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Multi-scale biomechanical modelling and simulation of the intervertebral disc

Final Report Summary - DISCSIM (Multi-scale biomechanical modelling and simulation of the intervertebral disc)

This project aimed to develop multi-scale Computational Biomechanics (CB) approaches to analyze the largest avascular structure in the human body, the intervertebral disc. In particular, the objectives of the project were to; (i) develop a new serial milling and imaging technique for 3D mapping of the intervertebral disc at high resolution; (ii) measure the mechanical properties of disc tissues at the micro-scale; (iii) generate combined micro-macro scale computational models of the disc; and (iv) validate and explore the sensitivity of the disc models.

Work performed during the project
(i) Serial milling and imaging system - A serial milling system was built based on a Proxxon MF70 micro-mill which was converted to CNC (computer numerical control). The mill was modified to allow mounting of a microscope camera to the milling head, and custom code was written to control the mill for a serial milling and imaging operation. A protocol for en bloc embedding of intervertebral discs prior to serial milling was developed based on a series of trials with different embedding media. In order to assess image quality when imaging the milled surface of each slice, the surface roughness of cured blocks of embedding medium after milling were measured using a surface profiler, and the surface roughness was found to be acceptable for subsequent microscopic imaging given the depth of focus of the microscopes being used. Two microscopes were mounted to the milling apparatus and used for serial milling during the course of the project, a UV fluorescent microscope and a circularly polarised light microscope. For both microscopes, entire milled cross-sections of disc could be imaged and stitched back together in image post-processing software using the CNC table’s precise translation capability. A series of 14 bovine tail intervertebral discs were processed and imaged, and processing was commenced on a series of five human intervertebral discs. The system was able to identify the relationship between the collagen and elastic fibre networks in the intervertebral disc, and this work was presented at the EuroSpine 2013 conference in Liverpool, UK. This work has led to a new collaborations with Prof Peter Winlove at the University of Exeter, UK on the mechanics of elastic fibres.
(ii) Micromechanical testing - A micro-tensile tester was designed and built to allow micro-tests on small specimens of disc in order to determine the micro-mechanical properties of the constituent tissues. An initial series of tests were performed on segments of bovine annulus fibrosus, and the tests were recorded using a video microscope with transmitted polarised light illumination during the tests. Due to slippage of the collagenous annular material between the grips of the micro-tester during testing at forces above 40N, an improved jaw design is underway. A visiting student from Brisbane, Australia used the system developed during the project to perform combined polarised light imaging and nanoindentation tests on bovine trabecular bone, in order to provide tissue-level elastic properties for bovine cancellous bone for use in computational models of the vertebra-disc unit. In a side project, another student used the milling and imaging system to provide the first micro-structural assessment of the relationship between osteogenesis imperfecta bone porosity and compressive mechanical strength and stiffness.
(iii) Multiscale computational models - A multi-scale (micro-macro) finite element computer model of the intervertebral disc was developed using the ABAQUS software. This is the first model of its kind to allow interlamellar sliding, shearing and separation. The model was based on the microanatomy obtaining using the serial milling system, and was used to explore the response of the disc to axial compression. The model was validated against a series of axial compression experiments performed using bovine tail intervertebral discs, in which the disc was first tested ‘intact’ to a maximum load of 400N, and then a nucleotomy was performed and the disc was re-tested in order to ascertain the loss of load carrying ability due to nucleus de-pressurization. The finite element model was validated against the results of the experimental program, and after validation, the sensitivity of the finite element model to changes in the interlamellar interface conditions was explored, as well as the sensitivity of the model to the presence of circumferentially discontinuous lamellae (which have been noted to occur in both human and bovine discs).
(iv) Validation and sensitivity of models – A series of compression experiments were performed on bovine tail intervertebral discs in order to provide validation data for the finite element model. Having validated the finite element model predictions against the experimental results, the sensitivity of the finite element model to various inter-lamellar interface conditions was explored as planned. An initial journal article from this work “On the biomechanical significance of inter-lamellar interfaces in the intervertebral disc” has been prepared and is currently under submission to the Journal of Biomechanics.
Results achieved
The images in Figure 1.1 and 1.2 (in attached document) show examples of stitched reconstructions of the intervertebral disc under fluorescent and polarized light illumination respectively. These images are the first high resolution maps of the disc microstructure ever produced to our knowledge, and show micron level detail across entire regions of disc in both 2D and 3D.
Figure 1.3 (in attached document) shows the finite element model with both lamellar micro-architecture and the capability to simulate inter-lamellar sliding and shearing . The model validity is demonstrated by the comparison graph showing a good match between model predictions and actual experimental results for a series of bovine tail disc compression tests.
Potential impact and use
The research performed during project DiscSim has important implications for both clinicians, scientists and engineers working on treatments for disorders of the spine, and in particular, the intervertebral disc. The insights into the intricately related collagen and elastic fibre networks in the disc, and the microstructural basis of disc mechanical resistance will be of benefit to clinicians and engineers interested in the design of disc nucleus replacement implants. In the area of spinal deformity, the role of disc microstructure in conferring disc resistance to asymmetrical growth can be further studied using the techniques developed in this project. The basic science established in this project will have an underlying benefit to the wider spine research community regarding particularly adolescent idiopathic scoliosis, back pain, ageing spine and disc degeneration/regeneration issues. It provides novel insight in disc biomechanics to face major socioeconomic burdens worldwide.

Contact details
Researcher: Associate Professor Clayton Adam, School of Chemistry, Physics and Mechanical Engineering, Queensland University of Technology, Brisbane, Australia. Email
Scientist in Charge of the Project: Professor Wafa Skalli, LBM Institut de Biomécanique Humaine Georges Charpak, Arts et Metiers ParisTech, Paris, France. Email