Biomechanics of muscle after rotator cuff tear: Multi-scale assessment of spatial and temporal effects

肩袖撕裂后肌肉的生物力学：空间和时间影响的多尺度评估

• 批准号: 10556219
• 负责人: Meghan Elise Vidt
• 金额: $ 46.46万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-02 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10556219
• 关键词: Adult; Affect; Animals; Architecture; Atrophic; Automobile Driving; Biological Assay; Biomechanics; Clinical; Closure by clamp; Computer Models; Development; Dissection; Elements; Euthanasia; Failure; Fascicle; Fatty acid glycerol esters; Fiber; Generations; Goals; In Vitro; Individual; Infiltration; Inflammation; Injury; Intervention; Knowledge; Link; Lipids; Location; MRI Scans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Mechanics; Modeling; Morphology; Multiscale Mechanics; Muscle; Muscle Fibers; Muscle function; Muscular Atrophy; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Outcome Study; Patient-Focused Outcomes; Patients; Property; Role; Rotator Cuff; Structure; Structure-Activity Relationship; Tendon structure; Testing; Time; Work; design; extracellular; functional disability; functional improvement; improved; improved outcome; innovation; mechanical properties; muscle form; muscle stiffness; muscular structure; novel; patient population; predictive modeling; reduced muscle strength; repaired; rotator cuff tear; spatiotemporal; supraspinatus muscle; targeted treatment; therapy design

PROJECT SUMMARY/ABSTRACT A rotator cuff tendon tear affects up to 64% of adults, resulting in muscular changes that drive functional disability and poor clinical outcomes. Rotator cuff tears are associated with muscle atrophy and fatty infiltration (accrual of fat in the muscle bulk), non-homogenous distribution of fatty infiltration within the muscle, and reduced muscle strength and contractile function. Changes to muscle morphology likely have a negative effect on the muscle’s architecture (number and organization of muscle fibers) and the mechanical properties dictating the muscle’s overall force-generating capacity. However, little is known about the mechanisms linking muscle structure and function or how these associations change over time, exposing a notable knowledge gap. Establishing the structure-function associations of muscle after rotator cuff tear will expose the targets and key time points for design of treatments to improve outcomes for patients with a rotator cuff tear. Thus, the objective of this project is to determine the spatial and temporal changes to muscle morphology, architecture, and multi-scale mechanics after rotator cuff tear and surgical repair, and develop a predictive model to identify the mechanisms driving biomechanical function. To achieve this goal, longitudinal experimental assessments will be performed in an established rabbit model; a novel computational model will also be developed based on experimental structural measurements of muscle to further probe the mechanisms of muscle function. Specifically, this project aims to: 1) Establish the structure-function relationships of muscle after rotator cuff tear and surgical repair; and 2) Develop and test a predictive model to examine mechanisms driving reduced biomechanical function after rotator cuff tear. A rotator cuff tear will be surgically introduced in rabbits by blunt dissection of the supraspinatus tendon, with assessments at 2, 4, 6, and 8 weeks after injury; surgical repair will be performed 8 weeks after injury, with a final assessment 8 weeks after repair. At each time point, muscle morphology and architecture, and intra- versus extra-cellular location of lipid accumulation will be quantified using magnetic resonance imaging (MRI). Multi-scale mechanics will be assessed at whole muscle and single fiber levels. Structure-function associations and how these associations change over time will be established. Structural measures of muscle morphology, architecture, and mechanics will be used to develop and test a predictive model to probe the mechanistic role of each structural parameter on biomechanical function. Models will be used to determine the mechanism and timing that should be targeted by treatment to improve functional outcomes. This work is significant because it will establish the structure-function relationship of muscle after rotator cuff tear and surgical repair and identify the mechanisms underpinning biomechanical function. Little work has examined both spatial and temporal changes to muscle structure and examined their influence on function, making this work innovative. Study outcomes will expand our understanding of the impact of rotator cuff tear and drive development of novel treatments for the rotator cuff tear patient population.

项目摘要/摘要 肩袖肌腱撕裂会影响多达64％的成年人，导致肌肉变化驱动功能 残疾和临床结果不佳。肩袖撕裂与肌肉萎缩和脂肪浸润有关 （肌肉大量脂肪的应计），肌肉内脂肪浸润的非遗传分布，以及 肌肉力量和收缩功能降低。肌肉形态的变化可能会产生负面影响 关于肌肉的建筑（肌肉纤维的数量和组织）和机械性能 决定肌肉的总体产生能力。但是，关于链接的机制知之甚少 肌肉结构和功能或这些关联如何随着时间而变化，暴露了知名度 差距。建立肩袖撕裂后肌肉的结构功能关联将暴露目标 以及设计治疗的关键时间点，以改善肩袖撕裂患者的预后。那， 该项目的目的是确定肌肉形态，建筑，临时变化 肩袖撕裂和手术修复后的多尺度力学，并开发一个预测模型以识别 驱动生物力学功能的机制。为了实现这一目标，纵向实验评估 将在既定的兔子模型中进行；还将根据 肌肉的实验结构测量，以进一步探测肌肉功能的机制。 具体而言，该项目的目的是：1）建立肩袖后肌肉的结构功能关系 撕裂和手术修复； 2）开发和测试一个预测模型以检查降低的机制 肩袖撕裂后的生物力学功能。 Bluet将在兔子中通过手术引入肩袖撕裂 在受伤后2、4、6和8周的评估时进行解剖。手术修复 受伤后8周将进行，并在修复后8周进行最终评估。在每个时间点，肌肉 形态和结构以及脂质积累的细胞内与细胞外位置将被量化 使用磁共振成像（MRI）。将在整个肌肉和单一的肌肉中评估多尺度机械师 纤维水平。结构功能关联以及这些关联将如何随着时间的推移而变化。 肌肉形态，建筑和力学的结构测量将用于开发和测试 预测模型探测每个结构参数在生物力学函数上的机械作用。型号 将用于确定应通过治疗来针对改善功能的机制和时机 结果。这项工作很重要，因为它将建立肌肉的结构功能关系 肩袖撕裂和手术修复，并确定生物力学功能支撑的机制。小的 工作已经检查了肌肉结构的空间和临时变化，并检查了它们对 功能，使这项工作创新。研究成果将扩大我们对旋转器影响的理解 袖口撕裂并推动肩袖撕裂患者种群的新型治疗方法的发展。