Simulation of biological therapies for degenerated intervertebral discs

Zhu, Qiaoqiao; Gao, Xin; Temple, H. Thomas; Brown, Mark D.; Gu, Weiyong

doi:10.1002/jor.23061

Cited by 15 publications

(20 citation statements)

References 46 publications

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“…When the disc severely degenerates, common features affecting the AF occur, such as decreased cellularity of the tissue matrix and disorganization and structure disruption of the AF [Lotz, 2004;Zhu et al, 2016]. There are also clues that mechanical stimuli have deleterious effects on the AF, such as catabolic matrix remodelling and structural damage [Mac lean et al, 2004;Walsh and Lotz, 2004;Gantenbein et al, 2006;Wuertz et al, 2009;Menard et al, 2016].…”

Section: Introductionmentioning

confidence: 99%

Biological Responses of the Immature Annulus Fibrosus to Dynamic Compression in a Disc Perfusion Culture

Wang

et al. 2016

Cells Tissues Organs

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Mechanical stimuli participate in disc development and remodelling. However, the effects of mechanical load on the immature annulus fibrosus (AF) are largely unclear. This study aimed to investigate how the immature AF responded to dynamic compressive magnitude and duration. Immature porcine discs were bioreactor-cultured for 7 days and then dynamically compressed at various magnitudes (0.1, 0.2, 0.4, 0.8 and 1.3 MPa at a frequency of 1.0 Hz for 2 h/day) and durations (1, 2, 4 and 8 h/day at a magnitude of 0.4 MPa and a frequency of 1.0 Hz). Non-compressed discs were used as controls. The immature AF tissue was analysed for histology, gene expression (aggrecan, collagen I, ADAMTS-4, MMP-3, TIMP-1 and TIMP-3), biochemical content of glycosaminoglycans (GAG) and hydroxyproline (HYP) and aggrecan immunohistochemical staining. In the lower-compressive-magnitude groups (0.1, 0.2 and 0.4 MPa), the immature AF showed an up-regulation in the expression of matrix genes, GAG and HYP content and aggrecan deposition. In the compression duration groups, the GAG and HYP content and aggrecan deposition declined to a minimum in the 8-hour group, in which a catabolic gene expression profile was found. In conclusion, this study indicated that the effects of dynamic compression on the immature AF are magnitude and duration dependent and that catabolic remodelling within the immature AF can be induced by high compressive magnitudes and long compressive durations.

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Section: Introductionmentioning

confidence: 99%

Biological Responses of the Immature Annulus Fibrosus to Dynamic Compression in a Disc Perfusion Culture

Wang

et al. 2016

Cells Tissues Organs

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Lin

Tang

2017

Ann Biomed Eng

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The intervertebral disc (IVD) is susceptible to degenerative changes that are associated with low back pain. Murine models are often used to investigate the mechanistic changes in the development, aging, and diseased states of the IVD, yet the detection of early degenerative changes in structure is challenging because of the minute size of the murine IVDs. Histology is the gold standard for examining the IVD structure, but it is susceptible to sectioning artifacts, spatial biases, and requires the destructive preparation of the sample. We have previously demonstrated the feasibility of using Ioversol for the contrast-enhanced micro-computed tomography (microCT) to visualize and quantitate the intact healthy murine IVD. In this work, we demonstrate utility of this approach to monitor the longitudinal changes of in vitro nucleolytic- and mechanical injury- degeneration models of the murine discs and introduce novel quantitative metrics to characterize the structure and composition of the IVD. Moreover, we compared the imaging quality and quantitation of these in vitro models to magnetic resonance imaging (MRI) and histology. Stab puncture, trypsin injection, and collagenase injection all induced detectable and significant changes in structure and composition of the discs overtime. Compared to MRI and histology, contrast-enhanced microCT produced superior images that capture the degenerative progression in these models. Contrast-enhanced microCT was also capable of monitoring the structural deteriorations via the changes in disc heights and volumes, and the nucleus pulposus intensity/disc intensity (NI/DI) parameter provides a surrogate measure of proteoglycan composition (R = 0.96). Overall, this approach allows for the nondestructive monitoring of the structure and composition of the IVD at very high resolutions.

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“…The coupling phenomena among tissue deformation, transport of fluid and solutes, and electro‐osmotic effects were modeled. The cell viability was dependent on local glucose level, and the GAG content was dependent on cell density, GAG synthesis rate and degradation rate (see Table 1 of Zhu et al for details) . This model is able to predict the distributions of cell density, oxygen tension, glucose concentration, lactate concentration, pH value, GAG content, ion concentrations, fluid pressure, water content, stresses and strains of the solid matrix, and tissue deformation in the disc.…”

Section: Methodsmentioning

confidence: 99%

“…The cell viability was dependent on local glucose level, and the GAG content was dependent on cell density, GAG synthesis rate and degradation rate (see Table 1 of Zhu et al for details). 14,18 This model is able to predict the distributions of cell density, oxygen tension, glucose concentration, lactate concentration, pH value, GAG content, ion concentrations, fluid pressure, water content, stresses and strains of the solid matrix, and tissue deformation in the disc. Moreover, this model has been validated by comparing model predictions of water content and GAG content distributions with those from experiments.…”

Section: Methodsmentioning

confidence: 99%

Simulation of water content distributions in degenerated human intervertebral discs

Zhu

Gao

Brown

et al. 2016

Journal Orthopaedic Research

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The objective of this study was to investigate the spatial and temporal variations of water content in intervertebral discs during degeneration and repair processes. We hypothesized that the patterns of water content distribution in the discs are related to the intensity patterns observed in T2-weighted MRI images. Water content distributions in the mildly (e.g., 80% viable cells in the disc, 2.3% decrease in disc height) and moderately (e.g., 40% viable cells in the disc, 9.3% decrease in disc height) degenerated discs were predicted using a finite element model. The variation of water content in the degenerated discs treated with three biological therapies [i.e., increasing the cell density in the NP (Case I), increasing glycosaminoglycan synthesis rate in the nucleus pulposus (Case II), and decreasing glycosaminoglycan degradation rate in the nucleus pulposus (Case III)] were also predicted. It was found that two patterns of water content distributions, a horizontal region with lower water content at the mid-axial plane of nucleus pulposus and a spot with higher water content at the posterior region, were shown during the degeneration progress for the disc simulated in this study. These two patterns disappeared after treatment in Case I, but in Case II and Case III. The implication of these patterns for the horizontal gray band and high intensity zone in T2-weighted MRI images was discussed. This study provided new guidance to develop a novel method for diagnosing disc degeneration and assessing outcomes of biological therapies with MRI techniques.

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Simulation of biological therapies for degenerated intervertebral discs

Cited by 15 publications

References 46 publications

Biological Responses of the Immature Annulus Fibrosus to Dynamic Compression in a Disc Perfusion Culture

Biological Responses of the Immature Annulus Fibrosus to Dynamic Compression in a Disc Perfusion Culture

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

Simulation of water content distributions in degenerated human intervertebral discs

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