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

项目概要/摘要 拟议研究的目的是确定创伤后的发病率和严重程度是否 骨关节炎（PTOA）与关节运动异常有关，无论是在体内前下 交叉韧带（ACL）移植物的生物力学特性足以诱导关节运动 异常ACL是最常见的膝关节韧带损伤。手术韧带重建使用 肌腱移植是ACL撕裂的金标准治疗，但该手术不能恢复正常关节 运动完全，并未能防止PTOA在许多科目。为什么ACL重建在这两个 注意事项不完全理解。来自动物模型和体外实验的大量信息表明， ACL移植物的功能不如自体ACL。第一个指导阶段研究将调查 ACL术后关节运动异常、长期关节损伤和移植物功能受损之间的关系 在临床患者队列中进行重建。将记录跳跃任务期间的准确3D膝关节运动 在一个正在进行的ACL重建前瞻性临床试验中， 结局（NCT 00434837）。将通过磁共振（MR）对软骨和骨损伤进行量化 图像.我们将从MR图像特性估计ACL移植物刚度，并确定 在该临床人群中，关节运动异常与移植物硬度降低有关。使用的数据来自 纵向临床试验将使我们能够量化早期时间点和晚期时间点之间的关节损伤进展。 10-年随访，并根据功能关节和ACL移植物的变化了解这些结构变化 第一次然而，不同的3D解剖结构和ACL移植物的非解剖位置 也可能导致我们预期在临床上观察到的残余异常关节运动。因此 第二个独立阶段研究将使用ACL重建动物模型和相同的MR成像 指导临床研究中使用的技术，以研究ACL移植物变化的时间过程 生物力学性能，同时使用天然ACL作为“移植物”。这项技术模拟了重要的 骨钻孔和移植物固定方面的临床ACL重建，但避免了混淆 肌腱移植物与自体韧带在解剖和功能上的差异。ACL“移植物” 在“重建”之前，将评估生物力学特性和关节运动，然后纵向评估 20周独立阶段项目将提供关于韧带功能阈值是否 保持关节运动。指导和独立研究的翻译设计将 解决当前金标准ACL治疗无法预防PTOA的原因，提供工具以监测功能 非侵入性地改变关节和组织，并为新治疗干预提供目标。

PROJECT SUMMARY/ABSTRACT The objective of the proposed studies is to establish whether the rate and severity of post-traumatic osteoarthritis (PTOA) is related to joint motion abnormalities, and whether inferior in vivo anterior cruciate ligament (ACL) graft biomechanical properties are 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 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 function is inferior to that of the native ACL. The first mentored phase study will investigate the relationships between abnormal joint motion, long-term joint damage, and impaired graft function following ACL reconstruction in a clinical patient cohort. Accurate 3D knee joint motion during a hopping task will be recorded in a subset of patients and healthy controls enrolled an ongoing prospective clinical trial of ACL reconstruction outcomes (NCT 00434837). Cartilage and bone damage will be quantified from magnetic resonance (MR) images. We will estimate ACL graft stiffness from the MR image properties, and determine whether the abnormal joint motions are related to inferior graft stiffness in this clinical population. Using data from the longitudinal clinical trial will allow us to quantify joint damage progression between earlier time points and the 10-year follow-up, and to understand these structural changes in light of functional joint and ACL graft changes for the first time. However, different 3D anatomical structure and non-anatomical placement of the ACL graft also likely contribute to the residual abnormal joint motions we expect to observe clinically. Therefore, the second independent phase study will utilize an ACL reconstruction animal model and the same MR imaging techniques used in the mentored clinical study to investigate the time course of changes in ACL graft biomechanical properties while using the native ACL as the “graft”. This technique simulates the important aspects of bone drilling and graft fixation in clinical ACL reconstruction, but circumvents the confounding effects of differences in anatomy and function between tendon graft and native ligament. ACL “graft” biomechanical properties and joint motion will be assessed prior to “reconstruction”, and then longitudinally for 20 weeks. The independent phase project will provide insight as to whether a threshold in ligament function exists that preserves joint motion. The translational design of the mentored and independent studies will address why the current gold standard ACL treatment fails to prevent PTOA, provide tools to monitor functional joint and tissue changes non-invasively, and provide targets for new treatment interventions.