Intervertebral Disc Nutrition

Mm, Katz; Ar, Hargens; Garfin,

doi:10.1097/00003086-198609000-00035

Cited by 56 publications

(7 citation statements)

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“…The cartilaginous endplates (EPs) are adjacent to the gelatinous nucleus pulposus (NP), which is surrounded by the anulus fibrosus (AF), a highly orientated fibrous tissue with a lamellar structure. As the largest avascular structure in the human body, 5 the IVD highly depends on diffusion of nutrients into the disc center. Because of low cell density (4000 -9000 cells/mm 3 ), 6 low cell activity and avascular condition, the disc has limited self-repair capabilities.…”

mentioning

confidence: 99%

The Combined Effects of Limited Nutrition and High-Frequency Loading on Intervertebral Discs With Endplates

Illien-Jünger¹,

Gantenbein²,

Grad³

et al. 2010

Spine

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mentioning

confidence: 99%

The Combined Effects of Limited Nutrition and High-Frequency Loading on Intervertebral Discs With Endplates

Illien-Jünger¹,

Gantenbein²,

Grad³

et al. 2010

Spine

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“…Therefore, the solute transport sensitivity is expected to be negligible via load-dependent diffusion. The negligible role of fluid velocity advection is congruent with other computational (13) and experimental evidences (169,170). Yet, Huang and coworkers (175) predicted small solute enhancements due to dynamic loadings after 200 cycles and at a frequency of 0.1 Hz.…”

Section: Development Of a Procedures For A Coupled Poromechanics-tran...supporting

confidence: 78%

Multi-scale biomechanical study of transport phenomena in the intervertebral disc

Malandrino

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Intervertebral disc (IVD) degeneration is primarily involved in back pain, a morbidity that strongly affects the quality of life of individuals nowadays. Lumbar IVDs undergo stressful mechanical loads while being the largest avascular tissues in our body: Mechanical principles alone cannot unravel the intricate phenomena that occur at the cellular scale which are fundamental for the IVD regeneration. The present work aimed at coupling biomechanical and relevant molecular transport processes for disc cells to provide a mechanobiological finite element framework for a deeper understanding of degenerative processes and the planning of regenerative strategies. Given the importance of fluid flow within the IVD, the influence of poroelastic parameters such as permeabilities and solid-phase stiffness of the IVD subtissues was explored. A continuum porohyperelastic material model was then implemented. The angles of collagen fibers embedded in the annulus fibrosus (AF) were calibrated. The osmotic pressure of the central nucleus pulposus (NP) was also taken into account. In a parallel study of the human vertebral bone, microporomechanics was used together with experimental ultrasonic tests to characterize the stiffness of the solid matrix, and to provide estimates of poroelastic coefficients. Fluid dynamics analyses and microtomographic images were combined to understand the fluid exchanges at the bone-IVD interface. The porohyperelastic model of a lumbar IVD with poroelastic vertebral layers was coupled with a IVD transport model of three solutes - oxygen, lactate and glucose - interrelated to reproduce the glycolytic IVD metabolism. With such coupling it was possible to study the effect of deformations, fluid contents, solid-phase stiffness, permeabilities, pH, cell densities of IVD subtissues and NP osmotic pressure on the solute transport. Moreover, cell death governed by glucose deprivation and lactate accumulation was included to explore the mechanical effect on cell viability. Results showed that the stiffness of the AF had the most remarkable role on the poroelastic behavior of the IVD. The permeability of the thin cartilage endplate and the NP stiffness were also relevant. The porohyperelastic model was shown to reproduce the local AF mechanics, provided the fiber angles were calibrated regionally. Such back-calculation led to absolute values of fibers angles and to a global IVD poromechanical behavior in agreement with experiments in literature. The inclusion of osmotic pressure in the NP also led to stress values under confined compression comparable to those measured in healthy and degenerated NP specimens. For the solid bone matrix, axial and transverse stiffness coefficients found experimentally in the present work agreed with universal mass density-elasticity relationships, and combined with continuum microporomechanics provided poroelastic coefficients for undrained and drained cases. The effective permeability of the vertebral bony endplate calculated with fluid dynamics was highly correlated with the porosity measured in microtomographic images. The coupling of transport and porohyperelastic models revealed a mechanical effect acting under large volume changes and high compliance, favored by healthy rather than degenerated IVD properties. Such effect was attributed to strain-dependent diffusivities and diffusion distances and was shown to be beneficial for IVD cells due to the load-dependent increases of glucose levels. Cell density, NP osmotic pressure and porosity were the most important parameters affecting the coupled mechano-transport of metabolites. This novel study highlights the restoration of both cellular and mechanical factors and has a great potential impact for novel designs of treatments focused on tissue regeneration. It also provides methodological features that could be implemented in clinical image-based tools and improve the multiscale understanding of the human spine mechanobiology.

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“…99 However, early in vivo studies found no significant effect of dynamic loading or "pumping" due to exercise on nutrient transport of small glucose and oxygen molecules in canine discs or rabbit spines which had undergone flexion and extension. 100,101 Despite this, another rabbit study demonstrated that diffusion through the CEP can be modestly enhanced by forced convection under low-rate dynamic loading. 102 Moreover, a study by Salvatierra et al 31 investigated the effect of dynamic compression on disc cell metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…With muscle activity shown to increase intradiscal pressure, it has been cautiously concluded that constantly changing position is important to promote fluid flow 99 . However, early in vivo studies found no significant effect of dynamic loading or “pumping” due to exercise on nutrient transport of small glucose and oxygen molecules in canine discs or rabbit spines which had undergone flexion and extension 100,101 . Despite this, another rabbit study demonstrated that diffusion through the CEP can be modestly enhanced by forced convection under low‐rate dynamic loading 102 .…”

Section: Discussionmentioning

confidence: 99%

Preclinical to clinical translation for intervertebral disc repair: Effects of species‐specific scale, metabolism, and matrix synthesis rates on cell‐based regeneration

McDonnell,

Wilson,

Barcellona

et al. 2023

JOR Spine

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BackgroundA significant hurdle for potential cell‐based therapies is the subsequent survival and regenerative capacity of implanted cells. While many exciting developments have demonstrated promise preclinically, cell‐based therapies for intervertebral disc (IVD) degeneration fail to translate equivalent clinical efficacy.AimsThis work aims to ascertain the clinical relevance of both a small and large animal model by experimentally investigating and comparing these animal models to human from the perspective of anatomical scale and their cellular metabolic and regenerative potential.Materials and MethodsFirst, this work experimentally investigated species‐specific geometrical scale, native cell density, nutrient metabolism, and matrix synthesis rates for rat, goat, and human disc cells in a 3D microspheroid configuration. Second, these parameters were employed in silico to elucidate species‐specific nutrient microenvironments and predict differences in temporal regeneration between animal models.ResultsThis work presents in silico models which correlate favorably to preclinical literature in terms of the capabilities of animal regeneration and predict that compromised nutrition is not a significant challenge in small animal discs. On the contrary, it highlights a very fine clinical balance between an adequate cell dose for sufficient repair, through de novo matrix deposition, without exacerbating the human microenvironmental niche.DiscussionOverall, this work aims to provide a path towards understanding the effect of cell injection number on the nutrient microenvironment and the “time to regeneration” between preclinical animal models and the large human IVD. While these findings help to explain failed translation of promising preclinical data and the limited results emerging from clinical trials at present, they also enable the research field and clinicians to manage expectations on cell‐based regeneration.ConclusionUltimately, this work provides a platform to inform the design of clinical trials, and as computing power and software capabilities increase in the future, it is conceivable that generation of patient‐specific models could be used for patient assessment, as well as pre‐ and intraoperative planning.

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Intervertebral Disc Nutrition

Cited by 56 publications

References 0 publications

The Combined Effects of Limited Nutrition and High-Frequency Loading on Intervertebral Discs With Endplates

The Combined Effects of Limited Nutrition and High-Frequency Loading on Intervertebral Discs With Endplates

Multi-scale biomechanical study of transport phenomena in the intervertebral disc

Preclinical to clinical translation for intervertebral disc repair: Effects of species‐specific scale, metabolism, and matrix synthesis rates on cell‐based regeneration

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