Competing Fluid Forces Control Endothelial Sprouting in a 3-D Microfluidic Vessel Bifurcation Model.

Sprouting angiogenesis-the infiltration and extension of endothelial cells from pre-existing blood vessels-helps orchestrate vascular growth and remodeling. It is now agreed that fluid forces, such as laminar shear stress due to unidirectional flow in straight vessel segments, are important regulators of angiogenesis. However, regulation of angiogenesis by the different flow dynamics that arise due to vessel branching, such as impinging flow stagnation at the base of a bifurcating vessel, are not well understood.

Flow dynamics control endothelial permeability in a microfluidic vessel bifurcation model.

Endothelial barrier function is known to be regulated by a number of molecular mechanisms; however, the role of biomechanical signals associated with blood flow is comparatively less explored. Biomimetic microfluidic models comprised of vessel analogues that are lined with endothelial cells (ECs) have been developed to help answer several fundamental questions in endothelial mechanobiology. However, previously described microfluidic models have been primarily restricted to single straight or two parallel vessel analogues, which do not model the bifurcating vessel networks typically present in physiology.

Microfluidic approaches to the study of angiogenesis and the microcirculation.

Microfluidic systems have emerged as a new class of perfusable in vitro culture models that have helped advance and refine our understanding of microvascular function. Cutting-edge microfluidic models have successfully integrated principles from quantitative analysis of vascular function, in vitro flow chambers, microfabrication techniques, and 3D tissue scaffolds. Here, we review the evolution of microfluidic systems, namely their progression from 2D planar microchannel arrays to 3D microtissue analogs, and highlight their recent contributions in elucidating the role of biomolecular transport and fluid mechanical stimuli in controlling angiogenesis.