Biophysical Modeling of Solute Transport in Human IVD

描述（由申请人提供）：腰痛是该国的一个主要社会经济问题。虽然腰痛的确切原因尚不清楚，但椎间盘（IVD）的退行性变化已被认为是可能的主要病因。营养供应不足被认为是椎间盘退变的机制之一。由于IVD组织中材料的独特组成和结构以及机械-电化学耦合现象的复杂性，缺乏对人体IVD的转运特性的了解或系统研究IVD中营养物质转运的适当理论模型。本申请的目的是确定运输性能和本构模型，这些属性在人类体外诊断所需的一个新的机械电化学运输理论和有限元模型的发展，在随后的拨款申请。该项目广泛的长期目标是（1）阐明椎间盘退变的病因，（2）帮助制定恢复组织功能或延缓进一步椎间盘退变的策略，以及（3）开发新的、侵入性较小的椎间盘退变诊断工具。在本研究中，我们将确定人腰椎IVD组织的机械、物理化学和运输特性（具体目标#1-#5），并开发和验证运输特性的新本构模型（具体目标#6和#7）。将开发基于机械电化学原理的新技术，用于测试IVD组织的传输特性，包括应变依赖性水力渗透率、应变依赖性固定电荷密度、应变依赖性电导率以及人体腰椎间盘中离子和营养物质（氧气和葡萄糖）的应变依赖性扩散率。这些性质将与组织的组成相关，并将用于发展新的组成理论，研究人类IVD的营养供应。理论、材料特性知识和技术的进步将对理解椎间盘退变的病因以及其他研究领域（如生物组织中的药物递送）产生重大影响。还包括分享和传播本研究中开发的理论，技术和数据的计划。

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.