Tendon Response to In Vivo Fatigue Damage

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DESCRIPTION (provided by applicant): Tendinopathy and tendon rupture are major clinical problems causing pain and disability. Many studies have suggested that accumulated fatigue damage from wear and tear underlies the tendon degeneration seen in tendinopathy and that this damage contributes to tendon weakening leading to rupture. Despite this, little is known about the mechanical and microstructural mechanisms of fatigue damage accumulation in tendons, and the biologic processes by which tendons respond to such damage are not understood. Animal models of tendon disease have generally been either acute laceration models which do not model the chronic degeneration seen in tendons prior to overt rupture, or exercise-overuse models with poorly defined mechanical insults (e.g. treadmill overuse) which do not allow teasing apart the tendon's mechanical and biologic response to precise doses of matrix injury. The proposed studies will use our recently developed rat patellar tendon model, which allows the production in living tendons of subfailure fatigue damage, to test the hypothesis that fatigue damaged tendons restore normal architecture and mechanical properties over time. In the first series of studies, we will characterize the fatigue process mechanically and and morphologically in living tendons at loaded at different stresses and to different damage endpoints. In experiment 2, we will introduce different levels of fatigue into living tendons, and examine mechanically and microstructurally how these tendon respond to this damage over time. In the third series of studies, we will determine at cellular and molecular levels whether tendon response to fatigue damage mirrors normal healing and whether it utilizes different mechanisms.