Engineering an artificial trachea: Quantitative benchmarks and modular strategies for mechanics, epithelialization, and vascular integration

Abstract Long‐segment tracheal defects remain a persistent clinical challenge because restoring airway patency is not equivalent to restoring airway function. The trachea is a mechanically anisotropic composite—cartilage rings provide radial rigidity while the posterior wall preserves longitudinal compliance—and its long‐term performance depends on rapid epithelial coverage, effective mucociliary clearance, and timely vascular support. Here, we synthesize clinical failure modes and native structure–function requirements into practical design benchmarks for artificial tracheae. We first outline why standard surgical repair reaches its limits and why stenting, while lifesaving, often incurs a high burden of migration, granulation, mucus plugging, and infection. We then map these complications to engineering constraints on geometry, mechanics, fixation, and degradation, highlighting the importance of junctional stress and time‐dependent remodeling. Next, we review major reconstruction routes—synthetic prostheses, allograft/autologous tissue strategies, decellularized matrices, patient‐tailored scaffolds, and scaffold‐free constructs—focusing on what enables (or prevents) durable patency across preclinical and clinical settings. Finally, we discuss biological strategies that govern “handover” from an implanted construct to a living airway segment, emphasizing coordinated cartilage restoration, epithelial regeneration, vascularization, and immunomodulation, alongside manufacturing and quality‐control considerations needed for translation. By reframing artificial trachea development as a coupled mechano‐biological timing problem, this review highlights actionable priorities for designing safer, more reproducible, and clinically scalable airway replacements.