In situ imaging of OA cartilage micro-fluidics

OA 软骨微流体原位成像

• 批准号: 8637932
• 负责人: Christopher Price
• 金额: $ 16.26万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8637932
• 关键词: Address; Adult; Behavior; Binding; Biological Process; Biology; Biomechanics; Bovine Cartilage; Cartilage; Cartilage Matrix; Cattle; Chondrocytes; Color; Convection; Coupling; Degenerative polyarthritis; Dependency; Development; Diagnostic; Diffusion; Environment; Extracellular Matrix; Fluorescence; Fluorescent Probes; Future; Goals; Grant; Human; Image; Imaging Techniques; In Situ; In Vitro; Intercellular Fluid; International; Investigation; Kinetics; Knowledge; Liquid substance; Lubrication; Maps; Measurement; Measures; Mechanics; Metabolism; Methods; Microfluidics; Microscopy; Modeling; Pathology; Patients; Perfusion; Phase; Physiological; Property; Proteins; Relaxation; Sampling; Series; Shock; Societies; Solid; Specimen; Spectrum Analysis; Speed; Stress; Testing; Time; Tissue Sample; Tissues; Tracer; articular cartilage; base; bioimaging; cartilage metabolism; cartilage repair; digital imaging; direct application; fluid flow; innovation; insight; knee replacement arthroplasty; mathematical model; nano; novel; nutrition; particle; public health relevance; solute; spatiotemporal; success; tool; Address; Adult; Behavior; Binding; Biological Process; Biology; Biomechanics; Bovine Cartilage; Cartilage; Cartilage Matrix; Cattle; Chondrocytes; Color; Convection; Coupling; Degenerative polyarthritis; Dependency; Development; Diagnostic; Diffusion; Environment; Extracellular Matrix; Fluorescence; Fluorescent Probes; Future; Goals; Grant; Human; Image; Imaging Techniques; In Situ; In Vitro; Intercellular Fluid; International; Investigation; Kinetics; Knowledge; Liquid substance; Lubrication; Maps; Measurement; Measures; Mechanics; Metabolism; Methods; Microfluidics; Microscopy; Modeling; Pathology; Patients; Perfusion; Phase; Physiological; Property; Proteins; Relaxation; Sampling; Series; Shock; Societies; Solid; Specimen; Spectrum Analysis; Speed; Stress; Testing; Time; Tissue Sample; Tissues; Tracer; articular cartilage; base; bioimaging; cartilage metabolism; cartilage repair; digital imaging; direct application; fluid flow; innovation; insight; knee replacement arthroplasty; mathematical model; nano; novel; nutrition; particle; public health relevance; solute; spatiotemporal; success; tool

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is a debilitating condition in which articular cartilage is damaged and its mechanical functions (i.e. load support and lubrication), which are dependent on the biphasic behaviors of the tissue, are progressively compromised. Cartilage's fluid phase, its most abundant component, not only acts as a shock absorber and load bearer (due to the viscoelastic coupling between the fluid and solid phases), but also influences cartilage nutrition/metabolism and chondrocyte mechanotransduction. Alterations in this fluid environment have been implicated in OA. While modeling and perfusion studies have provided valuable insight into cartilage's fluid behaviors, there remains an unmet need for real-time in situ measurement of fluid flow in cartilage. In this grant we propose a novel bioimaging approach to measure the cartilage micro-fluidic environment based upon spatiotemporal image correlation spectroscopy (STICS). STICS is a recently developed imaging technique that has been successfully applied to the study of intracellular solute/protein kinetics in vitro. The objective of this study is to develop and standardized STICS imaging for the in situ measurement of both matrix deformation and solute convection in mechanically loaded cartilage. A dual-color confocal STICS approach will be used to quantify the spatial and loading rate dependency of solid matrix and fluid phase behaviors in bovine cartilage plugs subjected to unconfined compression stress-relaxation tests. We will then extend dual-color STICS transport imaging to the quantification of solute convection in human OA cartilage specimens obtained from total knee arthroplasty patients. In which, we hypothesize that load-induced fluid velocity increases with OA is correlated with tissue damage, and indicative of early cartilage degeneration. The proposed in situ quantification of cartilage's fluid environment, given its critical influence on tissue function, represents an innovative tool for studying cartilage's fluid solid interactions. If successful, STICS will be the first bioimaging approach for the direct real-time quantification of cartilage microfluidics and local solid matrix deformations, which are both potent modulators of chondrocyte function. The proposed studies with the novel dual-color STICS approach will yield new quantitative knowledge of the fluid behavior in both normal and diseased cartilage, enabling future investigations of cartilage biomechanics, biology, and the mechanisms of OA initiation and progression.

描述（由申请人提供）：骨关节炎（OA）是一种令人衰弱的疾病，关节软骨受损，其机械功能（即负载支持和润滑）取决于组织的双相行为，逐渐损害。软骨的流体相，最丰富的成分，不仅充当减震器和负载载体（由于流体和固体相之间的粘弹性耦合），而且还影响软骨营养/代谢和软骨细胞机械装置。这种流体环境中的改变已与OA有关。虽然建模和灌注研究为软骨的流体行为提供了宝贵的见解，但仍然需要实时测量软骨中流体流量的实时需求。在这笔赠款中，我们提出了一种新型的生物成像方法，以基于时空图像相关光谱（STICS）来测量软骨微流体环境。 Stics是一种最近开发的成像技术，已成功应用于体外细胞内溶质/蛋白质动力学的研究。这项研究的目的是开发和标准化的Stics成像，以对机械负载软骨中基质变形和溶质对流的原位测量。双色共聚焦STICS方法将用于量化牛软骨插头中实心基质和流体相行为的空间和加载速率依赖性，并经受了未经限制的压缩应力 - 浮肿测试。然后，我们将将双色Stics运输成像扩展到对从总膝关节置换术患者获得的人OA软骨标本中溶质对流的定量。其中，我们假设负载诱导的流体速度与OA的增加与组织损伤相关，并指示早期软骨变性。鉴于其对组织功能的关键影响，提议的原位定量软骨的流体环境是研究软骨液的创新工具 固体相互作用。如果成功的话，Stics将是软骨微流体和局部实心基质变形的直接实时定量的第一种生物成像方法，它们都是软骨细胞功能的有效调节剂。提出的新型双色Stics方法的研究将在正常和患病软骨中对流体行为产生新的定量知识，从而使未来的软骨生物力学，生物学以及OA启动和进展的机制进行了研究。