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.

项目概要/摘要 肩袖肌腱撕裂影响多达 64% 的成年人，导致肌肉发生变化，从而驱动功能 残疾和不良的临床结果与肌肉萎缩和脂肪浸润有关。 （肌肉中脂肪的累积），肌肉内脂肪浸润的非均匀分布，以及 肌肉力量和收缩功能的降低可能会产生负面影响。 肌肉的结构（肌纤维的数量和组织）和机械性能 然而，人们对其中的联系机制知之甚少。 肌肉结构和功能或这些关联如何随时间变化，揭示值得注意的知识 建立肩袖撕裂后肌肉的结构与功能关联将暴露目标。 以及设计治疗方法以改善肩袖撕裂患者预后的关键时间点。 该项目的目标是确定肌肉形态、结构、 肩袖撕裂和手术修复后的多尺度力学，并开发预测模型来识别 为了实现这一目标，需要进行纵向实验评估。 将在已建立的兔子模型中进行；还将基于 肌肉的实验结构测量，以进一步探讨肌肉功能的机制。 具体来说，该项目旨在： 1）建立肩袖后肌肉的结构-功能关系 撕裂和手术修复；2) 开发和测试预测模型来检查驱动减少的机制 肩袖撕裂后的生物力学功能 将通过钝器手术将肩袖撕裂引入兔子体内。 冈上肌腱的解剖，在手术修复后 2、4、6 和 8 周进行评估； 将在受伤后 8 周进行，并在修复后 8 周对每个时间点的肌肉进行最终评估。 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）对整个肌肉和单个肌肉进行多尺度力学评估。 纤维水平。结构-功能关联以及这些关联如何随时间变化。 肌肉形态、结构和力学的结构测量将用于开发和测试 预测模型来探讨每个结构参数对生物力学功能的机械作用。 将用于确定治疗的目标机制和时机，以改善功能 这项工作意义重大，因为它将建立肌肉的结构与功能关系。 肩袖撕裂和手术修复，并确定支撑生物力学功能的机制。 工作检查了肌肉结构的空间和时间变化，并检查了它们对 函数，使这项工作具有创新性，将扩大我们对旋转器影响的理解。 肩袖撕裂并推动针对肩袖撕裂患者群体的新型治疗方法的开发。