Biophysical Modeling of Solute Transport in Disc
Low back pain, a major socio-economic concern in the United States, is strongly associated with intervertebral disc (IVD) degeneration. Poor nutritional supply is believed to be one of the mechanisms for disc degeneration. The unique composition and structure of the materials and the complexity of the mechano-electrochemical coupling phenomena in IVD tissues contribute to a lack of knowledge of transport properties of IVD or appropriate theoretical models for investigating nutrient transport in IVD systematically. By measuring the transport properties of IVD tissues, our goal is to develop a new realistic mechano-electrochemical theory and finite element model for investigating the transport of fluid and solutes in IVD under various loading conditions.
Development of an in-Vitro Disc Degeneration Model System
In-vitro organ/tissue culture model play an important role in clarifying pathomechanism and testing novel interventions. We have developed a novel bioreactor system for long-term disc culture in which the phydicochemical environment within the disc can be weell-controlled. Using this mofel system, we are studying the effects of different nutrient levels and mechanical loading conditions on the disc biology and investigating initiation of disc degeneration using deficient nutrient supply and over mechanical load. This bioreactor system not only can be used to study nutrition and mechanobiology of disc degeneration, but also can be used to test new therapeutic strategies.
Imaging Disc Nutrition and Composition
Nutrients supplied by the capillaries have to penetrate the cartilage endplate before reaching the disc matrix. Calcification of the endplate can act as a significant barrier to nutrient transport. Using micro-CT, we are studying the correlation between endplate properties and the rate of nutrient transport. In addition, we are developing new methodologies to visualize the zascular supply to the disc and to quantify tissue composition using novel contrast agents for micro-CT imaging. These imaging methodologies will be validated through a series of in-vitro studies involving controlled manipulation of disc compostion within the above bioreactor system. Ultimately, these approaches will be incorporated into clinically relevant modalities.
This figure illustrates how the mechanical forces on the tissue level affects the physical signals at the cellular level, and how the tissue growth or degeneration changes the physical signals through changes in the tissue material properties of the ECM. Although the physical signals are very complex, comprised of mechano-electrochemical events within the ECM, it may be quantified by appropriate, theoretical models with realistic material properties. The goal is to develop this kind of mathematic model of the disc to accurately predict the physical signals and solute transport under mechanical loading and during tissue remodeling.
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Last updated November 2011