Three-dimensional anisotropic hyperelastic constitutive model describing the mechanical response of human and mouse cervix

Abstract

The mechanical function of the uterine cervix is critical for a healthy pregnancy. During pregnancy, the cervix undergoes significant softening to allow for a successful delivery. Abnormal cervical remodeling is suspected to contribute to preterm birth. Material constitutive models describing known biological shifts in pregnancy are essential to predict the mechanical integrity of the cervix. In this work, the material response of human cervical tissue under spherical indentation and uniaxial tensile tests loaded along different anatomical directions is experimentally measured. A deep-learning segmentation tool is applied to capture the tissue deformation during the uniaxial tensile tests. A 3-dimensional, equilibrium anisotropic continuous fiber constitutive model is formulated, considering collagen fiber directionality, fiber bundle dispersion, and the entropic nature of wavy cross-linked collagen molecules. Additionally, the universality of the material model is demonstrated by characterizing previously published mouse cervix mechanical data. Overall, the proposed material model captures the tension–compression asymmetric material responses and the remodeling characteristics of both human and mouse cervical tissue. The pregnant (PG) human cervix (mean locking stretch ζ=2.4, mean initial stiffness ξ=12 kPa, mean bulk modulus κ=0.26 kPa, mean dispersion b=1.0) is more compliant compared with the nonpregnant (NP) cervix (mean ζ=1.3, mean ξ=32 kPa, mean κ=1.4 kPa, mean b=1.4). Creating a validated material model, which describes the role of collagen fiber directionality, dispersion, and crosslinking, enables tissue-level biomechanical simulations to determine which material and anatomical factors drive the cervix to open prematurely. Statement of significanceIn this study, we report a 3D anisotropic hyperelastic constitutive model based on Langevin statistical mechanics and successfully describe the material behavior of both human and mouse cervical tissue using this model. This model bridges the connection between the extracellular matrix (ECM) microstructure remodeling and the macro mechanical properties change of the cervix during pregnancy via microstructure-associated material parameters. This is the first model, to our knowledge, to connect the the entropic nature of wavy cross-linked collagen molecules with the mechanical behavior of the cervix. Inspired by microstructure, this model provides a foundation to understand further the relationship between abnormal cervical ECM remodeling and preterm birth. Furthermore, with a relatively simple form, the proposed model can be applied to other fibrous tissues in the future.