Collagen fiber interweaving is central to sclera stiffness

• Published in: Acta biomaterialia 2020-09, Vol.113, p.429-437
• Main Authors: Wang, Bingrui, Hua, Yi, Brazile, Bryn L., Yang, Bin, Sigal, Ian A.
• Format: Article
• Language: English
• Subjects: Anisotropy; Biomechanical Phenomena; Biomechanics; Collagen; Computer simulation; Connective tissue; Constitutive properties; Extracellular Matrix; Fibers; Finite element modeling; Humans; Interweaving; Mathematical models; Mechanical properties; Microstructure; Model matching; Modelling; Parameter estimation; Sclera; Soft tissues; Stiffness; Stress, Mechanical
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2020.06.026

The mechanical properties of the microstructural components of sclera are central to eye physiology and pathology. Because these parameters are extremely difficult to measure directly, they are often estimated using inverse-modeling matching deformations of macroscopic samples measured experimentally. Although studies of sclera microstructure show collagen fiber interweaving, current models do not account for this interweaving or the resulting fiber-fiber interactions, which might affect parameter estimates. Our goal was to test the hypothesis that constitutive parameters estimated using inverse modeling differ if models account for fiber interweaving and interactions. We developed models with non-interweaving or interweaving fibers over a wide range of volume fractions (36–91%). For each model, we estimated fiber stiffness using inverse modeling matching biaxial experimental data of human sclera. We found that interweaving increased the estimated fiber stiffness. When the collagen volume fraction was 64% or less, the stiffness of interweaving fibers was about 1.25 times that of non-interweaving fibers. For higher volume fractions, the ratio increased substantially, reaching 1.88 for a collagen volume fraction of 91%. Simulating a model (interweaving/non-interweaving) using the fiber stiffness estimated from the other model produced substantially different behavior, far from that observed experimentally. These results show that estimating microstructural component mechanical properties is highly sensitive to the assumed interwoven/non-interwoven architecture. Moreover, the results suggest that interweaving plays an important role in determining the structural stiffness of sclera, and potentially of other soft tissues in which the collagen fibers interweave. The collagen fibers of sclera are interwoven, but numerical models do not account for this interweaving or the resulting fiber-fiber interactions. To determine if interweaving matters, we examined the differences in the constitutive model parameters estimated using inverse modeling between models with interweaving and non-interweaving fibers. We found that the estimated stiffness of the interweaving fibers was up to 1.88 times that of non-interweaving fibers, and that the estimate increased with collagen volume fraction. Our results suggest that fiber interweaving is a fundamental characteristic of connective tissues, additional to anisotropy, density and orientation. Better characterization of interwea