Multiscale structural and mechanical analysis of soft tissue under complex loads

复杂载荷下软组织的多尺度结构和力学分析

• 批准号: 8402492
• 负责人: Spencer Park Lake
• 金额: $ 3.37万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8402492
• 关键词: Architecture; Behavior; Biological Models; Biomedical Engineering; Cells; Collagen; Collagen Fiber; Collagen Type I; Complex; Computer Simulation; Connective and Soft Tissue; Data; Development; Drug Formulations; Environment; Evaluation; Extracellular Matrix; Fiber; Future; Gel; Glycosaminoglycans; Human; Image; Injury; Length; Location; Mechanical Stress; Mechanics; Modeling; Modification; Nature; Pain; Property; Proteoglycan; Protocols documentation; Relative (related person); Reporting; Research; Rotator Cuff; Sampling; Scientist; Sepharose; Shoulder; Simulate; Soft Tissue Injuries; Structure; System; Techniques; Tendon structure; Testing; Thick; Tissues; Weight; Weight-Bearing state; analog; disability; experience; experimental analysis; in vivo; injured; insight; interest; mechanical behavior; multi-scale modeling; novel; organizational structure; polarized light; prevent; public health relevance; repaired; response; soft tissue; supraspinatus muscle

DESCRIPTION (provided by applicant): Soft tissues have complex mechanical properties that depend largely on their underlying structural organization. However, the relationship between microscale (collagen) properties and macroscale (tissue) behavior remains unclear. A multiscale modeling approach, which relates these two scales directly, was recently applied successfully to evaluate biaxial tensile testing of cell-seeded collagen Type I gels (tissue- equivalents, or TEs). TEs are particularly useful model systems whose compositional and organizational properties can be easily modified. Unfortunately, these tissue analogs have not been used to fully evaluate more complex loading protocols such as those experienced by many tissues in vivo, including compression and shear forces. One example is the supraspinatus tendon (SST) of the rotator cuff, which has a high rate of degeneration and injury that may be due to the complex loading environment of the shoulder. As a bridge to evaluating the SST (and other soft tissues that function in multiaxial loading environments), the use of TEs will allow for the development, testing, and analysis of progressively more complex systems. For example, a recent study that added agarose during collagen gel formation reported an increase in tissue stiffness with minimal changes to collagen fiber architecture. This presents a valuable modification to the TE model system, by enabling us to investigate the mechanical and structural contribution of non-collagenous extracellular matrix (ECM) (e.g., proteoglycans, glycosaminoglycan, etc.) to tissue properties. Therefore, the objective of this study is to characterize the three-dimensional behavior of soft tissues under complex loads by quantifying the mechanical and structural properties of organizationally- and compositionally-varying tissue-equivalents (TEs) using experimental analysis and multiscale modeling. We hypothesize that differences in the microscale collagen fiber organization and the relative stiffness of the non-collagenous ECM components (represented by agarose) will result in large changes in the macroscale mechanical and localized structural response of TEs in complex loading (i.e., indentation and shear). The following aims are proposed: Specific Aim #1: Fabricate tissue-equivalents (TEs) of varying organizational structure (collagen fiber alignment) and composition (collagen-only or collagen-agarose), and quantify their three-dimensional structural and mechanical properties under complex loading conditions (i.e., indentation and shear). Specific Aim #2: Utilize multiscale computational models of three-dimensional TE behavior to characterize the relationships among structural, compositional and mechanical properties. This study will provide valuable insight into the nature of, and relationships between, the mechanical, structural and compositional properties of TEs, which will lay the necessary groundwork for future experimental and computational evaluations of similar properties in healthy and injured native tissues. Such studies will provide data that will greatly aid clinicians and scientists in strategies for treating, repairing, or replacing soft tissues. PUBLIC HEALTH RELEVANCE: Degeneration and injury of soft tissues commonly result in pain and disability, and the inability to effectively prevent or treat these injuries is likely due to an incomplete understanding of tissue properties on multiple length-scales. The purpose of this study is to use mechanical/structural analyses and computer modeling to evaluate the microscale and macroscale properties of bioengineered tissue analogs, which present a simplified model system for native tissues. This study will provide valuable insight into the nature of, and relationships between, the mechanical, structural and compositional properties of tissue-equivalents, which will lay the necessary groundwork for future evaluations of similar properties in healthy and injured native tissues. Such studies will provide data that will greatly aid clinicians and scientists in strategies for treating, repairing, or replacing soft tissues.

描述(申请人提供)：软组织具有复杂的机械性能，这在很大程度上取决于其潜在的结构组织。然而，微观尺度(胶原蛋白)特性和宏观尺度(组织)行为之间的关系仍不清楚。最近，一种将这两个尺度直接联系起来的多尺度建模方法被成功地应用于评估细胞种植的I型胶原凝胶(组织等效物，或TES)的双向拉伸测试。TES是特别有用的模型系统，其组成和组织属性可以很容易地进行修改。不幸的是，这些组织类似物还没有被用来完全评估更复杂的加载方案，例如许多组织在体内经历的加载方案，包括压缩和剪切力。一个例子是肩袖的冈上肌腱(SST)，它有很高的退行性和损伤率，这可能是由于肩部复杂的负荷环境所致。作为评估SST(和其他在多轴载荷环境中起作用的软组织)的桥梁，TES的使用将允许开发、测试和分析逐渐复杂的系统。例如，最近的一项研究报告说，在胶原胶形成过程中加入琼脂糖可以增加组织的硬度，而对胶原纤维的结构影响很小。这是对TE模型系统的一个有价值的修改，使我们能够研究非胶原性细胞外基质(ECM)(例如蛋白多糖、糖胺多糖等)的机械和结构贡献。与组织属性有关。因此，本研究的目的是通过使用实验分析和多尺度建模来量化组织和成分变化的组织等效物(TES)的力学和结构特性，从而表征软组织在复杂载荷下的三维行为。我们假设，微尺度的胶原纤维组织和非胶原质ECM成分(以琼脂糖为代表)的相对硬度的不同将导致TES在复杂载荷(即压痕和剪切)下的宏观力学和局部结构响应的巨大变化。具体目标1：制备不同组织结构(胶原纤维排列)和组成(单纯胶原或胶原-琼脂糖)的组织等效物，并量化其在复杂加载条件下的三维结构和力学性能(即压痕和剪切)。具体目标#2：利用三维TE行为的多尺度计算模型来表征结构、成分和机械性能之间的关系。这项研究将对TES的力学、结构和组成特性的性质及其之间的关系提供有价值的见解，这将为未来在健康和受伤的自然组织中进行类似特性的实验和计算评估奠定必要的基础。这类研究提供的数据将极大地帮助临床医生和科学家制定治疗、修复或替换软组织的策略。 公共卫生相关性：软组织的退化和损伤通常会导致疼痛和残疾，而无法有效地预防或治疗这些损伤很可能是由于对多个长度尺度上的组织特性的不完全了解。本研究的目的是利用力学/结构分析和计算机模拟来评估生物工程组织类似物的微观和宏观性质，从而为天然组织提供一个简化的模型系统。这项研究将对组织等效物的机械、结构和组成特性的性质及其之间的关系提供有价值的见解，这将为未来评估健康和受损的天然组织的类似特性奠定必要的基础。这类研究提供的数据将极大地帮助临床医生和科学家制定治疗、修复或替换软组织的策略。