This is Shane Shapiro on how I can use bone marrow aspiration and lipoaspiration in your clinic. Thank you, Shane. SHANE SHAPIRO Thank you, Jason. Shane Shapiro. I work at Mayo Clinic in Florida, Department of Orthopedic Surgery, and want to talk today about how I use these therapeutics in my practice. My only disclosure is that I am co-chair of the Biologic Association, no financial disclosures. So what we're here to talk about, there are many different biologic products that are on the market, and in terms of those that we can use at the bedside or in the surgical environment, just three, the big three, we call them, and we've spent some time talking about PRP, so I'd like to talk to you about how I use BMAC and microfragment and adipose tissue in my practice. As Scott Bruder went over, none of these products have been approved for the treatment of any orthopedic condition, and the FDA is quick to point that out. But the reason for that is that these products have developed in a little bit of what I call an orthobiologic gray zone, where these products have not been approved by the FDA, but they are allowed under the practice of medicine, and Scott went over that as well. Little bit of a typo. There are some orthoregeneration products that are on the market that have been approved by the FDA, but talking about the bedside preparation of orthobiologics, those have not yet been approved. It's been mentioned, the same surgical procedure exception, where the only processing steps that are allowed are rinsing, cleansing, sizing, and shaping both BMAC and microfragment and adipose tissue follow that same surgical procedure exception. So we get back to this gray zone and this problem that we have, where we think of these as procedures that we're performing, and yet, if you look at the definition, FDA's definition of what a drug is, it's an article intended for use in a diagnosis, cure, mitigation treatment, or prevention of disease in man. That is how we are using these products, is to treat orthopedic disease. So we have this problem reconciling these procedures that we're doing with the fact that they are most likely drugs or products that we're using to treat disease. And so when I think about process development and product development, I think of this regenerative medicine roadmap, where we want to take the concepts of traditional surgical innovation that we're all very familiar with, but also navigate this pathway of conventional drug discovery and process development. We really need to borrow from both of these techniques in order to translate orthobiologics into routine clinical and surgical practice. So this is my clinical space, and it was mentioned how many of us have developed these procedure suites that are adjacent to a processing lab, and that allows us to keep the product with the patient at all time and fall under that same surgical procedure exception. I should point out that I'm not an orthopedic surgeon, but I practice with my orthopedic surgeon colleagues. We do sometimes perform these procedures in the OR as an adjunct to surgery, but mostly I'm performing them in a procedural suite such as this. And so this work has been done with one of our bioethicists at Mayo Clinic, where we talk about how we can start to translate these into practice. And Dr. Bugbee just gave a nice talk about how PRP is a standout in terms of high-level randomized controlled evidence for conditions like osteoarthritis, and mostly we are talking about osteoarthritis when it comes to using BMAC and MFAT in a clinical practice. And so if you look at Tier 1 products, what I call the Tier 1 products, these are things that we should feel comfortable using in our daily practice because of the support the scientific support, the level of evidence, and that would be PRP. If you look at this Tier 3, these are products that have far less evidence base or perhaps vague regulatory status like the perinatal products or even exosomes. And so BMAC and MFAT for me both fall into this Tier 2 classification. We've seen trials performed. We have proven safety. But the evidence isn't quite so as robust. So if you're going to talk to patients about Tier 2 options like BMAC and MFAT, we're using the best available scientific evidence. We're using our clinical expertise in interpreting the literature. And then patient values and preferences matter as well, and that's work that our bioethicists have helped us with. So we've got these 510k cleared devices that allow for the use of some of these procedures within our practice. Patient selection is very important. These are some of the things that I go over with my patients. When we started doing these, we did all of them with our plastic surgery colleagues in partnership to get us ready to do these procedures safely and effectively. The adipose tissue can allow us, that we harvest, can allow us to process both mechanically and enzymatically if you're making two different products, one being MFAT and the other being the stromal vascular fraction that Scott had previously mentioned. The intermediate FAT is the area that we want to live in in terms of the best safety and cellularity. We position these patients sterile, just like we would for any other procedure. And then we have dedicated equipment and supplies. This is all we need. We need VACLOX syringe with an 11-gauge infiltration trocar and then a 14-gauge aspiration trocar. Make a little bit of stab incision and infiltrate a tumescent solution of lidocaine epinephrine and lactated ringers. We let that sit for about 20 minutes and then that allows for the best tumescent lipo aspiration of a concentrated adipose tissue product. The actual aspiration goes in a fan-like distribution trying to stay parallel in that middle or intermediate FAT zone. And when done correctly, you can see on the bottom right, you get this very nice concentrated lipo aspirate that we can then process. As I mentioned, it can be processed a couple of different ways. NanoFAT really without much in the way of kit, just filtration. If we're rinsing, washing, and sizing as the 510K devices are cleared with, that's the MFAT. Of course, if you're under IND, you can process these enzymatically and create a very concentrated cellular pellet that then can be utilized for treatment. Again, 510K clear devices, we can do this in our clinical practice in a procedure suite or it can be done in the operating room safely. And so that's MFAT. If you wish to use bone marrow in your clinic or your surgical practices, that's done in much the same way. Again, learning appropriate harvest, we place the long finger at the base of the natal cleft and you can palpate the posterior superior iliac spine quite well. Hernegoo has demonstrated safe zones in Zone 6 where the PSIS is located is quite safe and had very few breaches in their CT-confirmed study. I show this video not to instruct on how to do a bone marrow aspiration, but to just point out if you look at this next view here of the patient, she is not sedated and has not taken any medications at all and is tolerating the procedure quite well. So I think a lot of my surgeon partners look at the bone marrow aspiration as having to be done in the operating room under sedation. That's not necessarily the case. We do these quite easily and patients do not complain much about the discomfort. We do multiple small volume aspirations now. This has been demonstrated in the laboratory studies. We can make multiple cortical penetrations. I don't usually use ultrasound to do this. We can really do it based on palpation guidance. Monoinjection therapy alone is never going to be successful to treat osteoarthritis. We want to limit the activities, work with our physical therapists, possibly provide them an unloader brace and speed along their recovery. Dr. Cole just mentioned patient education and I think that's the most important part about doing this, whether it's in your surgical practice or your clinical practice. Patients differ, obviously, about their knowledge of the scientific literature where most will rely on testimonials from friends, family, or the internet. We look at our program as a three-column program where we're consulting with patients, we're educating patients. If they're appropriately selected, we'll perform the procedure. I still do not do nearly as many bone marrow or fat procedures as I would PRP. PRP is the sort of foundation of our biologics practice based on the evidence. And then we're tracking all of our outcomes. Not enough evidence to recommend one procedure over the other when it comes to BMAC or MFAT, but I am recommending on the evidence that we use PRP as a first line for most patients in this situation. And of course, we're tracking all of our outcomes for every procedure that we do. So thank you again for the invitation. I would encourage everybody to think about all of these novel biologics as a product development pathway where we have to go through each one of these issues, not just the delivery, not just the procedure before we can get to scientific validation. Thank you.

Shane Shapiro

orthopedic surgery

bone marrow aspiration

lipoaspiration

clinical practice