Hello, my name is Dennis Crawford. I'm a professor of orthopedic surgery at Oregon Health and Sciences University. I'm going to chat with you about allograft for ACL reconstruction surgery. When we consider ACL reconstruction, we have to think of our aims and the considerations for that surgery. And of course, like any medical care, we want to first do no harm. Our goals are subsequently to restore and normalize the pre-injury level joint mechanics, of course, and then to concomitantly protect knee structures, which secondarily support knee stability and ACL function. This is to facilitate a return to health, fitness, and occupational activity by reducing this instability and improving functional capacity of the human and the knee. This may potentially reduce future risk of degenerative joint disease and arthritis as well. But in avoiding complications, we must think about those intraoperative, perioperative complications and the capacity to return to sports and work and the functional limitations that may result from the injury and or the surgery. And the graft choice, autogenous tissue versus allogenic tissue, is only one of the many factors that we should consider with respect to meeting our aims and these considerations. Other factors are the age of the person at the time of the injury, the age of the injury, the graft type, aside from allo or auto, where is it coming from, the intent to return to work or sports, associated injury, anatomical morphology, like the tibial slope, biological healing potential, and of course, the surgeon's experience. The spectrum of complications following ACL surgery should be considered, and unfortunately, they're fairly inconsistently reported in the literature. I've broken them down to intraoperative, like tunnel malposition, which is extraordinarily important, and unfortunately, all too commonly an issue. Hardware problems, which in the modern technology of intraosseous fixation, have reduced hardware complications to a low single-digit percentage. And patella fracture, which in the case of the autograft bone patellar tendon bone, can be as high and has been reported as high as 2%, so not inconsequential. Perioperative complications, like hematoma, are reported more commonly in autogenous autograft hamstring, up to 3%. And infection can be seen from anywhere negligible to up to 2%. Diabetes is a risk factor. Smoking, not yet proven to be. We did a comparative study many years ago and showed that the hamstring tendon allografts and allografts have a similar rate of infection, but that rate of infection was correlated with the increased diameter of the tibial tunnel, and when we changed our tibial fixation from the washer lock to something less aggressive, our infection rate dropped significantly. Postoperative complications, most famously, are graft failure, and in the allograft, that's been reported to be around 3%, up to 45%. We'll talk about that study. Autograft, similar, 3% at the low end, 8%, somewhere in that range. Stiffness and Cyclops lesions are known, but poorly defined in the literature, and manipulation under anesthesia and debris mine have been reported between 0% of the time to up to 5%. Weakness and pain are common. 27% of autograft bone patellar tendon bones report one of those two perioperative complications. And autograft hamstring tendon, similarly, up to 17%, whereas allograft is not immune from those reports, but definitely a lower rate. Vascular complications, fortunately rare, typically associated with fixation, particularly those types of fixation that are bicortical, can be associated with hamstring harvest as well. DVT and PE rates are about 2% for DVT, about 0.02% for PE. There are no comparative studies suggesting that autograft surgery or allograft surgery is particularly increasing or decreasing that circumstance. Advantages to allograft use in ACL reconstruction are that you preserve the native anatomy, that you reduce the complication risk for things like fracture, weakness, and probably stiffness, and that your early recovery downtime is minimized. There's less OR time typically, anesthesia, scar. Early physical therapy may be less urgently needed. And oftentimes, the cost can be lower because your OR time can be balanced against your graft purchase. In this recent JBJS Open Access publication describing the various factors of healthcare costs around the ACL, the OR time was significant. And in fact, they described an average time for bone patellar tendon bone in the OR of 104 minutes, slightly higher, almost two hours for a hamstring tendon. By comparison, my primary allograft tibialis anterior takes about 52 minutes, so about an hour less. OR time at $150 a minute, the graft's about $2,400. OR time at about $9,000 an hour. Do the math there. Predictable size is another advantage. Multiple grafts can be available. Is it safe? We'll talk about the considerations of graft source and how they're treated, but it seems to be. Equivalent outcomes, that's the big question. What's the re-rupture rate? Is it any different than the contralateral ACL injury with return to activities? When we talk about allograft tendon as a choice for ACL reconstruction, we must recognize that this is a shared decision-making opportunity. The surgeon's equipoise in presenting options for treatment is really about the patient ultimately deciding on a graft choice when they elect surgery. The allograft can be particularly favorable for revision reconstructions, particularly when limited autograft options remain. I use this often in ACL. The single stage for tunnel widening might require a two-staged approach, so I use an Achilles with bone and can often avoid the two-staged approach by using the bone block in the larger tunnel. Primary ACL reconstructions is often an option for the low to moderate demand functional population. I don't consider it an age issue as much as a functional issue. Patients with very limited window for surgical recovery may benefit from the advantage of limited anatomical disruption of the surgery, and I favor this for patients who have pain management issues. I used to put that under the atypical settings category. Unfortunately, pain management and narcotic use abuse is a prevalent issue. Atypical setting, the associated periarticular tissue trauma, limiting autograft options can be the case, you know, after a tibial plateau fracture or periarticular trauma care. Dysmorphic anatomy is pretty unusual but can sometimes limit your autogenous options as well, and then the allograft's a good option there. Let's talk about outcomes. You know, the MOON group is quite famous. They study the knee injury in surgery. It's a study group, the Measurement of Orthopedic Outcomes Network, founded in 93 by Spindler, Parker, and Andrisch. A cohort of studies, level two evidence, essentially more than 40 publications from the 19 physicians involved from seven academic centers. And famously, in 2015, Kading from that group published on risk factors for subsequent ACL injury, essentially failure. And he said, the group said that there was a four times greater risk of re-tear with allograft for younger and athletic patients. And the graph to the right suggests that this risk is highest in the youngest and dwindles with age. This may not be universally applicable as the allografts in this particular cohort were not well characterized. Other studies have looked at this, and I've selected some comparative case cohorts and reports. Famously, in 2005, a report in the American Journal of Sports Medicine showed a non-randomized study of bone patellar tendon bone, which was irradiated and treated with acetone solvent, the famous two-to-plus technique. 186 of 268 patients in six years were fallen. A failure rate of 45% was seen with this clearly chemically harmful treatment method in comparison to the 6% of autografts. Polling, however, at the same year, suggested that soft tissue allografts were in comparison to bone patellar tendon bones. He looked at five-year outcomes of 159 patients of 219, and he showed improved early functional metrics in the allograft and no difference in outcomes of five years. A classic article from 2015, looking at young military cohort that were operated on in 2002 and 2003, reported on 10-year results of the 99 patients randomized to either autograft hamstring or allograft posterior tib. He found a four-time risk of allograft rupture in a non-irradiated group, 8% versus 26% of those 79 patients that he evaluated 10 years later. We looked at a prospective randomized trial we reported in the knee in 2016. We took doubled allograft hamstring tendon and compared it to doubled allograft tibialis tendon and found that with low-level irradiated allo-washed tissue, there was no clinically significant difference between these two types of doubled allografts, and the failure rate was in the range of 6% to 4%. This is similar to what Malitis reported in 2017 from the massive Kaiser database. 80% of those patients were autograft, but in looking at bone patellar tendon allografts, the revision risk at two years was 4%, similar to our study, and this is in contrast to 2% for the autograft group. Now, systemic reviews at that time and since have suggested various things. If we look at Spindler Moon Group and his recommendations in 2009, he and Carey reported that short-term clinical outcomes were not significantly different between allo and otto. Tim Foster in 2010 similarly thought that graft source had minimal effect on the outcome of ACL reconstruction, and Lambine, in a review of 32 years of reports, showed no difference between non-irradiated allograft and autograft over that time. However, a report from the Moon Group in Sports Health in 2015 looking at seven studies in patients of younger age specifically showed that a 3.5 higher rate of failure with the allograft. They looked at 788 autografts and pooled failure prevalence of almost 10% with allografts, 228 with the prevalence of 25%. However, in the two of those seven studies that assessed autograft versus non-irradiated allograft, no statistically significant difference in graft failure for non-irradiated grafts. Well, you know, meta-analysis pool all this information, and I've got a number of these studies in micro font here, and I think fundamentally there are multiple findings. The red highlighted text suggests that autologous grafts have a lower rate of re-rupture, where the green text suggests the findings were that there was no statistically significant risk with regard to failure risk in the allograft group. And as you can tell, across these 11 meta-analysis, there's a mix of findings. Well, how do we explain that? Clinical heterogeneity may be the confounding variable which prejudices modern ACL allograft application. Clinical heterogeneity is the difference in participant characteristics. Examples are age, baseline disease severity, ethnicity, comorbidities, the types or timing of outcome measurements, and the interventional characteristics. Example, the dose or frequency of dose or the training of the surgeons. Well, for ACLs, that can include fixation methods, anatomic diversity, types of sports participation, which aren't always captured in these well-intended studies. And historical studies don't necessarily capture the spectrum of complications, as we pointed out, or the current modern approach. Rick Wright said it very well. The data is plentiful, but ultimately confusing due to poor control of a variety of factors and even well-intentioned studies. I think anyone here will probably think that an allograft has a little bit higher chance of failure, but that is not the only outcome to consider. These are the options for ACL reconstruction. It can be broken down into two broad categories, the soft tissue allografts, including hamstring, the tibialis, peroneal tendons, and fascia lata. Then there are the bone-associated allografts, including patellar tendon, quadriceps, and tendo-achilles. And these graphs have some unique risk factors and considerations. Bio-burden and immunological response are important. Tissue rejection, per se, is negligible. It's not like an organ. However, there are certainly residual, non-inert molecular elements present that may influence the host biological response. And I think these need to be considered. The allograft processing is intended to reduce bacterial viral load, but not necessarily the inert molecular elements. And this is done to achieve sterility. It may reduce immunological elements if there is some type of cleaning. We also need to think about the donor characteristics of how old is that donor, is the gender understood or known, and is that important? And are there other factors that may affect the quality of that tissue, like systemic disease like diabetes? And of course, the processing effects to achieve sterility can affect the structural integrity, specifically radiation and also the chemical effect we saw in that two-to-plus study. And then, you know, biological compatibility, not computability, can be affected by these treatments. For example, gamma radiation will cause oxidation and alter structural characteristics of molecules, like fatty acids, which could have an effect on biological bone healing or ligamentization. And these residual bioburden effects can alter healing, potentially the rate of incorporation to bone, potentially the rate of ligament remodeling. And, you know, we want to understand for these tissue, can that be optimized or enhanced? And are there roles for biologics or changing the methods of preparation? You know, and are there optimal donor characteristics? Well, just briefly on tissue processing and variations in source and process, you know, many tendon allograft handling processes are proprietary, and you should understand that. Some allograft tissue does not have terminal sterilization. Those are ones including live cells, not really a factor at this time for ACL allograft reconstruction, but certainly for fresh tissue processes. All tissue should undergo an aseptic processing, which minimizes contamination during prep. These are validated protocols employed by all certified U.S. tissue banks, and they allow the graft to be cleansed to a sterile assurance level of 10 to the minus 3. Additional treatment, additional procedure of terminal sterilization is completed on some allografts, and likely should be for any allograft using an ACL reconstruction. It employs validating gamma or electron beam radiation, and it destroys virtually all microorganisms to a level of the probability of one microorganism surviving as CDC defines of one in a million or 10 to the sixth. E-beam sterilization is something I think needs to be understood, because unlike gamma radiation, electron beam uses electrons produced by a typical normal high voltage current. They're accelerated to the speed of light and focused to create what is called a scan curtain, and graphs of many of the products we use all the time in orthopedic screws plates can be passed through that curtain, and this process inactivates the viable microorganisms. There is no gamma irradiation, and thus no residual radiation and no oxidative damage, so it sterilizes without the mechanic alterating structural effects of gamma radiation. And in the JBJS, Alanis clearly identified that the soft tissue allografts terminally sterilized with an electron beam are mechanically bioequivalent to aseptic non-sterilized tendons. And several authors have looked at allograft source and morphology as potential risk factors for graft failure. Malenis, in particular, in looking at that Kaiser database of almost 6,000 allografts at 80% irradiated, showed in a population of patients mean age 34, 24 to 42, so a bit older, where he controlled for age, BMI, and gender, that irradiation of greater than 1.8 milliretts significantly influenced the rate of re-rupture, and that chemical processing methods were independent increased risk. Chombrowski et al. from Australia published in AJSM in 2020, they looked at younger patients, more than 200. They looked at four fresh frozen grafts, posterior tib, Achilles, tibialis anterior, and patellar tendon, all non-irradiated. They found significantly more failure in the single-stranded group, patellar tendon and Achilles, in comparison to tiband and posterior tib, so almost three times more. Grafts from female donors and those older than 80 had a 50% re-rupture rate, and the tiband and posterior tib from donors less than 50 had a re-rupture rate of 7.5%. They explained this finding, at least with respect to the graft location of harvest, as the difference between a single-strand graft being a ribbon-shaped graft and multi-strand grafts being tubular, and having different cross-sectional areas. An 8-millimeter multi-strand graft will have a cross-sectional area of 50 millimeters squared, where an 8-millimeter patellar tendon or Achilles will have a smaller cross-sectional area. Taking a step back, Bach looked at variations of processing and preparation to influence performance of allograft tissue in ACL reconstruction, and looked at over 300 papers and found 48 that were relative to describing primary factors influencing allograft properties. Tissue type, sterilization method, preparation, donor parameters, and biological adjuncts were identified. And basically, they found low-dose irradiation had a variable effect, whereas high-dose irradiation consistently decreased load-to-failure. Chemical sterilization methods were associated with negative effects on biomechanical properties. Prolonged freezing decreased the load-to-failure, ultimate stress, and ultimate strain. Graft diameter strongly contributed to load-failure measurements. Age older than 40, especially 60, was negatively impacted on biomechanical properties. Gender had minimal effect, and biological adjuncts showed the potential for improving in vitro properties. So, you know, fundamentally, this is about the graft incorporating. And allograft and autograft have similar incorporation and ligamentization natural histories. It's a sequence of stages, including inflammation, graft necrosis, revascularization, cell infiltration, and extracellular remodeling, which are generally slower for the allograft. And these early events differ between the graft type, where bone healing would occur in about six weeks and soft tissue healing in eight to 12 weeks. However, placement, length in the bone tunnel, fixation, tensioning, host health, graft tunnel micromotion, and potentially biological supplements may influence that maturation process. Several studies have looked at how graft healing progresses and how that has effects on reconstruction success. Marumatsu in 2008 looked at MRI of auto versus allograft at two years and showed that the allograft had a slower onset and rate of revascularization, but no clinical difference in clinical outcomes. We looked at MRI assessment of allograft healing at six months and showed that the graft maturation was clearly associated with our orientation in the sagittal plane. When we matched the normal ACL, the graft healing was more normal and progression. Diebold in 2021 and KSSTA looked at 50 patients randomized to either auto or allograft and looked at the MRI signal to noise quotient, suggesting graft maturation, and that that was slower with the allografts at six months in the double posterior tendon non-irradiated grafts, but saw no clinical or functional difference in these patients at 6, 12, or 60 months. So in summary, regarding allografts for ACL reconstruction, this is an excellent option in properly educated patients. Some true advantages for both the patient and the surgeon. We must have equipoise discussing comprehensive surgical risks, especially re-rupture. Faster return to ADLs can be expected with the allograft, but longer return to high demand activities should be anticipated. There's less initial surgical trauma and anesthesia exposure. Those are clearly favorable, but we have to respect the time for graft remodeling and ligamentization if we are to apply the allograft. Understanding graft preparation and biology is essential. The source of the graft, the handling, and the storage process need to be understood for all of your allografts. It is an evolving science, and the future of biological adjuncts is extremely exciting for improving this process and improving the quality and safety of allografts. And my recommended optimal allograft choice in 2022-23 is to work with a state-of-the-art facility that uses aseptic handling of non-irradiated E-beam sterilized grafts. I choose patients younger than 35 who are well-screened donors, so they have an extremely well-known background, and I use double soft tissue cylinders rather than bone block ribbons with the exception of large bone voids in revision surgery. Thank you very much.

ACL reconstruction surgery

allograft

autogenous tissue

graft type

complications

graft performance