The Effects of Reduced ACL Stiffness on Dynamic In Vivo Joint Function

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PROJECT SUMMARY The objective of the proposed study is to establish whether inferior in vivo anterior cruciate ligament (ACL) graft stiffness is sufficient to induce joint motion abnormality. The ACL is the most frequently injured knee ligament. Surgical ligament reconstruction using a tendon graft is the gold standard treatment for an ACL tear, but the procedure does not restore normal joint motion completely and fails to prevent post- traumatic osteoarthritis (PTOA) in many subjects. Why ACL reconstruction fails in these two regards is not completely understood. Much information from animal models and ex vivo experiments suggests that ACL graft stiffness is inferior to that of the native ACL. One of the confounding factors in clinical studies is that different 3D anatomical structure and non-anatomical placement of the ACL graft likely contribute to residual abnormal joint motions that are known to exist. To circumvent the confounders, the proposed study will use an ACL reconstruction animal model and a non-invasive in vivo T2* MR imaging technique to investigate the time course of changes in ACL graft stiffness while using the native ACL as the “graft”. This surgical model simulates the important aspects of bone drilling and graft fixation in clinical ACL reconstruction without introducing the confounding variables described above. In a cross-sectional study design, ACL “graft” stiffness and joint motion will be assessed prior to “reconstruction”, and then at either 6, 12 or 24 weeks. Using this approach, the project will determine whether a threshold in ligament stiffness exists that preserves joint motion, and alongside the outcomes from the mentored K99 study, will provide new insight as to why the current gold standard ACL treatment fails to prevent PTOA. This project also generates new non-invasive tools to monitor functional joint and tissue changes in a clinically relevant model, while establishing the foundation from which to test targets new treatment interventions. Transferring recipient institutions has not changed these study aims, which are largely complete. The remaining 5 months of this project will be carried out at the new institution with activities directed towards augmenting the quantitative MR imaging data and the approach to record joint motion that was developed specifically for this study. The planned dissemination of the current study findings through conference presentations and manuscript publications will benefit from these proposed activities and will be prepared as part of the final study closeout.