Engineering primitive multiscale chimeric vasculature by combining human microvessels with explanted murine vessels.

Area of Science:

• Regenerative Medicine
• Vascular Biology
• Tissue Engineering

Background:

• Established methods for engineering macrovascular grafts and microvascular networks exist separately.
• Bridging these scales to create hierarchical vasculature for tissue support remains a challenge.

Purpose of the Study:

• To develop multiscale vascular constructs by connecting macroscopic mouse vessels to engineered capillary networks ex vivo.
• To assess the potential of isolated mouse vessels to form functional connections with microvasculature.

Main Methods:

• Isolated arterial and venous vessels from mice (thoracic aorta, vena cava, femoral vessels).
• Evaluated endothelial cell (EC) sprouting and inosculation with human cell-derived microvasculature in fibrin hydrogels.
• Integrated micromolded mesovessels to create a three-scale hierarchy (capillaries, mesovessels, macrovessels).

Main Results:

• The thoracic aorta showed the most significant sprouting and interconnection with capillaries.
• Cellular presence in the hydrogel reduced EC sprouting but did not prevent chimeric vessel formation.
• A primitive three-scale vascular hierarchy was successfully engineered.

Conclusions:

• Demonstrated proof-of-concept for creating hierarchical vasculature for regenerative medicine.
• Established an experimental model to study host-graft vessel anastomosis formation.