Natural Variation in the Growth and Development of the ACL Complex

确定预防前十字韧带(ACL)损伤的危险因素仍然是 肌肉骨骼研究。在美国，儿童和青少年的运动参与度 在过去30年中增加，导致前交叉韧带损伤的发生率更高。ACL的频率 尽管纳入了伤害，但自1994年以来，15岁以下个人的伤害增加了924% 青少年体育预防项目。此外，70%的前交叉韧带损伤发生在执行非接触性操作时 机动动作(如单脚着地、枢轴)。然而，目前尚不清楚这些伤害是否由单一的 超载事件或疲劳故障，其中干预时间段可用。损伤可能是多因素的 并受到个体自然解剖变异的影响。通过重复加载使前交叉韧带疲劳失效， 与个体之间解剖结构的自然差异相结合，在很大程度上被忽视了 作为意外ACL故障的解释机制。我们之前展示了前交叉韧带横截面 面积(CSA)是峰值相对应变的重要预测因子。然而，个体之间的伤害风险不是 由于这一特征有很大程度的变异，很容易被描绘出来。我们假设自然变异 在前交叉韧带中，CSA伴随着组织水平机械特性和/或其他大体的协调变化 共同使“前交叉韧带复合体”(即韧带和它的韧带) 在常规加载条件下具有机械功能。我们进一步假设，这种协调， 虽然有效地建立了前交叉韧带复合体的强度，但可能导致组织水平的变化 有害影响前交叉韧带复合体抗疲劳性能的力学性能 个人。我们将使用反映前交叉韧带复合体自然变异的小鼠模型来检验我们的假设 人类之间的特征。在这项工作完成后，我们将有一个建立的鼠标模型来生成 新的假说，以及对前交叉韧带复合体如何在出生后和 在功能上适应机械负荷。预计这些结果将指导旨在 最大化前交叉韧带强度，同时最大限度地减少儿童和青少年前交叉韧带断裂，并拥有广泛的 对韧带和肌腱损伤经常发生的其他解剖独特位置的积极影响 (例如肩袖、肘部、脊柱)，并可能受到类似的复杂适应系统的影响，其中 特征被协调以建立器官水平的力量和僵硬。

Identifying risk factors to prevent anterior cruciate ligament (ACL) injuries remains a major objective of musculoskeletal research. Athletic participation in the United States among children and adolescents has increased over the last three decades, resulting in a greater prevalence of ACL injuries. The frequency of ACL injuries among individuals under 15 years of age has risen 924% since 1994 despite the incorporation of injury prevention programs in youth sports. Further, 70% of ACL injuries occur while performing non-contact maneuvers (e.g. single foot landings, pivots). Yet, it remains unclear whether these injuries result from a single overload event or a fatigue failure wherein a period of intervention is available. Injuries are likely multifactorial and influenced by an individual’s natural anatomical variation. Fatigue failure of the ACL via repetitive loading, combined with the natural variation in anatomical structure between individuals, has largely been overlooked as an explanatory mechanism for unanticipated ACL failures. We showed previously that ACL cross-sectional area (CSA) is a significant predictor of peak relative strain. However, injury risk between individuals is not easily delineated because of the large degree of variation in this trait. We hypothesize that the natural variation in ACL CSA is accompanied by coordinated changes in tissue-level mechanical properties and/or other gross anatomical features that together allow the ‘ACL-complex’ (i.e. the ligament and its entheses) to be mechanically functional under routine loading conditions. We further hypothesize that this coordination, although effective in establishing the strength of the ACL-complex, may result in changes in tissue-level mechanical properties that deleteriously affect the fatigue resistance of the ACL-complex for certain individuals. We will test our hypotheses using a mouse model that mirrors the natural variation in ACL-complex traits among humans. At the completion of this work we will have an established mouse model for generating new hypotheses, along with a better understanding of how the ACL-complex develops postnatally and functionally adapts to mechanical loads. These outcomes are expected to guide interventions aimed at maximizing ACL strength while minimizing ACL rupture among children and adolescents, and to have a broad positive impact in other anatomically unique locations where ligamentous and tendinous injuries routinely occur (e.g. rotator cuff, elbow, spine) and are likely influenced by a similar complex adaptive system wherein multiple traits are coordinated to establish organ-level strength and stiffness.