Scaffold‐Free Tracheal Engineering via a Modular Strategy Based on Cartilage and Epithelium Sheets

Abstract

Tracheal defects lead to devastating problems, and practical clinical substitutes that have complex functional structures and can avoid adverse influences from exogenous bioscaffolds are lacking. Herein, a modular strategy for scaffold‐free tracheal engineering is developed. A cartilage sheet (Cart‐S) prepared by high‐density culture is laminated and reshaped to construct a cartilage tube as the main load‐bearing structure in which the chondrocytes exhibit a stable phenotype and secreted considerable cartilage‐specific matrix, presenting a native‐like grid arrangement. To further build a tracheal epithelial barrier, a temperature‐sensitive technique is used to construct the monolayer epithelium sheet (Epi‐S), in which the airway epithelial cells present integrated tight junctions, good transepithelial electrical resistance, and favorable ciliary differentiation capability. Epi‐S can be integrally transferred to inner wall of cartilage tube, forming a scaffold‐free complex tracheal substitute (SC‐trachea). Interestingly, when Epi‐S is attached to the cartilage surface, epithelium‐specific gene expression is significantly enhanced. SC‐trachea establishes abundant blood supply via heterotopic vascularization and then is pedicle transplanted for tracheal reconstruction, achieving 83.3% survival outcomes in rabbit models. Notably, the scaffold‐free engineered trachea simultaneously satisfies sufficient mechanical properties and barrier function due to its matrix‐rich cartilage structure and well‐differentiated ciliated epithelium, demonstrating great clinical potential for long‐segmental tracheal reconstruction.

The effect of bioactivity of airway epithelial cells using methacrylated gelatin scaffold loaded with exosomes derived from bone marrow mesenchymal stem cells

“…For the second strategy, these epithelial cells can be used as biological dressings to provide barrier function and signaling to enhance local regeneration. Buccal mucosa was preimplanted on the luminal surface of the tracheal graft and was degenerated with the postoperative use of immunosuppression 41 . Although these cells cannot be converted into ciliated epithelial cells, this mucosal source may contribute to the formation of a temporary infection barrier in long‐segment grafts, buying more time for regeneration of the regenerating airway mucosa at the anastomotic margin.…”

“…Buccal mucosa was preimplanted on the luminal surface of the tracheal graft and was degenerated with the postoperative use of immunosuppression. 41 Although these cells cannot be converted into ciliated epithelial cells, this mucosal source may contribute to the formation of a temporary infection barrier in long-segment grafts, buying more time for regeneration of the regenerating airway mucosa at the anastomotic margin. In fact, this bioactive dressing approach, using allogeneic or even lyophilized epithelial cells, can stimulate the regeneration of surrounding host cells.…”

Pre-epithelialized cryopreserved tracheal allograft for neo-trachea flap engineering

“…The goal of tracheal reconstruction is to provide a non-collapsible airway with a stable epithelial lining and reliable, well-vascularized tissue coverage (Yu et al, 2006;Delaere et al, 2010;Yu et al, 2011;Rendina and Patterson, 2022;Yang et al, 2023). To achieve this goal, in the present study, we applied a partially decellularized tracheal scaffold to provide airway support and successfully covered its lumen with RECs to provide a functional respiratory lining.…”

Surgical Innovations in Tracheal Reconstruction: A Review on Synthetic Material Fabrication

“…With the epithelial foundation, the model displayed beneficial ciliary differentiation capabilities. A combination of such characteristics demonstrates its clinical potential for long-segment tracheal reconstruction [45]. The 90-day mortality rate was low among patients who underwent airway bioengineering using cryopreserved aortic matrices.…”