Long-Term Creep Behavior of the Intervertebral Disk: Comparison between Bioreactor Data and Numerical Results

Abstract

The loaded disk culture system is an intervertebral disk (IVD)-oriented bioreactor developed by the VU Medical Center (VUmc, Amsterdam, The Netherlands), which has the capacity of maintaining up to 12 IVDs in culture, for approximately 3 weeks after extraction. Using this system, eight goat IVDs were provided with the essential nutrients and submitted to compression tests without losing their biomechanical and physiological properties, for 22 days. Based on previous reports (Paul et al., 2012, 2013; Detiger et al., 2013), four of these IVDs were kept in physiological condition (control) and the other four were previously injected with chondroitinase ABC (CABC), in order to promote degenerative disk disease (DDD). The loading profile intercalated 16 h of activity loading with 8 h of loading recovery to express the standard circadian variations. The displacement behavior of these eight IVDs along the first 2 days of the experiment was numerically reproduced, using an IVD osmo-poro-hyper-viscoelastic and fiber-reinforced finite element (FE) model. The simulations were run on a custom FE solver (Castro et al., 2014). The analysis of the experimental results allowed concluding that the effect of the CABC injection was only significant in two of the four IVDs. The four control IVDs showed no signs of degeneration, as expected. In what concerns to the numerical simulations, the IVD FE model was able to reproduce the generic behavior of the two groups of goat IVDs (control and injected). However, some discrepancies were still noticed on the comparison between the injected IVDs and the numerical simulations, namely on the recovery periods. This may be justified by the complexity of the pathways for DDD, associated with the multiplicity of physiological responses to each direct or indirect stimulus. Nevertheless, one could conclude that ligaments, muscles, and IVD covering membranes could be added to the FE model, in order to improve its accuracy and properly describe the recovery periods.

The Quantitative Structural and Compositional Analyses of Degenerating Intervertebral Discs Using Magnetic Resonance Imaging and Contrast-Enhanced Micro-Computed Tomography

“…This method can be used for monitoring the 3 dimensional structural changes of diseases and treatments of the intervertebral disc. Moreover, sophisticated modeling techniques could be applied to data obtained from high-resolution imaging to monitor degeneration and efficacy of therapies 35–38 . This hydrophilic contrast agent does not induce toxicity to the tissue 17,39 , thus providing a promising in vitro 17,40 and in vivo approach to monitor soft tissue degeneration.…”

Combined numerical and experimental biomechanical characterization of soft collagen hydrogel substrate

“…The biomechanical behaviour of collagen hydrogels was modelled through FE simulations with the biphasic module of V-Biomech [ 7 , 8 ]. For validation purposes, the simulations replicated the protocols of the confined compression experiments of Chandran and Barocas [ 9 ] and Busby et al [ 5 ], respectively.…”

Relevance of bioreactors and whole tissue cultures for the translation of new therapies to humans

“…86,87 For the future, there is a high need for predictive tools based on experimentally validated in silico models, and bioreactors (especially in high-throughput platforms) can provide a useful tool to validate computational models. 88 A huge challenge is the development of models capable of linking in vitro, ex vivo, in vivo outcomes. The organ on chip technology may provide a remarkable tool for this purpose.…”