3D curvature-instructed endothelial flow response and tissue vascularization

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Vascular Biology

Background:

• Engineering complex 3D vascular networks with controlled geometry remains a significant challenge in tissue engineering.
• Recapitulating continuous vascular features like defined diameter, curvature, and torsion is crucial for functional tissue development.
• Current methods lack precise control over microvessel architecture, hindering advancements in tissue perfusion and regeneration.

Purpose of the Study:

• To develop a novel spiral microvessel model for precise control of 3D vascular geometry, including curvature and torsion.
• To investigate the impact of 3D vascular architecture on endothelial cell (EC) behavior and gene expression.
• To demonstrate the utility of this model for tissue engineering applications, such as tumor modeling and cardiac tissue vascularization.

Main Methods:

• Development of a spiral microvessel system allowing precise control over curvature and torsion.
• Homogeneous tissue perfusion at the centimeter scale was achieved using the developed system.
• Proof-of-principle modeling of tumor progression and engineered cardiac tissue vascularization.
• Analysis of endothelial cell (EC) phenotypic and transcriptional changes induced by 3D curvature using bulk and single-cell RNA sequencing.

Main Results:

• The spiral microvessel model successfully controlled curvature and torsion, supporting centimeter-scale tissue perfusion.
• 3D curvature induced EC rotation and mixing under laminar flow, resulting in distinct phenotypic and transcriptional alterations.
• RNA sequencing identified specific EC gene clusters associated with a proinflammatory phenotype, vascular development, remodeling, and vascular stability.

Conclusions:

• The developed spiral microvessel model provides unprecedented control over 3D vascular geometry, crucial for tissue engineering.
• Heterogeneous vascular structures significantly influence endothelial cell development, pathogenesis, and inflammatory responses.
• This innovative tool offers potential improvements for tissue vascularization, regeneration, and understanding disease mechanisms.