Finite element and deformation analyses predict pattern of bone failure in loaded zebrafish spines

Abstract

<jats:p>The spine is the central skeletal support structure in vertebrates consisting of repeated units of bone, the vertebrae, separated by intervertebral discs (IVDs) that enable the movement of the spine. Spinal pathologies such as idiopathic back pain, vertebral compression fractures and IVD failure affect millions of people worldwide. Animal models can help us to understand the disease process, and zebrafish are increasingly used as they are highly genetically tractable, their spines are axially loaded like humans, and they show similar pathologies to humans during ageing. However, biomechanical models for the zebrafish are largely lacking. Here, we describe the results of loading intact zebrafish spinal motion segments on a material testing stage within a micro-computed tomography machine. We show that vertebrae and their arches show predictable patterns of deformation prior to their ultimate failure, in a pattern dependent on their position within the segment. We further show using geometric morphometrics which regions of the vertebra deform the most during loading, and that finite-element models of the trunk subjected reflect the real patterns of deformation and strain seen during loading and can therefore be used as a predictive model for biomechanical performance.</jats:p>

Zebrafish: A Resourceful Vertebrate Model to Investigate Skeletal Disorders

“…In a study by Newham et al (118), high resolution scans of vertebral bodies before and after mechanical compression were analyzed via geometric morphometrics. The obtained measurements were successfully used to determine the deformation zones and subsequently used to predict the deformation and strain during loading (118).…”

Potential of zebrafish as a model to characterise MicroRNA profiles in mechanically mediated joint degeneration

“…Other skeletal elements in zebrafish, such as the vertebral centra, have also been demonstrated to be mechanically sensitive, and to undergo remodelling in response to load (Fiaz et al 2012 ; Ofer et al 2019 ), which could be regulated by miRs. Finite element models also exist for the zebrafish vertebral column (Newham et al 2019 ; Ofer et al 2019 ). However, as patterning and mineralisation of the vertebral column occur somewhat later than that of the jaw (from 8dpf onwards) (Wopat et al 2018 ), testing the role of specific miRs in the vertebral column is likely to be more technically challenging.…”

Patient-Specific Bone Multiscale Modelling, Fracture Simulation and Risk Analysis—A Survey

“…Parallel to the work conducted on modelling human bone, there have been efforts to model bone of several animals. Studies range from small animals such as mice [287,[329][330][331][332][333][334][335][336], rats [288,[337][338][339][340][341][342][343] and zebrafish [344], to medium-sized animals such as dogs [345], as well as large animals such as pigs [346][347][348][349][350][351][352], sheep [353][354][355], bovine [220,[356][357][358][359][360][361][362][363] and horses [273,364].…”

“…The influence of CT resolution was investigated by [357,363,366]. Some works used µCT to create high-resolution animal bone geometry models [287,344,365,366].…”

“…Research directives within the field of animal bone modelling and analysis include 12A 1 -12A 3 . 12A 1 : Usage of animal bone experimental data to estimate mechanical properties [220,287,288,330,331,340,342,347,363,369] and conception of animal bone failure models [331,338,349,351,356,358,362] that may be similar to human bone failure models [342,344,370]. This directive includes studies in which pathological changes to the skeleton are purposefully induced in test animals by genetic manipulation [371] or malnutrition [332,338,354] in order to create models to study osteoporosis [338,354].…”