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QUANTIFYING TRACER TRANSPORT IN CYCLICALLY LOADED BONE

量化循环负载骨中的示踪剂运输

基本信息

批准号：
6375283
负责人：
SUSANNAH P. FRITTON
金额：
$ 6.76万
依托单位：
CITY COLLEGE OF NEW YORK
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-01 至 2003-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6375283
关键词：
animal tissue biological models biological transport biomechanics bone bone metabolism fluid flow fluorescent dye /probe horseradish peroxidase immunocytochemistry laboratory rat mechanical stress model design /development osteocytes sensory mechanism

项目摘要

Although it is well accepted that bone adapts to its mechanical loading environment, the underlying mechanisms of this process have not been ascertained. It has been proposed that bone fluid flow plays a role in bone's mechanosensory system via the shear stresses that it produces on bone cells, stresses that have been shown to produce biochemical responses in bone cells in vitro. Stress-induced bone fluid flow has also been proposed to enhance mass transport in cyclically loaded bone. The activities outlined in this proposal would enable the PI to investigate a new line of research to develop novel methods to quantify microstructural fluid flow in mechanically loaded bone. Recent theoretical models developed by the PI and coworkers have proposed that in cyclically loaded bone fluid pressure gradients arc amplified around the vascular canals and that the primary relaxation of the excess bone fluid pressure occurs through this vascular porosity. In addition, in this proposal a new conceptual model is proposed to explain the enhanced molecular transport observed in recent experiments during cyclic loading. The new hypothesis proposed is that although there is no net fluid transport in the lacunar-canalicular porosity during cyclic loading, there is an enhanced convective mixing in the lacunae due to the asymmetry of the inward and outward solute fluxes arising from the molecular mixing process that occurs in each lacuna during the loading cycle. To explore this hypothesis regarding enhanced molecular transport due to an asymmetric mixing in cyclically loaded bone, the following specific aims arc proposed: (1) To develop a detailed theoretical model to describe molecular transport in mechanically loaded bone based on the assumption that net solute transport will only occur if mixing is the lacuna occurs during each loading cycle; (2) To develop novel methods to quantify this mixing process by building a mechanical loading device that will non-invasively deliver physiological loads to bone in vivo, and to refine an experimental protocol to quantify tracer transport in mechanically loaded bone; and (3) To use the developed device and protocol to explore for the first time the sequential spread of tracers in cyclically loaded bone as a function of number of cycles and distance from the vascular canal. The proposed experiments should provide new information on tile mechanisms of bone's mechanosensory system, information that could be used to design clinical devices or protocols to improve the methods of prevention and treatment of osteoporosis as well as osteopenia caused by immobilization, bed rest, or a microgravity environment, and to improve the design and functionality of orthopaedic implants such as total joint replacements and fracture fixation devices as well as biological bone tissue replacements.

虽然骨适应其机械载荷环境是公认的，但这一过程的潜在机制尚未确定。已经提出，骨流体流动通过其在骨细胞上产生的剪切应力在骨的机械感觉系统中起作用，所述剪切应力已经被证明在体外在骨细胞中产生生化反应。应力诱导的骨液流动也被提出来增强循环加载骨中的质量传输。本提案中概述的活动将使PI能够调查一系列新的研究，以开发新的方法来量化机械负载骨中的微观结构流体流动。 PI及其同事开发的最新理论模型提出，在循环加载的骨液压力梯度在血管管周围放大，并且过量骨液压力的主要松弛通过该血管孔隙发生。此外，在这个建议中，提出了一个新的概念模型，以解释在最近的实验中观察到的增强的分子传输在循环加载。提出的新的假设是，虽然没有净流体运输的腔隙-小管孔隙率在循环加载过程中，有一个增强的对流混合的腔隙中由于不对称的向内和向外的溶质通量所产生的分子混合过程中发生在每个腔隙在加载周期。为了探索由于周期性负载骨中的不对称混合而增强分子转运的假设，提出了以下具体目标：（1）基于净溶质转运仅在混合时才会发生的假设，建立一个详细的理论模型来描述机械负载骨中的分子转运每个负载周期期间发生的空隙;（2）开发新的方法来量化这种混合过程，通过构建将非侵入性地将生理负荷传递到体内骨的机械负荷装置，并改进实验方案来量化机械负荷骨中的示踪剂运输;和（3）使用所开发的装置和方案首次探索示踪剂在循环加载的骨中的顺序扩散作为循环次数和距血管管的距离的函数。拟议的实验应提供有关骨的机械感觉系统的机制的新信息，这些信息可用于设计临床设备或方案，以改进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的方法。并改进整形外科植入物的设计和功能，例如全关节置换和骨折固定装置以及生物骨组织置换。