Role of Fluid Flow in Bone's Response to Applied Loading

流体流动在骨骼对施加载荷的响应中的作用

• 批准号: 7225579
• 负责人: SUSANNAH P. FRITTON
• 金额: $ 19.89万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7225579
• 关键词: Actins; Apoptotic; Bed rest; Biochemical; Biological; Bone Density; Bone Growth; Bone Matrix; Bone Tissue; Cell membrane; Cells; Cellular Structures; Clinical; Complex; Confocal Microscopy; Cytoskeleton; Deposition; Devices; Elements; Ensure; Environment; Goals; Immobilization; Implant; In Vitro; Intercellular Fluid; Link; Liquid substance; Maintenance; Measurement; Measures; Mechanics; Metabolic; Methods; Microgravity; Modeling; Movement; Numbers; Orthopedics; Osteoblasts; Osteocytes; Osteogenesis; Osteoporosis; Permeability; Personal Satisfaction; Play; Porosity; Process; Protocols documentation; Rate; Rattus; Research Personnel; Role; Signal Transduction; Skeleton; System; Theoretical model; Thick; Time; Tissues; Tracer; Transport Process; Walking; Week; Work; bone; bone cell; density; design; fluid flow; improved; in vivo; insight; pressure; prevent; programs; research study; response; shear stress; simulation; size

DESCRIPTION (provided by applicant): Load-induced interstitial fluid flow is believed to enhance mass transport in bone to ensure the metabolic function of bone cells and it is also believed to play a role in bone's mechanosensory system via cell shear stresses or cytoskeletal deformations. Understanding how interstitial fluid moves through the bone porosities in normal and diseased states is an important step in elucidating bone's mechanosensory and mass transport processes. We would like to expand our work investigating interstitial fluid flow in cortical bone to study fluid flow in cancellous bone, which has largely been unexamined. We would also like to examine the effect of the metabolic perturbation of osteoporosis on fluid flow in both cortical and cancellous bone. We will do this by applying mechanical loading and observing tracer movement as well as cell and tissue adaptation over time. We will also quantify the fluid space surrounding the osteocytes of normal and osteoporotic bone to provide a much more complete determination of bone's three-dimensional lacunar-canalicular porosity to link microstructure more directly to fluid flow. We propose the following specific aims: (1) Compare the movement of exogenous tracers throughout the cancellous and cortical bone porosities in normal and ovariectomized rats (a) with no applied mechanical loading, (b) immediately after application of mechanical loading, and (c) after a four-week loading experiment where cell and tissue responses are also measured; and (2) Quantify the three-dimensional microstructure of the lacunar-canalicular porosity in normal and ovariectomized rats and use these measurements to calculate bone permeability and interstitial fluid flow in response to mechanical loading. By investigating the links between in vivo interstitial fluid flow, microstructure, and cell and tissue responses to mechanical loading in normal and osteoporotic bone, we believe this work will make a significant contribution to understanding bone's mechanosensory system and may provide insights into the mechanical-related aspects of osteoporosis. This project fits into our long-term goal to better understand the processes of bone adaptation and maintenance. A mechanistic understanding of these important processes should aid in the design of clinical devices or protocols to prevent and treat osteoporosis as well as osteopenia caused by immobilization, bed rest, or a microgravity environment, and should help to improve the design of orthopaedic implants as well as biological bone tissue replacements.

描述（由申请人提供）：负载诱导的间质液流动被认为可增强骨中的质量运输，以确保骨细胞的代谢功能，并且还被认为通过细胞剪切应力或细胞骨架变形在骨的机械感觉系统中发挥作用。了解在正常和患病状态下间质液如何通过骨孔隙移动是阐明骨的机械感觉和质量运输过程的重要一步。我们想扩大我们的工作，研究皮质骨间质液流，以研究松质骨中的流体流动，这在很大程度上是未经检查的。我们还想研究骨质疏松症的代谢紊乱对皮质骨和松质骨中液体流动的影响。我们将通过施加机械载荷和观察示踪剂运动以及细胞和组织随时间的适应来做到这一点。我们还将量化正常骨和骨化骨的骨细胞周围的流体空间，以提供更完整的骨的三维腔隙-小管孔隙度的测定，从而将微观结构更直接地与流体流动联系起来。我们提出了以下具体目标：（1）比较正常和卵巢切除大鼠（a）未施加机械负荷，（B）施加机械负荷后即刻，和（c）四周负荷实验后（其中还测量细胞和组织反应）中外源性示踪剂在松质骨和皮质骨孔隙中的运动;和（2）量化正常和卵巢切除大鼠中腔隙-小管孔隙度的三维显微结构，并使用这些测量值来计算响应于机械负荷的骨渗透性和间质液流量。通过研究正常骨和骨质疏松骨中体内间质液流动、微观结构以及细胞和组织对机械负荷的反应之间的联系，我们相信这项工作将为理解骨的机械感觉系统做出重大贡献，并可能为骨质疏松症的机械相关方面提供见解。该项目符合我们的长期目标，以更好地了解骨骼适应和维护的过程。对这些重要过程的机械理解应有助于临床器械或方案的设计，以预防和治疗骨质疏松症以及由固定、卧床休息或微重力环境引起的骨质减少，并应有助于改善骨科植入物和生物骨组织替代物的设计。