Towards a bioengineered airway: advances in tracheal tissue engineering and biofabrication

Tracheal damage arising from inflammation, trauma, congenital anomalies, or tumors can lead to life-threatening complications, yet current treatments, including surgical reconstruction, stenting, laser therapies, autografts, and allografts, remain inadequate, especially for long-segment defects. As a result, tracheal tissue engineering has emerged as a promising alternative, aiming to create functional biomimetic constructs that reduce dependence on complex surgeries, long-term stenting, and immunosuppression. Advances in additive manufacturing and 3D bioprinting have accelerated progress toward engineered tracheal substitutes; however, a fully functional, clinically viable 3D-bioprinted human tracheal graft has yet to be realized. This review assesses current bioengineering strategies, with a particular emphasis on the interplay between cell sources, scaffold materials, and fabrication methods, specifically focusing on 3D bioprinted tracheal constructs. Across existing studies, the most promising direction lies in multi-material, multicellular, spatially patterned bioprinting approaches that can better recapitulate the trachea's complex biomechanics and heterogeneous tissue composition. Finally, we summarize regulatory considerations and outline key scientific and translational barriers, emphasizing that overcoming challenges in vascularization, innervation, and long-term functional integration will be essential to achieving a physiologically aligned, clinically deployable tracheal substitute.