Science Advances

DLP-bioprinted ultrabiomimetic trachea with spatiotemporal angiogenesis regulation for segmental airway reconstruction

2026-05-12

Segmental airway reconstruction requires tracheal grafts that emulate the hierarchical structure and biochemical functions of native trachea. However, achieving both biomimetic fidelity and efficient vascularization remains challenging. Here, we present a digitally light-processed tissue-engineered trachea featuring anatomically biomimetic C-shaped cartilage rings, alternating fibrous rings, and dorsal fibrous bands, precisely replicating the structural hierarchy of native trachea. To promote rapid neovascularization, we develop a stress-relaxing and degradable alginate-based hydrogel capable of dynamic vascular endothelial growth factor loading and sustained release, thereby facilitating endothelial cell migration and angiogenesis. Within the fibrous regions, pre-engineered vascular channels are incorporated to guide host vascular ingrowth, resulting in a 2.6-fold increase in neovascular density compared to no-channel scaffolds. This platform integrates spatial control through precise structural design with temporal bioactive signal modulation, enabling synchronized vascularization. When transplanted via end-to-end anastomosis with native tracheae, the vascularized grafts exhibit enhanced survival and functional integration, offering a robust strategy for tracheal tissue engineering and segmental airway reconstruction.

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DOI https://doi.org/10.1126/sciadv.adz9453