Bioengineered tracheal graft with enhanced vascularization and mechanical stability for functional airway reconstruction.

Tracheal reconstruction remains a formidable clinical challenge due to the complex structural, biomechanical, and physiological requirements of the airway. Traditional approaches, including autologous grafts, allografts, and synthetic prostheses, suffer from limitations such as donor site morbidity, immune rejection, and mechanical instability. Tissue-engineered tracheal grafts have emerged as a promising alternative, integrating advanced biomaterials, cellular therapies, and biofabrication techniques to create functional airway replacements. Synthetic polymers, such as polycaprolactone and polylactic acid, provide mechanical stability and tunable degradation properties, while extracellular matrix - derived biomaterials enhance biocompatibility and support cellular integration. Recent advances in stem cell biology, particularly the application of mesenchymal stem cells, induced pluripotent stem cells, and adipose-derived stem cells, have facilitated cartilage regeneration, epithelialization, and immune modulation within engineered constructs. However, achieving adequate vascularization remains a major bottleneck, necessitating the development of pre-vascularized scaffolds, growth factor delivery systems, and in vivo bioreactor strategies. Emerging technologies, including 3D bioprinting, electrospinning, and AI-driven scaffold design, are transforming the landscape of tracheal tissue engineering by enabling precise control over scaffold architecture, cellular distribution, and functional integration. Despite these advances, challenges such as mechanical failure, chronic inflammation, and regulatory hurdles must be addressed to ensure clinical translation. This review critically examines the latest advancements, persisting challenges, and future perspectives in artificial trachea engineering, providing a comprehensive roadmap for its development and clinical implementation.