Long-term observation of airway reconstruction using decellularized tracheal allografts in micro-miniature pigs at growing stage

Abstract

Introduction: Decellularized tissue exhibits cell matrix-like properties, along with reduced antigenicity. We explored the potential of decellularized allogeneic trachea to restore the upper respiratory tract, focusing on pediatric application. This study specifically aimed at long-term observation of tissue regeneration using a micro-miniature pig model. Methods: Artificial defects (15 × 15 mm) in the subglottis and trachea of micro-miniature pigs were repaired by transplantation of either allogeneic decellularized or fresh (control) tracheal patches. Pigs were evaluated in situ, by bronchoscopy, every three months, and sacrificed for histological examination at six and twelve months after transplantation. Results: No airway symptom was observed in any pig during the observation period. Bronchoscopy revealed the tracheal lumen to be restored by fresh grafts, showing an irregular surface with remarkable longitudinal compression; these changes were mild after restoration with decellularized grafts. Histologically, while fresh graft patches were denatured and replaced by calcified tissue, decellularized patches remained unchanged throughout the observation period. There were regeneration foci of cartilage adjacent to the grafts, and some foci joined the decellularized graft uniformly, suggesting the induction of tracheal reconstitution. Conclusion: Allogeneic decellularized tracheal tissue could serve as a promising biomaterial for tracheal restoration, especially for pediatric patients at the growing stage.

Keywords

• Tracheal restoration
• Decellularized tracheal tissue
• Tissue-engineering
• Regeneration
• Pig
• High hydrostatic pressure