Biophysical Modeling of Solute Transport in Human IVD

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DESCRIPTION (provided by applicant): Low back pain is a major socio-economic concern in this country. Although the exact cause for low back pain is unclear, the degenerative changes of the intervertebral disc (IVD) have been implicated as a possible primary etiologic factor. Poor nutritional supply is believed to be one of the mechanisms for disc degeneration. 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 IVDs or appropriate theoretical models for investigating nutrient transport in IVD systematically. The purpose of this application is to determine the transport properties and the constitutive models for these properties in human IVDs required for the development of a new mechano-electrochemical transport theory and finite element model in a subsequent grant application. The broad, long-term objectives of this project are to (1) elucidate the etiology of disc degeneration, (2) help develop strategies for restoring tissue function or retarding further disc degeneration, and (3) develop novel, less-invasive diagnostic tools for disc degeneration. In this research, we will determine the mechanical, physicochemical, and transport properties of human lumbar IVD tissues (Specific Aims #1-#5) and develop and validate new constitutive models for transport properties (Specific Aims #6 & #7). New technologies, based on mechano-electrochemical principles, will be developed for testing transport properties of IVD tissues, including strain-dependent hydraulic permeability, strain-dependent fixed charge density, strain-dependent electrical conductivity, and strain-dependent diffusivity of ions and nutrients (oxygen and glucose) in human lumbar discs. These properties will be correlated to the composition of the tissue, and will be used in developing the new constitutive theories in the research of nutritional supply in human IVDs. The advance in theory, knowledge on material properties, and techniques will have a significant impact on understanding the etiology of disc degeneration as well as on other areas of research, such as drug delivery in biological tissues. A plan for sharing and disseminating the theory, techniques, and data developed in this research is also included.