Hello, and welcome. My name is William Bugbee, and my task is to tell you something about fresh osteocondroallografts for cartilage repair in the knee. I'm an orthopedic surgeon specializing in arthritis, surgery, and joint preservation at Scripps Clinic in La Jolla, California. My disclosures, I'm a consultant for Joint Restoration Foundation, provider of fresh allografts and Arthrex. I have no intellectual properly related to osteocondroallografts, and everything that I know is in the public domain, and I'm happy to share that with you. Finally, I have nothing against cell-based therapy or any other cartilage restoration technique. I just have found that fresh allografts works well for me, and I found no reason to use a variety of techniques in my practice, which admittedly is quite tertiary referral in nature. First thing I want to say is there's a large amount of clinical and scientific data supporting fresh allografts. The available literature is growing exponentially, as interest in this technique grows as well, period. I think we all know that there are two basic fundamental strategies of cartilage restoration. The cell-based group, such as microfracture, ACI, and other newer techniques such as minced tissues or allogeneic cell sources, conceptually designed to induce cells to form articular cartilage or chondral tissue in situ. The other group or strategy would be whole tissue-based, and this would include the allografts, of course, but also autografts and processed acellular allografts, which have been on the market more recently. Some background and understanding of the governing principles of allografting helps. Think of an allograft as a whole tissue or organ transplant containing viable chondrocytes in a mature hyaline matrix. Chondrocytes survive transplantation and maintain the matrix, and we know this from long-term retrieval studies, and we believe some proof that cells within the matrix are immunoprivileged by way of being in the matrix and being in non-vascularized tissue. The osseous portion of the allograft is essentially a non-living osteoconductive scaffold. It acts as an interface for attachment and integration, and technically, we try to transplant as little bone as possible that's necessary for restoration of the defect or fixation because we know these grafts incorporate by creeping substitution, and we want that to be only a few millimeters if possible. This of course is the potential site for immunologic response, and therefore, in many cases, the behavior of the osseous component of the allograft is most important factor in clinical outcome. If one compares cell-based versus whole tissue-based transplants, a visual concept would be something akin to this. Sodding along would be a whole tissue transplant, and seeding along would be a cell-based repair. The advantage, of course, in my mind is that you have a mature construct and a quicker time to be able to load this with mature tissue. Another concept is the subchondral bone in the osteoconductive unit, which is increasingly recognized in cartilage injury and repair. This is an integrated organ system with an interdependent structure and function relationship, and the behavior of this is critical in understanding cartilage lesions and repair. Now some misconceptions about fresh osteoconductive allografts. Historically, they were introduced as a joint reconstructive procedure for trauma, tumors, and arthritis, more or less in salvage situations as a salvage intervention. However, now allografts are firmly established in the cartilage restoration paradigm, often as a first-line technique for chondro and osteocondylesions, and not just for salvage of other surgeries. I like to think of the indications for allografts in diagnostic groups as listed here. Tachycarditis dissecans or osteocondylesion of the talus, traumatic or osteocondylesions, and of course revising previous cartilage surgery that did not work. Uniquely, allografts are useful for necrosis, fracture malunion with bone defect, and finally in salvage situations for focal degenerative chondrolesions and carefully selected patients with osteoarthritis, although this is a very small group. Fresh allografts are safe. Tissue banks processing allografts have validated protocols, donor suitability criteria, and standardized recovering processes. This includes multiple levels of testing, signing off by a medical director, and in the U.S., in spite of all this, the waiting time for a graft is less than 30 days. People also want to know what is the infection risk of allograft surgery. I believe infection risk is probably equivalent to a blood transfusion, and we've done over a thousand surgeries with 1,500 grafts in the last 30 years and only have had two postoperative infections, neither of which were associated with the graft. Therefore, I believe allograft surgery is quite safe, and in my practice, arthroplasty is a far more dangerous undertaking. Here's a fresh allograft timeline to help everyone understand the process from recovery, processing, testing, matching the donor and the recipient, release of the graft, and then We believe that most grafts are probably better off not being used after day 28, although this is arguable. Nonetheless, the important concept is that storage decreases chondrocyte viability, particularly in the superficial zone. What are the clinical consequences of this discrete decreased cell viability and tissue metabolism? Well, we know from our animal studies that stored grafts perform less well than fresh grafts. But the balance between safety and efficacy provides a safe graft with acceptable viability, and in a clinical study we performed, we could not detect clinical consequences of storage versus non-storage in match groups. Finally, surgery. I think allograft surgery is fun to do, familiar instrumentation for most orthopedic surgeons. It does require a smaller arthrotomy, but we've seen little consequence of this in our studies. Here you can see that we do not drill deeply into the bone in this focal lesion. We harvest the graft, match the depths, wash the graft to remove marrow elements to decrease immunogenicity, and we press fit the graft. For most instruments, a press fit is appropriate for a contained lesion and a single plug, so we rarely use extra fixation except in complex situations. You can see here the graft is washed, trimmed, washed, and implanted. One of the advantages of allografts is rapid recovery and simple rehab because we require no tissue maturation for this graft to function. Unless there's a patellofemoral graft, there are no range of motion restrictions. We get initial excellent graft stability, and we're looking for bone healing, which occurs often rapidly within four to six weeks. Therefore, recovery and return to sports and recreation or normal life is more based on the functional recovery of the individual rather than on graft or tissue maturation. This usually occurs somewhere between three and six months. What about outcome? As I mentioned, allografts are versatile, but the outcome does vary by diagnosis. You can see here for focal lesions, failure rate's low, improvement is excellent, satisfaction high, but as you get into more difficult situations, you get higher failure rate as you would for any technique, and outcome, although improved, does not reach normal knee function. Return to sports after allografts is about 75%. This has been shown in a number of studies, and it's very similar to a return to sport in other surgeries such as ACL surgery and meniscus surgery. Satisfaction is about 90% in all comers, which is quite high, but understanding the relationship between patient variables and allograft outcome is important. Older age is also a risk factor for failure, as it is in any cartilage surgery, and as I mentioned, diagnosis, thus one should think twice about doing an allograft in a person over 50 with established osteoarthritis. What about the opposite? Using a modern technique as described for typical cartilage repair indications such as traumatic lesions, degenerative, focal lesions, or OCD, what kind of outcome can you expect in a single defect using precision surgical instruments and a plug technique with a minimum amount of transplanted bone? We looked at this group amongst our entire cohort, and this was about 200 patients. We excluded most of the complicated situations, and here's our outcome. At six years, with a graft size of about six square centimeters, and for those of you that are wondering how big that is, that's about the size of a quarter, and six millimeter graft thickness, quite thin, that would be two to three millimeters of cartilage and two to three millimeters of bone. We had improvement in all patient-reported outcome measures, a low failure rate, reoperation rate relative to cartilage repair in general, and as I mentioned, return to sport at 75%, survivorship and satisfaction at 90%. This outcome is comparable to any other cartilage repair technique that is available to you today. So what should you do in your early cartilage repair practice, and how would you use allografts? Well, I would use them as you would any other technique and decide what works best for you. My best experience with allografts is in patients under 30 with OCD or traumatic lesions of the femoral condyle or trochlea, and lesions size less than eight centimeters. In this group, the outcome has been quite excellent. Of course, allografts can also be used for the difficult cases, but they are more challenging. So thank you for your attention. And I hope that I conveyed my experience with allografts, how I think they fit into a cartilage repair practice, and ideas on how you might incorporate them into yours. Thank you for your attention.

Dr. William Bugbee

orthopedic surgeon

arthritis

cartilage repair

fresh osteocondroallografts