Angiogeneis and the Extracellular Matrix

描述（由申请人提供）：本生物工程研究基金的主要目标是在微观水平上研究血管生成微血管与细胞外基质（ECM）的生物力学相互作用，以开发血管生成的计算模型。我们之前的工作已经导致假设邻近血管生成微血管的ECM结构和机械负载条件是血管生成发芽和新血管生长和引导的潜在决定因素。为了验证这一假设，我们将评估在机械边界条件改变、胶原纤维结构和凝胶特性受到干扰的情况下，以胶原凝胶为基础的微血管三维器官培养系统中的血管生成。血管生成芽和新血管在培养系统中与邻近胶原基质形成的相互作用动力学以及整体组织构建行为将使用物质点法（MPM）建模和分析。微血管行为和胶原结构动力学的实验数据，结合先进的成像技术，将为建模工作提供框架和参数。由于微血管和ECM之间局部、微观尺度的相互作用的重要性，该模型将强调这些方面。除了更好地理解血管生成血管、周围ECM结构和血管生成组织力学之间的关系外，该项目还将为改善对天然组织（例如，修复缺血组织）和组织工程构建中的组织血管化的控制提供基础。公共卫生相关性：拟议的研究将阐明机械力和细胞外基质结构在血管生成中的作用的基本方面。血管生成的过程是伤口愈合和肿瘤转移的一个整体特征。本研究结果将提供血管生成微血管与细胞外基质相互作用的机制理解，并为血管化组织替代物的设计和开发提供指导。

DESCRIPTION (provided by applicant): The broad objective of this Bioengineering Research Grant is to study biomechanical interactions of angiogenic microvessels with the extracellular matrix (ECM) on the microscale level to develop a computational model of angiogenesis. Our previous work has lead to the hypothesis that the ECM structure adjacent to angiogenic microvessels and the mechanical loading conditions are potential determinants of angiogenic sprouting and neovessel growth and guidance. To test this hypothesis, we will evaluate angiogenesis in a collagen gel-based, 3- dimensional organ culture system of microvessels in the presence of altered mechanical boundary conditions and perturbed collagen fibril structure and gel properties. The interaction dynamics between the angiogenic sprouts and neovessels that form in this culture system with the adjacent collagen matrix and the overall tissue construct behavior will be modeled and analyzed using material point method (MPM). Experimental data of both microvessel behavior and collagen structure dynamics, gathered with advanced imaging techniques, will provide the framework and parameters for the modeling effort. Because of the importance of the local, microscale, interactions between the microvessel and the ECM, the model will emphasize these aspects. In addition to establishing a better understanding of the relationship between angiogenic vessels, the surrounding ECM structure, and the mechanics of the tissue undergoing angiogenesis, the project will provide the basis for improved control of tissue vascularization in both native tissues (e.g., repairing ischemic tissue) and tissue engineered constructs. PUBLIC HEALTH RELEVANCE: The proposed research will elucidate fundamental aspects of the roles of mechanical forces and extracellular matrix structure in angiogenesis. The process of angiogenesis is an integral feature of wound healing and tumor metastastis. The results of this research will provide a mechanistic understanding of the interaction of angiogenic microvessels with the extracellular matrix, and provide guidelines for the design and development of vascularized tissue replacements.