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

项目摘要 本研究的目的是确定体内下前交叉韧带是否 (ACL)移植物硬度足以引起关节运动异常。ACL是最常见的 膝盖韧带受伤使用肌腱移植物的手术韧带重建是治疗 ACL撕裂，但手术不能完全恢复正常关节运动，也不能防止术后 创伤性骨关节炎（PTOA）。为什么ACL重建在这两个方面失败， 完全理解来自动物模型和离体实验的大量信息表明，ACL移植物 刚度低于原生ACL。临床研究中的一个混杂因素是， ACL移植物的3D解剖结构和非解剖位置可能导致残留异常 已知存在的关节运动。为了避免混杂因素，拟定研究将使用ACL 重建动物模型和一种无创的在体T2* MR成像技术来研究时间 使用自体ACL作为“移植物”时ACL移植物刚度的变化过程。这个手术模型 模拟了临床ACL重建中骨钻孔和移植物固定的重要方面， 引入上述混杂变量。在一项横断面研究设计中，ACL“移植物”刚度 在“重建”之前，然后在第6、12或24周时评估关节活动。使用此 方法，该项目将确定是否存在韧带刚度阈值，以保持关节运动， 以及指导K99研究的结果，将提供新的见解，为什么目前的黄金 标准ACL治疗不能预防PTOA。该项目还产生了新的非侵入性工具来监测 在临床相关模型中的功能性关节和组织变化，同时建立基础， 以测试新的治疗干预措施。转移受援机构并没有改变这些研究 目标，基本上是完整的。该项目的剩余5个月将在新的 该机构的活动旨在增加定量MR成像数据和方法， 记录专门为此研究开发的关节运动。目前计划的传播 通过会议报告和手稿出版物的研究结果将受益于这些建议 活动，并将作为最终研究关闭的一部分进行准备。

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.