Thank you. Good morning. Well, maybe this will set the stage for all the cases to come. I'll try to go through some basics on how we might augment our repairs. Here we go. These disclosed really covers a lot of our laboratory work. So I think you think about the whole area of biologics, all the different choices we have, PRP and cell-based things. Ask yourself, what's the target? What is it I'm trying to treat? We want to increase vascularity in the tissue, stimulate cell proliferation, chemotaxis. I think synovial cell homing to the meniscus is something that may be important, and we know synovial cells probably initiate and regulate the healing process. Affect matrix synthesis or remodeling. All those are important, but they're all different. I would submit to you the important targets we should think about if using biologics, number one, I think the goal of stimulating synovial cell homing to the site would be critically important. Synovial cells probably play a critically important role in meniscus healing. Obviously, it stimulates cell proliferation and matrix synthesis. Another important goal would be to affect the excessive inflammatory response and associated proteases that we know are present in the injured or post-surgical joint. So what's available to us as clinicians today to kind of go through this practically and try to marry some of the basic science data we know with what do we do clinically? We can start simply with synovial rasping, just to kind of simulate a healing response. I think most of us do this. You get this little fibrinous membrane that covers that area over a tear, and I think to rasp that makes sense. I kind of go through a little bit, give you a sense of what the data is. Steve Arnosky showed us years ago in a dog model. If you make a meniscus lesion that connects to the peripheral synovial tissue, it heals kind of by this pannus that sort of walks over the meniscus. So if you stimulate that adjacent synovial tissue, it makes sense. You know, if you irritate or rasp synovium, you upregulate a lot of cytokines. This is just from an animal model demonstrating TGF-beta upregulation in rasped synovium. Further support comes from the fact that, you know, this rasping is not effective for a tear that is farther from the synovial rim. In this particular sheep model, the tear may be more in the central part. Rasping did not make a difference. So it kind of supports this. Clinically, not a lot of data. A little bit out there, but really none of these have some DSR studies have control groups. And, you know, to our mercury group, we need better studies in this area. We really see that in a lot of areas in orthopedics, I think in particular in this area quite honestly. We can make a fibrin clot. Simply take 30 cc's of blood, stir it in a little glass beaker like a little shot glass. It will make a clot and use this for many years early on. This is just an example of how you might do this. Whatever you're going to do. If you're going to do some device or a fibrin clot, try to put a suture across your repair. You can do it inside out or outside in, whatever your preferred technique is, but use that to kind of attach to your material. This just shows attaching the suture to a fibrin clot. This is probably a 20-year-old video or more, but just using that to tuck the clot into your repair site there. What's the evidence? A little bit out there. Chuck Henning, 30 years ago, started this. The concept comes from work from Steve Arnofsky and Russ Warren, HSS, in 1988. Chuck Henning, 1990, published a study where he used a fibrin clot in complex meniscus tears. He found the isolated failure rate was 41% without a clot versus 8% in tears treated with a clot. So really an improvement there. Thought that isolated tears really did heal better with this. He then went on to use a fascial sheath. He would sew over the meniscus, very tedious, and then he'd inject a clot underneath that fascial sheath and found improved healing rates in these complex meniscus tears. And a little more recently, Tom Wickrick did a small series of his five lateral meniscus repairs that extended all the way to the puppeteer's hiatus, and he did second-look arthroscopy. He thought the clot helped healing, and all these had healed there. Obviously, we can do marrow venting, just kind of access underlying bone marrow-derived cells. I think many of us do it. Simple technique for isolated repairs, just simulates the hemoarthrosis that, of course, you get through an ACL reconstruction. And to that point, Bob LaPrazzi did a nice, pretty simple paper of patients isolated meniscus repair with marrow venting compared to meniscus repair with concomitant ACL reconstruction. And he found, essentially, they evaluated these patients carefully as far as healing of the meniscus, really largely based on need for reoperation or revision meniscus repair. Overall, comparable healing outcomes. So the isolated repair with venting was the same as the repair with the concomitant ACL reconstruction. So the marrow venting technique, the hemoarthrosis you get seems to be equivalent to that that you get with the ACL reconstruction. More recently, we can use a platelet-rich plasma type of material. This is making a platelet-rich fibrin matrix. If you take PRP PrEP, and there's a million ways to make it, of course, do a second spin and add calcium chloride back to the PrEP, you'll get, you'll initiate the fibrin-clotting cascade, and you can make sort of a material that you can actually put a suture in, kind of like a fibrin clot. And this just shows, similar to the video, using the fibrin clot, same way I've used this to kind of tuck a platelet-rich fibrin matrix into your, at your repair site. And that's what it looks like there. Data. There's a lot of data out there. There's some early clinical data mixed on using PRP. This group from Poland has a study looking, this is a randomized, well-done study, randomized double-blind trial. Small group of patients here. Looks are rich. PRP was used in meniscus repair, and they found higher healing rates based on MR and second look. You can see that graphically here, the PRP group on the hatched bars there. So then they found better results on their patient-part outcome measure. So this kind of supports the potential for PRP. Now Walter Lowe in Houston, a little different, this is a group of patients, a match, a case control study. All these patients had ACL reconstruction and meniscus repair, and then he added PRP. So they all have ACL, so keep that in mind. So 162 patients with PRP, 162 without. They used the leukocyte-rich formulation. They matched these patients appropriately. Essentially, he didn't find any differences in all your patient-reported outcome measures. And interestingly, the PRP group demonstrated a higher rate of knee stiffness. So they kind of concluded that PRP is not effective, and kind of suggested that PRP may in fact have a negative consequence for gaining motion. But again, all these racial reconstructions, the hemoarthrosis is already there, so probably PRP doesn't add much in that setting. A couple systematic reviews, so we should focus on isolated meniscus tears. So from Nicola Maffoli, a good friend in London, this is a systematic review or a meta-analysis here of isolated repairs with or without PRP. Got a good number of patients here. They really found no differences in outcome scores as well as the failure rate. Here's your rate of revision, your rate of failure, force plots really did not demonstrate a significant improvement. So they concluded that the current published evidence does not support PRP augmentation. Seth Sherman and Mark Schaaf and the guys at Stanford had this systematic review, a little bit different outcomes here. Again, isolated repairs with or without PRP, five papers reviewed here. They found meniscus repairs augmented with PRP, again, isolated repairs, had a lower failure rate. And here's your failure rates, 11 percent with PRP, 27 percent without PRP. So they demonstrated a difference here, and you see that in the force plot here in favor of PRP. Now, four out of five of these studies, though, did not have any differences in your standard patient-reported outcome measure. So essentially, despite lower failure rates, you know, anatomically, objective evaluation, most studies did not report any differences in patient-reported outcomes. So we're left with sort of a mixed bag here as far as PRP. We can try to use cells. This is using bone marrow aspirate. I've usually used a marrow aspirate clotted with these thrombin and calcium chloride. You can clot your material. There's fibrinogen already in your PRP, so fibrinogen and thrombin initiates the clotting cascade here. Just using this for a root repair. Another example of a young patient, this is a discoid. After resecting the discoid, you had this horizontal cleavage tear. Try to close this down. This is a young adolescent. We put cells there, again, to try and do some healing. An area where we need clinical data. There's some animal data to support this, preclinical data. We need better data here. Just one preclinical study, you know, a well-done study from a group in Regensburg, Germany. Animal model, so limitations that they have, but in a rabbit model with BMAC, they found the bone marrow aspirate did improve healing. This is histologically here. Clinically, you can look at the study, a nice, well-done study, Tom's Vang Ness some years ago. A randomized trial, patients undergoing meniscectomy, where they were treated with allogeneic bone marrow-derived cells about seven to 10 days after their meniscectomy. A randomized, 55 patients. They used MR to see, is there any meniscus regeneration? Well, they had MRI evidence of moderate regeneration based on increased meniscus volume in about a quarter of the patients. So, you know, kind of a mild effect there. They do see improvements in the patient-reported outcome measures. So like a lot of these things, this suggests these treatments are symptom-modifying. They improve your subjective scores. But are they really structure-modifying? Data is much, much less convincing there. Another important source we consider is synovial cells. They have real promise. Ichiro Sekiya, that was a neat guy in Tokyo, did a lot of work in this area, just in an outcome model he started with. Synovial-derived cells, using those to treat a meniscus repair and use histology and some well-done MR techniques. He found they had a positive effect on healing. And importantly, he sticks to a clinical model, which he's published several years ago. Five patients. So degenerative meniscus tears. They take the patient to the OR. They do a synovial biopsy two weeks prior. They culture-expand these cells, which of course we can't do in this country. But they can isolate and concentrate or select these synovial-derived stromal cells. Then they injected these cells in the patients. And they found improvements, not just clinical outcomes, but on MR. Again, small group of patients, but these are rigorous researchers. So there's some promise to synovial-derived cells. Lastly, using collagen scaffolds. A guy named Thomas Piontek in Poland has popularized this. Working with Rola Jakub as well, he's got a series of papers putting a collagen matrix around your tear. And here's a video that Thomas had given me a couple years ago, just putting this in. It's like the ChondroGuide, collagen 1, 3, collagen membrane, you can use any of the different matrices or ECM patch materials that are out there. It looks a little bit technically complex. He kind of brings this in and uses, and here's an all-inside suturing technique to essentially put this membrane over, around, under your tear, and he injected marrow in this. So I think the concept of combining a scaffold with cells certainly makes sense. That's what this looks like after the end here. This ChondroGuide membrane, again, it'll take a bone marrow aspirate concentrate, which he just took marrow from the paroxysmal tibia. You're better with marrow. You get more cells from your axial skeleton, your pelvis. Little data out there. This is a study from his group. This ChondroGuide membrane kind of wrapped around the meniscus tear, 53 patients. There was no control group, so it's limited, so kind of a level three study. But they found improvements in their outcome scores, and importantly, MR demonstrated healing in about three-quarters of patients. So some promise there. I've never used this technique. You can go back to Chuck Henning, though, 30 years ago, putting a fascial sheath around the meniscus. He injected a clot. Not a whole lot of difference. But Chuck Henning reported he thought that that improved healing as well. So the idea of combining a scaffold with cells kind of makes sense. Lastly, what about physical modalities? There's actually some decent data on using shockwaves or low-intensity pulsed ultrasound, like the extragen. That's lipase, which there's animal data. There's one representative animal study, just to give you a sense of what's out there. There's a number you could look at, but this particular animal model, tears in the vascular region of the meniscus, they treat the animals with one dose of shockwaves a week after creating the injury. Improved healing based on histology. You can quantify the histology. They looked at cell proliferation, expression of relevant matrix proteins. All these standard outcome measures demonstrate an effect. So it's something we can use. I'm not using it, but it might be something you might consider. So what is my current approach here? What can we practically use as clinicians today? I will abrade the synovium on kind of microfracture the knots, so-called marrow venting for the isolated repairs. I think it's reasonable to consider a leukocyte-rich PRP for your isolated repairs. Consider using marrow cells. Again, we need further data in this area. If you do that, I think to clot it with thrombin and calcium chloride would make sense to isolate it to that site. Maybe you should consider using these exogen devices. The problem would be getting insurance approval. Probably wouldn't happen in a million years, but maybe if the insurance part goes away. Lastly, I make the point, we need to consider the role of mechanical load in the biology of healing. All these biology studies ignore the important role of mechanics. This has obvious implications for the rehab. Consider your tear pattern. If you have a standard vertical longitudinal tear, probably a partial compressive loading extension is okay. That may almost compress the tear site. In contrast, if you have a radial tear, a more complex tear, it makes you go much slower with your weight bearing. I'll just go through this last slide briefly. Just future options to consider. A lot of pharmacologic agents that have relevant roles and may affect matrix proteins synthesis in menisci. The idea of repurposing existing drugs is kind of a hot concept. We're learning more about immune cell populations. And lastly, the last point at the bottom, the ability to stimulate the intrinsic stem cell niche that is present in many tissues has great potential. We just need to get further data to really research to understand how do we really do that? How do we leverage those cells? I'll stop there. Thanks. Male Speaker 1 We'll start cases, but I do have one question for you, Scott. And by the way, for everyone who came in who's at these chairs right here, can you guys come at a table? Kirk Campbell is one of our faculty right here. And can we get some of you guys along the side to come up to this table here and then fill in elsewhere? Because this will be case-based, and so we're going to have faculty at each of the round tables to facilitate discussion, okay? But my question, Scott, is leukocyte poor versus leukocyte rich. So I've heard more benefit of leukocyte poor, and you're saying leukocyte rich. How good is that data right now? Scott Gottfried Not very. Very complex. Very to very simplified in two sentences. With leukocytes, you have the ability to kind of turn on inflammation, which is valuable for healing. Healing, you need inflammation to initiate healing. But leukocytes also have all the degradative and inflammatory enzymes. Actually, real important point I make is this leukocyte rich, leukocyte poor classification is, we need to get way beyond that. It's very rudimentary. I think what's more important is probably the ratio of platelets to leukocytes, the leukocyte differential, the absolute number of platelets. So it's a place to start, but I would be careful making any dogmatic conclusions, leukocyte rich versus poor. In general, leukocyte rich, though, will kind of turn on the biology. You use that for chronic tendinopathy. You want to make a chronic process acute, whereas your leukocyte poor is used in the setting of arthritis where you already have an inflammatory environment. So it is complex. Interesting. Thank you. All right. Thank you very much, Scott. Appreciate it.

orthopedics

biologics

tissue healing

meniscus tears

research