Multi-faceted Approach to Modeling ACL Injury Mechanisms

前交叉韧带（ACL）损伤是一个主要的医疗和经济负担。尽管鉴定出 可改变的危险因素和有效的预防措施，全球ACL损伤的发生率仍然很大程度上 不受影响在父母的资助下，我们确定了ACL损伤的合理外翻塌陷机制， 伴随内侧副韧带（MCL）损伤。我们在以下条件下开发了一种新型尸体测试装置： 一项由基金资助的研究表明，ACL撕裂率接近90%。我们的研究结果表明，联合膝关节 外展力矩（KAM）、胫骨前剪切力（ATS）和胫骨内旋转力矩（ITR）产生 ACL的应变显著大于MCL，并再现了与观察到的运动学相似的运动学 在ACL损伤期间。虽然这些类型的负荷，在孤立的情况下，增加ACL应变和潜在的受伤风险， 它们对ACL生物力学的联合作用还没有被很好地理解。在此竞争性更新应用程序中， 将制定一个高度有效和独特的ACL损伤风险评估方案， 生物力学该方案将通过一种新的、整合的体内、体外和计算机模拟（in sim） approach.具体目标是：I）开发并验证多平面ACL损伤风险评估 基于动态ACL应变预测ACL损伤风险的算法，以及II）为了在体内、体外和体内整合， silico方法来建立一个“连续的风险”，占KAM，ITR， ATS至ACL断裂。两个目标之间的关键区别是生物力学背景： 确定在实验室进行的非损伤性筛查任务中ACL的应变情况 或临床环境。目的II将建立高应变运动模式和ACL损伤之间的直接联系 机制。我们假设：I）来自体内数据的KAM、ITR和ATS的峰值输入值将 当着陆生物力学在体外和计算机中重现时，准确预测峰值ACL应变，以及II） KAM、ITR和ATS的增量增加（从“高风险”体内测量值缩放）将导致ACL断裂 体外和计算机模拟。在具体目标I中，多平面运动学和动力学将直接用作我们的 经验证的性别特异性粘弹性FE膝关节模型和体外试验方案，以检验我们的假设。我们将 还旨在识别和验证KAM，ITR和ATS的简单，基于临床的预测因子，以最大限度地提高 方案的临床适用性。在Aim II中，我们将直接检查KAM、ITR和胫骨前部的作用。 ACL断裂的可能性。KAM、ATS和ITR的高风险体内值将递增 增加直至在尸体中达到组织失效，或在FE模型中达到ACL失效应变。 此外，在Aim II中，我们将通过验证方法来优化FE建模方法， 自定义模型，考虑解剖结构和组织力学的变化。这项研究将大大 提高研究人员和临床医生有效筛查运动员ACL损伤风险的能力， 增加ACL损伤预防计划的注册人数和有效性。

Anterior cruciate ligament (ACL) injury is a major medical and financial burden. Despite identification of modifiable risk factors and effective preventive measures, global ACL injury incidence remains largely unaffected. Under the parent grant we identified plausible valgus collapse mechanisms for ACL injury without concomitant medial collateral ligament (MCL) injury. A novel cadaveric testing setup we developed under the funded grant has demonstrated a nearly 90% rate of ACL tear. Our findings show that combined knee abduction moment (KAM), anterior tibial shear force (ATS) and internal tibial rotation moment (ITR) generates significantly greater strain in the ACL relative to the MCL, and reproduces kinematics similar to those observed during ACL injury. While these types of loading, in isolation, increase ACL strain and potentially risk of injury, their combined effects on ACL biomechanics are not well understood. In this competing renewal application we will develop a highly impactful and unique ACL injury risk assessment protocol that accounts for multiplanar biomechanics. The protocol will be developed through a novel, integrative in vivo, in vitro and in silico (in sim) approach. The Specific Aims are: I) To develop and validate a multiplanar ACL injury risk assessment algorithm that predicts ACL injury risk based on dynamic ACL strain, and II) To integrate in vivo, in vitro and in silico approaches to establish a 'continuum of risk' that accounts for the relative contributions of KAM, ITR, and ATS to ACL rupture. The critical distinction between the two Aims is the biomechanical context: Aim I will determine how the ACL is strained during non-injurious screening tasks that can be performed in a laboratory or clinical setting. Aim II will establish a direct link between high strain movement patterns and the ACL injury mechanism(s). We hypothesize that: I) Peak input values of KAM, ITR, and ATS from in vivo data will accurately predict peak ACL strain when landing biomechanics are reproduced in vitro and in silico, and II) Incremental increases in KAM, ITR and ATS, scaled from 'high-risk' in vivo measures will lead to ACL rupture in vitro and in silico. In Specific Aim I, multi-planar kinematics and kinetics will be directly used as inputs to our validated, sex-specific, viscoelastic FE knee models and in vitro test protocols to test our hypotheses. We will also aim to identify and validate simple, clinically-based predictors for KAM, ITR, and ATS to maximize the clinical applicability of the protocol. In Aim II, we will directly examine the roles of KAM, ITR and anterior tibial shear on the likelihood of ACL rupture. High-risk in vivo values for KAM, ATS, and ITR will be incrementally increased until tissue failure is achieved in cadavers, or ACL failure strains are reached in FE models. Furthermore, in Aim II we will optimize our FE modeling approach through validation of a methodology to customize models that accounts for variability in anatomy and tissue mechanics. This research will significantly improve the ability of researchers and clinicians to effectively screen athletes for ACL injury risk, and will increase ACL injury prevention program enrollment and efficacy.