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Updated: Nov 22, 2025

Micropatterning and Assembly of 3D Microvessels
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Flow-Induced Vascular Network Formation and Maturation in Three-Dimensional Engineered Tissue.

Barak Zohar1, Yaron Blinder1,2, David J Mooney3,2

  • 1Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 3200003, Israel.

ACS Biomaterials Science & Engineering
|January 9, 2021
PubMed
Summary

Directly perfusing engineered tissues with flow significantly enhances blood vessel network formation and maturation. This vascularization improvement is crucial for developing larger, clinically relevant tissue substitutes.

Keywords:
endothelial cellsengineered tissueflow bioreactorsfluid shear stressvascular networks

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Area of Science:

  • Biomaterials Engineering
  • Tissue Engineering
  • Regenerative Medicine

Background:

  • Engineered 3D constructs are valuable for studying cell interactions and as potential tissue substitutes.
  • Diffusion limitations and lack of perfusable blood vessels hinder cell viability in larger engineered tissues (>hundreds of microns).
  • Flow-induced shear stress in 2D models promotes endothelial cell migration and angiogenesis, but its effect in 3D implantable tissues is less understood.

Purpose of the Study:

  • To investigate the impact of direct flow-induced shear stress on vascularization within implantable 3D engineered tissues.
  • To quantify the differential effects of various shear stress levels on vascular parameters under constant culture conditions.

Main Methods:

  • Culturing 3D scaffold tissues under direct flow conditions with varying shear stress levels.
  • Comparing vascular network development and maturation under flow versus static conditions.
  • Measuring vessel network morphogenesis parameters, ECM protein distribution, and alpha-smooth muscle actin (α-SMA) colocalization.

Main Results:

  • Direct flow conditions led to significant (>100%) increases in vessel network morphogenesis parameters compared to static cultures.
  • Enhanced depth distribution of vessels and extracellular matrix (ECM) proteins was observed under flow.
  • Flow promoted vessel network complexity and maturation, evidenced by increased α-SMA colocalization with endothelial networks.

Conclusions:

  • Direct flow-induced shear stress significantly promotes 3D neovascularization in engineered tissues.
  • Flow conditions are advantageous for improving vascular network development in large-volume tissue substitutes.
  • This approach may be critical for creating clinically relevant engineered tissues.