All right, hopefully the pizza and beer were nice and filling. Always good, the Chicago style. So now we're going to get much more specific, as Brian was saying, and so this is more of a case presentation type of format. So here goes our proposed patient that we all have in our clinic, 34-year-old, so early, with more significant arthritis. This is patellofemoral arthritis, but also involving the medial and lateral compartments. He has an occasional effusion, has no real injury history, no previous surgery, does have a past medical history of asthma, which may play into part of this area here, as far as the findings, and certainly has had no improvement in physical therapy and anti-inflammatory medications. And so from a perspective of the use of biologics in osteoarthritis patients, there appears to be two main, or really three main areas that have pretty reasonable data to suggest that this could make our osteoarthritis patients feel better. And one of them is the thing that we have talked about previously, is this little cohort, this little group of patients within the osteoarthritis population that have a component of inflammation. So it keeps coming up time and time again in the talks in a deliberate way. Excuse me. This is the same slide I showed you before with the same sort of thought process, now focused on osteoarthritis. What do we do? These patients are different than the other patients that come into the door with have that no history of swelling and no history of stiffness in the knee. When you look at it from an arthroscopic perspective, these patients are also different. And we are not used to this degree of synovitis and osteoarthritis. But they're seen, and you guys probably concur, we see them all the time. Classic scenario there in right-of-way, this patient is particularly different. And maybe the data is showing that this may be a patient that would be a good intervention with orthobiologics. Obviously, the treatment with synovectomy is not the topic for today. But what are the anti-inflammatory things that we can offer if we have a patient with inflammation? A previous slide that we talked about in PRP, non-inflammatory or anti-inflammatory-based PRP. We have multiple preparations that can do it. The most classic is the non-white blood cell-containing, or now being more specific, non-neutrophil-containing types of PRP. And if you look at the literature, there is definitely level one data to suggest that the non-inflammatory PRP can work better than hyaluronic acid in patients with osteoarthritis. So pretty good, reasonable evidence. OK. What about the cellular therapy as with respect to osteoarthritis? In the back, if we can click it, our second video, or maybe I can here, if you can hear me back there. There we go. So we're going to be introducing two main techniques to harvest adipose tissue. The first is on your left, which is abdominal or thigh-modified liposuction or tumescent lipoplasty. And so this will be going over at length in the clinic, and we'll all have time to get our hands familiar with the abdomen and familiar with the thigh and buttock. From an orthopedic side, we just don't do that very often. The other technique is to the right. And this involves the arthroscopic resection of the infant patella portion of the infant patella fat pad. This is one where I'm going to show you the arthroscopic setup tomorrow. Because of all the arthroscopic towers and the true basic nature of this procedure, we are not going to do this at the individual stations. But nonetheless, you will really see the ease with which this procedure is done and the difficulty is in the setup. So that is the thing that we're going to be going over in the lab tomorrow. Now when we go forward, and there we go, that if you do adipose harvest, there are special things that you need, special equipment you need. And here is a list of that. This is for you to take home is that the number one requirement as an FDA-approved sterile canister for the fat tissue. There is multiple of them on the market. For the ease of you using something, we are going to show you one that is called the Aquavage. It's FDA-approved. There is no conflict of interest. I have nothing to gain by saying that. But we have to give you guys some practical information to go home with. Everyone can do their own research on all the available canisters, but it must be sterile and FDA-approved for the use of adipose tissue. The second is some method to break up the fat or to fracture the fat tissue. That is a requirement, because if fat tissue is as a whole, there is too much mature fat tissue or fat cells, and those are inflammatory. Versus if you break it apart and get the MSCs, then that is, as we've talked about at length here today, anti-inflammatory effects for those. So fractionization of the fat is required. The next is a third is the Luerlach adapters. And this is only if you're using this Adiprep system, which I will talk to you about. Two different types of systems. The first to the right is the ball-bearing system. This is the Lipogem, which will be hands-on in the lab tomorrow. All of the necessary equipment comes in one pack, which you can see below there. And this is one method to break up the fat. This is to get the parasites off of the microvasculature, so you have to break up the microvasculature. And that's the key to fat harvest. To the left is the technique called syringe emulsification. This comes from the plastic surgery profession. And this is how they do it, for a large degree, by taking the fat, which is condensed down, and breaking it up through decreasing apertures of Luerlach adapters. It's amazing to feel this. And we have this again at your stations tomorrow. And this is a little bit of a feel to understand how this fat will change in its consistency from this whole, even arthroscopically disrupted fat, to what you will end up with at the ends of this emulsification process. What I want you guys to know is that the homework has been done for you. both the LipoGEM system and with the Adiprep system, that you get lots of usable MSCs at the end of your preparatory procedure. And this is really showing the data, which mimics the previous speakers' saying. Roughly 20% of the fat tissue that you get, or the cells at the end of the day, is usable. Let's call them progenitor cells. And so then that is high amounts in comparison to the bone marrow. Next is the literature. And the literature here is weak, yet very promising. And this is, again, with the meta-analysis show. This is from Korea. And this is showing, basically, the picture of the Holy Grail, which we are attempting to do with cellular therapy. This is in an N of 18 patients. And it's uncontrolled. So it's far from proof, positive, that this will work. Yet nonetheless, pretty good follow-up with regards to the clinical outcome. And that's what we've been talking about, modification of inflammation and pain. But also the prospect that actual tissue can be laid down in osteoarthritis cases. And this is arthroscopy pictures from a six-month follow-up patient. With this article, you can actually see MRI images. And you can see this. I'm sorry that this is probably small for the screen. But you can see actual thickness changes with light cuts of MRI at baseline through six months. So again, a very promising study that can be used to build our randomized controlled trials. Speaking of that, we have now seven trials at Stanford where we're really putting this through the test. And I want to be able to report to you guys in a couple of years a couple of things. The first is, how do these patients do in comparison to placebo? And so for osteoarthritis, this is arthroscopic debridement versus arthroscopic debridement plus the use of the autologous cell preparation. We're going to be looking at how they do over time in comparison, but also the cartilage thickness. So they're all studied with T2 mapping and cartilage thickness studies over time. We're also using chondral defect study to see how, in comparison to modified microfracture, these fat preparatory cells do. As far as BMAC in the literature, at this time, no significant evidence to suggest that the use of BMAC for osteoarthritis is a reasonable option. Now I say that also coming from a biologic practice where I actually use this all the time. And I can actually report as a practitioner anecdotally that most of these patients are feeling better. Now this is with a placebo-controlled trial, and maybe that's the difference where does it perform above the placebo control. That is very unclear at this point. It's also very unclear the nature of BMAC, where you have all of the good, including the MSCs, and you have maybe things that we've learned from the PRP literature that may be bad, such as the white blood cells. So it's confusing at best. A lot of these patients after BMAC do have effusions after administration, so unclear of the overall effect of BMAC in the face of osteoarthritis. One of the important things that we can also look at, and this was mentioned as a previous question, is what about those patients with osteoarthritis that have involvement of the subchondral bone? Well, this is different, just like the different little group of patients with osteoarthritis that also have an inflammatory component. And we see with the MRI, both in T2 and T1, really documented by the arrows here, that this is more than just an interarticular disease. This involves the subchondral tissue as well. And I don't think if you're—well, let me say this. If you're after data, evidence-based medicine, here it is, there's nothing really stronger than this. This is high-level rheumatology data to suggest that the presence of bone marrow lesions are highly correlated with pain in patients with osteoarthritis. And they have more than nine times more likelihood to progress to a total knee replacement. Very strong data. As we're beginning to understand how to treat this, there is two main ways of addressing this. One is to the right, which is the structural type of technique. And tomorrow morning, again in the didactic sessions, Jack Farr will be talking about this particular technique, and I will not mention it today here. The other is the biologic technique, as we're all used to talking about. And this is disruption of the disordered subchondral bone and an attempt to get a biologic reaction to remodel it. The technique is as follows. Number one, placement of a K-wire or similar instrument to the area of the subchondral bone abnormality. In contrast to the structural technique, this biologic technique really biologically requires that this needle goes through normal bone, because that's the tissue that's going to drag the biologics, et cetera, to the side of the abnormal bone. If you take the shortest cut, it's a medial femoral condyle, and you go in through the medial femoral condyle, you're not really traversing any normal bone, so you have less chance of good biologic disruption and dragging in biologic factors. Over the K-wire, you certainly can use a reamer to increase, again, the local disruption of that tissue and potentially increase the area for addition of growth factors, including BMAC. The BMAC can be injected by leaving the drill bit in and taking the K-wire out. There's many methods of application, including this particular picture, which shows that you can use BMAC and thrombin and inject it down the center part of the drill bit, which you have already fluoroscopically positioned at the side of the subchondral bone problem. So therefore, it's easy and very percutaneous. At this point with the literature, this is anecdotal, but astonishing, promising results. This is this patient that we've been talking about after three months using a research MRI. And although this isn't completely cured, you can see that from the pre-op to the post-op at only three months, the rather astonishing amount of the subchondral remodeling of the bone. And that has matched in this particular patient with pain relief. So then what is it that we're doing to improve this patient? I don't know. Is it the treatment of the subchondral bone? Is it the treatment of the interarticular area? Or is it this complete treatment of the patient? And then the bottom line is looking at our patients one by one and not putting our osteoarthritis in one single category. If they have inflammation, it may be very reasonable for a biologic intervention for an anti-inflammatory of choice. If this is involving a subchondral bone, it may be reasonable to treat the subchondral bone lesions in those particular patients with osteoarthritis that have that problem. This is part of the rapidly changing climate of orthobiologics. These slides will definitely be outdated in a year. So please stay tuned, as many randomized controlled trials and upper-level type of studies are coming due here. So we'll have much more information on the orthobiologics of osteoarthritis within the year. Thank you very much.

biologics

osteoarthritis

inflammation

platelet-rich plasma

cellular therapy