Integrated bioprinting of trachea-like structures based on tissue-specific bioink.

Segmental tracheal reconstruction remains clinically challenging due to insufficient blood supply and mechanical instability in current graft materials. Inspired by the natural trachea's alternating cartilage-fiber structure, we developed a 3D-bioprinted chondro-fibrous integrated trachea (CFT) using customized tissue-specific hydrogels modified with glucomannan-peptide copolymer (GM-P). This design mimics the native tissue's layered organization, combining cartilage-like rings (from iPSC-derived chondrocytes) and fibrous connective layers (from fibroblasts) through precise bioprinting. The GM-P hydrogel improved interlayer bonding and supported vascularization. Furthermore, in vivo trachea regeneration in nude mice showed satisfactory mechanical adaptability and efficient physiological regeneration. Finally, in situ segmental trachea reconstruction by direct end-to-end anastomosis in rabbits was successfully achieved without collapse. Altogether, this study combines layered bioprinting, tissue-specific multifunctional hydrogel, and stem cell technology, providing a technical reference for construction of complex tissues and promotes the clinical translation and application of engineered tissues or organs.