A nanoporous hydrogel-based model to study chemokine gradient-driven angiogenesis under luminal flow.

Area of Science:

• Biomedical Engineering
• Cell Biology
• Vascular Biology

Background:

• Angiogenesis, the formation of new blood vessels, is crucial for development and disease.
• Endothelial cell sprouting is initiated by chemokine gradients and influenced by mechanical cues like shear stress from fluid flow.
• The synergistic effects of biochemical and mechanical signals on angiogenesis remain incompletely understood.

Purpose of the Study:

• To investigate the combined effects of chemokine gradients and luminal fluid flow on angiogenic sprouting.
• To develop and utilize a 3D biomimetic model simulating in vivo conditions for studying angiogenesis.

Main Methods:

• Created a 3D biomimetic model with endothelial cells in a hydrogel matrix connected to a perfusion system.
• Employed a nanoporous hydrogel to maintain chemokine gradients despite luminal flow.
• Controlled fluid flow rates to modulate shear stress on the vessel wall.

Main Results:

• Luminal flow and shear stress were identified as key regulators of angiogenic sprouting speed and morphogenesis.
• The observed effects of shear stress on sprouting were mediated by changes in vascular permeability.
• The developed model successfully recapitulated chemokine gradient-driven angiogenesis under controlled flow conditions.

Conclusions:

• Mechanical forces from luminal flow significantly impact angiogenesis, acting in concert with biochemical signals.
• Vascular permeability is a critical mediator linking shear stress to endothelial cell sprouting.
• This 3D model provides a valuable platform for dissecting the complex interplay of factors regulating angiogenesis.