Low back pain is a major socio-economic concern in the United States. Although the exact cause for low back pain is unclear, degeneration of the intervertebral disc (lVD) has been implicated as a possible primary etiologic factor. Poor nutritional supply is believed to be one of the mechanisms for disc degeneration and hampers any tissue engineering or repair attempt. Due to the unique composition and structure of the materials and the complexity of the mechano-electrochemical coupling phenomena in IVD tissues, there is a lack of knowledge on transport properties of human lVDs and appropriate theoretical models for investigating nutrient transport in IVD systematically. The goal of this research is to fill this gap by measuring transport properties of human IVD tissues, and develop a new mechano-electrochemical transport theory and finite element model for investigating the transport of fluid and solute in human IVD. The proposed study will focus on determination of the electromechanical and transport properties of human lumbar cartilaginous end-plate (CEP), which is thought to play an important role in disc nutrition and load distribution. Our hypothesis is that human CEP, compared to human articular cartilage, is stiffer and more permeable to the interstitial fluid and solutes, and mechanical loading affects the rates of fluid and solute transport in this tissue by changing tissue hydration.
Two specific aims will be pursued during this study.
Specific Aim #1 is to determine hydraulic permeability, fixed charge density, and electrical conductivity of human CEP under various mechanical strains, obtain ion diffusivities from electrical conductivity data, and develop new constitutive relationships between transport properties (hydraulic permeability and solute diffusivity) and tissue hydration to establish strain-dependent transport properties.
Specific Aim #2 is to determine the compressive and shear mechanical properties of human CEP and correlate the material properties to the tissue composition. The obtained material properties will be used in developing a new multiphasic finite element model of human IVD to systematically quantify the physicochemical environment within the disc under various loading conditions. The advance in theory, numerical tools, data on material properties, and measuring techniques will have a significant impact on understanding etiology of disc degeneration as well as on developing new strategies for tissue regeneration.

Public Health Relevance

Project Narrative The goal of this project is to determine the mechanical and transport properties of human cartilaginous end- plate and investigate the effect of mechanical strain on the fluid and solute transport for understanding the nutrition-related mechanism of intervertebral disc degeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR055775-02
Application #
7772312
Study Section
Special Emphasis Panel (ZAR1-EHB-D (M1))
Program Officer
Tyree, Bernadette
Project Start
2009-07-01
Project End
2012-12-31
Budget Start
2010-07-01
Budget End
2012-12-31
Support Year
2
Fiscal Year
2010
Total Cost
$73,111
Indirect Cost
Name
Clemson University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
042629816
City
Clemson
State
SC
Country
United States
Zip Code
29634
Cisewski, Sarah E; Wu, Yongren; Damon, Brooke J et al. (2018) Comparison of Oxygen Consumption Rates of Nondegenerate and Degenerate Human Intervertebral Disc Cells. Spine (Phila Pa 1976) 43:E60-E67
Wu, Y; Cisewski, S E; Wei, F et al. (2017) Fluid pressurization and tractional forces during TMJ disc loading: A biphasic finite element analysis. Orthod Craniofac Res 20 Suppl 1:151-156
Wu, Yongren; Cisewski, Sarah E; Sun, Yi et al. (2017) Quantifying Baseline Fixed Charge Density in Healthy Human Cartilage Endplate: A Two-point Electrical Conductivity Method. Spine (Phila Pa 1976) 42:E1002-E1009
Hepfer, R Glenn; Brockbank, Kelvin G M; Chen, Zhen et al. (2016) Comparison and evaluation of biomechanical, electrical, and biological methods for assessment of damage to tissue collagen. Cell Tissue Bank 17:531-9
Wu, Yongren; Cisewski, Sarah E; Wegner, Nicholas et al. (2016) Region and strain-dependent diffusivities of glucose and lactate in healthy human cartilage endplate. J Biomech 49:2756-2762
Wu, Y; Kuo, J; Wright, G J et al. (2015) Viscoelastic shear properties of porcine temporomandibular joint disc. Orthod Craniofac Res 18 Suppl 1:156-63
Cisewski, S E; Zhang, L; Kuo, J et al. (2015) The effects of oxygen level and glucose concentration on the metabolism of porcine TMJ disc cells. Osteoarthritis Cartilage 23:1790-6
Wu, Yongren; Cisewski, Sarah E; Sachs, Barton L et al. (2015) The region-dependent biomechanical and biochemical properties of bovine cartilaginous endplate. J Biomech 48:3185-91
Shi, Changcheng; Cisewski, Sarah E; Bell, P Darwin et al. (2014) Measurement of three-dimensional anisotropic diffusion by multiphoton fluorescence recovery after photobleaching. Ann Biomed Eng 42:555-65
Wright, Gregory J; Brockbank, Kelvin G M; Rahn, Eliza et al. (2014) Impact of storage solution formulation during refrigerated storage upon chondrocyte viability and cartilage matrix. Cells Tissues Organs 199:51-8

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