Good day, this is a recording on a talk for the now-canceled ANA course, HIT course. Topic is new cartilage technologies in 2020 ready for prime time. Here are my disclosures. The ninth theory is why does the cartilage fail? So it's focused on the most central one, trauma, age generation, FAI, dysplasia, and instability. Certainly are major players in having an impact on cartilage failing. So what's the holy grail? If you have cartilage damage, you want to have and reconstitute hyaline cartilage, so articular cartilage, the high content of type 2 collagen, not fiber cartilage with a high type 1 collagen content. You want to have layers of functional cells, an extracellular matrix, and the concern is for chondral layer, subchondral plate, and subchondral trabecular bone. So if you're thinking about tissue engineering for cartilage repair, successful cartilage repair components are the cells, signaling molecules, and the matrix scaffold. These are the foundations for tissue engineering for articular cartilage. Well, the traditional model has been to take technologies that were developed for the knee and apply them to the hip. So does that make sense? Can you really transfer all that knowledge one by one and apply it to the hip? So that gets to the question, is this the same kind of cartilage or environment? So there's certain distinct differences between hip and knee articular cartilage, and these could have relevant implications for tissue engineering for hip articular cartilage and therefore also repair strategies with regards to that. What's very different, obviously, as we know also from talks about label repairs and reconstruction, it's that label seal, the suction seal, needs to be there. It helps to maintain a pressurized fluid layer, which is also, in turn, important to preserve and maintain the cartilage, the articular cartilage, to minimize germ changes. So defect size and location. So compared to knee, the hip is more constrained. So defect size, location, and combination may be more important, therefore. Context versus the periphery. So threshold size for lesions may be different for lesions near the labrum or adjacent to the femoral head. Some patients with FAI femoral head does observe to settle into anterosuperarticular cartilage defects, so all of those defects associated with label tear. So what options do we have? So think about the acetabulum, debridement, microfracture, autologous, matrix-induced chondrogenesis, and then also AMIG techniques, cartilage repair, and ACI techniques. So for these, limited exposure is required, hip arthroscopy seems to be functional and working for this kind of lesions. Femur a little bit more tricky, a little bit more constrained, more difficult to get to. So we can do osteochondral autograft or allograft transplantation, ACI, or partial resurfacing. So again, larger exposures require more difficult to get to. So surgical hip dislocation as a surgical technique would certainly be valuable in this setting. So indications. So chondroplasty, minimal signs of osteoarthritis, less than tau squared one. Focal well-contained lesions measuring less than two centimeters squared. Partial thickness defects or loose flaps. For microfracture, minimal signs of arthritis as well. Focal well-contained lesions measuring less than four centimeters squared. Full thickness defects with intact subchondral bone. So microfracture. So Phil Pond in 2008 published a study looking at revisions 20 months out, showing a mean percent fill of defects of 91%. So that's pretty encouraging. And then 2012, another study reported on a mean percent fill, a second look arthroscopy of 93%. Certainly, this is some reconstitution now. Doesn't mean that the quality of the tissue is the same as articular cartilage initially, obviously. But certainly, there's some filling effect that's going on. So microfracture. So certainly, what are the innovations there? So as opposed to microfracture, all classical holes with a slightly bigger diameter, drilling has become an option. So there's no bone compaction, no fracture, no sealing effect, and less necrosis. We also have deeper marrow access. So we expect to get better outcomes. We went on to why hip microfracture? Well, it's a single surgery, efficient, reproducible, and gets stem cells from inner pelvic table. And largely from the knee, however, there's certainly historical literature to support its effectiveness. So outcomes in terms of the hip. So percent of patients converted to total hip replacement, two years. Bits and acetaldehyde lesion, only 12%. Adrenaline had only 8%. Combined, these are slightly higher at 17%. What are the next-generation marrow simulation techniques? Well, here Ms. Enkelman has stem cells, growth factors, and scaffolds. Again, scaffolds are important to help get a phenotype that's more consistent with articular cartilage to collagen too. Growth factors as well can modulate that. So adjuvant techniques to microfracture. So it could be MACI, AMIC. It can do fibrin-clue scaffolds, hyaluronic acid, and stylet fusions. So biologic augmentation. So hyaluronic acid injection, low platelet PRP, growth factor augmentation, BMP7, 4-FGF18-NJF1. And therefore, you can also achieve some cytokine modulation. So mesenchymal augmentation scaffold stimulation, or MAST technology. So basically, what you want to do, you want to help the macrofracture along a little bit and try to get better results with mesenchymal sterase-based chondroinduction. So tissue engineering principles apply to microfracture. So microfracture. So scaffold augmentation can collagen membrane, chitosan, hydrogel, or micronized allografts like bicarbonate, for example. So effects on chemotaxis, MSC differentiation, clot stabilization, and also pro-anabolic effect. So improved quality quantities are certainly the thought behind this. So then autologous matrix-induced chondrogenesis. So AMIC, the single-stage procedure, bilayer membrane type 103 or 201 collagen. The idea is to facilitate cell migration adhesion, chondrogenic differentiation, stabilize the MSC clot. You can fixate that with fiberglue and augment it also with PRP. High tensile strength shown in the membrane and resorbs. What are the outcomes? So increased tissue quantity, no effect on repair tissue quality, however, and no effect on biomechanical properties. So biomechanical overgrowth and chemical results are similar to ACI and MAC. Better durability was shown as well. Let's move on to the next. So AMIC, autologous membrane-induced chondrogenesis. So Andrea Fontana in 2012 published a paper on this. So again, it kind of is a single-step approach trying to augment a microfracture by putting a collagen 1,3 matrix in there to help establish a phenotype and a more stable phenotype as well. So I spent a few days with him in 2014 or 15 and saw his technique. It seemed to work fairly well. Obviously, long-term outcomes are not available really yet. So then also another scaffold technique is chitosan. So 3D injectable liquid scaffold increases the chondrogenic differentiation, arthroscopic mini-open techniques. Erranda-Musk trials showed increased fill-in quality. So the other one, a mass technique, would be a biocartilage, so micronized cartilage that's injectable. Increased histologic quality was seen in tissue volume. So Lisa Forte published on it in HSM in 2016. Then Andrea Fontana also published in 2012 a MACE two-stage technique showing initially positive results as well. So the tolerance of chondrocyte implantation, you all remember the New England Journal article in 1994 by Britt Berg, showing excellent, good and excellent results, primarily in the femoral condyle, not so great in the patella, showing a highland-like articular cartilage repair. To date, in 2020, more than 60,000 implantations have been performed worldwide. So certainly one of the most widely used techniques. So for cell implantation, the histology is shown about 70% to 72% highland-like cartilage, so high-content chondrogen too. Five to 11-fear follow-up shows high content, 67% type 2 chondrogen and 83% show complete integration. So functional and clinical outcomes, functional improvement, 67% to 96% reported and also shown best durability of all repair techniques. Long-term results, so 15-year follow-up in 113 patients, study Andreolo HSM 2020 showed 15% failure rate and maintained the IKD-C and Tegner factors affecting the outcome were age, durational symptoms, prior surgery, germs, defects and gender. So in general, if you think about mesenchymal stem cells, certainly age-related changes in infants, higher regenerative capacity, less fibrosis, less inflammation in adults that tips the scale. So less regeneration capacity, more fibrosis risk and inflammation. Certainly something to keep in mind as we develop techniques applying MSCs. So are there stem cells, BMACs or bone marrow aspirate concentrate? So outperforms chondrocytes, non-exercise matrix-derived scaffolds. So the effects of the progenitor cells have growth factors available and anti-inflammatory effect. Experimental studies seem to point to their outcomes in comparison to microfracture or better results. So clinical results, significant knee function scores are reported. So again, primarily, it needs to have been used on the knee. There are studies as late as 2016, better in patients younger than 45 years small and I see defects. Results are comparable to MACI, 80% of complete failed seen on MRI. Hyaline-like histology was seen, so high collagen II content. So other techniques, allogenic techniques, so like umbilical cord, blood-derived techniques. Certainly no long-term data on this either. Some reports showed promising results. So moving on, femoral head defect again. So these are more difficult to get to, to do arthroscopically, but there's been the first and second generation cartilage repair techniques shown for impingement as well and used in this setting. This was studied by Professor Lornig of Zurich in our results. Surgical retinitis was reported by Professor Lornig, also Professor Gans. Surgical hip dislocation to cartilage lesions. So here's a video where you will see the defect, then demarcating the defect and preparing the defect or contained lesion for the AMIC technique, templating so an adequate size of the scaffold can be obtained for the surgical hip dislocation technique, and then preparing or inserting the scaffold and then fixating the sutures and fibroblock can be used as well. So, alternatives, also called autografts, so open treatment surgical hip dislocation or autografts as well for, you know, this specific technique, established procedure from a head of patch and fracture study and technique reported out of Switzerland. So, developing novel techniques, so as reported, Dr. Fantana had this technique, this amic in the hip, so chondroguide developed by a company out of Switzerland. So with a lot of the Carthage techniques, it seems that there's more coming out of Europe that is very largely related to the fact that less stringent regulations there and approval processes. So, the head of the curve compared to the U.S. because they have more access to some of these techniques and technologies. So, then HyloFast, Anika, a company in the U.S., hyaluronic membrane as a matrix, again a three-dimensional scaffold to help prevent de-differentiation of cartilage, of carticides. Basically, again, a lot of these studies and pushing for the technologies and boundaries on cartilage repair and regeneration are coming out of Europe, particularly in Germany there's a lot of activity going on, so some arthroscopic techniques showing some very promising outcomes and again they have access to technologies we don't yet have in the U.S., so but injectable hydrogels and also guidelines are being developed. So summary, what's the best, what's the basic science, so some but not all Carthage basic science treatment options, the initial development they are applicable to the hip, there's some distinct differences in the atomic and biologic features that are different in the hip than the knee, so that may require some different approaches. So better understanding of biology and biomechanics will certainly be helpful. So what are the options, so acetal lesions, again, retreat arthroscopically, so microfracture augmented with some technology talked about, certainly can be helpful, PMAC as well, your P in combination as well, and then femoral lesions frequently require open techniques, so surgical hip dislocations, grafting, also ACI techniques certainly can be used here. So the decision on treatment depends on the location, size, and the type, so are these amenable to any of those restorative procedures, or are they uncontained lesions, so basically representing arthritis. So treatment only successful if significant osteoarthritis is absent and these are contained lesions. So acknowledgements, I want to acknowledge Al Stops for some of the input on the tissue engineering part, Professor Lohenig on some of the techniques as well, and Dr. Mithoffer, one of my partners and colleagues, who is an expert in knee articular cartilage, I certainly appreciate some input he's given me here. So thank you very much, unfortunately I won't be able to answer your questions since it's not interactive, but I hope this was helpful, and hopefully next year we can go back to a normal kind of setup. Be well, and stay safe, thanks.

cartilage technologies

hip cartilage repair

tissue engineering

surgical techniques

biology and biomechanics