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

• DOI: 10.1002/adhm.202202022
• Publication Date: 2022-12-03T04:20:50Z
• Authors: Minglei Yang; Jiafei Chen; Yi Chen; Weikang Lin; Hai Tang; Ziwen Fan; Long Wang; Yunlang She; Feng Jin; Lei Zhang; Weiyan Sun; Chang Chen
• Keywords: Chondrogenesis; Matrix (chemical analysis)

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