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

Abstract

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.