Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, United States; Department of Mechanical Science and Engineering, University of Illinois Urbana-Champaign, Urbana, IL, United States.
Department of Mechanical Engineering, University of Colorado Boulder, Boulder, CO, United States; Biomedical Engineering Program, University of Colorado Boulder, Boulder, CO, United States; BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, United States.
Acta Biomater. 2023 Sep 15;168:252-263. doi: 10.1016/j.actbio.2023.07.002. Epub 2023 Jul 9.
Soft tissue injuries (such as ligament, tendon, and meniscus tears) are the result of extracellular matrix damage from excessive tissue stretching. Deformation thresholds for soft tissues, however, remain largely unknown due to a lack of methods that can measure and compare the spatially heterogeneous damage and deformation that occurs in these materials. Here, we propose a full-field method for defining tissue injury criteria: multimodal strain limits for biological tissues analogous to yield criteria that exist for crystalline materials. Specifically, we developed a method for defining strain thresholds for mechanically-driven fibrillar collagen denaturation in soft tissues, using regional multimodal deformation and damage data. We established this new method using the murine medial collateral ligament (MCL) as our model tissue. Our findings revealed that multiple modes of deformation contribute to collagen denaturation in the murine MCL, contrary to the common assumption that collagen damage is driven only by strain in the direction of fibers. Remarkably, hydrostatic strain (computed here with an assumption of plane strain) was the best predictor of mechanically-driven collagen denaturation in ligament tissue, suggesting crosslink-mediated stress transfer plays a role in molecular damage accumulation. This work demonstrates that collagen denaturation can be driven by multiple modes of deformation and provides a method for defining deformation thresholds, or injury criteria, from spatially heterogeneous data. STATEMENT OF SIGNIFICANCE: Understanding the mechanics of soft tissue injuries is crucial for the development of new technology for injury detection, prevention, and treatment. Yet, tissue-level deformation thresholds for injury are unknown, due to a lack of methods that combine full-field measurements of multimodal deformation and damage in mechanically loaded soft tissues. Here, we propose a method for defining tissue injury criteria: multimodal strain thresholds for biological tissues. Our findings reveal that multiple modes of deformation contribute to collagen denaturation, contrary to the common assumption that collagen damage is driven by strain in the fiber direction alone. The method will inform the development of new mechanics-based diagnostic imaging, improve computational modeling of injury, and be employed to study the role of tissue composition in injury susceptibility.
软组织损伤（如韧带、肌腱和半月板撕裂）是细胞外基质因组织过度拉伸而损伤的结果。然而，由于缺乏能够测量和比较这些材料中发生的空间异质损伤和变形的方法，软组织的变形阈值在很大程度上仍然未知。在这里，我们提出了一种定义组织损伤标准的全场方法：类似于晶体材料中存在的屈服标准的生物组织的多模态应变极限。具体来说，我们开发了一种方法，用于定义软组织结构中纤维状胶原蛋白变性的应变阈值，该方法使用区域多模态变形和损伤数据。我们使用鼠内侧副韧带 (MCL) 作为我们的模型组织来建立这种新方法。我们的研究结果表明，与纤维方向应变驱动胶原蛋白损伤的常见假设相反，多种变形模式有助于鼠 MCL 中的胶原蛋白变性。值得注意的是，静水应变（此处通过平面应变假设计算）是韧带组织中机械驱动胶原蛋白变性的最佳预测因子，这表明交联介导的应力传递在分子损伤积累中起作用。这项工作表明，胶原蛋白变性可以由多种变形模式驱动，并提供了一种从空间异质数据定义变形阈值或损伤标准的方法。
了解软组织损伤的力学机制对于开发用于损伤检测、预防和治疗的新技术至关重要。然而，由于缺乏结合机械加载软组织结构的全场多模态变形和损伤测量的方法，组织水平的损伤阈值仍然未知。在这里，我们提出了一种定义组织损伤标准的方法：生物组织的多模态应变阈值。我们的发现表明，与纤维方向应变驱动胶原蛋白损伤的常见假设相反，多种变形模式有助于胶原蛋白变性。该方法将为新的基于力学的诊断成像的发展提供信息，改进损伤的计算建模，并用于研究组织成分在损伤易感性中的作用。
