Microstructure-informed biphasic-osmotic modeling of intervertebral disc degeneration

The intervertebral disc (IVD) plays a fundamental role in load absorption and redistribution during daily activities. Its mechanical behavior arises from the intricate interplay between the structural anisotropy of the annulus fibrosus (AF) and osmotic swelling driven by fixed charge density in the nucleus pulposus (NP). This behavior is further governed by fluid redistribution through the porous matrix and across its boundaries, including interactions with the adjacent endplates and the surrounding physiological environment. Despite advances in IVD modeling, few computational tools accurately capture these coupled mechanisms while accounting for progressive degeneration under realistic loading conditions. This study introduces a microstructure-informed and degeneration sensitive finite element model of the human IVD, integrating regional fiber architecture, biphasic fluid-solid interactions, and osmotic swelling within a unified mechanistic framework. A multiscale calibration strategy is employed to identify the solid, osmotic, and fluid transport parameters, based on targeted mechanical experiments. Degenerative changes are incorporated at both macroscopic (e.g., IVD height loss) and microscopic (e.g., fiber uncrimping, proteoglycan depletion, and increased matrix porosity) levels. Model predictions are compared against physiological loading scenarios representative of everyday life-including lying down, standing upright, and trunk motions-revealing the evolving contribution of each mechanism with degeneration, while model robustness is assessed through a parametric sensitivity analysis. This framework provides a mechanistic understanding of the evolving roles of IVD constituents across degeneration and defines representative parameter sets for different degenerative states, providing a basis for future patient-adapted modeling approaches. It also enables the exploration of degeneration-dependent mechanical responses and loading sensitivities, offering perspectives for improved mechanobiological understanding of IVD degeneration.