Good afternoon. Thank you everyone for being here today. I'd like to thank my co-authors as well in helping with this study and allowing me to present my research. Our disclosures can be seen on the Academy app. So a little bit of background on meniscal deficiency. We know it affects millions worldwide and it alters knee biomechanics such that complete meniscectomy may increase tibiofemoral contact pressures greater than 100%, which potentiates the development and progression of knee osteoarthritis. And despite this newfound importance placed on maintaining meniscus, partial meniscectomy still far outpaces meniscal repair. One procedure to combat meniscal deficiency is meniscal allograft transplantation, or MAT, which is shown to be a successful treatment and consistently improves functional outcomes with graft survivorship up to 75% at 10 years. And this is performed by a variety of surgical techniques. Of course, like any surgical procedure, MAT is not without its complications and reoperation rates may be as high as 32% for a variety of reasons, as you can see here. And part of the problem is there's no way to know until it's too late as far as success or failure of the graft. And this enters into the realm of biomarkers in the hopes of either predicting or diagnosing success or failure. The purpose of our study was to analyze serum and urine biomarker concentrations for their capabilities in delineating differences in assessment of pain and functional outcomes in a preclinical K9 model six months after MAT with the hypothesis that assessment of serum and urine biomarkers can be used to develop prognostic at the one and three post-surgical time point and diagnostic at the six-month time point biomarker panels based on strong associations with clinically relevant outcomes metrics obtained six months after surgery. So to perform this, we had 12 research hounds. Symptomatic medial meniscal deficiency was induced by a validated arthroscopic medial release surgery. Three months after meniscal release surgery, medial MAT was performed by three different techniques with four dogs in each group, either with fresh frozen, fresh, or fresh meniscal tibial OCA. And we performed it in such a manner to provide a spectrum of outcomes with different techniques. And then serum and urine were collected at one, three, and six months post-surgery with a six-month end point for the study. Animals were assessed clinically for limb function, lameness, effusion, comfortable range of motion, vast pain, and force MAT kinematics at six months. A variety of biomarkers were assessed in both the serum and urine. Linear mixed models were used to develop prognostic biomarker panels at the one and three-month biomarker data, and diagnostic panels were created using six-month biomarker data with final models chosen using conditional R-squared to find best fit. Our primary outcomes for pain was the vast pain score based on physical exam, and function was the operated limb total pressure index from force MAT kinetics. As predicted, our model demonstrated a spectrum of improvements in pain and function following MAT surgery. Regarding the actual biomarker panels, prognostic for pain were serum CTX-2 and OPG. Prognostic for function were IL-6, 8, 10, and 18. Diagnostic for pain were CTX-1, CTX-2, IL-8, MMP-2, and TINP-1. And diagnostic for function were serum MMP-1, MMP-3, and urine PINP and TINP-1. There are obvious limitations to our study, mostly that it is a surgically induced canine model with a relatively small number of dogs with varied MAT techniques, although, again, this was purposeful to provide a spectrum of outcomes following surgery, and the study endpoint was short at six months, although there's been a validated time point in canine models. So in conclusion, serum and urine biomarker panels may model clinically relevant metrics for function and pain in a preclinical model of meniscus allograft transplantation. Serum appears to be the preferred fluid for predictive applications, while urine may be preferred for diagnostic capabilities. CTX-2 and IL-8 appear to be important for use in both panels, and further refinement and translational validation of these biomarker panels may allow for optimizing patient selection, rehab, and return to support protocols. Thank you.

meniscal deficiency

knee biomechanics

knee osteoarthritis

meniscal allograft transplantation

biomarkers