Decellularized extracellular matrix-loaded exosome hydrogel for cell-free tracheal scaffold in tracheal defect reconstruction and repair

Tracheal reconstruction presents a significant global clinical challenge due to the unique structure and function of the trachea, which complicates its repair. Key challenges include restoring tracheal function post-transplantation, managing surgical complications, and ensuring the long-term survival of transplanted tissue. Furthermore, adequate vascularization of the transplanted trachea, along with the repair of cartilage and epithelial cells, is critical for facilitating functional recovery and successful reconstruction. In this study, a decellularized tracheal matrix was extracted to preserve its natural bioactivity. Nanoclay and GelMA were then employed as carrier materials to integrate with the decellularized tracheal matrix, forming a hydrogel scaffold. Both nanoclay and GelMA offer tunable porous structures and surface properties that promote cell adhesion and proliferation, while providing sufficient mechanical support. By leveraging the biological functions of endothelial progenitor cell-derived exosomes, we successfully loaded exosomes onto the decellularized extracellular matrix, creating a novel cell-free tracheal scaffold for investigating tracheal defect repair. The scaffold exhibited excellent biocompatibility, promoting graft vascularization and facilitating the repair of tracheal cartilage and epithelium. These findings hold significant promise for advancing tracheal reconstruction surgery and offer valuable insights for future research in this area. Graphical abstract