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Local Regulation of Angiogenesis by Microenvironment

微环境对血管生成的局部调节

基本信息

批准号：
10376043
负责人：
CHRISTOPHER S CHEN
金额：
$ 37.13万
依托单位：
BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10376043
关键词：
3-Dimensional Actins Adhesions Adhesiveness Adhesives Angiogenic Factor Apoptosis Architecture Automobile Driving Behavior Binding Biochemical Biocompatible Materials Blood Vessels Blood capillaries Capillary Endothelial Cell Cell Adhesion Cell physiology Cells Chemicals Chronic Complex Cues Cytoskeleton Development Devices Disease Endothelial Cells Engineering Engraftment Environment Equilibrium Extracellular Matrix Failure Gene Expression Goals Grant Growth Growth Factor Human body Implant In Vitro Invaded Investigation Ischemia Link Malignant Neoplasms Mechanics Mediating Methods Morphogenesis Movement Nutrient Organ Oxygen Pathogenesis Pathology Pattern Perfusion Play Positioning Attribute Postoperative Period Process Property Receptor Signaling Recovery Regulation Replacement Therapy Research Research Personnel Role Signal Pathway Signal Transduction Structure Testing Tissue Engineering Tissues Translating Vascular Diseases Vascularization angiogenesis clinically relevant crosslink design diabetic improved in vivo in vivo Model insight mechanical properties mechanical signal notch protein novel physical property rational design response rho success three-dimensional modeling tumor growth

项目摘要

Project Description and Summary The vascularization of engineered tissues is critical to the ultimate success of tissue engineering as an organ replacement therapy. The formation of new capillary vessels from existing vasculature, or angiogenesis, also is linked to the pathogenesis of numerous diseases including cancer, and is regulated by local cues within the tissue microenvironment. The general goal of this renewal project is to understand the mechanism by which local extracellular matrix (ECM) properties regulate endothelial cell invasion and sprout morphogenesis required in angiogenesis, and to use these insights to guide design of biomaterials to enhance angiogenesis for clinically relevant applications. The investigator has found that adhesion to ECM generates not only biochemical, but also mechanical signals that are important in driving endothelial cell function. Preliminary studies from the investigator suggest that ECM stiffness, adhesiveness, and degradability could be used to regulate the angiogenic invasion process through such materials by modulating key signaling pathways regulating the actin cytoskeleton. In this proposal, the investigator proposes to further investigate the role of these ECM cues in regulating angiogenic behaviors. The project proposes to develop biomaterials to investigate the contributions of different matrix properties and their cooperation in regulating angiogenesis using both in vitro and in vivo models, and to examine the morphodynamics of developing vasculature within those materials. The investigator will examine whether these materials can be used to control the architecture of angiogenic vessels. Together, these studies will define the mechanisms by which local structural and mechanical properties within ECM modulate endothelial cell function and capillary morphogenesis, and establish new biomaterials design strategies to promote angiogenesis in ex-vivo engineered tissues as well as native ischemic tissues.

项目描述及总结