All right, my name is Tom Carter and we'll get started here. So we're on time First of all, I want to give credit to Lee pace. I don't know if any of you know him. He's down in Dallas He was the one that oversaw this originally His wife had a baby. So as we all talk about family first Scott Rodeo from New York He's talking about biologics. He had to go back to New York because of a family event. So we have him on video Catherine Robertson from San Diego. She'll talk about complex tears ones that will always space We always say save the meniscus. So she'll tell you how to do that as best as possible Tom D. Bernadette. Oh, we'll talk about Ramp lesions and root and then last I'll talk about Meniscus substitutes not just alagrass, but some of the things also coming down the line so that you're aware of it so, can you please go ahead and play Scott's video In This talk I will review biologic augmentation techniques for meniscus Use the disclosures that support our research efforts. I Think the first step in any Biologic augmentation talk is to define was a biologic target that we're trying to treat. Do we want to increase vascularity? stimulate cell proliferation Improve cell chemotaxis improve synovial cell homing to the meniscus perhaps accelerate matrix synthesis or modeling I would submit to you that the following biologic targets should be considered number one to stimulate synovial cell homing to be parasite number two to stimulate cell proliferation a new matrix synthesis that the healing meniscus be parasite Lastly to ameliorate the excessive inflammatory response and associated protease activity that we know ensues in the injured joint So what is available to us as clinicians today, and what is the evidence? We can use synovial abrasion to essentially abrade the adjacent synovium to stimulate some bleeding What is the evidence for this? Some years ago, Steve Arnozzi, using his dog model, demonstrated that a meniscus lesion connected to the peripheral synovial tissue heals by this fibrovascular scar tissue that proliferates from that synovial tissue. We know that hypertrophic synovium can express a number of cytokines. This particular rabbit model demonstrated TGF-beta being produced by synovial cells. Furthermore, this technique is not effective for a tear that is further from the synovial rim. In this particular sheep model, demonstrated the need for proximity of the tear to the synovial rim. At this time, there are some positive results in limited clinical studies, but most of these studies did not have a control group, so we certainly need further data in this area. We can use an autogenous fibron clot. We can take peripheral blood, stir this to make a clot, and then insert that at the repair site. When I've done this, I have typically put a suture across the meniscus at the repair site, bring that suture out of cannula, and then tie the clot to the suture, and use that suture to place the clot into the repair site as a way to kind of localize and stabilize your clot at your repair site. What is the data for using a fibrin clot? If you go back to Chuck Henning 30 years ago, he used a fibrin clot for repair of isolated tears, and he found the isolated tear failure rate was 41% without a clot versus 8% with a clot. So they reported that isolated repairs healed significantly better with an exogenous fibrin clot. He then went on a year later and published a paper where they did the same thing, but they used a fascial sheath. They'd sew a fascial sheath over the meniscus and then inject this exogenous fibrin clot, and they found improved healing rates. More recently, von Trommel with Tom Wickowitz had a small series of five patients' lateral meniscus tears extending to the popliteus hiatus sewn over a fibrin clot, where they found healing using second look arthroscopy. Another option to induce bleeding is to simply microfracture the intercontinental notch, so-called marrow venting, to access underlying bone marrow-derived cells. This is typically used in isolated meniscus repair. Brian Cole, some years ago, just described the technique of microfracture the notch, and the concept being to provide marrow elements to the healing meniscus. And then Bob LaPrade did a nice study where they compared healing rates in meniscal repairs in ACL reconstructed knees versus isolated tears, and they found essentially a marrow venting technique led to healing rates were equivalent to the hemoarthrosis in ACL reconstruction, so they concluded that this is an effective biologic augmentation technique. More recently, we've used a platelet-rich fibrin matrix. This is essentially a PRP-type material with a second spin, second centrifugation, where you can make this into sort of a fibrin matrix, and that can be attached to a suture similar to using a fibrin clot. The suture used here to pull the material into the repair. is what this looks like after placement. What is the evidence? Clinically, Kaminski from Poland has a prospective randomized trial where they treated patients with PRP or just with repair. They used a leukocyte-rich PRP formulation. And they found a higher meniscus healing rate in the PRP-treated patients using both MRI as well as second look arthroscopy. See the right side of the graph, the proportion of healing repairs was higher in the patients receiving PRP. In fact, the patient-reported outcome measures were also significantly higher in the PRP group. In contrast, a group from Walter Low in Houston has a series of patients, a retrospective matched case control study, patients undergoing ACL reconstruction with concomitant meniscus repair, either with or without PRP. They're all matched appropriately by age, sex, the graph type for the ACL reconstruction. And they found no differences in the patient-reported outcome measures or return to activity in their patients. And in fact, the PRP group demonstrated a higher rate of post-operative knee motion loss compared to the control groups. They concluded that PRP was not effective. And in fact, their data suggested that PRP may have a negative consequences for gaining knee motion after surgery. A group from Taiwan looks at a group of meniscus repairs, retrospective review, where patients in the PRP group received repeated PRP injections. So three injections over six weeks, as you see here. At 24-month follow-up, they found no differences in their patient-reported outcome measures demonstrated graphically here. No difference in healing rates between the PRP and the control groups. They concluded that the PRP group had similar functional outcomes and similar healing rates compared to the non-PRP group. Groups from Nicola Mofulli in Italy and London. This is a meta-analysis where they looked at arthroscopic meniscus repairs, either isolated repairs or augmented with PRP. 837 patients were included in this analysis, mean age of 35. And they found really no differences in the patient-reported outcome measures or failure rates. We see graphically here the rate of revision and the rate of failure were similar in the PRP and control groups. They concluded that the current published scientific evidence does not support PRP augmentation for arthroscopic meniscal repair. And lastly, a meta-analysis from the group at Stanford University with Seth Sherman and Mark Chaffin and others. They looked at isolated arthroscopic meniscal repairs augmented with PRP versus no PRP. They were able to look at five papers. They found that meniscal repairs augmented with PRP had significantly lower failure rates in this particular systematic review. They found the meniscal repair failure rates about 11% in PRP-treated tears versus 27% in those without PRP. You can see that depicted graphically here at the bottom in favor of PRP as far as failure rates. Now, four out of the five of the studies did not report any differences in the patient-reported outcome measures as far as their clinical outcomes. So they concluded that despite significantly lower failure rates with PRP augmentation, most studies reported no significant difference in patient-reported outcomes. What about cell therapy? I've used bone marrow aspirate on a limited occasion. This is here, we show using a bone marrow aspirate concentrate clouded with thrombin and calcium chloride to augment a meniscus root repair. Another example of a patient who had undergone saucerization of a discoid meniscus where I tried to repair the big horizontal cleavage split in the meniscus and used a cell-based approach here. But in this scenario, we certainly need further data. Now, there is some good preclinical data. This is a particular rabbit study where they found that bone marrow aspirate concentrate did improve healing. You can see the histologically on the left side, no PRP or cells rather, and the right side, those animals treated with a bone marrow aspirate concentrate clearly better healing. Clinically, Tom's Vang's Nest had a series of patients, of 55 patients undergoing arthroscopic meniscectomy. They received allogeneic bone marrow-derived cells seven to 10 days following meniscectomy. Then they used MRI and they found MRI evidence of some degree or moderate meniscus regeneration based on meniscal volume in about a quarter of the patients. And they found there was improvements in the patient-reported outcome measures. So some early data here to support some potential for meniscus regeneration, but clearly we need further robust data in this area. I think synovial cells is another promising cell source. Ichiro Sakia in Tokyo has done a lot of nice work in this area. They first started with some work in animals as a micro-mini-pig model treated with allogeneic synovial cell suspension. And using the number of outcome measures, they demonstrated the transplantation of synovial MSCs did improve meniscus healing. And he went on clinically now and published a report of five cases. These are five patients undergoing surgery for a degenerative needle meniscus lesion. They first do a synovial tissue biopsy. Then they culture expand these cells for two weeks and then they inject these cells at the repair site at the time of surgery. And they reported that there were significant clinical improvements by two years and MRI scans showed no evidence of residual tear at the repair site at this two-year follow-up. So some early, but encouraging data. Lastly, what about use of a collagen scaffold? Thomas Piontek in Poland has popularized the use of a collagen matrix to wrap around the meniscus, sort of analogous to patches used for tendon repair. He's published some papers in this area. It's a video that he gave to me showing putting this in arthroscopically, kind of technically complex, bringing this collagen matrix in at the repair site and then going ahead and suturing that in using standard arthroscopic suturing techniques. And then he would actually go ahead and inject bone marrow cells under this sheath after putting this in. This is another video kind of showing what this collagen matrix looks like. He sewed this in and then inject bone marrow. Similar to what actually Chuck Henning did some years ago. Evidence here for collagen scaffolds. Thomas Piontek has this series where they use a chondroguide collagen membrane sort of wrapped around the meniscus tear in 53 patients. Now there's no comparison group, no control, but they reported improvements in their patient-reported outcome measures and they found that using the follow-up MRI, they found no residual meniscus tear in 76% of these menisci. Again, 30 years ago, Chuck Henning used a fascial sheath in a similar fashion, sewn over the meniscus tear and then injected a fibrin clot in that area and demonstrated improved healing rates. Lastly, we should consider physical modalities that have been found to potentially augment meniscus healing in preclinical studies. Animal studies have looked at both extracorporeal shockwaves as well as low-intensity pulse ultrasound. This particular animal study, or a rat study, where they made full thickness tears in the vascular region of meniscus, animals received just one single session of the shockwave therapy and they found the shockwave therapy promoted meniscal healing based on histologic scores. You see on the bottom right there in the graph there, they found a higher number of proliferating cells in those menisci treated with shockwaves and they found upregulated expression of various relevant cartilage matrix genes as well. So some promising early data here. So lastly, what can we practically use? Well, currently I will typically use synovial abrasion. I will consider and use microfracture or marrow venting of the intercolon or not for isolated meniscal repairs. I think you can still consider a leukocyte-rich PRP, although again, the data is certainly mixed. If using cells, you might consider combining that with thrombin or calcium chloride to form a clot to maintain the material at the repair site. We may, maybe we should consider using low-intensity pulse ultrasound in our patients. I think we need to carefully consider the role of mechanical load in the biology of meniscus healing. This has real implications for post-op rehab. We need to consider the tear patterns. For example, I think the partial compressive loading with the knee and extension is reasonable for a vertical longitudinal tear where weight-bearing may kind of compress or oppose the meniscus to the capsule. In contrast, I would recommend minimal load for radial or complex tear patterns. Thank you.

meniscus repair

biologic augmentation techniques

synovial cell homing

matrix synthesis

shockwave therapy