In situ imaging of OA cartilage micro-fluidics

OA 软骨微流体原位成像

• 批准号: 8445794
• 负责人: Christopher Price
• 金额: $ 18.38万
• 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 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8445794
• 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

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）是一种使人衰弱的疾病，其中关节软骨受损，并且其取决于组织双相行为的机械功能（即负载支撑和润滑）逐渐受损。软骨的液相是其最丰富的成分，不仅充当减震器和负荷承受者（由于液相和固相之间的粘弹性耦合），而且还影响软骨营养/代谢和软骨细胞力转导。这种液体环境的改变与骨关节炎有关。虽然建模和灌注研究为了解软骨的流体行为提供了有价值的见解，但对软骨中流体流动的实时原位测量的需求仍然未得到满足。在这笔资助中，我们提出了一种基于时空图像相关光谱（STICS）的新型生物成像方法来测量软骨微流体环境。 STICS是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。本研究的目的是开发和标准化 STICS 成像，用于机械加载软骨中基质变形和溶质对流的原位测量。双色共焦 STICS 方法将用于量化经过无侧限压缩应力松弛测试的牛软骨塞中固体基质和流体相行为的空间和加载速率依赖性。然后，我们将双色 STICS 传输成像扩展到从全膝关节置换术患者获得的人类 OA 软骨样本中溶质对流的量化。其中，我们假设负载引起的流体速度随 OA 的增加与组织损伤相关，并表明早期软骨退化。鉴于软骨液体环境对组织功能的关键影响，拟议的软骨液体环境原位定量代表了研究软骨液体的创新工具 牢固的互动。如果成功，STICS 将成为第一个直接实时量化软骨微流体和局部固体基质变形的生物成像方法，这两者都是软骨细胞功能的有效调节剂。所提出的采用新型双色 STICS 方法的研究将产生正常软骨和患病软骨中流体行为的新定量知识，从而使未来能够研究软骨生物力学、生物学以及 OA 发生和进展的机制。