Natural Variation in the Growth and Development of the ACL Complex

ACL 复合体生长和发育的自然变异

• 批准号: 10231086
• 负责人: Stephen Schlecht
• 金额: $ 24.15万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-21 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10231086
• 关键词: 15 year old; Address; Adolescent; Adult; Affect; Age; Anatomy; Anterior Cruciate Ligament; Applications Grants; Area; Athletic; Atomic Force Microscopy; Biological Markers; Biomedical Engineering; Child; Clinical; Complex; Development; Diagnostic; Elbow; Event; Exercise; Failure; Fatigue; Frequencies; Future; Genotype; Goals; Growth; Growth and Development function; High Pressure Liquid Chromatography; Human; Inbred Mouse; Individual; Individual Differences; Injury; Intervention; Lead; Ligaments; Location; Mechanics; Mentors; Methods; Modeling; Morphology; Mus; Musculoskeletal; Musculoskeletal System; Organ; Outcome; Phase; Phenotype; Population; Predisposition; Prevalence; Prevention program; Process; Raman Spectrum Analysis; Research; Resistance; Risk; Risk Factors; Rotator Cuff; Structure; Study models; System; Testing; Tissues; Training; Translating; United States; Variant; Vertebral column; Work; anterior cruciate ligament injury; anterior cruciate ligament rupture; bone; emerging adult; foot; functional adaptation; high risk; in vivo; injury prevention; mechanical load; mechanical properties; mouse model; novel strategies; postnatal; postnatal development; prevent; response; trait; youth sports

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.

确定防止前交叉韧带（ACL）损伤的危险因素仍然是 肌肉骨骼研究。在儿童和青少年参加美国的体育参与 在过去的三十年中，增加了ACL损伤的率更高。 ACL的频率 自1994年以来，15岁以下个人的伤害增长了924％ 青年运动中的预防计划。此外，执行非接触术时发生了70％的ACL损伤 演习（例如，单足着陆，枢轴）。然而，尚不清楚这些伤害是否是由单个伤害造成的 超负荷事件或疲劳失败，其中有一段时间的干预期。受伤可能是多因素的 并受个人自然解剖变化的影响。 ACL通过重复负载的疲劳失败， 结合个体之间的解剖结构的自然变化，很大程度上被忽略了 作为意外ACL失败的爆炸性机制。我们先前证明了ACL横截面 面积（CSA）是峰值相对应变的重要预测指标。但是，个人之间的伤害风险不是 由于该性状的变化很大，因此很容易被描绘。我们假设自然变化 在ACL中，CSA是通过组织级机械性能和/或其他总体的协调变化来完成的 解剖学特征共同允许“ ACL-Complex”（即韧带及其热情）成为 在常规加载条件下机械起作用。我们进一步假设这种协调， 尽管有效地建立了ACL复合物的强度，但可能会导致组织级别的变化 在某些方 个人。我们将使用鼠标模型测试我们的假设，该模型反映了ACL复合物的自然变化 人类中的特征。完成这项工作时，我们将拥有一个已建立的鼠标模型来生成 新的假设，以及更好地了解ACL复合事件的发展方式和 在功能上适应机械载荷。这些结果有望指导针对的干预措施 最大化ACL强度，同时最大程度地减少儿童和青少年的ACL破裂，并具有广泛的 在其他解剖学独特的位置的积极影响，常规发生韧带和肌腱损伤 （例如肩袖，肘，脊柱），并且可能受到类似的复合自适应系统的影响，其中多个 特征是协调的，以建立器官水平的强度和刚度。

项目成果

An Adolescent Murine In Vivo Anterior Cruciate Ligament Overuse Injury Model.

青少年小鼠体内前十字韧带过度使用损伤模型。

• DOI: 10.1177/03635465231165753
• 发表时间: 2023
• 期刊: The American journal of sports medicine
• 作者: Loflin,BenjaminE;Ahn,Taeyong;Colglazier,KaitlynA;BanaszakHoll,MarkM;Ashton-Miller,JamesA;Wojtys,EdwardM;Schlecht,StephenH
• 通讯作者: Schlecht,StephenH

Endurance running during late murine adolescence results in a stronger anterior cruciate ligament and flatter posterior tibial slopes compared to controls.

• DOI: 10.1186/s40634-021-00439-7
• 发表时间: 2022-01-03
• 期刊: Journal of experimental orthopaedics
• 影响因子: 1.8
• 作者: Ochocki DN;Loflin BE;Ahn T;Colglazier KA;Young AR;Snider AA;Bueckers EP;Wojtys EM;Schlecht SH
• 通讯作者: Schlecht SH