Programming the Self-Organization of Endothelial Cells into Perfusable Microvasculature

Area of Science:

• Biomaterials science
• Cell biology
• Tissue engineering

Background:

• Constructing 3D microvascular networks is challenging.
• Bioprinting offers potential for patterning endothelial cells (ECs).
• Microenvironmental cues for EC self-organization into microvessels are not fully understood.

Purpose of the Study:

• Investigate microenvironmental factors influencing EC self-organization into microvessels.
• Identify conditions promoting cohesive and perfusable 3D microvascular network formation.
• Establish design principles for bioprinting-based microvascular engineering.

Main Methods:

• Patterned densely packed ECs within a 3D extracellular matrix (ECM).
• Varied ECM composition (e.g., collagen I) and media components (e.g., fetal bovine serum).
• Observed EC behavior, cord formation, lumenization, and fluid flow.

Main Results:

• Fibrillar matrices like collagen I promoted EC condensation into cords.
• A high-molecular-weight protein in fetal bovine serum inhibited EC condensation and destabilized cords.
• Optimized conditions (fibrillar collagen, no inhibitory protein) led to polarized, lumenized cords with mural cells.
• Branched, perfusable microvascular networks formed in 3 days.

Conclusions:

• Fibrillar collagen and specific media modifications are crucial for EC self-organization.
• Microenvironmental control is key for engineering perfusable microvascular networks.
• These findings provide design principles for bioprinting and micropatterning techniques in tissue engineering.