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

ABSTRACT The human vascular system is a sophisticated hierarchical network branching from large‐diameter vessels to fine capillaries. Recapitulating this hierarchy remains a major biofabrication challenge, as oxygen diffusion from the nearest capillary is limited to ≈200 µm in native tissues, while current vascularized constructs struggle to maintain stable perfusion and functional multiscale architectures. To address this, a hybrid fabrication strategy is introduced that combines top‐down microfabrication of tubular scaffolds via electrospinning with bottom‐up bioprinting of cell‐laden bioinks. This approach enables the engineering of spatially programmable endothelialized tubular networks across three scales: macrovessels (≈3 mm), mesovessels (500–2000 µm), and capillaries (10–25 µm). Electrospun macrovessels exhibit artery‐like mechanical properties in longitudinal and circumferential directions. Bioprinting enables precise control over meso‐ and capillary‐scale vessels, facilitating the hierarchical patterning of complex architectures. Integrated triple‐scale endothelialized tubular networks formed interconnected, perfusable architectures comprising spatially patterned capillaries and enhanced diffusive transport by more than fivefold. Dynamic culture within endothelialized tubular networks of 5 mm thick tissue constructs supports high cell viability, rapid capillary formation, and in vivo‐like endothelial phenotypes under moderate flow. This work uniquely enables scalable vascular–mimetic architectures with artery‐like mechanical properties and spatially defined capillaries, representing a previously unattainable integration in angiogenesis, bioprinting, electrospinning, scaled‐up tissue constructs, vascular tissue engineeringlarge‐scale vascular constructs.