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 Clemson & MUSC Joint Bioengineering Lab | Invertebral Disc

 Invertebral Disc Degeneration

Introduction 

In human spine, the intervertebral disc is a plaint, fibrocartilagenous tissue between the vertebral bodies, and contributes flexibility and load support in the spine. The disc is composed of two tissues: an outer-layer annulus fibrosus and a central proteoglycan-rich nucleus pulposus. The major compositions of these tissues include interstitial water, collagen fiber and proteoglycans. Multiple cell types are contained in these tissues, such as fibrochondrocytes within the annulus and notochondral cells within the nucleus. These cells maintain the health of the extracellular matrix for accomplishing the mechanical function of the disc. 

Disc degeneration happens once the disc cells fail to maintain the balance between the matrix synthesis and the matrix degradation. The most significant biochemical change in disc degeneration is loss of proteoglycan. This loss is responsible for a drop of osmostic pressure in the disc and the decrease of hydration. Such major changes will significantly affect the mechanical function of the disc. Disc degeneration has been strongly linked to the low back pain, a very popular health problem which affect more than 5% of the population per year and cost about $20 billion dollars annually in this country. Numerous studies have been done to understand the etiology of disc degeneration. However, the mechanism is still remain unknown. One of the primary causes of disc degeneration is thought to be failure of the nutrient supply to the disc cells due to its avascular feature. Abnormal mechanical loads are also thought to provide a pathway to disc degeneration. Besides, recent work suggest that disc degeneration may have genetic components. 

The disc is an avascular, negetively charged tissue and experiences mechanical load at all times. These features lead disc cells facing a complex physicochemical environment, which includes mechanical signals, such as strain, stress and fluid pressure, chemical signals, such as concentrations of nutrients and growth factors, and electrical signals which refer to ionic environment. Both in vivo and in vitro studies have shown that such changes of the physicochemical environment have strong influence on the disc cell activity. Most are dose dependent. The cellular response can alter the matrix, and initiate structure remodeling. These process are important for disc homeostasis. But they can also lead to disorganization and dysfunction, such as disc degeneration. Therefore, one of the key points to clarify the mechanism of the disc degeneration is to understand the cell response to the change of physicochemical environment induced by mechanical loading or induced by the change of the tissue composition during the tissue remodeling. As a first step, it is necessary to quantitatively determine the physicochemical environment within the disc under different mechanical loading condition. Currently, in vivo direct measurement of all these signals seems impossible. However, it might be possible to predict these signal by appropriate, biomechanical models with realistic material properties. 

The study has three major objectives. First, to develop function constitutive relationship between hydraulic permeability and tissue composition for disc tissues. Second to develop constitutive relation of solute diffusivity. Last to develop a 3D triphasic finite element model for analyzing physical signals and nutrient transport in the disc. This research is important for understanding the mechanism of disc degeneration, and will be useful to develop strategies either for restoring tissue function or retarding further disc degeneration. Also, the quantified physical signals may be used as an indicator for the diagnosis of disc degeneration. 


 

Our 3D finite element model was based on the mechano-electrochemical triphasic theory proposed by Lai et al. The disc tissue was modeled as an isotropic homogeneous mixture consisting of an elastic solid with fixed charge, interstitial water, ions and uncharged solute species. The balance of the linear momentum for the mixture and the conservation of mass for each species lead to the governing equations. Xigema is the total stress of the tissue. J stands for the flux for the each species. K, H, D are the transport properties. K is the hydraulic permeability. For each solute, H are the hindrance factor for the convection and D are the diffusivities in the tissue. 


 

The conservation of fixed charge on the solid matrix was included in the governing equation. New constitutive relationships for transport properties were also proposed. In these two equations, both permeability and diffusivity are related to the tissue water content. Since water content is a function of the tissue deformation, both permeability and diffusivity are all strain dependent.



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Last updated November 2011