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

Abstract

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.

Keywords: Regenerative medicine; Stem cell; Tissue engineering; Trachea reconstruction; Vascularization.

Fig. 1

Strategies for Tracheal Replacement and Reconstruction. Note: Different approaches for tracheal replacement when direct end-to-end anastomosis is not feasible. These include synthetic prostheses, allografts, tracheal transplantation, autologous tissue grafts, and bioengineered constructs using bioreactors. Bioengineering offers a promising alternative by integrating stem cells and biomaterials to create functional airway grafts.

Fig. 2

Histological Image of Tracheal Restenosis. Note: Histological section showing restenosis at the site of a synthetic tracheal prosthesis. The arrow indicates the presence of excessive fibroproliferative tissue, leading to airway narrowing. Restenosis is a common complication of synthetic implants, often resulting from chronic inflammation and tissue overgrowth.

Fig. 3

PCR Confirmation of Recipient-Derived Tissue in Engineered Trachea. Note: Polymerase chain reaction (PCR) analysis showing SRY gene amplification (a male-specific marker) and IGF1 gene amplification in native tracheal tissue, allogeneic airway segments (AAs) at 8 weeks, and control samples. The absence of SRY amplification in female controls and its presence in male-derived tissues confirm that regenerated tracheal structures originate from the recipient rather than the donor.