Good morning, we have no relevant disclosures to report. ACL ruptures commonly occur with a pivot shift mechanism, which is seen as bone marrow edema lesions on MRI in up to 80% of cases. During the event, the articular cartilage is exposed to significant loads, leading to the release of numerous cytokines into the joint space. While ACL reconstruction is a successful operation, the post-operative recovery is variable and procedure has not been proven to prevent the development of post-traumatic osteoarthritis. Large epidemiologic studies have shown that even following a well-performed ACL reconstruction, radiographic arthritis is seen in up to 60% of patients 20 years post-procedure. In an effort to improve our outcomes and understand the pathogenesis of post-traumatic osteoarthritis, a better characterization of the alterations in the joint microenvironment that occur between ACL injury and surgery is warranted. A biomarker is defined as a measurable indicator of a specific biological state and can be used clinically for making a diagnosis, establishing a prognosis, monitoring disease activity or therapeutic response, and can serve as potential treatment targets. Synovial fluid is an ideal source to mine for potential disease markers because it's readily available and the markers that we're interested in are present in significantly higher concentrations compared to blood or urine. The purpose of the current pilot study was to evaluate the change in concentration of select synovial fluid biomarkers during the interval period between injury and ACL surgery. We hypothesized that synovial fluid samples collected in the acute injury phase would exhibit higher concentrations of pro-inflammatory cytokines and lower concentrations of anti-inflammatory cytokines than samples collected at the time of surgery. Synovial fluid samples in the study were obtained at the time of the initial office visit and again at the time of surgery prior to incision. The samples were transferred to sterile tubes containing protease inhibitor and were centrifuged prior to storage. The samples were then analyzed for the concentrations of 10 biomarkers using a multiplex bead assay. These specific biomarkers were chosen based on our prior work as known players in joint pain, inflammation, and cartilage degeneration. Comparisons were made between our two study time points. This table highlights the 10 synovial fluid biomarkers that were assessed in our study. Our cohort was comprised of 16 patients with a mean age of 32 years. The acute injury samples were collected a mean of 10 days following the traumatic event and the surgical samples were collected a mean 38 days later. As you see, significant difference were present in eight of the 10 synovial fluid biomarkers that were assessed between the two time points. From the time of the initial presentation to the time of surgery, there were significant increases in the pro-inflammatory Rantes and the growth factor beta FGF, while significant decreases were seen in the concentrations of interleukin 6, monocyte chemotactic protein 1, VEGF, TMP2, and interleukin 1 receptor antagonist. So as an example of how this type of data can be used moving forward, synovial fluid IL-6 has been implicated in cartilage destruction and the development of post-traumatic osteoarthritis. Patients undergoing early as opposed to delayed ACL reconstruction have been shown to have sustained elevation of interleukin 6 up to eight months after surgery. So monitoring interleukin 6 synovial fluid levels may prove to be a key indicator for identifying the optimal time for surgical intervention, and IL-6 may also be a good treatment target for preventing post-ACL rupture arthritis. As a pilot study, we're limited by a relatively low N, and our samples are collected at only two time points. Serial sampling will provide greater detail with respect to the overall natural history of biomarker changes in the setting of ACL injury. As a descriptive study, no correlations were made with respect to clinical or functional outcomes or the incidence of complications, and this is an area of ongoing work. And finally, additional biomarkers of interest that may play roles in intraarticular inflammation and healing are currently being investigated. So the current data demonstrates the ongoing alterations in the intraarticular microenvironment during the initial injury phase following ACL rupture. Further study of the role that each of these cytokines plays in the body's response to injury and the impact they have on outcomes following ACL reconstruction may allow for individualized management protocols and the identification of treatment targets to not only limit complications, but potentially reduce the incidence of post-traumatic osteoarthritis. Thank you very much, and a special thanks to the Beaty Family Foundation for supporting our work.

ACL ruptures

articular cartilage

synovial fluid biomarkers

post-traumatic osteoarthritis

interleukin 6