Instant trachea reconstruction using 3D-bioprinted <i>C</i>-shape biomimetic trachea based on tissue-specific matrix hydrogels.

Abstract

Currently, 3D-bioprinting technique has emerged as a promising strategy to offer native-like tracheal substitutes for segmental trachea reconstruction. However, there has been very limited breakthrough in tracheal repair using 3D-bioprinted biomimetic trachea owing to the lack of ideal bioinks, the requirement for precise structural biomimicking, and the complexity of multi-step surgical procedures by mean of intramuscular pre-implantation. Herein, we propose a one-step surgical technique, namely direct end-to-end anastomosis using <i>C</i>-shape 3D-bioprinted biomimetic trachea, for segmental trachea defect repair. First, two types of tissue-specific matrix hydrogels were exploited to provide mechanical and biological microenvironment conducive to the specific growth ways of cartilage and fibrous tissue respectively. In contrast to our previous <i>O</i>-shape tracheal design, the tubular structure of alternating <i>C</i>-shape cartilage rings and connecting vascularized-fibrous-tissue rings was meticulously designed for rapid 3D-bioprinting of tracheal constructs with optimal printing paths and models. Furthermore, <i>in vivo</i> trachea regeneration in nude mice showed satisfactory mechanical adaptability and efficient physiological regeneration. Finally, <i>in situ</i> segmental trachea reconstruction by direct end-to-end anastomosis in rabbits was successfully achieved using 3D-bioprinted <i>C</i>-shape biomimetic trachea. This study demonstrates the potential of advanced 3D-bioprinting for instant and efficient repair of segmental trachea defects.