Open Access Dissertation
Date of Award
Howard W. Matthew
Post-traumatic osteoarthritis (PTOA) is a prevalent condition following rupture of the anterior cruciate ligament (ACL). While numerous animal models of PTOA exist, most are based on surgical disruption of a stabilizing structure. In the rat, surgical ACL transection is the most commonly employed model, but it may introduce confounding biological factors due to surgery. The purpose of this dissertation was to utilize the tibial compression model of ACL injury to induce a noninvasive ACL rupture in the rat. First, a biomechanical characterization of four different loading protocols was undertaken, and a high-speed, high-displacement protocol was deemed optimal for inducing a repeatable, complete ACL injury. Tibiofemoral joint motion was found to be representative of motion during human injury. Next, a chronic, biological comparison of the noninvasive injury model to the surgical ACL transection model was performed. Results indicate that the two models both cause extensive degenerative joint changes, and articular cartilage degeneration was most profound in the medial compartment of the femur. The two models yield in a differential bony remodeling response, and surgical ACL transection causes more drastic degenerative changes of articular cartilage. Furthermore, the ACL transection group had elevated biomarkers of cartilage breakdown compared to the noninvasive rupture group. Lastly, the acute response following noninvasive and surgical injury was investigated. Both injuries cause the systemic mobilization of mesenchymal stem cells (MSCs) and elevated stromal-cell derived factor (SDF-1) concentrations in the joint acutely. Biomarkers of cartilage breakdown and metabolism are elevated only slightly immediately after injury. In conclusion, while some studies may benefit from the more rapid onset of PTOA in the surgical ACL transection model, a noninvasive injury model avoids confounding biological factors and may be beneficial for future studies assessing pathology or potential treatment strategies.
Maerz, Tristan, "Biomechanical And Biological Evaluation Of A Model Of Post-Traumatic Osteoarthritis Following Noninvasive, Traumatic Rupture Of The Anterior Cruciate Ligament" (2015). Wayne State University Dissertations. 1291.