Cross-species structure-mechanics prediction in the intervertebral disc

Abstract

Despite long-standing uncertainty regarding the suitability of animal intervertebral disc (IVD) models for the study of human IVD pathophysiology, few cross-species studies have integrated hierarchical structure with mechanical function. In this study, we present a multiscale structure-mechanics framework combining synchrotron computed tomography (sCT), fibre tracing, digital volume correlation (DVC) with structure-based mechanical inference and finite-element modelling. Rat, mini-pig and human IVDs (n = 3/species) were imaged by sCT, with rat and mini-pig discs additionally subjected to in situ uniaxial compression and DVC. A Structure Index (SI), integrating local structural anisotropy and fibre orientation, was developed to regionally pinpoint the location of mechanically vulnerable regions. Cross-species comparison showed scale-dependent structural conservation: gross disc and lamellar organisation retained common regional features, whereas fibre-bundle architecture exhibited greater species- and regional divergence. Despite these differences, lower SI was consistently associated with elevated deformation in rat and mini-pig discs across multiple strain measures. Structure-strain inverse correlations became tighter within progressively higher-strain domains, reaching Spearman p values of approximately -0.5 to -0.7 for several strain components. Synthetic fibre phantoms confirmed that SI reflects a coupling of fibre orientation and organisation, with additional sensitivity to fibre number in poorly organised configurations. In human discs with varying degrees of degeneration, SI revealed spatial heterogeneity and redistribution of structurally vulnerable regions. Fibril-informed homogenisation provided anisotropic material properties for organ-scale finite-element modelling that independently supported SI-based predictions. Overall, these findings establish a cross-species framework linking hierarchical collagen architecture to mechanical vulnerability and provide a basis for non-invasive, structure-driven biomechanical assessment of human IVD degeneration and mechanical risk.