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Image-Based Modeling for Improved Functionality in Tissue Engineered Constructs

基于图像的建模可改善组织工程结构的功能

基本信息

批准号：
7626360
负责人：
EDWARD A SANDER
金额：
$ 5.17万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-01 至 2010-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Tissue engineering has tremendous potential to improve health and quality of life, but to produce a mechanically functional tissue requires precise understanding of the interplay between a tissue's microstructure and its overall mechanical properties. Because of the complexity of native tissues, we must begin with a simple test system - a collagen gel - that shares some properties of native tissue and provides a "backbone" for the step-wise addition of other matrix components. In addition, we require an experimental system that simultaneously provides mechanical testing and imaging capabilities, and can track the evolution of local gel network arrangement with load. Finally, a theoretical framework, in the form of a multiscale computational model, is needed to connect each scale and relate microscopic structure to macroscopic function. Our essential hypothesis is that the mechanical properties of an engineered tissue are determined by the microstructure, which can be elucidated with modern imaging techniques. In order to test the hypothesis, we need to assess agreement between experiments and computational models at both the tissue and the network scale. A successful model must do three things: the predicted macroscopic mechanical response must match the gel's; the predicted local matrix rearrangements and strains must match the gel's; and the local matrix representation in the model must reflect the arrangement and composition of components in the gel. We propose first to produce, to image, and to test mechanically collagen gels that differ in fiber alignment. We will simultaneously acquire collagen gel mechanical data via biaxial testing, local alignment via polarized light microscopy, and strain maps via phase correlation. High resolution SEM images will provide supplemental microstructural information. Second, we will generate a multi-scale model based of the gel's local fiber microstructure and compare it to experimental data. The experiment's boundary conditions, loading protocol, and initial alignment map will serve as inputs for the multi-scale model. Comparisons between macroscopic mechanical behavior and local evolution of network orientation, alignment, and strain will be made. Finally, we will repeat this process for gels under confined compression and with the step-wise addition of other matrix components, starting with decorin, a proteoglycan known to effect cell behavior and gel mechanical properties. If successful, this project will lay the groundwork for more rational design of engineered tissues and for future analysis of structure-function relationships in native tissues. A means of repairing or replacing diseased and damaged tissues would be of enormous value to the health and quality of life of a patient

描述（由申请人提供）：组织工程具有改善健康和生活质量的巨大潜力，但要产生具有机械功能的组织，需要精确了解组织的微观结构及其整体机械性能之间的相互作用。由于天然组织的复杂性，我们必须从一个简单的测试系统（胶原蛋白凝胶）开始，该系统具有天然组织的一些特性，并为逐步添加其他基质成分提供“支柱”。开始。此外，我们需要一个实验系统，同时提供机械测试和成像能力，并可以跟踪局部凝胶网络排列与负载的演变。最后，需要一个多尺度计算模型形式的理论框架来连接每个尺度，并将微观结构与宏观功能联系起来。我们的基本假设是，工程组织的机械性能是由微观结构决定的，这可以用现代成像技术来阐明。为了验证这一假设，我们需要评估实验和计算模型在组织和网络尺度上的一致性。一个成功的模型必须做三件事：预测的宏观力学响应必须匹配凝胶的;预测的局部基质重排和应变必须匹配凝胶的;模型中的局部基质表示必须反映凝胶中组分的排列和组成。我们建议首先生产，图像，并测试不同的纤维排列的胶原蛋白凝胶机械。我们将同时通过双轴测试获得胶原凝胶力学数据，通过偏振光显微镜进行局部对准，并通过相位相关进行应变图。高分辨率 SEM图像将提供补充的微观结构信息。其次，我们将生成一个多尺度模型的凝胶的局部纤维微观结构的基础上，并将其与实验数据进行比较。实验的边界条件、加载协议和初始对准图将作为多尺度模型的输入。宏观力学行为和网络方向，对齐和应变的局部演化之间的比较。最后，我们将在受限压缩下对凝胶重复该过程，并逐步添加其他基质组分，从核心蛋白聚糖开始，核心蛋白聚糖是一种已知影响细胞行为和凝胶机械性能的蛋白聚糖。如果成功，该项目将为更合理地设计工程组织和未来分析天然组织中的结构-功能关系奠定基础。一种修复或替换患病和受损组织的方法对患者的健康和生活质量具有巨大价值