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

描述（由申请人提供）：在患者中，前交叉韧带（ACL）是一个经常受伤的膝关节结构，手术后其重建可在高达27%的病例中失败。失去前交叉韧带功能会极大地改变关节的运动学，在中短期内造成次级韧带约束的不利负荷，在长期内造成软骨损伤、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盖的三维运动学。然而，控制这些运动学的至关重要的3-D组织力仍然无法在患者中直接测量，只能通过记录韧带表面应变来推断。可以想象，在动物模型中可以确定韧带力，但前提是：a)关节运动和组织力传感器输出同时在体内记录日常生活活动（ADLs）；b)在实验室模拟这些体内运动时，对这些仪器化的肢体进行校准。在这项资助中，我们建议这样做：在正常和受伤的成年羊膝盖上测量多个adl的体内膝盖运动，然后使用机器人技术在实验室中模拟这些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，为现有和新的ACL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我们的初步数据，我们现在提出在绵羊模型中研究活动相关的垂直地面反作用力（VGRFs），膝关节运动，以及控制内侧副韧带（MCL）损伤和/或内侧半月板切除术（MM）前后的膝关节和ACL力的变化。我们目前的研究旨在回答五个重要的研究问题：1)改变正常羊膝的步态表面倾斜度如何影响这些反应测量（vgrf，膝关节运动，膝关节和前交叉韧带力）？MCL损伤或内侧半月板切除术如何影响这些措施？4) MCL损伤联合内侧半月板切除术对这些措施有何影响？5)与两种损伤相比较，两种损伤相结合会如何改变这些反应指标？目的1：检查与水平和上坡表面相比，在下坡步态表面上走羊如何改变正常的膝关节vgrf、3d膝关节运动、前交叉韧带力和膝关节总力。目的2：确定术后12周MCL损伤或内侧半月板切除术对三种步态表面倾斜和一种速度的所有反应测量的影响。目的3：确定联合MCL损伤和内侧半月板切除术对术后12周相同步态表面倾斜度的反应测量的影响。将这些结果与个体损伤的结果进行对比。

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. PUBLIC HEALTH RELEVANCE: Measuring ligament forces and motions for different ADLs in a large animal model will permit us to study existing and novel treatment strategies for ACL reconstruction. This proposed research serves as the platform for subsequent investigation into ACL injury and reconstruction so we can develop more rational reconstruction strategies for common orthopaedic injuries.