Nutrient Related Mechanisms of Intervertebral Disc Degeneration

The intervertebral disc (IVD) separates the vertebrae allowing flexibility, strength, as well as a wide range of mechanical motion in the spine. Millions of Americans are afflicted with IVD degeneration which can cause low back pain and limited functionality of the spine. Deviation from physiological nutrient levels due to abnormal mechanical loading and age is believed to be one of the main mechanisms for low back pain associated disc degeneration. Since the IVD is the largest avascular structure in the body, transport of nutrients (e.g., O2 and glucose) is primarily done through the passive transport mechanism of diffusion. Transport of nutrients and solutes through the extracellular matrix is important in maintaining the normal function of tissues, so deviation from physiological levels can cause tissue necrosis and matrix degradation. The objective of this research is to investigate the effect of mechanical loading on nutrient transport and cell nutrition of the IVD in order to develop a 3D imaging based finite element model to better understand in vivo fluid and nutrient transport within the human IVD as well as the biomechanical etiology of disc degeneration. Therefore, our central hypothesis is that sustained mechanical loading can alter solute transport and nutrient concentrations in the IVD, resulting in changes to the cellular metabolism, tissue composition, and mechanical function, ultimately leading to disc degeneration in the human IVD disc. To address this hypothesis, this dissertation established a set of aims including;

Aim 1: Determine the metabolic phenotype of human IVD cells.

Aim 2: Examine the effect of mechanical strains on glucose and lactate diffusivity values of the cartilage endplate region of human IVDs in vitro.

Aim 3: Develop and validate a 3D multiphasic mechano-electrochemical finite element model of the human IVD to quantify and predict changes in nutrient levels under various loading conditions that occur in vivo.

The ultimate goal of this project is to characterize the nutrient diffusivities and metabolic phenotype of the IVD to develop and validate a 3D multiphasic mechanoelectrochemical finite element model in an effort to quantify and predict changes in nutrient levels under various loading conditions that occur in vivo and better understand low back pain associated disc degeneration. The outcome of this study will yield 1) a new realistic anisotropic mechano-electrochemical theory and finite element model for investigating the transport of fluid and solutes in human IVDs under various loading conditions and 2) the first study to characterize the effect of mechanical strains on nutrient diffusivity values of the cartilage endplate region of human IVDs in vitro. Finally, the project will bring a human biomechanical model for improving clinical diagnosis of disc degeneration.

Year	Entry
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Year

Entry

2001

Pfirrmann CWA, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine. September 1, 2001;26(17):1873-1878.

1995

Ohshima H, Urban JPG, Bergel DH. Effect of static load on matrix synthesis rates in the intervertebral disc measured in vitro by a new perfusion technique. J Orthop Res. January 1995;13(1):22-29.

1975

Maroudas A, Stockwell RA, Nachemson A, Urban J. Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro. J Anat. September 1975;120(1):113-130.

1988

Urban JPG, McMullin JF. Swelling pressure of the lumbar intervertebral discs influence of age, spinal level, composition, and degeneration. Spine. February 1988;13(2):179-187.

1985

Urban JPG, McMullin JF. Swelling pressure of the inervertebral disc: influence of proteoglycan and collagen contents. Biorheology. 1985;22(2):145-157.