Matrix stiffening in the formation of blood vessels

Abstract

Angiogenesis, the process where new blood vessels form from existing vasculature, is essential for the successful integration of most tissue-engineered constructs and is dysregulated in many diseases, including cancer. To be functional, the newly formed vasculature must have similar structure and integrity as existing blood vessels, both of which are dependent upon mechanical and chemical cues from the surrounding extracellular matrix (ECM). ECM stiffness has emerged as a critical extracellular parameter that can modulate capillary network formation and barrier integrity. Moreover, matrix stiffness can alter how endothelial cells respond to soluble, angiogenic factors released by stromal cells, such as vascular endothelial growth factor (VEGF). In this review, we will discuss how matrix stiffness can affect the formation and structure of angiogenic vessels, and we will highlight the role of this work in the development of therapeutics to treat angiogenesis in cancer. Knowledge of the governing parameters for vessel formation is critical to the intelligent design of materials made to foster blood vessel growth for tissue-engineering applications and pharmaceuticals designed to intervene with newly formed vasculature in diseased tissue.