Successful tracheal regeneration using biofabricated autologous analogues without artificial supports

Abstract

Tracheas have a tubular structure consisting of cartilage rings continuously joined by a connective tissue membrane comprising a capillary network for tissue survival. Several tissue engineering efforts have been devoted to the design of scaffolds to produce complex structures. In this study, we successfully fabricated an artificial materials-free autologous tracheal analogue with engraftment ability by combining in vitro cell self-aggregation technique and in-body tissue architecture. The cartilage rings prepared by aggregating chondrocytes on designated culture grooves that induce cell self-aggregation were alternately connected to the connective tissues to form tubular tracheal analogues by subcutaneous embedding as in-body tissue architecture. The tracheal analogues allogeneically implanted into the rat trachea matured into native-like tracheal tissue by covering of luminal surfaces by the ciliated epithelium with mucus-producing goblet cells within eight months after implantation, while maintaining their structural integrity. Such autologous tracheal analogues would provide a foundation for further clinical research on the application of tissue-engineered tracheas to ensure their long-term functionality.