Establishing Design Criteria and Large Animal Model for Evaluation of ACL Repair

描述(申请人提供)：在患者中，前十字韧带(ACL)是一种常见的膝关节结构损伤，其术后重建可能失败的病例高达27%。失去前交叉韧带功能可以显著改变关节运动学，在短期和中期会对次级韧带约束造成不利的负荷，长期会导致软骨损伤、退行性关节疾病和骨关节炎。研究人员现在开始准确地描述正常膝关节的三维运动学特征。然而，控制这些运动学的至关重要的3-D组织力仍然不可能在患者身上直接测量，只能通过记录韧带表面应变来推断。可以想象，韧带力可以在动物模型中确定，但前提是：a)在体内同时记录关节运动和组织力传感器的输出，以进行日常生活活动(ADL)；以及b)然后在实验室对这些体内运动进行模拟时，对这些装有仪器的肢体进行校准。在这项资助中，我们建议这样做：在正常和受伤的成年绵羊膝关节上测量多个ADL的活体运动，然后使用机器人在实验室模拟这些ADL，以确定3-D ACL力。这些结果将在一个大型和相关的临床前模型中提供为现有和新的前交叉韧带治疗策略(如组织工程修复)设定设计标准和评估基准的能力。为了满足这些需求并建立在我们初步数据的基础上，我们现在建议在绵羊模型中进行研究，以检查受控内侧副韧带(MCL)损伤和/或内侧半月板切除术(MM)前后垂直地面反作用力(VGRF)、膝关节运动以及膝关节和前交叉韧带总力的活动相关变化。我们目前的研究旨在回答五个重要的研究问题：1)改变正常绵羊膝关节的步态表面倾斜度如何影响这些反应指标(VGRF、膝关节运动、膝盖和前交叉韧带力量)？2)MCL损伤或3)内侧半月板切除对这些测量有何影响？4)MCL损伤和内侧半月板切除联合对这些测量有何影响？5)与两个单独损伤相比，这两种损伤组合如何改变这些反应测量？目的1：研究与平坦和上坡相比，在下坡步态表面上遛羊如何改变正常膝关节VGRF、3-D膝关节运动、前交叉韧带力和总膝力。目的2：确定MCL损伤或内侧半月板切除对术后12周三种步态表面倾斜度和一种速度的所有反应测量的影响。目的3：确定MCL损伤和内侧半月板切除如何影响我们对术后12周相同步态表面倾斜度的反应措施。将这些结果与个人伤害的结果进行比较。

DESCRIPTION (provided by applicant): In patients, the anterior cruciate ligament (ACL) is a frequently injured knee structure and its reconstructions after surgery can fail in up to 27% of cases. Losing ACL function can dramatically alter joint kinematics, causing adverse loading on secondary ligamentous restraints in the short to intermediate term and cartilage damage, degenerative joint disease and osteoarthritis in the longer term. Investigators are now beginning to accurately characterize 3-D kinematics in the normal knee. However, critically important 3-D tissue forces that control these kinematics remain impossible to directly measure in patients and can only be inferred by recording ligament surface strains. Ligament forces can conceivably be determined in animal models, but only if: a) joint motions and tissue force transducer outputs are simultaneously recorded in vivo for activities of daily living (ADLs); and b) these instrumented limbs are then calibrated during simulations of these in vivo motions in the laboratory. In this grant, we propose to do just this: to measure in vivo knee motions for multiple ADLs in the normal and injured adult sheep knee and then use robotics to simulate these ADLs in the laboratory in order to determine the 3-D ACL force. These results will provide, in a large and relevant preclinical model, the ability to set design criteria and evaluation benchmarks for both existing and novel ACL treatment strategies such as tissue engineered repairs. To address these needs and build on our preliminary data, we now propose studies in the sheep model to examine activity-related changes in vertical ground reaction forces (VGRFs), knee motions, and total knee and ACL forces before and after controlled medial collateral ligament (MCL) injury and/or medial meniscectomy (MM). Our current studies are designed to answer five important research questions: 1) How does altering gait surface inclination in the normal sheep knee affect these response measures (VGRFs, knee motions, and knee and ACL forces)? How does 2) MCL injury or 3) medial meniscectomy affect these measures? 4) How does combining MCL injury and medial meniscectomy affect these measures? 5) How does combining these two injuries alter these response measures compared to those for both individual injuries? Aim 1: Examine how, compared to level and uphill surfaces, walking a sheep on a downhill gait surface alters normal knee VGRFs, 3-D knee motions, ACL force, and total knee force. Aim 2: Determine how MCL injury or medial meniscectomy influences all response measures for three gait surface inclinations and one speed at 12 weeks post surgery. Aim 3: Determine how combined MCL injury and medial meniscectomy influence our set of response measures for identical gait surface inclinations at 12 weeks post surgery. Contrast these results with those of the individual injuries.