not advocating for a single biologic in a single clinical application today. What I'm advocating for is using biologics responsibly to help improve your outcomes based on some literature that we have. The two most important areas for biologics in my practice include platelet-rich plasma to help augment meniscus repair. There's great literature to support that. As well as PRP for lateral epicondylitis. There's great evidence for that. And there's good to great evidence for the use of leukocyte-poor PRP for mild to moderate osteoarthritis. So those are the three biggest uses of PRP in my clinic. And for bone marrow, I typically use that in the operating room as our non-operative partners use that more in the clinic. And I typically use that as an augment to surgical procedures, including osteochondroallograft transplantation. What we need to better understand is when do we use these biologics? How do we get them there? But more importantly, how do we keep them there? Those are really the keys to understanding if biologics will become a mainstay of our practice, and I firmly believe that they will. Thank you very much. Thank you.

biologics

surgical procedures

mechanics

patient expectations

orthobiologic options