While collagen is recognized as the predominant mechanical component of soft connective tissues, the role of the non-fibrillar matrix (NFM) is less well understood. Even model systems, such as the collagen-agarose co-gel, can exhibit complex behavior, making it difficult to identify relative contributions of specific tissue constituents. In the present study, we developed a two-component microscale model of collagen-agarose tissue analogs and used it to elucidate the interaction between collagen and NFM in uniaxial tension. Collagen fibers were represented with Voronoi networks, and the NFM was modeled as a neo-Hookean solid. Model predictions of total normal stress and Poisson’s ratio matched experimental observations well (including high Poisson’s values of ~3), and the addition of NFM led to composition-dependent decreases in volume change and increases in fiber stretch. Because the NFM was more resistant to volume change than the fiber network, extension of the composite led to pressurization of the NFM. Within a specific range of parameter values (low shear modulus and moderate Poisson’s ratio), the magnitude of the reaction force decreased relative to this pressurization component resulting in a negative (compressive) NFM stress in the loading direction, even though the composite tissue was in tension.

Excessive tissue-level forces communicated to the microstructure and extracellular matrix of soft tissues can lead to damage and failure through poorly understood physical processes that are multiscale in nature. In this work, we propose a multiscale mechanical model for the failure of collagenous soft tissues that incorporates spatial heterogeneity in the microstructure and links the failure of discrete collagen fibers to the material response of the tissue. The model, which is based on experimental failure data derived from different collagen gel geometries, was able to predict the mechanical response and failure of type I collagen gels, and it demonstrated that a fiber-based rule (at the micrometer scale) for discrete failure can strongly shape the macroscale failure response of the gel (at the millimeter scale). The model may be a useful tool in predicting the macroscale failure conditions for soft tissues and engineered tissue analogs. In addition, the multiscale model provides a framework for the study of failure in complex fiber-based mechanical systems in general.

Ascending thoracic aortic aneurysms (ATAA) have a high propensity for dissection, which occurs when the hemodynamic load exceeds the mechanical strength of the aortic media. Despite our recognition of this essential fact, the complex architecture of the media has made a predictive model of medial failure-even in the relatively simple case of the healthy vessel-difficult to achieve. As a first step towards a general model of ATAA failure, we characterized the mechanical behavior of healthy ascending thoracic aorta (ATA) media using uniaxial stretch-to-failure in both circumferential (n ¼ 11) and axial (n ¼ 11) orientations and equibiaxial extensions (n ¼ 9). Both experiments demonstrated anisotropy, with higher tensile strength in the circumferential direction (2510 6 439.3 kPa) compared to the axial direction (750 6 102.6 kPa) for the uniaxial tests, and a ratio of 1.44 between the peak circumferential and axial loads in equibiaxial extension. Uniaxial tests for both orientations showed macroscopic tissue failure at a stretch of 1.9. A multiscale computational model, consisting of a realistically aligned interconnected fiber network in parallel with a neo-Hookean solid, was used to describe the data; failure was modeled at the fiber level, with an individual fiber failing when stretched beyond a critical threshold. The best-fit model results were within the 95% confidence intervals for uniaxial and biaxial experiments, including both prefailure and failure, and were consistent with properties of the components of the ATA media.

A tissue's microstructure determines its failure properties at larger length scales, but the specific relationship between microstructure and macroscopic failure in native and engineered soft tissues (such as capsular ligaments, aortic aneurysms, or vascular grafts) has proven elusive. In this study, variations in the microscale fiber alignment in collagen gel tissue analogs were modeled in order to understand their effects on macroscale damage and failure outcomes. The study employed a multiscale finite-element (FE) model for damage and failure in collagen-based materials. The model relied on microstructural representative volume elements (RVEs) that consisted of stochastically-generated networks of discrete type-I collagen fibers. Fiber alignment was varied within RVEs as well as between layers of RVEs in a macroscopic FE model of a notched dogbone geometry. The macroscale stretch and the microscale response of fibers for each of the differently aligned cases was compared as the dogbone was uniaxially extended to failure. Networks with greater fiber alignment parallel to the direction of extension failed at smaller strains (with a 6–22% reduction in Green strain at failure) but greater grip forces (28–60% increase) than networks with fibers aligned perpendicular to the extension. Alternating layers of crisscrossed network alignments (aligned +/− 45 degrees to the direction of extension) failed at smaller strains but at greater grip forces than those created using one fiber alignment type. In summary, variations in microscale structure via fiber alignment produced different macroscale failure trends. These findings, to conclude, may be significant in the realm of tissue engineering and in soft tissue biomechanics.

Recent work has demonstrated that enzymatic degradation of collagen fibers exhibits strain-dependent kinetics. Conceptualizing how the strain dependence affects remodeling of collagenous tissues is vital to our understanding of collagen management in native and bioengineered tissues. As a first step towards this goal, the current study puts forward a multiscale model for enzymatic degradation and remodeling of collagen networks for two sample geometries we routinely use in experiments as model tissues. The multiscale model, driven by microstructural data from an enzymatic decay experiment, includes an exponential strain-dependent kinetic relation for degradation and constant growth. For a dogbone sample under uniaxial load, the model predicted that the distribution of fiber diameters would spread over the course of degradation because of variation in individual fiber load. In a cross-shaped sample, the central region, which experiences smaller, more isotropic loads, showed more decay and less spread in fiber diameter compared to the arms. There was also a slight shift in average orientation in different regions of the cruciform.