In vitro microvessels for the study of angiogenesis and thrombosis

TLDR

Microvascular networks support metabolic activity and define microenvironmental conditions within tissues in health and pathology. Recapitulation of functional microvascular structures in vitro could provide a platform for the study of complex vascular phenomena, including angiogenesis and thrombosis. We engineered living microvascular networks in 3‑D tissue scaffolds using a lithographic technique to form endothelialized microfluidic vessels in native collagen, characterizing morphology, mass transfer, long‑term stability, angiogenic activity, perivascular interactions, and demonstrating non‑thrombotic endothelium that becomes pro‑thrombotic under inflammation. The success of these microvascular networks in recapitulating angiogenesis and thrombosis demonstrates the platform’s broad potential for studying cardiovascular biology and pathophysiology.

Abstract

Microvascular networks support metabolic activity and define microenvironmental conditions within tissues in health and pathology. Recapitulation of functional microvascular structures in vitro could provide a platform for the study of complex vascular phenomena, including angiogenesis and thrombosis. We have engineered living microvascular networks in three-dimensional tissue scaffolds and demonstrated their biofunctionality in vitro. We describe the lithographic technique used to form endothelialized microfluidic vessels within a native collagen matrix; we characterize the morphology, mass transfer processes, and long-term stability of the endothelium; we elucidate the angiogenic activities of the endothelia and differential interactions with perivascular cells seeded in the collagen bulk; and we demonstrate the nonthrombotic nature of the vascular endothelium and its transition to a prothrombotic state during an inflammatory response. The success of these microvascular networks in recapitulating these phenomena points to the broad potential of this platform for the study of cardiovascular biology and pathophysiology.