Age and region dependent biomechanical and ultrastructural differences in porcine white matter

The biofidelity of computational models for paediatric traumatic brain injury (TBI) is dependent on age and region-specific material data that captures the brain's complex mechanical behaviour. This study performs a comprehensive, multiscale characterisation of porcine white matter, a high-fidelity model for the human brain, across three key developmental stages (0.5, 7, and 36 months) and three anatomically distinct regions (brain stem, parietal lobe, and temporal lobe). Oscillatory shear rheometry was employed to measure the linear viscoelastic properties (storage/loss moduli) and the non-linear response under 0-12% compressive pre-strain. In parallel, transmission electron microscopy was used to quantify the underlying ultrastructural architecture. The results reveal three principal findings. First, biomechanical maturation is a highly asynchronous and heterogeneous process; the brain stem undergoes rapid early stiffening, while the cerebral white matter stiffens more gradually. Second, porcine white matter exhibits pronounced non-linear compression-dependent increase in apparent shear stiffness, a behaviour whose magnitude is strongly modulated by both anatomical region and developmental age, with stiffness increasing by up to 839% under 12% compression in mature tissue. Third, a multivariate partial least squares regression identified mean axon radius as a significant microstructural correlate of bulk tissue stiffness (r = 0.70, p = 0.036). These findings provide a baseline dataset for the development and calibration of biofidelic, age-specific, non-linear constitutive models essential for more accurate brain computational modelling. STATEMENT OF SIGNIFICANCE: : Current computational models of paediatric traumatic brain injury (TBI) are limited by a critical lack of biofidelic material data, often relying on simplified, linear viscoelasticity from adult tissue. This study provides a comprehensive, multiscale dataset to address this gap. Using a high-fidelity porcine model, we link age- and region-specific biomechanics to the underlying ultrastructure across three key developmental stages. We demonstrate that the brain's non-linear strain-stiffening is not a static property but is profoundly modulated by both age and anatomical location. This dataset provides the essential, age-resolved parameters for a new generation of non-linear constitutive models, enabling more accurate prediction of paediatric brain injury.