Cross-scale interactions between mineral and collagen for tendon-bone attachment

矿物质和胶原蛋白之间的跨尺度相互作用，用于腱骨附着

• 批准号: 8913701
• 负责人: Guy M Genin
• 金额: $ 46.65万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-20 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8913701
• 关键词: Age; Anterior Cruciate Ligament; Bone Tissue; Clinical; Collagen; Collagen Fiber; Collagen Fibril; Communities; Computer Simulation; Data; Elderly; Electron energy loss spectroscopy; Failure; Fluorescence; Foundations; Future; Geometry; Goals; Healed; Health; Individual; Lead; Length; Ligaments; Maps; Mechanics; Methods; Microscope; Minerals; Modeling; Musculoskeletal; Natural regeneration; Operative Surgical Procedures; Outcome; Pain; Pathologic; Phase; Physiological; Plant Roots; Polarization Microscopy; Property; Raman Spectrum Analysis; Resolution; Rotator Cuff; Scanning Transmission Electron Microscopy Procedures; Source; Stress; Synchrotrons; System; Techniques; Tendon structure; Testing; Tissue Engineering; Tissue Model; Tissues; Transmission Electron Microscopy; Work; X ray diffraction analysis; X-Ray Computed Tomography; X-Ray Diffraction; anterior cruciate ligament reconstruction; base; bone; bone geometry; bone healing; clinical care; clinical practice; clinically relevant; crosslink; data modeling; disability; healing; injured; ligament injury; meetings; millimeter; multi-scale modeling; musculoskeletal injury; nanometer; nanoscale; novel; older patient; repaired; research study; resilience; response; skeletal; tool

DESCRIPTION (provided by applicant): Torn tendons and ligaments often require surgical repair to their bony insertions. A large percentage of these repairs have poor outcomes; for example, up to 94% of surgical rotator cuff repairs fail. At the root of these failures is the fundamental challenge of attaching two materials, tendon and bone, with vastly different mechanical properties. The natural tendon-to-bone insertion involves a number of mechanisms that create a strong and tough attachment. Unfortunately, this tissue degrades with age, and is not regenerated in healing. Our overall goal is to develop a multiscale model of the tendon-to-bone insertion that will lead to (1) tissue toughness metrics that can guide clinical decisions for elderly patients, and (2) foundations for future tissue- engineered surgical grafts. Based on our previous work, we hypothesize that toughening and strengthening mechanisms exist across several length scales, and that these are most pronounced in a the compliant region of tissue between tendon and bone that does not regrow in the healing setting. We will characterize the stiffening, strengthening, and toughening mechanisms that contribute to this resilience across scales in natural and pathologic tendon-to-bone insertions as a function of age. The work involves three aims: (1) At the nanoscale, elemental spatial maps will be acquired using transmission electron microscopy electron energy loss spectroscopy to determine mineral and collagen distributions across the insertion. Individual mineralized collagen fibrils will be mechanically tested; we have recently performed such tests on mammalian collagen fibrils. In silico experiments will identify and quantify deformation mechanisms underlying the toughness of mineralized collagen fibrils. (2) At the microscale, synchrotron X-ray diffraction, Raman spectroscopy, and polarized light microscopy will be used to determine the distributions of mineral content and collagen orientation. Mechanics of the tendon-to-bone insertion will be examined with micrometer resolution using a confocal microscope-mounted testing frame. In silico, nonlinear homogenization methods will be used to incorporate mineralized collagen fiber mechanics from Aim 1 into constitutive models of connected networks of mineralized and cross-linked collagen fibers. (3) At the millimeter scale, the 3D inter-digitation geometry of tendon and bone will be determined using phase contrast X-ray computed tomography and the mechanics of the tendon-to-bone insertion will be determined using tissue level tensile tests. In silico experiments combining tendon-to-bone geometry with microscale tissue models will produce hypotheses of mechanisms underlying tendon-to-bone insertion toughness. Mechanical fields will be passed down hierarchical model levels to evaluate collagen fibril response to predicted physiologic and pathologic tendon-to-bone insertion loading. Together, these models and data form the foundation of future tissue engineering efforts and efforts to identify clinically useful metrics of tendon-to-bone tissue health.

描述（由申请人提供）：撕裂的肌腱和韧带通常需要手术修复其骨插入。这些修复中有很大一部分效果不佳；例如，高达94%的手术肩袖修复失败。这些失败的根源是连接两种材料的根本挑战，肌腱和骨头，具有截然不同的机械性能。肌腱到骨的自然插入涉及许多机制，这些机制创造了一个强大而坚韧的附着。不幸的是，这种组织随着年龄的增长而退化，并且在愈合过程中不能再生。我们的总体目标是建立一个肌腱-骨插入的多尺度模型，这将导致(1)组织韧性指标，可以指导临床决策