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

降低 ACL 刚度对动态体内关节功能的影响

• 批准号: 9896238
• 负责人: Jillian Elizabeth Beveridge
• 金额: $ 24.74万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-19 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9896238
• 关键词: 3-Dimensional; Acute; Address; Affect; Anatomy; Animal Model; Animals; Anterior; Anterior Cruciate Ligament; Autopsy; Biomechanics; Cartilage; Clinical; Clinical Research; Clinical Trials; Data; Degenerative polyarthritis; Enrollment; Gait; Gold; Image; Imaging Techniques; Impairment; Inferior; Inflammation; Inflammatory; Intervention; Joints; Knee; Knee joint; Ligaments; Light; Limb structure; Longitudinal Studies; Longitudinal cohort; Magnetic Resonance; Magnetic Resonance Imaging; Measures; Mechanics; Mentors; Modeling; Monitor; Morphology; Motion; Operative Surgical Procedures; Outcome; Outcome Measure; Patient Outcomes Assessments; Patients; Phase; Population; Positioning Attribute; Postoperative Period; Procedures; Process; Property; Residual state; Risk; Rotation; Series; Severities; Sheep; Signal Transduction; Structure; Surface; Techniques; Tendon structure; Testing; Time; Tissues; Translations; Work; anterior cruciate ligament reconstruction; anterior cruciate ligament rupture; base; bone; cohort; design; experimental study; follow-up; functional outcomes; graft function; graft healing; imaging properties; improved; in vivo; injured; insight; joint function; joint injury; mechanical properties; patient subsets; preservation; prevent; prospective; reconstruction; sample fixation; standard care; tool; translational model; translational study

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.

项目摘要/摘要 拟议研究的目的是确定创伤后的率和严重性是否 骨关节炎（PTOA）与关节运动异常有关，并且体内较低。 交叉韧带（ACL）移植生物力学特性足以诱导关节运动 紊乱 etc。 ACL是最常见的膝盖韧带。使用A的手术韧带重建 肌腱移植是ACL撕裂的黄金标准处理，但该过程无法恢复正常关节 运动完全，无法防止许多受试者的PTOA。为什么ACL重建在这两个中失败 认为尚未完全理解。来自动物模型和离体实验的许多信息表明 ACL移植功能不如天然ACL的功能。第一次修补阶段研究将调查 ACL之后的关节运动异常，长期关节损伤和移植功能受损之间的关系 临床患者队列中的重建。将记录在跳跃任务期间的准确3D膝关节运动 在一部分患者和健康对照中，ACL重建的前瞻性临床试验招募了 结果（NCT 00434837）。软骨和骨损伤将从磁共振（MR）中量化 图像。我们将估算MR图像特性的ACL移植刚度，并确定是否是否 在该临床人群中，异常关节运动与较低的谷物僵硬有关。使用来自 纵向临床试验将使我们能够量化早期时间点和 10年的随访，并了解功能关节和ACL移植物变化的这些结构变化 首次。但是，ACL移植物的不同3D解剖结构和非解剖学位置 还可能有助于我们期望在临床上观察到的残留异常关节运动。因此， 第二个独立阶段研究将利用ACL重建动物模型和相同的MR成像 修订的临床研究中使用的技术研究了ACL移植的时间过程 使用天然ACL作为“移植”时，生物力学特性。这种技术模拟了重要的 临床ACL重建中骨钻孔和移植固定的各个方面，但绕过混杂的 肌腱移植和天然韧带之间解剖学和功能差异的影响。 ACL“移植” 生物力学特性和关节运动将在“重建”之前进行评估，然后纵向评估 20周。独立阶段项目将提供有关韧带功能阈值的见解 存在可以保留联合运动的情况。指导和独立研究的翻译设计将 解决当前金标准ACL处理无法预防PTOA的原因，提供监控功能的工具 关节和组织无创变，并为新的治疗干预措施提供目标。