Triple-Scale Endothelialized Tubular Networks via Hybrid Biofabrication for Scalable Vascular Tissue Engineering

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Biofabrication

Background:

• The human vascular system's hierarchical structure is challenging to replicate in engineered tissues.
• Limited oxygen diffusion restricts engineered vessel functionality and scale.
• Current vascularized constructs face challenges in stable perfusion and maintaining multiscale architectures.

Purpose of the Study:

• To develop a hybrid biofabrication strategy for engineering hierarchical, multi-scale vascular networks.
• To overcome limitations in oxygen diffusion and perfusion in engineered vascular constructs.
• To create scalable vascular-mimetic architectures with artery-like mechanical properties and spatially defined capillaries.

Main Methods:

• Combined top-down electrospinning of tubular scaffolds with bottom-up bioprinting of cell-laden bioinks.
• Engineered endothelialized tubular networks across three scales: macrovessels (≈3 mm), mesovessels (500–2000 µm), and capillaries (10–25 µm).
• Assessed mechanical properties of electrospun macrovessels and perfusability of integrated networks.

Main Results:

• Successfully engineered interconnected, perfusable vascular architectures with hierarchical patterning.
• Achieved enhanced diffusive transport ( >5-fold) via spatially patterned capillaries.
• Demonstrated high cell viability, rapid capillary formation, and in vivo-like endothelial phenotypes in 5 mm thick constructs under moderate flow.

Conclusions:

• The hybrid approach enables scalable vascular-mimetic architectures with artery-like mechanical properties.
• This integration of electrospinning and bioprinting achieves previously unattainable control over multi-scale vessel patterning.
• The developed method supports angiogenesis and the creation of large-scale vascular constructs for tissue engineering.