3D‐printed Engineered Trachea Functionalized by Diverse Extracellular Matrix Particles

Abstract It remains a significant challenge to construct a tracheal substitute with both a native‐like structure and multiple essential physiological functions. In this study, a combination of 3D printing techniques and a modular strategy is employed to fabricate an engineered trachea, in which the decellularized extracellular matrix particles (DEPs) from diverse sources determined specific regenerative environments in different spatial regions. Costal cartilage‐derived DEPs are integrated within the cartilage rings of the engineered trachea. They effectively activated chondrocytes to secrete specific matrix proteins and develop into mature cartilage with a natural pattern of collagen deposition, which provided sufficient mechanical properties to maintain tracheal ventilation. Lung‐derived DEPsare strategically placed between the cartilage rings, and are able to accelerate endothelial cell migration to form a transmural vessel network. Additionally, lung‐derived DEPs exhibited a great capability to recruit macrophages and facilitate their polarization, which is beneficial for tissue regeneration. The engineered trachea underwent heterotopic vascularization and utilized for long‐segmental trachea replacement in a rabbit model, demonstrating a satisfactory physiological function. Through DEP functionalization, the tracheal substitute developed a native‐like complex structure with adequate mechanical supply, abundant blood perfusion, and favorable immune conditions, demonstrating significant clinical potential for patients requiring tracheal reconstruction.