A multiscale computational framework coupling poromechanics, metabolism, and matrix turnover to investigate the long-term evolution of intervertebral disc degeneration

Intervertebral disc (IVD) degeneration involves coupled interactions between tissue mechanics, nutrient transport, cellular metabolism, and extracellular matrix (ECM) turnover. This work presents a multiscale mechanobiological framework integrating these processes within a continuous description of degeneration. A multiphasic mechanical model is calibrated and assessed against experimental mechanical and osmotic responses, including independent creep datasets, and subsequently coupled with experimentally informed metabolic and matrix-turnover mechanisms. Depending on the applied load and metabolic configuration, the simulations reveal three distinct model-emergent degeneration regimes characterized by decelerating, fluctuating, and accelerating progression. The decelerating regime exhibits an age-dependent decrease in degeneration rate qualitatively similar to trends reported in cross-sectional and longitudinal clinical studies, whereas the accelerating regime is associated with a cascade involving nutrient depletion, proteoglycan loss, and progressive loss of mechanical function. These findings illustrate how interactions between mechanical, metabolic, and matrix-turnover processes can give rise to nonlinear long-term degeneration trajectories. Long-term simulations rely on sustained compression rather than physiological diurnal loading and do not account for direct mechanotransduction, structural damage, or injury-induced degeneration. Accordingly, the framework is intended to explore the mechanisms underlying long-term IVD degeneration rather than to predict individual degeneration trajectories.