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An experimentally informed statistical elasto-plastic mineralised collagen fibre model at the micrometre and nanometre lengthscale.

ABSTRACT: Bone is an intriguingly complex material. It combines high strength, toughness and lightweight via an elaborate hierarchical structure. This structure results from a biologically driven self-assembly and self-organisation, and leads to different deformation mechanisms along the length scales. Characterising multiscale bone mechanics is fundamental to better understand these mechanisms including changes due to bone-related diseases. It also guides us in the design of new bio-inspired materials. A key-gap in understanding bone's behaviour exists for its fundamental mechanical unit, the mineralised collagen fibre, a composite of organic collagen molecules and inorganic mineral nanocrystals. Here, we report an experimentally informed statistical elasto-plastic model to explain the fibre behaviour including the nanoscale interplay and load transfer with its main mechanical components. We utilise data from synchrotron nanoscale imaging, and combined micropillar compression and synchrotron X-ray scattering to develop the model. We see that a 10-15% micro- and nanomechanical heterogeneity in mechanical properties is essential to promote the ductile microscale behaviour preventing an abrupt overall failure even when individual fibrils have failed. We see that mineral particles take up 45% of strain compared to collagen molecules while interfibrillar shearing seems to enable the ductile post-yield behaviour. Our results suggest that a change in mineralisation and fibril-to-matrix interaction leads to different mechanical properties among mineralised tissues. Our model operates at crystalline-, molecular- and continuum-levels and sheds light on the micro- and nanoscale deformation of fibril-matrix reinforced composites.

SUBMITTER: Groetsch A

PROVIDER: S-EPMC8324897 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Extracellular matrix microfibrils are critical components of connective tissues with a wide range of mechanical and cellular signalling functions. Collagen VI is a heteromeric network-forming collagen which is expressed in tissues such as skin, lung, blood vessels and articular cartilage where it anchors cells into the matrix allowing for transduction of biochemical and mechanical signals. It is not understood how collagen VI is arranged into microfibrils or how these microfibrils are arranged into tissues. Therefore we have characterised the hierarchical organisation of collagen VI across multiple length scales. The frozen hydrated nanostructure of purified collagen VI microfibrils was reconstructed using cryo-TEM. The bead region has a compact hollow head and flexible tail regions linked by the collagenous interbead region. Serial block face SEM imaging coupled with electron tomography of the pericellular matrix (PCM) of murine articular cartilage revealed that the PCM has a meshwork-like organisation formed from globular densities ∼30nm in diameter. These approaches can characterise structures spanning nanometer to millimeter length scales to define the nanostructure of individual collagen VI microfibrils and the micro-structural organisation of these fibrils within tissues to help in the future design of better mimetics for tissue engineering.Statement of significanceCartilage is a connective tissue rich in extracellular matrix molecules and is tough and compressive to cushion the bones of joints. However, in adults cartilage is poorly repaired after injury and so this is an important target for tissue engineering. Many connective tissues contain collagen VI, which forms microfibrils and networks but we understand very little about these assemblies or the tissue structures they form. Therefore, we have use complementary imaging techniques to image collagen VI microfibrils from the nano-scale to the micro-scale in order to understand the structure and the assemblies it forms. These findings will help to inform the future design of scaffolds to mimic connective tissues in regenerative medicine applications.

Project description:Background: Plate osteosynthesis is a widely used technique for bone fracture fixation; however, complications such as plate bending remain a significant clinical concern. A better understanding of the failure mechanisms behind plate osteosynthesis is crucial for improving treatment outcomes. This study aimed to develop finite element (FE) models to predict plate bending failure and validate these against in vitro experiments using literature-based and experimentally determined implant material properties. Methods: Plate fixations of seven cadaveric tibia shaft fractures were tested to failure in a biomechanical setup with various implant configurations. FE models of the bone-implant constructs were developed from computed tomography (CT) scans. Elasto-plastic implant material properties were assigned using either literature data or the experimentally derived data. The predictive capability of these two FE modelling approaches was assessed based on the experimental ground truth. Results: The FE simulations provided quantitatively correct prediction of the in vitro cadaveric experiments in terms of construct stiffness [concordance correlation coefficient (CCC) = 0.97, standard error of estimate (SEE) = 23.66, relative standard error (RSE) = 10.3%], yield load (CCC = 0.97, SEE = 41.21N, RSE = 7.7%), and maximum force (CCC = 0.96, SEE = 35.04, RSE = 9.3%), when including the experimentally determined material properties. Literature-based properties led to inferior accuracies for both stiffness (CCC = 0.92, SEE = 27.62, RSE = 19.6%), yield load (CCC = 0.83, SEE = 46.53N, RSE = 21.4%), and maximum force (CCC = 0.86, SEE = 57.71, RSE = 14.4%). Conclusion: The validated FE model allows for accurate prediction of plate osteosynthesis construct behaviour beyond the elastic regime but only when using experimentally determined implant material properties. Literature-based material properties led to inferior predictability. These validated models have the potential to be utilized for assessing the loads leading to plastic deformation in vivo, as well as aiding in preoperative planning and postoperative rehabilitation protocols.

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An experimentally informed statistical elasto-plastic mineralised collagen fibre model at the micrometre and nanometre lengthscale.

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