Three-dimensional modeling of flow through microvascular beds and surrounding interstitial spaces

Area of Science:

• Biomedical Engineering
• Computational Biology
• Vascular Biology

Background:

• Microvascular beds are vital for tissue health, with fluid flow generating critical mechanical forces.
• Accurate measurement of these forces is difficult; current computational fluid dynamics (CFD) models often simplify vessel networks or ignore interstitial flow.
• Extraluminal flow and endothelial permeability significantly influence microvascular dynamics but are often overlooked in existing models.

Purpose of the Study:

• To develop a novel 3D computational fluid dynamics (CFD) model for engineered microvascular networks.
• To investigate the impact of endothelial permeability and interstitial space on intraluminal flow dynamics.
• To provide a robust framework for studying vascular physiology and pathology in vitro.

Main Methods:

• Image processing algorithms were used to segment 3D confocal image stacks of engineered capillary networks.
• A 3D computational model was reconstructed, incorporating vascular permeability and matrix porosity.
• Simulations were performed to assess fluid flow dynamics within the 3D network, including intraluminal and interstitial spaces.

Main Results:

• Including the endothelial monolayer and interstitium significantly altered predicted intraluminal flow magnitude and interstitial flow profiles.
• Cytokine (IL-1β) treatment increased vessel permeability but did not alter network architecture.
• Increased permeability led to decreased wall shear stress and intraluminal flow velocities.

Conclusions:

• The developed 3D modeling framework accurately captures flow dynamics in engineered microvascular networks.
• This approach enhances understanding of how endothelial permeability and interstitial flow affect vascular mechanics.
• The methodology provides valuable insights into vascular physiology and the mechanisms underlying vascular diseases.