The role of mechanical stresses in angiogenesis.

Angiogenesis is the formation of new capillary blood vessels from preexisting vessels. It is involved in many normal and diseased conditions, as well as in the application of tissue-engineered products. There has been extensive effort made to develop strategies for controlling pathological angiogenesis and for promoting vascularization in biomedical engineering applications. Central to advancing these strategies is a mechanistic understanding of the angiogenic process. Angiogenesis is tightly regulated by local tissue environmental factors, including soluble molecules, extracellular matrices, cell-cell interactions, and diverse mechanical forces. Great advances have been made in identifying the biochemical factors and intracellular signaling pathways that mediate the control of angiogenesis. This review focuses on work that explores the biophysical aspect of angiogenesis regulation. Specifically, we discuss the role of cell-generated forces, counterforces from the extracellular matrix, and mechanical forces associated with blood flow and extravascular tissue activity in the regulation of angiogenesis. Because angiogenesis occurs in a mechanically dynamic environment, future investigations should aim at understanding how cells integrate chemical and mechanical signals so that a rational approach to controlling angiogenesis will become possible. In this regard, computational models that incorporate multiple epigenetic factors to predict capillary patterning will be useful.