Biology subjects

Marussi, S.

Publications and source records attributed to Marussi, S..

7 recordsLinked to original sources

bioRxiv2026

Cross-species structure-mechanics prediction in the intervertebral disc

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.

bioengineering↗

bioRxiv2026

Articular calcified cartilage microarchitecture has a predictive role in abnormal osteochondral strain distributions in murine age-related osteoarthritis

Even though osteoarthritis is considered a disease of the whole joint, integrated analysis of articular calcified cartilage (ACC) behaviour with adjacent tissues remains a persistent limitation. Herein, we performed synchrotron X-ray computed tomography in intact loaded joints and coupled anatomical analysis with digital volume correlation to examine whether microarchitectural ACC features serve as predictive mechano-biomarkers of osteoarthritis. We reveal that male osteoarthritis-prone STR/Ort mice have thicker yet more porous ACC that contains larger but less spherical chondrocyte lacunae than their healthy parental-control CBA mice. This was linked to asymmetrical distribution of tensile and compressive strains generated under physiological loads in the ACC and underlying subchondral bone in tibial epiphyses of STR/Ort mice. Together these data suggest that murine ACC microarchitecture has a mechano-predictive role in age-related osteoarthritis.

physiology↗

bioRxiv2025

In situ profiling of nanoscale displacements uncovers mechano-architectural predictors of osteoarthritis emergence

Mechanical and anatomical interplay between the distinct tissues of the knee joint is essential for maintaining functional integrity during healthy ageing and contributes to the mechanisms that drive osteoarthritis (OA). In this study, we investigate how age- and disease-associated alterations in joint anatomy influence load transmission and tissue-level strain distribution. Using full-field synchrotron X-ray computed tomography coupled with digital volume correlation, we hierarchically characterised in situ nanoscale strains generated in response to mechanical loading across the tibial epiphysis. Our findings show that greater compressive strains accumulate in the articular condyle of male OA-prone (STR/Ort) epiphyses. Finite element modelling further demonstrated that these strain concentrations are associated with reduced load-bearing capacity, which arise from architectural differences localised to the subchondral bone plate. By coupling high-resolution imaging with computational modelling, our work provides new insights into how structural-function changes to joint anatomy contribute to the initiation and progression of mechanically driven OA. Our approach offers a means to identify early imaging biomarkers prior to OA diagnosis and has potential for monitoring interventions aimed at preserving joint mechanics while promoting healthy joint ageing.

bioengineering↗

bioRxiv2024

Synchrotron Tomography-Based Finite Element Analysis of Vertebral Endplate Loading Reveals Functional Roles for Architectural Features

Lower back pain is linked to vertebral biomechanics, with vertebral endplates (VEPs) playing a key role. Finite element modelling (FEM) is a powerful tool for studying VEP biomechanics but relies on accurate material property inputs, which remain difficult to obtain. Synchrotron computed tomography (sCT) allows for detailed visualisation of the microstructure of intact VEPs under near-physiological loads and, when coupled with digital volume correlation (DVC), can be used to quantify three-dimensional (3D) strain fields, providing experimental reference data for FEM validation. We developed an inversion pipeline to spatially couple DVC data with an image-based FE model, and thus to estimate the elastic properties of rat VEPs. On the first rat lumbar FEM, the pipeline estimated a VEP elastic modulus of 129 MPa and a Poissons ratio of 0.24. Welchs ANOVA revealed statistically significant differences between FEM and DVC strain distributions (p < 0.001) but with small effect sizes ({superscript 2} = 0.1%-0.6%), indicating high practical similarity. Its efficacy was further validated using Bland-Altman analysis, demonstrating over 95% spatial agreement between the FEM-predicted strains and the DVC measurements across multiple loading steps. The pipelines consistency was further evaluated across multiple rat lumbar FE models (n = 3), yielding an estimated VEP elastic modulus = 145 {+/-} 18 MPa and a Poissons ratio = 0.28 {+/-} 0.04. Statistically significant regional variations of strain distribution in VEPs were also identified (p < 0.05 to p < 0.001, {superscript 2} up to 41.8%). This study highlighted the efficacy of the developed pipeline in estimating the isotropic elastic modulus and Poissons ratio of VEP FEMs in a physiologically relevant, complex load transfer system. Our pipeline may be used in estimating properties of VEP in larger animals and humans.

bioengineering↗

bioRxiv2022

Preparation of large biological samples for high-resolution, hierarchical, multi-modal imaging

Imaging the different scales of biological tissue is essential for understanding healthy organ behavior and pathophysiological changes. X-ray micro-tomography using both laboratory ({micro}CT) and synchrotron sources (sCT) is a promising tool to image the 3D morphology at the macro- and micro-scale of large samples, including intact human organs. Preparation of large samples for high resolution imaging techniques remains a challenge due to limitations with current methods, such as sample shrinkage, insufficient contrast, movement of the sample and bubble formation during mounting or scanning. Here, we describe a protocol to prepare, stabilize, and image large soft-tissue samples with X-ray microtomography. We demonstrate the protocol using intact human organs and Hierarchical Phase-Contrast Tomography (HiP-CT) imaging at the European Synchrotron Radiation Facility, but the protocol is equally applicable to a range of biological samples, including complete organisms, for both laboratory and synchrotron source tomography. Our protocol enhances the contrast of the sample, while preventing sample motion during the scan, even in case of different sample orientations. Bubbles trapped during mounting and those formed during scanning (in case of synchrotron X-ray imaging) are mitigated by multiple degassing steps. The sample preparation is also compatible with magnetic resonance imaging (MRI), CT, and histological observation. We describe a protocol for sample preparation and mounting which requires 25 to 34 days for a large organ such as an intact human brain or heart. This preparation time varies depending on the composition, size, and fragility of the tissue. Use of the protocol enables scanning of intact organs with a diameter of 150 mm with a local pixel size of one micron using HiP-CT.

physiology↗

bioRxiv2021

A multiscale X-ray phase-contrast tomography dataset of whole human left lung

Technological advancements in X-ray imaging using bright and coherent synchrotron sources now allows to decouple sample size and resolution, while maintaining high sensitivity to the microstructure of soft, partially dehydrated tissues. The recently developed imaging technique, hierarchical phase-contrast tomography, is a comprehensive approach to address the challenge of organ-scale (up to tens of centimeters) soft tissue imaging with resolution and sensitivity down to the cellular level. Using this technique, we imaged ex vivo an entire human left lung at an isotropic voxel size of 25.08 m along with local zooms down to 6.05 - 6.5 m and 2.45 - 2.5 m in voxel size. The high tissue contrast offered by the fourth-generation synchrotron source at the European Synchrotron Radiation Facility reveals complex multiscale anatomical constitution of the human lung from the macroscopic (centimeter) down to the microscopic (micrometer) scale. The dataset provides complete organ-scale 3D information of the secondary pulmonary lobules and delineates the microstructure of lung nodules with unprecedented detail.

physiology↗

bioRxiv2021

Multiscale three-dimensional imaging of intact human organs down to the cellular scale using hierarchical phase-contrast tomography

Human organs are complex, three-dimensional and multiscale systems. Spatially mapping the human body down through its hierarchy, from entire organs to their individual functional units and specialised cells, is a major obstacle to fully understanding health and disease. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique utilising the European Synchrotron Radiation Facilitys Extremely Brilliant Source: the worlds first high-energy 4th generation X-ray source. HiP-CT enabled three-dimensional and non-destructive imaging at near-micron resolution in soft tissues at one hundred thousand times the voxel size whilst maintaining the organs structure. We applied HiP-CT to image five intact human parenchymal organs: brain, lung, heart, kidney and spleen. These were hierarchically assessed with HiP-CT, providing a structural overview of the whole organ alongside detail of the organs individual functional units and cells. The potential applications of HiP-CT were demonstrated through quantification and morphometry of glomeruli in an intact human kidney, and identification of regional changes to the architecture of the air-tissue interface and alveolar morphology in the lung of a deceased COVID-19 patient. Overall, we show that HiP-CT is a powerful tool which can provide a comprehensive picture of structural information for whole intact human organs, encompassing precise details on functional units and their constituent cells to better understand human health and disease.

physiology↗