sets the stage here for, I'll leave this here if that's yours, first of all we'll talk about here as we move forward here, our laboratory research report is here, so when we think about biologic augmentation, it kind of goes for anything, certainly not just meniscus here, I think the first question I always ask myself is, you know, what are we trying to accomplish? What is the biologic target? Do we want to improve vascularity, stimulate cell proliferation, do something to simulate cell chemotaxis in and around the meniscus? Do we want to attract synovial cells to home into the meniscus repair site, do something about matrix synthesis, improve remodeling, all those are important but they're different and ultimately choosing our biologic agent as we learn more about biologic approaches will be important to define what that biologic approach is. I would submit to you, these should be our desired biologic targets if you will. We want to attract synovial cells, a lot of the healing seems to come from adjacent synovial cells, stimulate cell proliferation and in fact new matrix synthesis, do something to impact the excessive inflammatory response and associated proteases that we know are present in the injured joint. So some thoughts here, what is available to us today as clinicians, just kind of a quick overview here to set the stage. We can certainly do synovial abrasion in the adjacent, at the meniscal capsular junction there, the synovium there, turn on some healing there or blood supply, just a very brief data out there, Steve Barnosky looked at this many years ago in a dog model, if you connect a meniscus tear to the peripheral synovial tissues you get this vascular pandas that kind of forms there, we know that hypertrophic synovium expresses a number of different cytokines so there's a rationale for kind of stimulating the synovium here, not a lot of clinical data out there, just kind of move along here for the sake of time here. We can use a fibrin clot, we can take blood, spin it down, make a clot, we can attach that to a suture, this is what I've done in the past, still use this occasionally, now we've used other approaches but just putting a suture across the meniscus, you can use that to attach it to your clot, if you use a candula to bring this in, make sure you remove the diaphragm or else you'll kind of pull this thing apart when you pull it into the joint, but that's what these fibrin clots would look like and there's some data out there, let's go back to work from Steve Barnosky years ago, a more recent study where they isolated meniscus repairs, 24 patients, these are degenerative meniscal tears, I put this particular study in because this mean age is 47, degenerative tears, kind of like this case you just showed a moment ago, quite honestly, so where they put a fibrin clot in and tried to get these to heal and they found that three-quarters of these did go ahead and heal, so they thought in well-aligned knees, degenerative meniscus tears might be a role for doing something to augment the biology like using a fibrin clot here. Instead of a fibrin clot, maybe we can use a clot derived from bone marrow that may be superior as far as the cytokines and other signaling molecules that are present, study a couple years ago from connective tissue research, they took peripheral blood and bone marrow and made clots and just quite simply compared them, they used standard laboratory techniques to look at various cytokines in clots derived from peripheral blood versus bone marrow and you see that the cytokine content, the number of signaling molecules, chemokines and cytokines were higher in clots derived from bone marrow versus peripheral blood. In fact, in some cell culture models, the clots derived from bone marrow also had superior effects, so maybe we should consider if you're going to use a fibrin clot approach, use marrow instead of peripheral blood. If you're going to do that, you should inject it, I would suggest with thrombin and calcium chloride so you can clot it, there's fibrinogen in your, any blood will have fibrinogen, combine that with thrombin and calcium chloride and you can make a clot to kind of localize this at your repair site. Obviously, we can microfracture the knot, so-called marrow venting, to kind of, in the incentive of isolated meniscus repair, I'll routinely do this to get some bleeding in the joint. There's some data out there, look at work from Bob LaPrade, a simple study where they had patients undergoing meniscus repair with or without ACL reconstruction, so those undergoing isolated meniscus repair where they did marrow venting versus meniscus repair with a concomitant ACL reconstruction. Certainly, obviously, with an ACL, you've got access to bone marrow from your drill tunnels already and they evaluated these carefully and they found comparable healing outcomes, so they found the marrow venting technique was equivalent to the hemarthrosis that you see in ACL reconstruction, so some support here for this concept of marrow venting here. They thought this might be an effective biologic augmentation technique that we can certainly use. We can use a platelet-rich fibrin matrix material, this is essentially the PRP material, you do a second spin, add calcium chloride back into the prep, you'll get kind of clotting, you get this fibrin matrix where it's almost suturable, it can look like this, you can attach it to a suture, kind of like I showed a moment ago, the peripheral blood-derived fibrin clot. Same concept here, attach it to a suture, kind of bring this into your repair site, so PRP-type materials, data is mixed, it's out there, just kind of a brief summary here, some recent studies here. This group from Poland actually looked at isolated meniscus repairs and they found a positive effect using a leukocyte-rich PRP, they used MR and second look arthroscopy, so they evaluated these pretty rigorously and found that PRP had a role here. A group from Ohio State, they compared PRP in meniscus repairs with or without ACL reconstruction, and they found that PRP was associated with a lower risk of failure for isolated meniscus tears, so without an ACL, however, PRP did not reduce the risk of meniscus repair failure in the setting of a concomitant ACL reconstruction, so as you might expect, you've already got blood there in the setting of an ACL reconstruction. Two systematic reviews, this one here from the Stanford group, a couple of years ago, a systematic review, meniscus repairs augmented with PRP had lower failure rate, but no real differences in the patient-reported outcomes, so they thought there was a structural benefit, in contrast, this one from Nicola and Bufuli, another systematic review of meta-analysis, they concluded that the current published scientific evidence, in fact, does not support PRP augmentation for arthroscopic meniscus repair, so like a lot of our literature, kind of mixed, and that gets to the heterogeneity in these biologic formulations. What about cells? We can use cells now, obviously, from bone marrow or from adipose derivatives, as shown before. If you're going to use cells like from bone marrow, you can clot that. This is an example of a root repair, where I've often used a marrow here, clot it at the site if it's an isolated root repair. Here's an example of a horizontal cleavage tear, this is a young patient with a discoid meniscus, we tried to put this together, in the case you just showed, I'm pessimistic, you can get these horizontal cleavage tears to truly, A, heal, and B, function, but here we tried it, and this young patient here, he's in cells here. Cell therapy, evidence, data, very little, very, very little, but the animal data is promising. This is a study that kind of shows you the potential, it's just a rabbit study, but they found that bone marrow aspirate concentrate in this study did, in fact, lead to improved healings. Controls on one side versus the marrow treated, so there's some rationale for trying to use cells. Clearly, we need more data on what type of cell, what concentrations, how do we deliver these cells, a number of important factors. Look at data, Tom's vangeness study from nearly 10 years ago now, where these are patients undergoing meniscus surgery, meniscectomy, they used allogeneic bone marrow-derived cells, they were injected about a week and a half after surgery, and using MR, they found evidence for moderate meniscus regeneration, just actually the low cell dose group, interestingly, so the lower dose group, there's some meniscus regeneration, there's improvement in the patient outcome scores, you know, the improvements in symptoms may have been due to the signaling molecules that you see in cell-based approaches, so clearly a symptom modifying, the question is, is our cells really structure modifying, that is, do they lead to healing? We certainly need further data. Collagen scaffolds have been used, this guy Thomas Piontek in Poland has popularized putting a collagen matrix around the material, at your site here, some videos he had given me where he'd suture in a type 1, type 3 collagen matrix, suture this over your repair, and then he would inject marrow cells around this, kind of a patch technique like is used in rotator cuff repair. There's very little data out there, a study from his own group here that uses chondroguide collagen membrane, they would inject marrow around it, there are no real control group, but they thought that the majority were healed based on follow-up MRI, so you can try that as another augmentation approach. And lastly, physical modalities, there's actually some data out there on using shockwaves or low-intensity pulse ultrasound. Animal studies demonstrate a potential, actually there's a couple studies out there that demonstrate that extracorporeal shockwave can actually heal or stimulate healing, it's just kind of placed right against the knee, right across the skin, so I've not used this, but it might be something that we should kind of consider looking at, it's certainly easy to do. And lastly, simvastatin, the statin drug. Statin drugs stimulate the anabolic activity of fibrochondrocytes, in this particular animal model here they made a cylindrical defect and quite simply treated it, empty defect versus with simvastatin, and the summary here is improved healing based on histology, based on mechanics, simvastatin seemed to have a role, so they concluded that the local administration of simvastatin promotes regeneration of avascular, of healing in the avascular zone in the meniscus, so maybe something we should consider here. So to finish up my current approach, I will abrade the synovium, I will microfracture the notch in the setting of an isolated meniscus repair, consider using a leukocyte-rich PRP, if I use marrow I will combine that with thrombin and calcium chloride to form a clot at that site there. Maybe we should consider using a low-intensity pulse ultrasound, these stimulating units. I think we need to consider the role of mechanical load on the biology, it's critically important, you know, the tear pattern makes a difference, if we have a typical vertical longitudinal tear, weight-bearing, at least partial, may be helpful to compress the meniscus, in contrast, a more complex tear pattern, a radial tear, maybe we should go much slower, obviously, we need more data on the effect of mechanical loading and how much load and when. In the future we may consider things like simvastatin TXA as a fibrinolysis inhibitor, may well prevent breakdown of the fibrin clot that forms, other biologic approaches that I'll kind of list here. People are looking at various tissue adhesives that may have a role in kind of holding the meniscus together preliminarily while we're waiting for a biology. And I think, lastly, ways to modulate the intra-articular milieu to affect the inflammatory mediators will have a profound effect on healing, and as we understand more about the role of immune cells, immune cell populations on inflammation and healing, that's probably where the future lies. So, we'll stop there. Thank you. Go down, right? Yeah. Okay. All right. And then we're going to have Laith come up to talk about bucket handles. And again, what we want to do here is Laith is going to, the presenters are going to present a case, and then the tables are going to discuss it amongst the faculty. So we want to have faculty at each table, and then if there's some tables where we're maybe a little bit more overloaded, if you kind of want to even out to be with the faculty, that would be great. And for people in the back, if you want to come up and find a spot to sit where one of the faculty members is at, that'd be awesome.

biologic approaches

meniscus tears

cell therapy

collagen scaffolds

immune cell modulation