Abstract

In this study, we developed a new procedure for the rapid partial decellularization of the harvested trachea. Partial decellularization was performed using a combination of detergent and sonication to completely remove the epithelial layers outside of the cartilage ring. The post-decellularized tracheal segments were assessed with vital staining, which showed that the core cartilage cells remarkably remained intact while the cells outside of the cartilage were no longer viable. The ability of the decellularized tracheal segments to evade immune rejection was evaluated through heterotopic implantation of the segments into the chest muscle of rabbits without any immunosuppressive therapy, which demonstrated no evidence of severe rejection or tissue necrosis under H&E staining, as well as the mechanical stability under stress-pressure testing. Finally, orthotopic transplantation of partially decellularized trachea with no immunosuppression treatment resulted in 2 months of survival in two rabbits and one long-term survival (2 years) in one rabbit. Through evaluations of posttransplantation histology and endoscopy, we confirmed that our partial decellularization method could be a potential method of producing low-immunogenic cartilage scaffolds with viable, functional core cartilage cells that can achieve long-term survival after in vivo transplantation.

Highlights

  • Tracheal damage typically results from trauma, neoplastic diseases, congenital anomalies, and intubation procedures

  • The viability of the remaining chondrocytes in the scaffold could be clearly observed through vital staining, as shown in Figure 3, where red represents cells that have been damaged by the decellularization process, and green represents viable cells

  • We demonstrated that through our new partial decellularization protocol, we were able to create tracheal allograft scaffolds that were transplantable in a rabbit model

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Summary

Introduction

Tracheal damage typically results from trauma, neoplastic diseases, congenital anomalies, and intubation procedures. Severe injury or damage to the structure or luminal surface of the trachea can significantly reduce patient quality of life due to difficulties with breathing, speaking, and swallowing [1]. Anastomoses can be performed to reconnect two tracheal segments after resection for tracheal lesions less than 5 cm in length. For defects larger than 5 cm, there are few therapeutic options, which represents a major challenge in trachea reconstruction [2]. Several clinical and experimental studies have shown that homograft tracheal transplantation is one of the most promising methods for treating major tracheal lesions. An ideal solution for tracheal replacement has not been found. This encourages scientists to increased effort in this research field

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