Thank you, Robyn, and thank you, Anna, for the opportunity to present. How do I forward this? Not moving. It's not forwarding. Okay. There we go. No. There we go. So there are three concepts that are the underpinning of this study. The first is that ASL graphs undergo a process of ligamentization. The second is that MRI signals correlate with graph remodeling along with structural properties. The first aim of our study was to look at T2 signals and to see what the effect of BMAC was on graft signal intensity ratios. This we believe is a proxy for remodeling and ligamentization. At three months we expect higher signal with increased remodeling, and at nine months we expect decreased signaling secondary to integration and homeostasis of the graft tissue. We also followed patient-reported and clinical outcomes up to two years. We are currently presenting one-year data. The evolution of ACL surgery from a technical standpoint has evolved tremendously. Orthobiologics we believe might provide a pathway to accelerating healing of allograft tissue. We are also similarly familiar with causes of ACL graft failure, and biological incorporation plays a central role. There are three phases of ACL graft healing, beginning with avascular necrosis, where cytokines and growth factors are released. Remodeling is cell-mediated. Inflammation is the acquisition of histologic and biomechanical properties of the native ACL. These slides demonstrate inflammation with macrophage and erythrocyte infiltration, along with remodeled grafted tendon on the right juxtaposed with cartilage deposition. We obtained MRIs at three months and at nine months. Three months marks the end of the early phase of healing and the beginning of remodeling. Nine months represents the end of remodeling and subsequent maturation. The Moon Group demonstrated that allografts had a five-fold increase in risk of re-tear. Autografts performed better. A study by Motadi at five years, which was randomized, suggested that B-to-B allografts are still a suitable graft choice. So what's in BMAC? It's got a high concentration of beta-FGF. It has VEGF. It has pluripotent cells, and these are concentrated five times. It also contains interleukins. It's been applied to chondral and osteoarthritic lesions. These stromal cells can differentiate into bone, cartilage, muscle, and tendon ligament tissue. The primary outcome that Hakuzaki utilized was the T2 intensity signal, and he found that it correlated strongly with graft function. It correlated with KT values, and it had 90% specificity for graft failure with AP translation greater than four millimeters. Bercevitz demonstrated that signal intensity ratios also correlated with structural properties. Both graft volume and signal ratio affected both yield, load, and stiffness. Our study was registered with the FDA. We randomized by Excel. We utilized Hakuzaki's study for a power analysis, and to detect a 20% difference required 15 patients per group. We enrolled 40. We included patients between the ages of 18 and 60. You can read the exclusion criteria on the right. All of those procedures were not included unless it was a municipal debridement. I'm sorry, just a simple chondral debridement. With respect to technique, three fellowship high-volume trained surgeons performed all ACL reconstructions via medial portal technique. B2B allografts were acquired from Allisworse with low-dose gamma irradiation. We harvested 50 to 90 mLs of marrow aspirates. The control group had a stab incision, and we did not aspirate. We injected two ccs of BMAC into the proximal, middle, and distal regions of the tendinous graft. We sent 0.5 ccs for ELISA assay and receptor testing, and both groups follow the same standard accelerated protocol. So flow cytometry is useful, and it allows us to follow the position statement from the International Society for Cellular Therapy. We established the presence of MSCs by testing for CD markers. We also confirmed adherence to plastic and differentiation of these cells into adipocytes, chondroblasts, and osteoblasts. We utilized the ARTEC system to concentrate. This is a short video demonstrating electrograst harvesting, spinning, and intratendinous injection with a 25-gauge needle. The graft is passed through a dry joint to prevent extravasation of cells. The peak screw is utilized for fixation on both sides, which allows for MRI analysis. This is what the sagittal T2 looks like. We evaluate the ACL graft at proximal, middle, and distal regions. We look at the ratio to the patellar tendon, which is our baseline. We enrolled 80 patients. We lost four to follow-up, one to pregnancy, and one withdrew. We had one re-rupture in the control group, and we had 91% follow-up data at one year. There were no significant differences demographically between the two groups or with respect to their preoperative outcome scores or KTs. The T2 MRI signal-intensity ratio was significantly different at three months in the inferior third of the ACL graft. It's almost a 50% increase. The other time points did not reach significance, but it's about a 20% to 30% increase at every interval. There was no dose-dependent response with the stem cells, which we did, in fact, try to correlate. With respect to physical exam findings, a KT1000 and range of motion, there were no significant differences. We came close to increased flexion at six weeks in the BMAC group. With respect to Tegner, iKDC, and Koos, there was an improved iKDC score at nine months in the BMAC group, and this was statistically significant. There's a trend for a higher Tegner score in the BMAC group at one year. The average volume of BMAC harvested was 2.8 milliliters after centrifugation. The concentration decreased after the age of 30 significantly with respect to the cells. We averaged 900 cells per milliliter, and these were CD34 negative. We injected approximately 2,000 of these cells into each allograft construct. So in conclusion, BMAC injection into ACL allografts results in increased signal intensity ratio at three months. This may be a marker for metabolic activity and increased remodeling. BMAC also results in higher iKDC scores at nine months. It's only seven points, which is below the MCID. To my knowledge, this is the first randomized trial investigating this subject matter. Discussion points. MSCs have potential. We need to better determine if they can accelerate ligamentization. We need to determine whether the effect of BMAC is from the cytokines or the cells. Animal studies might provide insight into the effect on structural properties, and larger studies would be necessary to evaluate rerupture rates. And thank you, Anna, for generously awarding me this talk.

BMAC injection

ACL allografts

remodeling

iKDC scores

ligamentization acceleration