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

Area of Science:

• Biomedical Engineering
• Vascular Biology
• Fluid Dynamics

Background:

• Sprouting angiogenesis is crucial for vascular growth and remodeling.
• Fluid forces like shear stress regulate angiogenesis, but flow dynamics at vessel bifurcations remain poorly understood.
• Understanding these dynamics is key to controlling vascular development.

Purpose of the Study:

• To investigate the role of flow conditions at vessel bifurcations on endothelial sprouting.
• To elucidate the mechanisms by which bifurcating flow and shear stress regulate angiogenesis.
• To explore the influence of transvascular flow in conjunction with shear stress.

Main Methods:

• Utilized a novel 3-D microfluidic model to simulate physiological flow conditions.
• Applied controlled shear stress and transvascular flow across endothelial monolayers.
• Observed and quantified endothelial cell sprouting in response to varying flow dynamics.

Main Results:

• Bifurcating fluid flow at vessel junctions suppressed angiogenic sprouting.
• Laminar shear stress (~3 dyn/cm²) downstream of bifurcations also inhibited sprouting.
• Co-application of transvascular flow (~1 µm/s) with shear stress induced angiogenic sprouting.

Conclusions:

• Bifurcating flow dynamics play a stabilizing role, suppressing endothelial sprouting.
• Transvascular flow counteracts the inhibitory effects of bifurcating flow and shear stress.
• Local flow dynamics dictated by vessel geometry are critical determinants of sprouting angiogenesis location.