Poster 203: Mechanical Loading Effects on OA Progression Following ACL Injury and Reconstruction in a Murine Model: Radiographic Assessment of Synovial Fibroblast Activity

Objectives: Anterior cruciate ligament (ACL) injury is one of the leading orthopedic injuries in young individuals and even with surgical repair it is reported that around 50% of patients develop post-traumatic osteoarthritis (PTOA). Although ACL reconstruction improves anterior-posterior knee joint stability and cartilage contact biomechanics, some studies have shown persistent abnormalities in the tibiofemoral kinematics. Extensive rehabilitation work is often required following both ACL tear and ACL reconstruction surgery. New bone formation (osteophyte) and synovial inflammation (synovitis) are often associated with the progression and severity of OA post-injury and surgery, however the effect of mechanical loading stimulus in musculoskeletal repair remains relatively unexplored. The role played by resident synovial stromal cells in the activation of their local inflammatory and regenerative programming is poorly understood. Work in our laboratory has shown that in vivo imaging of activated fibroblasts using 68Ga-FAP radiotracer may be a valuable tool to follow the progression of OA and the bone-tendon interface healing. This study aims to explore the therapeutic effect of exercise following ACL reconstruction on the progression or mitigation of PTOA following an ACL injury, evaluating the mechanism and contribution of synovial fibroblast activation using microPET/CT imaging. Methods: All study procedures were approved by Weill Cornell IACUC (#2019-0034). Thirty, 12 week old male C57BL/6 mice underwent a non-invasive ACL rupture induced by a single axial compressive load of the tibia at a rate of 1mm/s on the right knee (Fig. 1). One week following injury, the animals were allocated into 4 treatment groups (n=6 per group): non-treated (G1); non-treated with sham surgery (G2); treated with ACL reconstruction (G3); treated with ACL reconstruction and treadmill exercise starting 1 week post-operatively (G4). Six mice were used to harvest the ACL tendon graft (allograft) and their knees scanned in the microCT as healthy controls.Treadmill exercise was performed 5 days/week, at 10m/min for 40min. PET/CT (Inveon scanner - Siemens Medical Solutions) imaging was performed pre-injury (baseline) and at 1, 2, 3, 4 and 8 weeks post-injury to measure fibroblast activation in the joint. One hundred μl of a 7% v/v EtOH/saline solution containing our 68Gallium (Ga)68-labeled fibroblast activation protein alpha (FAP-α) inhibitor (3.7-18.5MBq) was administered by tail v